WO2021078301A1 - Protein degrading agent and use thereof in treatment of diseases - Google Patents

Abstract

Disclosed are compounds of formulae (I) and (II), or a salt, enantiomer, stereoisomer, solvate or polymorph thereof, and the use thereof for treating diseases. R ¹-A ¹-LIN-A ²-R ² (I) R ₁₂-A ₁₂-LIN-A ₂₂-R ₂₂ (II)

Description

Protein degradation agent and its application in disease treatment Technical field

The present disclosure relates to compounds of formula (I) and formula (II) or their salts, enantiomers, stereoisomers, solvates, polymorphs, and their use in the treatment of diseases.

R ¹ -A ¹ -LIN-A ² -R ² (I)

R ₁₂ -A ₁₂ -LIN-A ₂₂ -R ₂₂ (II)

Background technique

Apoptosis (programmed cell death) is a form in which cells undergo a series of programmed events to cause cell death, eliminate aging, unnecessary or unhealthy cells, and develop and maintain the health of the body. Play a vital role. Apoptosis is considered to be an important part of various processes, including normal cell renewal, immune system development and function, embryonic development and chemically induced cell death (Elmore, S., Toxicol Pathol, 2007.35(4): p. 495-516.). When cell apoptosis is abnormal, the cells that should be eliminated can escape apoptosis and continue to exist, such as cancer and leukemia; when cell apoptosis is excessive, it will kill too many cells and cause serious tissue damage, such as neurodegeneration Sexual diseases. Research and development have shown that blocking apoptosis signaling is a key sign of cancer (Radha, G. and SC Raghavan, Biochim Biophys Acta Rev Cancer, 2017.1868(1): p.309-314.; Reed, JC, Cancer Cell, 2003.3 (1): p.17-22.). Therefore, activating apoptosis signals in tumors is an effective anti-tumor strategy.

The BCL-2 (B cell lymphoma-2) protein family is a key regulator of programmed cell death or apoptosis. They are mainly located on the mitochondria and regulate the release of cytochrome c. Structurally, the BCL-2 family is characterized by an evolutionarily conserved BCL-2 homology (BH) domain, which is mainly divided into two subgroups, namely anti-apoptotic proteins and pro-apoptotic proteins. BCL-2 anti-apoptotic proteins, such as BCL-2, BCL-XL, MCL-1, BFL-1, BCL-W and BCL2L10, have four conserved regions: BH1, BH2, BH3 and BH4, which promote apoptosis by inhibiting Members to maintain the integrity of the outer mitochondrial membrane (Ivanova, H., et al., Oncotarget, 2016.7(34): p.55704-55720; Chang, BS, et al., Mol Cell Biol, 1999.19(10): p. 6673-81.). Pro-apoptotic proteins are effector proteins with multiple BH domains, such as BAK, BAX and BOK; or a large number of proteins containing only conserved BH3 (BH3-only) domains, such as BIM, PUMA, NOXA, and BID. Under physiological conditions, BCL-2 family protein levels maintain a dynamic balance, and cell signal transduction can affect the dynamic balance process to regulate the expression of pro-apoptotic proteins or anti-apoptotic proteins, thereby tilting the balance toward cell survival or death. When the balance is conducive to cell death, the oligomerization of the pro-apoptotic effector protein on the outer mitochondrial membrane leads to permeabilization of the outer mitochondrial membrane and release of cytochrome c, triggers the activation of the caspase enzyme cascade, and cleaves downstream substrates Cause cell death (Opferman, JT and A. Kothari, Cell Death Differ, 2018.25(1): p.37-45.).

In recent years, the development of small molecule inhibitors targeting the BCL-2 protein family has become a hot spot in the oncology field. The anti-apoptotic BCL-2 protein uses the BH3 domain containing the hydrophobic groove to chelate the pro-apoptotic protein BAK/BAX to exert its anti-apoptotic function. BCL-2 family protein antagonists, also known as "BH3 domain mimetics", are mainly used to prevent the binding of BH3 domains shared by the anti-apoptotic BCL-2 family proteins to the pro-apoptotic proteins BAX and BAK , Inhibit the effect of BCL-2 anti-apoptotic protein, and then induce tumor cell apoptosis.

So far, ABT-199 is the only BCL-2 inhibitor approved by the FDA for the clinical treatment of chronic myeloid leukemia and acute lymphoblastic leukemia (Carter, PJand GALazar, Nat Rev Drug Discov, 2018.17(3): p. 197-223.). However, since the growth of most solid tumors does not depend on the BCL-2 protein, a purely targeted BCL-2 inhibitor has no obvious effect in the treatment of solid tumors. Interestingly, BCL-XL protein is effective in many leukemia cells and entities. The expression in tumors is significantly increased (Davis, JM, et al., Sci Transl Med, 2015.7(279): p.279fs11.); on the other hand, studies have shown that the expression of BCL-XL in tumor tissues is positively correlated with tumor drug resistance (Vogler, M., Adv Med, 2014: p.943648.), showing that targeting BCL-XL is a potential and ideal anti-tumor molecular target.

MCL-1 (Myeloid cell leukemia-1) is one of the key members of the anti-apoptotic protein of the BCL-2 protein family. It is mainly located in the mitochondria of the cell. It is inserted into the mitochondrial membrane through a hydrophobic tail and is a key regulator of mitochondrial homeostasis Factors (Perciavalle, RM and JTOpferman, Trends Cell Biol, 2013.23(1): p.22-9.). The anti-apoptotic function of MCL-1 is essential for cell survival and homeostasis, and for promoting early embryonic development and neuron development and maintenance. It is reported that there is amplification and overexpression of MCL-1 in a variety of human tumors, including hematological malignancies and solid tumors (such as non-small cell lung cancer, breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer) (Campbell, KJ ,et al.,Cell Death Dis,2018.9(2):p.19.;LaBelle,JL,etal.,J Clin Invest,2012.122(6):p.2018-31.;Young,AI,etal. ,Breast Cancer Res,2016.18(1):p.125.;Zervantonakis,IK,et al.,Nat Commun,2017.8(1):p.365.;Akgul,C.,Cell Mol Life Sci,2009.66(8) :p.1326-36.). The analysis of 3131 cancer specimens showed that 36% of breast cancer and 54% of lung cancer specimens showed elevated levels of MCL-1 expression (Beroukhim, R., et al., Nature, 2010.463(7283): p.899 -905.). MCL-1 amplification and overexpression are also often associated with poor prognosis and resistance to anticancer drugs. For example, breast cancer, especially triple-negative breast cancer, is characterized by the amplification (~20%) of the MCL-1 locus (Balko, JM, et al., Cancer Discov, 2014.4(2): p.232-45 .). Studies have shown that MCL-1 is an intrinsic and acquired resistance factor, which limits the efficacy of various anti-tumor agents, including paclitaxel, cisplatin, erlotinib and other standard anti-cancer drugs, while down-regulating the expression of MCL-1 can increase The sensitivity of cancer cells to drug therapy (Wertz, IE, et al., Nature, 2011.471(7336): p.110-4.; Wei, SH, et al., Cancer Chemother Pharmacol, 2008.62(6): p. 1055-64.). For example, knockdown of MCL-1 in neuroblastoma cell lines increases its sensitivity to etoposide, doxorubicin, and ABT-737 by 2-300 times. The deletion of MCL-1 can reverse the chemoresistance of osteosarcoma cell lines in vitro and xenograft tumors in vivo to cisplatin and adriamycin (Lestini, BJ, et al., Cancer Biol Ther, 2009.8(16): p.1587 -95.).

MCL-1 is often overexpressed in human cancers and has been identified as a key to cancer drug resistance in multiple tumor types, making it an attractive therapeutic target. This emphasizes the necessity of developing MCL-1 inhibitors. At present, the development of MCL-1 inhibitors is mainly focused on BH3-mimics. Now several small molecules with high MCL-1 affinity and selectivity have been discovered. However, most MCL-1 inhibitors are still in the pre-clinical or early clinical development stage. Therefore, exploring novel small molecule drugs that can degrade MCL-1 protein has important clinical significance. We use protein degradation targeting drugs (Proteolysis Targeting Drugs). , PROTAD) technology platform developed MCL-1 protein degradation agent can effectively remove pathogenic proteins and used in the development of anti-tumor drugs (Neklesa, TK, JD Winkler, and CMCrews,. Pharmacol Ther, 2017.174: p.138-144 .; Xiang, W., CYYang, and L. Bai, Onco Targets Ther, 2018.11: p.7301-7314.).

The abnormally activated Hedgehog (Hh) signaling pathway is closely related to the occurrence and development of many human tumors, such as basal cell carcinoma, medulloblastoma, etc. (Nat Genet, 2016.48(4): p.398-406; Cancer Cell, 2014.25( 3): p.393-405). The signal transduction of Hh in cells is a form of cascade. Its key molecules include PTCH receptor with 12 transmembrane domains, SMO (Smoothened) receptor with 7 transmembrane structure, SUFU protein and nuclear transcription factor GLI protein. family. In the absence of exogenous HH ligand, PTCH inhibits SMO activity and the signal pathway is in an inhibited state; when exogenous HH ligand binds to PTCH, the inhibition of SMO is released, and activated SMO promotes the dissociation of inhibitory protein SUFU and GLI, GLI enters the nucleus to initiate transcription of downstream target genes and activate the Hh signaling pathway (Nat Rev Mol Cell Biol, 2013.14(7): p.416-29; Genes Dev, 2010.24(7): p.670-82). At present, the drugs approved by the FDA for the treatment of basal cell carcinoma all target SMO (Cell, 2016.164(5): p.831). It is obvious that SMO mutations, SUFU loss-of-function mutations and other key downstream SMO signaling molecules are inherited. Tumors with abnormal Hh activation caused by the changes have no growth inhibitory effect. Recently, studies have reported that SUFU protein contains a conserved BH3 sequence, which can bind to anti-apoptotic proteins such as BCL-XL, BCL-2, MCL-1, etc. in the cell, thereby releasing the inhibitory effect of SUFU on GLI protein and ultimately leading to Hh Pathway activation; inhibiting the binding of BCL-XL and other anti-apoptotic proteins to SUFU can effectively inhibit the activation of the Hh signaling pathway (Nat Cell Biol, 2017.19(10): p.1226-1236). Based on this, targeting BCL-2 family proteins is also a strategy for developing inhibitors targeting the Hh signaling pathway.

Summary of the invention

Therefore, an object of the present disclosure is to provide a compound of formula (I):

R ¹ -A ¹ -LIN-A ² -R ² (I)

Or its salts, enantiomers, stereoisomers, solvates, polymorphs,

Where R ¹ means:

A ¹ does not exist or represents a carbonyl group;

A ² does not exist or represents a carbonyl group;

R ² represents the structural formula of formula (I-1) or formula (I-2):

Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl; and

LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The group consisting of interrupted groups, where when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1), wherein the R ³ group represents Ethynylene or vinylene;

However, the following compounds are excluded (that is, the following compounds are excluded), of which:

R ¹ means:

A ¹ does not exist or represents a carbonyl group;

LIN represents a substituted or unsubstituted linear or branched alkylene group interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof;

A ² does not exist or represents a carbonyl group; and

R ² represents the structural formula of formula (I-1) or formula (I-2):

Where X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), and R ⁴ represents H.

The compounds of formula (I) or their salts, enantiomers, stereoisomers, solvates, and polymorphs of the present disclosure further exclude the following compounds:

In formula (I), R ¹ represents:

A ¹ does not exist or represents a carbonyl group;

LIN represents a substituted or unsubstituted linear or branched alkylene group; and

A ² does not exist or represents a carbonyl group, and R ² represents the structural formula of formula (I-1):

Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), wherein R ⁴ represents H or C _1-3 alkyl;

or

A ² represents a carbonyl group, and R ² represents the structural formula of formula (I-2):

Another object of the present disclosure is to provide a pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

Another object of the present disclosure is to provide the compound of formula (I), or a pharmaceutically acceptable salt thereof, which is used in the preparation for the prevention and/or treatment of BCL-2 family proteins or Hedgehog signaling pathway. Drugs for diseases (including but not limited to tumors and non-neoplastic diseases such as liver cirrhosis, renal fibrosis, liver fibrosis, bone marrow fibrosis, etc.):

R ¹ -A ¹ -LIN-A ² -R ² (I).

Another object of the present disclosure is to provide the compound of formula (I), or a pharmaceutically acceptable salt thereof, for use as a medicament:

R ¹ -A ¹ -LIN-A ² -R ² (I).

The compound of formula (I) described in the present disclosure, or a pharmaceutically acceptable salt thereof, is used for the prevention and/or treatment of diseases related to BCL-2 family proteins or Hedgehog signaling pathway (including but not limited to tumors and diseases). Tumor diseases such as liver cirrhosis, renal fibrosis, liver fibrosis, bone marrow fibrosis, etc.).

The tumor is a tumor that depends on BCL-2 family proteins (for example, BCL-2 and/or MCL-1 and/or BCL-XL), or a tumor that depends on the Hedgehog signaling pathway.

The diseases related to BCL-2 family proteins or Hedgehog signaling pathway include tumors and non-neoplastic diseases, including but not limited to myeloma, including multiple myeloma (MM); leukemia, including chronic lymphocytic leukemia (CLL) , Acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML); lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B cell lymphoma; myelodysplastic syndrome; bone marrow Fibrosis, renal fibrosis, liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer; prostate cancer; medulloblasts Tumor; Basal cell carcinoma; Goering syndrome; Esophageal cancer; Colorectal cancer; Medulloblastoma; Rhabdomyosarcoma; Hepatoblastoma; Glioma; Astrocytoma; Liver cancer; Liver cirrhosis; Soft tissue sarcoma; And pancreatic cancer.

Another object of the present disclosure is to provide a method for preventing and/or treating diseases related to BCL-2 family proteins or Hedgehog signaling pathway, which comprises administering a therapeutically effective amount of the formula (I) to a subject in need thereof The compound, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition.

On the other hand, an object of the present disclosure is to provide a compound of formula (II):

R ₁₂ -A ₁₂ -LIN-A ₂₂ -R ₂₂ (II)

Where R ₁₂ means:

Where R _x means

The symbol * represents the connection point with NH, and the symbol ** represents _{the connection point with A 12} , n represents an integer of 1-3, R _b1 , R _b2 , R _b3 and R _{b4 are the} same or different and are independently H Or oxo group, and R _b5 represents H or C _1-3 alkyl;

Where R _y means

The symbol * represents the connection point with O, and the symbol ** represents _{the connection point with A 12} , m represents an integer of 1-3, and

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group;

R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1) or formula (II-2):

Where X represents CH ₂ or CO, R _c does not exist or represents N(R _c1 ), O, S, ethynylene, vinylene, or five- or six-membered heterocyclylene, where R _c1 and R _c2 are independent of each other地 represents H or C _1-3 alkyl, and R _d represents H or methyl; and

LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1- 9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optionally substituted heterocyclylene or any The group consisting of the combination is interrupted, wherein when LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are not present, and R ₂₂ represents optionally A substituted adamantyl group, or R ₂₂ represents the structural formula of formula (II-1), wherein R _c does not exist or represents an ethynylene group, a vinylene group, or a five- or six-membered heterocyclylene;

The condition is when R ₁₂ represents any of the following structural formulas:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12,}

R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents a five-membered or six-membered heterocyclylene, and R _c2 represents H or C _1-3 alkyl, and LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1- 15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optional substitution The group consisting of the heterocyclylene or any combination thereof is interrupted, wherein in the absence of LIN, one of A ₁₂ and A ₂₂ does not exist and the other represents a carbonyl group or both A ₁₂ and A ₂₂ Does not exist, or

R ₂₂ represents the structural formula of formula (II-1) wherein X represents CH ₂ or CO.'S, and R _c represents O, and R _c2 represents H or C _{1- 3} alkyl, LIN, and a substituted or unsubstituted straight or Branched alkylene, or

R ₂₂ represents the structural formula of formula (II-2), wherein R _d represents a methyl group, and A _{22 is} not present, and LIN represents a substituted or unsubstituted linear or branched alkylene group;

as well as

The condition is when R ₁₂ represents any of the following structural formulas:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12;}

R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents a five-membered or six-membered heterocyclylene or O, and R _c2 represents H or C _1-3 alkyl, and LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, can The group consisting of optionally substituted heterocyclylene or any combination thereof is interrupted, wherein in the absence of LIN, one of A ₁₂ and A ₂₂ does not exist and the other represents a carbonyl group or both A ₁₂ and A ₂₂ Neither is present, and R ₂₂ represents an optionally substituted adamantyl group, or R ₂₂ represents the structural formula of formula (II-1), wherein R _c represents a five-membered or six-membered heterocyclylene, or

R ₂₂ represents the structural formula of formula (II-1), where X represents CH ₂ or CO, and R _c represents vinylene or ethynylene, and R _c2 represents C _1-3 alkyl, and LIN does not exist or represents substitution Or an unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof Interrupt, or

R ₂₂ represents the structural formula of formula (II-2), wherein R _d represents a methyl group, and LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (E.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1 A) interrupted by a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof.

Another object of the present disclosure is to provide a pharmaceutical composition comprising the compound of formula (II) or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

Another object of the present disclosure is to provide the compound of formula (II), or a pharmaceutically acceptable salt thereof, which is used in the preparation for the prevention and/or treatment of BCL-2 family proteins or Hedgehog signaling pathway. Medicines for diseases:

R ₁₂ -A ₁₂ -LIN-A ₂₂ -R ₂₂ (II).

Another object of the present disclosure is to provide the compound of formula (II), or a pharmaceutically acceptable salt thereof, for use as a medicament:

R ₁₂ -A ₁₂ -LIN-A ₂₂ -R ₂₂ (II).

The compound of formula (II) described in the present disclosure, or a pharmaceutically acceptable salt thereof, is used to prevent and/or treat diseases related to BCL-2 family proteins or Hedgehog signaling pathway (including tumors and non-neoplastic diseases) , Such as bone marrow fibrosis, renal fibrosis, liver fibrosis, liver cirrhosis, etc.).

The tumor is a tumor that depends on the BCL-2 family protein (for example, BCL-2 and/or MCL-1 and/or BCL-XL) oncogene, or a tumor that depends on the Hedgehog signaling pathway. In a sub-embodiment, the tumor includes hematological tumors and solid tumors, including but not limited to myeloma, including multiple myeloma (MM); leukemia, including chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML); lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B cell lymphoma; myelodysplastic syndrome; bone marrow fibrosis, renal fibrosis , Liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer; prostate cancer; medulloblastoma; basal cell carcinoma; Goering syndrome; esophageal cancer; colorectal cancer; medulloblastoma; rhabdomyosarcoma; hepatoblastic carcinoma; glioma; astrocytoma; liver cancer; liver cirrhosis; soft tissue sarcoma; and pancreatic cancer.

Another object of the present disclosure is to provide prevention and/or treatment of diseases related to BCL-2 family proteins or Hedgehog signaling pathway (including tumor and non-neoplastic diseases, such as myelofibrosis, renal fibrosis, liver fibrosis, and cirrhosis). Etc.), which comprises administering a therapeutically effective amount of the compound of formula (II), or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition to a subject in need thereof.

Brief description of the drawings

Figure 1 is a schematic diagram of the results of Western blotting experiments, which shows that the PROTAD drug of the present invention can significantly degrade MCL-1 protein compared with ABT-199.

Figure 2 is a schematic diagram of the results of Western blotting experiments, which shows that the PROTAD drug of the present invention can significantly degrade MCL-1 protein compared with ABT-199.

Figure 3 is a schematic diagram of the results of western blot experiments, which show that compounds SAIS361022 and SIAIS361023 can significantly degrade MCL-1 and BCL-XL proteins; SAIS361043, SAIS361044, SAIS361048, and SAIS361049 can significantly degrade BCL-XL proteins.

Figure 4 is a schematic diagram of the results of Western blot experiments, which show that compounds SIAIS363021, SIAIS363022, SIAIS363025, SIAIS363026, SIAIS363037, SIAIS363038, SIAIS364048, SIAIS364049, SIAIS364051, SIAIS364056, and SIAIS364057 can significantly degrade BCL-XL.

Figure 5 is a schematic diagram of the results of Western blot experiments, which shows that the compounds of the present invention SIAIS346014, SIAIS268027, SIAIS292113, SIAIS255134 can significantly degrade MCL-1 and BCL-XL proteins in Molt-4 cells, MV4; 11 cells, and NIH-3T3 cells .

Detailed ways

Designing degradants that target specific proteins is a new model for drug development, which can remove target proteins from cells. We use the protein degradation targeting drug (Proteolysis Targeting Drug, PROTAD) technology platform and use it for BCL-2 family proteins (Including BCL-2, MCL-1 protein and/or BCL-XL protein) clearance and used in the development of related diseases including tumor treatment drugs. PROTAD uses a specially designed bispecific protein regulator to "degrade" the BCL-2 family proteins (including BCL-2, MCL-1 protein and/or BCL-XL protein), and activate the protein degradation inside the cell. The pathway targeted degradation of BCL-2 family proteins (including BCL-2, MCL-1 protein and/or BCL-XL protein). Compared with traditional drug design, the targeted protein modulator small molecule developed by the PROTAD technology platform can induce the degradation of the target protein, and is essentially different from the traditional small molecule inhibitor in the mechanism. Therefore, we use the protein degradation technology platform to develop small molecule degradation agents that can degrade BCL-2 family proteins (including BCL-2, MCL-1 protein and/or BCL-XL protein), and apply them to the treatment of related diseases . A series of compounds designed and synthesized in the present disclosure have a wide range of pharmacological activities, and have the function of degrading BCL-2 family proteins (including BCL-2, MCL-1 protein and/or BCL-XL protein)/inhibiting BCL-2 family proteins (including The function of BCL-2, MCL-1 protein and/or BCL-XL protein) activity can be used in the treatment of related diseases including tumors.

i) Therefore, one aspect of the present disclosure provides a compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof,

R ¹ -A ¹ -LIN-A ² -R ² (I)

Where R ¹ means:

A ¹ does not exist or represents a carbonyl group;

A ² does not exist or represents a carbonyl group;

R ² represents the structural formula of formula (I-1) or formula (I-2):

Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl; and

LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1- 9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optionally substituted heterocyclylene or any The group consisting of the combination is interrupted, wherein when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1), wherein the R ³ group Represents ethynylene or vinylene;

However, the following compounds are excluded (that is, the following compounds are excluded from the scope of the present invention), in which:

R ¹ means:

A ¹ does not exist or represents a carbonyl group;

LIN represents a substituted or unsubstituted linear or branched alkylene group interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof;

A ² does not exist or represents a carbonyl group; and

R ² represents the structural formula of formula (I-1) or formula (I-2):

Where X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), and R ⁴ represents H.

In the compound of formula (I) of the present disclosure, when LIN represents a substituted or unsubstituted linear or branched alkylene group, the alkylene group is optionally substituted by one or more (e.g., 1-20, 1 -15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optional The group consisting of the substituted heterocyclylene or any combination thereof is interrupted. Preferably, either one of the two ends of the alkylene group may be connected to the group A ¹ , and the other end is connected to the group A ² .

In the present disclosure, the structural formula of formula (I-1) can also be expressed as a combination of the following structural formulas:

Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl.

In the present disclosure, the expression "the alkylene group is interrupted by one or more... groups" means that one or more (for example 1- 10, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1) groups as defined herein, That is, any one or more pairs of two adjacent carbon atoms in the carbon chain main chain structure of the linear or branched alkylene are covalently connected through the group. For example, the expression "the alkylene group is interrupted by one or more oxygens" means that one or more carbon atoms are interspersed between any two adjacent carbon atoms in the carbon chain main chain structure of the linear or branched alkylene group. (E.g. 1-10, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1) oxygen atom, thereby The formation contains one or more (e.g. 1-10, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1 A) the oxaalkylene group of the _{"-CH 2 -O-CH 2} -" fragment.

In a sub-embodiment of the present disclosure, the compound of formula (I) further does not include the following compounds (that is, the following compounds are excluded from the scope of the present invention):

In formula (I), R ¹ represents:

A ¹ does not exist or represents a carbonyl group;

LIN represents a substituted or unsubstituted linear or branched alkylene group; and

A ² does not exist or represents a carbonyl group, and R ² represents the structural formula of formula (I-1):

Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), wherein R ⁴ represents H or C _1-3 alkyl;

or

A ² represents a carbonyl group, and R ² represents the structural formula of formula (I-2):

In a sub-embodiment of the present disclosure, in the compound of formula (I), R ² represents:

In a sub-embodiment of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ^{2 is} not present.

In a sub-embodiment of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ^{2 is} not present.

In a sub-embodiment of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof interrupted; and A ² represents a carbonyl group.

In a sub-embodiment of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof interrupted; and A ² represents a carbonyl group.

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN does not exist, one of A ¹ and A ² does not exist and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1) , Wherein the R ³ group represents an ethynylene group or a vinylene group.

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _1-30 alkylene group, and the substituent is selected from a C ₁ -C ₃ alkyl group , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted, wherein _{the substituents of the C 2-30} alkylene and heterocyclylene are independently Is selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkane) Oxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be One or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -, -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O (CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _a3 , R _a4 , R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (such as C _1-6 alkylamino) or any combination thereof, wherein when in the same LIN, R _a1 , R _a2 , R _a3 , R _a4 , or R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , and R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of the present disclosure, LIN represents the following substituted or unsubstituted groups:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) _3- (O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) _4- (O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH _2- (O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) _8- , -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) _4- , -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O (CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) _3- (O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) _8- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH ₂ -, -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH _2- O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -( O(CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH _2- O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) an optionally substituted heterocyclylene (especially a five-membered or six-membered heterocyclylene) having a heteroatom selected from O, N and S interrupted, wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (for example C _5-14 aryl, especially C _6-10 aryl), alkoxy (for example C _1-6 alkoxy), alkyl Alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more ( For example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _{n7 -heterocyclylene} -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is unsubstituted or It is substituted with a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof. In a sub-embodiment of the present disclosure, examples of the heterocyclylene include, but are not limited to, azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, Imidazolylidene, pyrazolidine, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, Tetrahydrothiopyranyl, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazole, Piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein The heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or Any combination of substituents is substituted.

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperidinylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents -CH ₂ -piperidinylene-CH ₂ -, -(CH ₂ ) ₂ -piperidinylene-CH ₂ -,- CH ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperidinylene -(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperidinylene -(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperidinide Ridinyl -(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -piperidinyl-(CH ₂ ) ₃ -.

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperazinylidene -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1. 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of the present disclosure, the compound of formula (I) in the LIN represents - (CH _{2) 2} - piperazinyl alkylene -CH ₂ -, - CH ₂ - piperazinyl alkylene -CH ₂ -, - CH ₂ -piperazinyl-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperazinyl -(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperazinyl -(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperazine Azinyl-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -piperazinyl-(CH ₂ ) ₃ -, or -(CH ₂ ) ₄ -piperazinyl-(CH ₂ ) ₄ -.

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -triazolylidene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of the present disclosure, the compound of formula (I) in the LIN represents -CH ₂ - triazolyl alkylene -CH ₂ -, - CH ₂ - triazolyl alkylene _{- (CH 2) 2 -,} - CH ₂ -triazolylidene-(CH ₂ ) ₃ -, -CH ₂ -triazolylidene-(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -triazolylidene-CH ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₄ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) _4- Triazolylidene -(CH ₂ ) ₂ -.

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -imidazolylidene-(CH ₂ ) _n8 -, where n7 and n8 independently represent integers 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of the present disclosure, the compound of formula (I) in the LIN represents -CH ₂ - imidazolyl alkylene -CH ₂ -, - CH ₂ - imidazolyl alkylene _{- (CH 2) 2 -,} - CH 2 -Imidazolylidene-(CH ₂ ) ₃ -, -CH ₂ -imidazolylidene-(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -imidazolylidene-CH ₂ -, -(CH ₂ ) _2- Imidazolyl -(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₄ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₄ -, Or -(CH ₂ ) ₄ -imidazolylidene -(CH ₂ ) ₂ -.

In a sub-embodiment of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -pyrazolylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of the present disclosure, the compound of formula (I) in the LIN represents -CH ₂ - pyrazolyl alkylene -CH ₂ -, - CH ₂ - pyrazol-alkylene group _{- (CH 2) 2 -,} - CH ₂ -Pyrazolylene-(CH ₂ ) ₃ -, -CH ₂ -Pyrazolylene-(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -Pyrazolylene-CH ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₄ -, -(CH ₂ ) ₃ -Pyrazolylene -(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -Pyrazolylene -(CH ₂ ) ₃ -, -(CH ₂ ) _3- Pyrazolyl -(CH ₂ ) ₄ -or -(CH ₂ ) ₄ -pyrazolylene -(CH ₂ ) ₂ -.

ii) The present disclosure further provides another embodiment of the compound of formula (I):

R ¹ -A ¹ -LIN-A ² -R ² (I)

Where R ¹ means:

A ¹ does not exist or represents a carbonyl group;

A ² does not exist or represents a carbonyl group;

R ² represents the structural formula of formula (I-1):

Wherein X represents CH ₂ or CO, and R ³ represents S, ethynylene or vinylene; and

LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (eg 1-20, 1-15, 1-10, 1- 9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optionally substituted heterocyclylene or any The group consisting of the combination is interrupted, wherein when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1), wherein the R ³ group Represents ethynylene or vinylene.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) a group selected from the group consisting of oxygen, (having a heteroatom selected from O, N and S) optionally substituted heterocyclylene or any combination thereof interrupted; and A ² does not exist.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) a group selected from the group consisting of oxygen, (having a heteroatom selected from O, N and S) optionally substituted heterocyclylene or any combination thereof interrupted; and A ² does not exist.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) a group selected from the group consisting of oxygen, (having a heteroatom selected from O, N and S) optionally substituted heterocyclylene or any combination thereof; and A ² represents Carbonyl.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) a group selected from the group consisting of oxygen, (having a heteroatom selected from O, N and S) optionally substituted heterocyclylene or any combination thereof; and A ² represents Carbonyl.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN does not exist, one of A ¹ and A ² does not exist and the other represents a carbonyl group, and R ² represents formula (I-1 ), wherein the R ³ group represents an ethynylene group or a vinylene group.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), R ² represents:

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _1-30 alkylene group, and the substituent is selected from C ₁ -C ₃ Alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino ( For example, C _1-6 alkylamino), haloalkyl (e.g., C _1-3 haloalkyl, such as trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The alkyl group is optionally substituted by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1- 3 or 1-2, or 1) interrupted by a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof, wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl, Amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 Alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -, -(CH ₂ ) _n1 -(O (CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, _or- (CR a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _a3 , R _a4 , R _a5 , R _a6 , R _a7 , R _a8 , R _a9 and R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _{5 to 14} aryl, especially C _6-10 aryl), alkoxy Group (such as C _1-6 alkoxy), alkylamino (such as C _1-6 alkylamino) or any combination thereof, wherein when in the same LIN, R _a1 , R _a2 , R _a3 , R _a4 , or R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , and R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₄ -( O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -( O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH _2- , -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O (CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) _2- (O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O- (CH ₂ ) ₂ -O-CH _2- , -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH _2- O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The alkyl group is optionally substituted by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1- 3 or 1-2, or 1) optionally substituted heterocyclylene (especially five-membered or six-membered heterocyclylene) having heteroatoms selected from O, N and S interrupt, wherein the substituents are selected from From C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy) ), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or Multiple (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _{n1 -heterocyclylene} -(CH ₂ ) _n2 -, wherein n1 and n2 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is not Substituted or substituted by a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof . In a sub-embodiment of the present disclosure, examples of the heterocyclylene include, but are not limited to, azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, Imidazolylidene, pyrazolidine, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, Tetrahydrothiopyranyl, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazole, Piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein The heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or Any combination of substituents is substituted.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperidinylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents -CH ₂ -piperidinylene-CH ₂ -, -(CH ₂ ) ₂ -piperidinylene-CH ₂ -, -CH ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperidinylene-(CH ₂ ) ₄ -or -(CH ₂ ) ₄ -piperidinylene-(CH ₂ ) ₃ -.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperazinylidene -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub ii) the disclosed embodiment, in the compound of formula (I) in the LIN represents - (CH _{2) 2} - piperazinyl alkylene -CH ₂ -, - CH ₂ - -CH ₂ alkylene piperazinyl -, -CH ₂ -piperazinyl -(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperazinyl-(CH ₂ ) ₄ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₃ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₄ -.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -triazolylidene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub ii) the disclosed embodiment, in the compound of formula (I) in the LIN represents -CH ₂ - triazolyl alkylene -CH ₂ -, - CH ₂ - triazolyl alkylene - (CH _{2) 2} -, -CH ₂ -triazolylidene -(CH ₂ ) ₃ -, -CH ₂ -triazolylidene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -triazolylidene -CH ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -triazolylidene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Triazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -imidazolylidene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure a sub ii) embodiment, in the compound of formula (I) in the LIN represents -CH ₂ - imidazolyl alkylene -CH ₂ -, - CH ₂ - imidazolyl alkylene - (CH _{2) 2} -, -CH ₂ -imidazolylidene -(CH ₂ ) ₃ -, -CH ₂ -imidazolylidene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -imidazolylidene -CH ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₄ -,- (CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -imidazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of ii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -pyrazolylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub ii) the disclosed embodiment, in the compound of formula (I) in the LIN represents -CH ₂ - pyrazolyl alkylene -CH ₂ -, - CH ₂ - pyrazol-alkylene group - (CH _{2) 2} -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₃ -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -Pyrazolylene -CH ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -Pyrazolylene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Pyrazolylene-(CH ₂ ) ₂ -.

iii) The present disclosure further provides another embodiment of the compound of formula (I):

R ¹ -A ¹ -LIN-A ² -R ² (I)

R ¹ means:

A ¹ does not exist or represents a carbonyl group;

LIN represents a substituted or unsubstituted linear or branched alkylene group; and

A ² does not exist or represents a carbonyl group, and R ² represents the structural formula of formula (I-1):

Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), wherein R ⁴ represents H or C _1-3 alkyl;

or

A ² does not exist, and R ² represents the structural formula of formula (I-2):

In a sub-embodiment of iii) of the present disclosure, in the compound of formula (I), R ² represents the structural formula of formula (I-1), and A ¹ does not exist; LIN represents a substituted or unsubstituted linear or branched chain的alkylene; and A ² does not exist.

In a sub-embodiment of iii) of the present disclosure, in the compound of formula (I), R ² represents the structural formula of formula (I-1), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched chain的alkylene; and A ² does not exist.

In a sub-embodiment of iii) of the present disclosure, in the compound of formula (I), R ² represents the structural formula of formula (I-1), and A ¹ does not exist; LIN represents a substituted or unsubstituted linear or branched chain And A ² represents a carbonyl group.

In a sub-embodiment of iii) of the present disclosure, in the compound of formula (I), R ² represents the structural formula of formula (I-1), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched chain And A ² represents a carbonyl group.

In a sub-embodiment of iii) of the present disclosure, in the compound of formula (I), R ² represents the structural formula of formula (I-2), A ¹ does not exist; and A ² does not exist.

In a sub-embodiment of iii) of the present disclosure, in the compound of formula (I), R ² represents the structural formula of formula (I-2), A ¹ represents a carbonyl group; and A ² does not exist.

In a sub-embodiment of iii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _1-30 alkylene group, and the substituent is selected from C ₁ -C ₃ Alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino ( For example, C _1-6 alkylamino), haloalkyl (e.g., C _1-3 haloalkyl, such as trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of iii) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

iv) The present disclosure further provides another preferred embodiment of the above-mentioned compound of formula (I):

R ¹ -A ¹ -LIN-A ² -R ² (I)

Where R ¹ means:

A ¹ does not exist or represents a carbonyl group;

A ² does not exist or represents a carbonyl group; and

R ² represents the structural formula of formula (I-1) or formula (I-2):

Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl; and

LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (eg 1-20, 1-15, 1-10, 1- 9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optionally substituted heterocyclylene or any The group consisting of the combination is interrupted, wherein when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1), wherein the R ³ group Represents ethynylene or vinylene.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) oxygen interruption; and A ² does not exist.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ^{2 is} not present.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof interrupted; and A ² represents a carbonyl group.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof interrupted; and A ² represents a carbonyl group.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), R ² represents:

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _1-30 alkylene group, and the substituent is selected from C ₁ -C ₃ Alkyl, hydroxyl, amino, mercapto, halogen, aryl (such as C _5-14 aryl, especially C _6-10 aryl), alkoxy (such as C _1-6 alkoxy), alkylamino (E.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, such as trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The base is optionally divided by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 Or 1-2, or 1) oxygen interruption, wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (such as C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, such as trifluoromethyl Group), cyano group or any combination thereof. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -, -(CH ₂ ) _n1 -(O (CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _a3 , R _a4 , R _a5 , R _a6 , R _a7 , R _a8 , R _a9 and R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _{5 to 14} aryl, especially C _6-10 aryl), alkoxy Group (such as C _1-6 alkoxy), alkylamino (such as C _1-6 alkylamino) or any combination thereof, wherein when in the same LIN, R _a1 , R _a2 , R _a3 , R _{a4 is} not H at the same time, or R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , and R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₄ -( O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -( O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH _2- , -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O (CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) _2- (O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH _2- , -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) _6- (O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) _2- (O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O (CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) _3- (O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino) or any combination thereof. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The alkyl group is optionally substituted by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1- 3 or 1-2, or 1) optionally substituted heterocyclylene (especially five-membered or six-membered heterocyclylene) having heteroatoms selected from O, N and S interrupt, wherein the substituents are selected from From C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy) ), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or Multiple (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _{n1 -heterocyclylene} -(CH ₂ ) _n2 -, wherein n1 and n2 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is not Substituted or substituted by a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof . In a sub-embodiment of the present disclosure, examples of the heterocyclylene include, but are not limited to, azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, Imidazolylidene, pyrazolidine, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, Tetrahydrothiopyranyl, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazole, Piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein The heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or Any combination of substituents is substituted.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperidinylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents -CH ₂ -piperidinylene-CH ₂ -, -(CH ₂ ) ₂ -piperidinylene-CH ₂ -, -CH ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperidinylene-(CH ₂ ) ₄ -or -(CH ₂ ) ₄ -piperidinylene-(CH ₂ ) ₃ -.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperazinylidene -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure iv) is a sub-embodiment, the compound of formula (I) in the LIN represents - (CH _{2) 2} - piperazinyl alkylene -CH ₂ -, - CH ₂ - -CH ₂ alkylene piperazinyl -, -CH ₂ -piperazinyl -(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperazinyl-(CH ₂ ) ₄ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₃ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₄ -.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -triazolylidene -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure iv) is a sub-embodiment, the compound of formula (I) in the LIN represents -CH ₂ - triazolyl alkylene -CH ₂ -, - CH ₂ - triazolyl alkylene - (CH _{2) 2} -, -CH ₂ -triazolylidene -(CH ₂ ) ₃ -, -CH ₂ -triazolylidene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -triazolylidene -CH ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -triazolylidene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Triazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -imidazolylidene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure iv) is a sub-embodiment, the compound of formula (I) in the LIN represents -CH ₂ - imidazolyl alkylene -CH ₂ -, - CH ₂ - imidazolyl alkylene - (CH _{2) 2} -, -CH ₂ -imidazolylidene -(CH ₂ ) ₃ -, -CH ₂ -imidazolylidene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -imidazolylidene -CH ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₄ -,- (CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -imidazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of iv) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -pyrazolylidene -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure iv) is a sub-embodiment, the compound of formula (I) in the LIN represents -CH ₂ - pyrazolyl alkylene -CH ₂ -, - CH ₂ - pyrazol-alkylene group - (CH _{2) 2} -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₃ -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -Pyrazolylene -CH ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -Pyrazolylene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Pyrazolylene-(CH ₂ ) ₂ -.

v) The present disclosure further provides another embodiment of the above-mentioned compound of formula (I):

R ¹ -A ¹ -LIN-A ² -R ² (I)

Where R ¹ means:

A ¹ does not exist or represents a carbonyl group;

A ² does not exist or represents a carbonyl group, and R ² represents the structural formula of formula (I-1):

Wherein X represents CH ₂ or CO, and R ³ represents S, ethynylene or vinylene; and

LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The groups of the composition group are interrupted, where when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and the R ³ group represents an ethynylene group or a vinylene group.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) the group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ^{2 is} not present.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) the group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ^{2 is} not present.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ² represents a carbonyl group.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ² represents a carbonyl group.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN is absent, one of A ¹ and A ² is absent and the other represents a carbonyl group, and the R ³ group represents an ethynylene group Or vinylidene.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), R ² represents:

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _1-30 alkylene group, and the substituent is selected from C ₁ -C ₃ Alkyl, hydroxyl, amino, mercapto, halogen, aryl (such as C _5-14 aryl, especially C _6-10 aryl), alkoxy (such as C _1-6 alkoxy), alkylamino (E.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, such as trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The alkyl group is optionally substituted by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1- 3 or 1-2, or 1) interrupted by a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof, wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl, Amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 Alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -, -(CH ₂ ) _n1 -(O (CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _a3 , R _a4 , R _a5 , R _a6 , R _a7 , R _a8 , R _a9 and R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _{5 to 14} aryl, especially C _6-10 aryl), alkoxy Group (such as C _1-6 alkoxy), alkylamino (such as C _1-6 alkylamino) or any combination thereof, wherein when in the same LIN, R _a1 , R _a2 , R _a3 , R _{a4 is} not H at the same time, or R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of v) of the present disclosure, LIN represents the following substituted or unsubstituted groups:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₄ -( O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -( O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH _2- , -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH _2- (O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O (CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) _2- (O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH _2- , -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH _2- O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The alkyl group is optionally substituted by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1- 3 or 1-2, or 1) optionally substituted heterocyclylene (especially five-membered or six-membered heterocyclylene) having heteroatoms selected from O, N and S interrupt, wherein the substituents are selected from From C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy) ), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or Multiple (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _{n1 -heterocyclylene} -(CH ₂ ) _n2 -, wherein n1 and n2 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is not Substituted or substituted by a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof . In a sub-embodiment of the present disclosure, examples of the heterocyclylene include, but are not limited to, azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, Imidazolylidene, pyrazolidine, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, Tetrahydrothiopyranyl, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazole, Piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein The heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or Any combination of substituents is substituted.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperidinylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents -CH ₂ -piperidinylene-CH ₂ -, -(CH ₂ ) ₂ -piperidinylene-CH ₂ -, -CH ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperidinylene-(CH ₂ ) ₄ -or -(CH ₂ ) ₄ -piperidinylene-(CH ₂ ) ₃ -.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperazinylidene -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure v) of a sub-embodiment, the compound of formula (I) in the LIN represents - (CH _{2) 2} - piperazinyl alkylene -CH ₂ -, - CH ₂ - -CH ₂ alkylene piperazinyl -, -CH ₂ -piperazinyl -(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperazinyl-(CH ₂ ) ₄ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₃ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₄ -.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -triazolylidene -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure v) of a sub-embodiment, the compound of formula (I) in the LIN represents -CH ₂ - triazolyl alkylene -CH ₂ -, - CH ₂ - triazolyl alkylene - (CH _{2) 2} -, -CH ₂ -triazolylidene -(CH ₂ ) ₃ -, -CH ₂ -triazolylidene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -triazolylidene -CH ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -triazolylidene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Triazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -imidazolylidene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure v) of a sub-embodiment, the compound of formula (I) in the LIN represents -CH ₂ - imidazolyl alkylene -CH ₂ -, - CH ₂ - imidazolyl alkylene - (CH _{2) 2} -, -CH ₂ -imidazolylidene-(CH ₂ ) ₃ -, -CH ₂ -imidazolylidene-(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -imidazolylidene-CH ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₄ -,- (CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -imidazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of v) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -pyrazolylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure v) of a sub-embodiment, the compound of formula (I) in the LIN represents -CH ₂ - pyrazolyl alkylene -CH ₂ -, - CH ₂ - pyrazol-alkylene group - (CH _{2) 2} -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₃ -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -Pyrazolylene -CH ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -Pyrazolylene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Pyrazolylene-(CH ₂ ) ₂ -.

vi) The present disclosure further provides another embodiment of the above-mentioned compound of formula (I):

R ¹ -A ¹ -LIN-A ² -R ² (I)

Where R ¹ means:

A ¹ does not exist or represents a carbonyl group;

A ² does not exist, and R ² represents the structural formula of formula (I-2)

as well as

LIN represents a substituted or unsubstituted linear or branched alkylene group.

In a sub-embodiment of vi) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group; and A ² is absent.

In a sub-embodiment of vi) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group; and A ² does not exist.

In a sub-embodiment of vi) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _1-30 alkylene group, and the substituent is selected from C ₁ -C ₃ Alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino ( For example, C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, such as trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of vi) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

vii) The present disclosure further provides another embodiment of the above-mentioned compound of formula (I):

R ¹ -A ¹ -LIN-A ² -R ² (I)

Where R ¹ means:

A ¹ does not exist or represents a carbonyl group;

A ² does not exist or represents a carbonyl group;

R ² represents the structural formula of formula (I-1) or formula (I-2):

Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl; and

LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The group consisting of interrupted groups, where when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1), wherein the R ³ group represents Ethynylene or vinylene.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), R ² represents:

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Is optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene, or any combination thereof; and A ^{2 is} not present.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Is optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene, or any combination thereof; and A ^{2 is} not present.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof; and A ² represents a carbonyl group.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof; and A ² represents a carbonyl group.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN is absent, one of A ¹ and A ² is absent and the other represents a carbonyl group, and R ² represents formula (I-1 ), wherein the R ³ group represents an ethynylene group or a vinylene group.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched alkylene group, and preferably represents a substituted or unsubstituted linear or branched alkylene group. Chain C _1-30 alkylene, wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _5-14 aryl, especially C _6-10 aryl) , Alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or Any combination of it. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g., C _1-3 haloalkyl, such as trifluoromethyl), cyano, or any combination thereof. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The group is optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof, wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl, amino, Mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkyl Amino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -, -(CH ₂ ) _n1 -(O (CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _a3 , R _a4 , R _a5 , R _a6 , R _a7 , R _a8 , R _a9 and R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _{5 to 14} aryl, especially C _6-10 aryl), alkoxy Group (for example, C _1-6 alkoxy), alkylamino (for example, C _1-6 alkylamino) or any combination thereof, wherein in the same LIN, R _a1 , R _a2 , R _a3 , R _{a4 is} not H at the same time, or R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , and R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₄ -( O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -( O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH _2- , -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O (CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) _2- (O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH _2- , -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) _2- (O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) _2- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O (CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) _3- (O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl , Amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _{1- 6} alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The group is optionally interrupted by one or more optionally substituted heterocyclylenes (especially five- or six-membered heterocyclylenes) having heteroatoms selected from O, N and S, wherein the substituents are selected from From C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy) ), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or Multiple (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _{n1 -heterocyclylene} -(CH ₂ ) _n2 -, wherein n1 and n2 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is not Substituted or substituted with a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof . In a sub-embodiment of the present disclosure, the heterocyclylene is azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, imidazolylidene, Pyrazolidinyl, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranyl, furanylene, tetrahydropyranyl, tetrahydrothienyl, thienylene, tetrahydrothiopyran Group, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazolyl, piperidinylene, Piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein the heterocyclylene is Unsubstituted or substituted by a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof replace.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperidinylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents -CH ₂ -piperidinylene-CH ₂ -, -(CH ₂ ) ₂ -piperidinylene-CH ₂ -, -CH ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperidinylene-(CH ₂ ) ₄ -or -(CH ₂ ) ₄ -Piperidinylene-(CH ₂ ) ₃ -.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperazinylidene -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of embodiment of the present disclosure vii), the formula (I) compounds, the LIN represents - (CH _{2) 2} - piperazinyl alkylene -CH ₂ -, - CH ₂ - -CH ₂ alkylene piperazinyl -, -CH ₂ -piperazinyl -(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperazinyl-(CH ₂ ) ₄ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₃ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₄ -.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -triazolylidene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure vii) a sub-embodiment of embodiment, in the compound of formula (I) in the LIN represents -CH ₂ - triazolyl alkylene -CH ₂ -, - CH ₂ - triazolyl alkylene - (CH _{2) 2} -, -CH ₂ -triazolylidene -(CH ₂ ) ₃ -, -CH ₂ -triazolylidene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -triazolylidene -CH ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -triazolylidene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Triazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -imidazolylidene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure a sub vii) in the embodiment, in the compound of formula (I) in the LIN represents -CH ₂ - imidazolyl alkylene -CH ₂ -, - CH ₂ - imidazolyl alkylene - (CH _{2) 2} -, -CH ₂ -imidazolylidene -(CH ₂ ) ₃ -, -CH ₂ -imidazolylidene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -imidazolylidene -CH ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₄ -,- (CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -imidazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -pyrazolylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure vii) a sub-embodiment of embodiment, in the compound of formula (I) in the LIN represents -CH ₂ - pyrazolyl alkylene -CH ₂ -, - CH ₂ - pyrazol-alkylene group - (CH _{2) 2} -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₃ -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -Pyrazolylene -CH ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -Pyrazolylene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Pyrazolylene-(CH ₂ ) ₂ -.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), R ¹ represents:

R ² means:

Wherein A ¹ , LIN, A ² , X and R ³ are as defined in vii) above and include all sub-embodiments thereof.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), R ¹ represents:

R ² means:

A ¹ , LIN, A ² , X and R ³ are as defined in vii) above and include all sub-embodiments thereof.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), R ¹ represents:

R ² means:

A ¹ , LIN, A ² , X and R ³ are as defined in vii) above and include all sub-embodiments thereof.

In a sub-embodiment of vii) of the present disclosure, in the compound of formula (I), R ¹ represents:

R ² means:

A ¹ , LIN, A ² , X and R ³ are as defined in vii) above and include all sub-embodiments thereof.

viii) The present disclosure further provides another embodiment of the above-mentioned compound of formula (I):

R ¹ -A ¹ -LIN-A ² -R ² (I)

Where R ¹ means:

A ¹ does not exist or represents a carbonyl group;

A ² does not exist or represents a carbonyl group;

R ² represents the structural formula of formula (I-1) or formula (I-2):

Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl; and

LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof. The group is interrupted.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), R ² represents:

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Is optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene, or any combination thereof; and A ^{2 is} not present.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Is optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene, or any combination thereof; and A ^{2 is} not present.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), A ¹ is absent; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof; and A ² represents a carbonyl group.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), A ¹ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof; and A ² represents a carbonyl group.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted linear or branched alkylene group, preferably a substituted or unsubstituted C _1-30 Alkylene, where the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy ( For example, C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g., C _1-3 haloalkyl, such as trifluoromethyl), cyano, or any combination thereof. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted C _2-30 alkylene group, wherein the C _2-30 alkylene group is optionally substituted by One or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof are interrupted, wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aromatic Group (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (E.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -, -(CH ₂ ) _n1 -(O (CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _a3 , R _a4 , R _a5 , R _a6 , R _a7 , R _a8 , R _a9 and R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _{5 to 14} aryl, especially C _6-10 aryl), alkoxy Group (for example, C _1-6 alkoxy), alkylamino (for example, C _1-6 alkylamino) or any combination thereof, wherein in the same LIN, R _a1 , R _a2 , R _a3 , R _a4 , or R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , and R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents the following substituted or unsubstituted group:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₄ -( O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -( O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH _2- , -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O (CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) _2- (O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH _2- , -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) _2- (O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) _2- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O (CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) _3- (O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g., C _1-3 haloalkyl, such as trifluoromethyl), cyano, or any combination thereof. The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Or 20).

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents a substituted or unsubstituted C _2-30 alkylene group, wherein the C _2-30 alkylene group is optionally substituted by One or more optionally substituted heterocyclylenes (especially five- or six-membered heterocyclylenes) having heteroatoms selected from O, N and S interrupt, wherein the substituents are selected from C ₁ -C ₃ alkyl group, a hydroxyl group, an amino group, a mercapto group, a halogen, an aryl group (e.g., C _5-14 aryl, especially C _6-10 aryl group), an alkoxy group (e.g., C _{1- 6} alkoxy), alkylamino (E.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, such as trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _{n1 -heterocyclylene} -(CH ₂ ) _n2 -, wherein n1 and n2 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is not Substituted or substituted with a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof . In a sub-embodiment of the present disclosure, the heterocyclylene is azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, imidazolylidene, Pyrazolidinyl, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranyl, furanylene, tetrahydropyranyl, tetrahydrothienyl, thienylene, tetrahydrothiopyran Group, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazolyl, piperidinylene, Piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein the heterocyclylene is Unsubstituted or substituted by a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof replace.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperidinylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents -CH ₂ -piperidinylene-CH ₂ -, -(CH ₂ ) ₂ -piperidinylene-CH ₂ -, -CH ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperidinylene-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperidinylene-(CH ₂ ) ₄ -or -(CH ₂ ) ₄ -Piperidinylene-(CH ₂ ) ₃ -.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -piperazinylidene -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In a sub-embodiment of embodiment of the present disclosure viii), the formula (I) compounds, the LIN represents - (CH _{2) 2} - piperazinyl alkylene -CH ₂ -, - CH ₂ - -CH ₂ alkylene piperazinyl -, -CH ₂ -piperazinyl -(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -piperazinyl-( CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Piperazinyl-(CH ₂ ) ₄ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₃ -, or-(CH ₂ ) ₄ -Piperazinyl-(CH ₂ ) ₄ -.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -triazolylidene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure viii) a sub-embodiment of embodiment, in the compound of formula (I) in the LIN represents -CH ₂ - triazolyl alkylene -CH ₂ -, - CH ₂ - triazolyl alkylene - (CH _{2) 2} -, -CH ₂ -triazolylidene -(CH ₂ ) ₃ -, -CH ₂ -triazolylidene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -triazolylidene -CH ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -triazolylidene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Triazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -imidazolylidene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure a sub viii) embodiment, in the compound of formula (I) in the LIN represents -CH ₂ - imidazolyl alkylene -CH ₂ -, - CH ₂ - imidazolyl alkylene - (CH _{2) 2} -, -CH ₂ -imidazolylidene -(CH ₂ ) ₃ -, -CH ₂ -imidazolylidene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -imidazolylidene -CH ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₄ -,- (CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -imidazolylidene-(CH ₂ ) ₂ -.

In a sub-embodiment of viii) of the present disclosure, in the compound of formula (I), LIN represents -(CH ₂ ) _n7 -pyrazolylene-(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

In the present disclosure viii) a sub-embodiment of embodiment, in the compound of formula (I) in the LIN represents -CH ₂ - pyrazolyl alkylene -CH ₂ -, - CH ₂ - pyrazol-alkylene group - (CH _{2) 2} -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₃ -, -CH ₂ -Pyrazolylene -(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -Pyrazolylene -CH ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -Pyrazolylene- (CH ₂ ) ₄ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -Pyrazolylene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -Pyrazolylene-(CH ₂ ) ₂ -.

Particularly preferred are the compounds in Table 1 of the present invention and their salts (especially pharmaceutically acceptable salts), enantiomers, diastereomers, solvates, and polymorphs:

Table 1 Compounds of formula (I) of the present invention

ix) Another aspect of the present disclosure provides a compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof,

R ₁₂ -A ₁₂ -LIN-A ₂₂ -R ₂₂ (II)

Where R ₁₂ means:

Where R _x means

The symbol * represents the connection point with NH, and the symbol ** represents _{the connection point with A 12} , n represents an integer of 1-3, R _b1 , R _b2 , R _b3 and R _{b4 are the} same or different and are independently H Or oxo group, and R _b5 represents H or C _1-3 alkyl;

Where R _y means

The symbol * represents the connection point with O, and the symbol ** represents _{the connection point with A 12} , m represents an integer of 1-3, and

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group;

R ₂₂ represents an optionally substituted adamantyl group, formula (II-1) structural formula, or formula (II-2) structural formula:

Where X represents CH ₂ or CO, R _c does not exist or represents N(R _c1 ), O, S, ethynylene, vinylene, or five- or six-membered heterocyclylene, where R _c1 and R _c2 are independent of each other地 represents H or C _1-3 alkyl, and R _d represents H or methyl; and

LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The group of the composition is interrupted, wherein when LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are not present, and R ₂₂ represents an optional substitution Or R ₂₂ represents the structural formula of formula (II-1), wherein R _c does not exist or represents an ethynylene group, a vinylene group, or a five- or six-membered heterocyclylene;

The condition is when R ₁₂ represents any of the following structural formulas:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12,}

R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents a five-membered or six-membered heterocyclylene, and R _c2 represents H or C _1-3 alkyl, and LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene, wherein the alkylene is optionally substituted by one or more selected from oxygen, optionally substituted The group consisting of heterocyclylene or any combination thereof is interrupted, wherein in the absence of LIN, one of A ₁₂ and A ₂₂ does not exist and the other represents a carbonyl group or neither _{A 12} nor A ₂₂ Exists, or

R ₂₂ represents the structural formula of formula (II-1) wherein X represents CH ₂ or CO.'S, and R _c represents O, and R _c2 represents H or C _{1- 3} alkyl, LIN, and a substituted or unsubstituted straight or Branched alkylene, or

R ₂₂ represents the structural formula of formula (II-2), wherein R _d represents a methyl group, and A _{22 is} not present, and LIN represents a substituted or unsubstituted linear or branched alkylene group;

as well as

The condition is when R ₁₂ represents any of the following structural formulas:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12;}

R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents a five-membered or six-membered heterocyclylene or O, and R _c2 represents H or C _1-3 alkyl, and LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally selected from oxygen, optionally The group consisting of substituted heterocyclylene or any combination thereof is interrupted, wherein in the absence of LIN, one of A ₁₂ and A ₂₂ is absent and the other represents a carbonyl group or both A ₁₂ and A ₂₂ None, and R ₂₂ represents an optionally substituted adamantyl group, or R ₂₂ represents the structural formula of formula (II-1), wherein R _c represents a five-membered or six-membered heterocyclylene, or

R ₂₂ represents the structural formula of formula (II-1), where X represents CH ₂ or CO, and R _c represents vinylene or ethynylene, and R _c2 represents C _1-3 alkyl, and LIN does not exist or represents substitution Or an unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof Interrupt, or

R ₂₂ represents the structural formula of formula (II-2), wherein R _d represents a methyl group, and LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted.

In the compound of formula (II) of the present disclosure, when LIN represents a substituted or unsubstituted linear or branched alkylene group, the alkylene group is optionally substituted by one or more (e.g., 1-20, 1 -15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optional The group consisting of the substituted heterocyclylene or any combination thereof is interrupted. Preferably, either one of the two ends of the alkylene group may be connected to the group A ₁₂ , and the other end is connected to the group A ₂₂ .

In the present disclosure, the structural formula of formula (II-1) is also a combination of the following general structural formulas:

Where X represents CH ₂ or CO, R _c does not exist or represents N(R _c1 ), O, S, ethynylene, vinylene, or five- or six-membered heterocyclylene, where R _c1 and R _c2 are independent of each other Denotes H or C _1-3 alkyl (for example, methyl, ethyl, n-propyl or isopropyl).

In a sub-embodiment of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A _{22 is} not present.

In a sub-embodiment of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A _{22 is} not present.

In a sub-embodiment of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof interrupted; and A ₂₂ represents a carbonyl group.

In a sub-embodiment of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally One or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2 , Or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof interrupted; and A ₂₂ represents a carbonyl group.

In a sub-embodiment of the present disclosure, in the compound of formula (II), LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are not present, and R ₂₂ represents an optionally substituted adamantyl group, or R ₂₂ represents the structural formula of formula (II-1), wherein R _c is absent or represents an ethynylene group, a vinylene group, or a five- or six-membered heterocyclylene.

In a sub-embodiment of the present disclosure, in the compound of formula (II), when the R _c represents a five-membered or six-membered heterocyclylene, the five-membered or six-membered heterocyclylene includes but is not limited to Triazolylidene, azetidinylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, imidazolylidene, pyrazolidinylene, pyrazolylidene, tetrahydrofuranylene, furanylene, sub Tetrahydropyranyl, tetrahydrothienylene, thienylene, tetrahydrothiopyranyl, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine , Thiazolylidene, isothiazolylidene, thiadiazolylidene, piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, sub Thiomorpholinyl and dioxanyl, wherein the five-membered or six-membered heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, C _{Substituents of 1-3} alkoxy, alkylamino, halogenated C _1-3 alkyl, cyano, or any combination thereof.

In a sub-embodiment of the present disclosure, in the compound of formula (II), R ₂₂ represents an adamantyl group, and the adamantyl group is adamantane-1-yl, adamantane-2-yl, or adamantane-3-yl. Adamantane-4-yl, adamantane-5-yl, adamantane-6-yl, adamantane-7-yl, adamantane-8-yl, adamantane-9-yl or adamantane-10-yl , Which is optionally selected from halogen, hydroxy, mercapto, oxo, cyano, C _1-3 alkyl, halo C _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkane amino group, C _1-3 alkyl -NHC (O) - group, or any combination thereof one or more substituents (e.g., 1,2,3,4,5,6,7,8, or 9) replace.

In a sub-embodiment of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _1-30 alkylene group, and the substituent is selected from a C ₁ -C ₃ alkyl group , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (II), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted, wherein _{the substituents of the C 2-30} alkylene and heterocyclylene are independently Is selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkane) Oxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be One or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (II), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -, -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O (CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where _Ra1 , _Ra2 , _Ra3 , _Ra4 , _Ra5 , _Ra6 , _Ra7 , _Ra8 , _Ra9 , R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (such as C _1-6 alkylamino) or any combination thereof, wherein when in the same LIN, R _a1 , R _a2 , R _a3 , R _a4 , or R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , and R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of the present disclosure, in the compound of formula (II), LIN represents the following substituted or unsubstituted group:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₄ -( O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -( O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH _2- , -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O (CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) _2- (O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH _2- , -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) _6- (O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O- (CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) _2- (O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -,- (CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O (CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) _3- (O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl , Amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _{1- 6} alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) an optionally substituted heterocyclylene (especially a five-membered or six-membered heterocyclylene) having a heteroatom selected from O, N and S interrupted, wherein C _2-30 alkylene The substituents of the group and the heterocyclylene group are each independently selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _5-14 aryl, especially C _6-10 aryl) , Alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or Any combination thereof, wherein the number of substituents can be one or more (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of the present disclosure, in the compound of formula (II), LIN represents -(CH ₂ ) _{n7 -heterocyclylene} -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent an integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is unsubstituted or It is substituted with a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof. In a sub-embodiment of the present disclosure, examples of the heterocyclylene include, but are not limited to, azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, Imidazolylidene, pyrazolidine, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, Tetrahydrothiopyranyl, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazole, Piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein The heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkyl Oxy group (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any of them The combined substituents are substituted.

In a sub-embodiment of the present disclosure, in the compound of formula (II), LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are not present, and R ₂₂ represents an optionally substituted adamantyl group. In a sub-embodiment of the present disclosure, the adamantyl group is adamantane-1-yl, adamantane-2-yl, adamantane-3-yl, adamantane-4-yl, and adamantane-5-yl. , Adamantane-6-yl, adamantane-7-yl, adamantane-8-yl, adamantane-9-yl or adamantane-10-yl, which are optionally selected from halogen, hydroxyl, mercapto, oxygen Substitute, cyano, C _1-3 alkyl, halo C _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkylamino, C _1-3 alkyl -NHC(O)- One or more substituents (for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9) of a group consisting of any combination thereof.

x) The present disclosure further provides another embodiment of the compound of formula (II):

R ₁₂ -A ₁₂ -LIN-A ₂₂ -R ₂₂ (II)

Where R ₁₂ means:

Where R _x means

The symbol * represents the connection point with NH, and the symbol ** represents _{the connection point with A 12} , n represents an integer of 1-3, R _b1 , R _b2 , R _b3 and R _{b4 are the} same or different and are independently H Or an oxo group (for example, where one of R _b1 , R _b2 , R _b3 and R _b4 is an oxo group, and the rest are H; or R _b1 , R _b2 , R _b3 and R _b4 are all H), and R _b5 Represents H or C _1-3 alkyl;

Where R _y means

The symbol * represents the connection point with O, and the symbol ** represents _{the connection point with A 12} , m represents an integer of 1-3, and

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group;

R ₂₂ represents an optionally substituted adamantyl group, formula (II-1) structural formula, or formula (II-2) structural formula:

Where X represents CH ₂ or CO, R _c does not exist or represents N(R _c1 ), O, S, ethynylene, vinylene, or five- or six-membered heterocyclylene, where R _c1 and R _c2 are independent of each other地 represents H or C _1-3 alkyl, and R _d represents H or methyl; and

LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1- 9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optionally substituted heterocyclylene or any The interruption of the group consisting of combination, where when LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are not present, and R ₂₂ represents an optionally substituted Adamantyl, or R ₂₂ represents the structural formula of formula (II-1), wherein R _c does not exist or represents an ethynylene group, a vinylene group, or a five- or six-membered heterocyclylene.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) the group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A _{22 is} not present.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) the group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A _{22 is} not present.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) to group interrupted selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof; and A ₂₂ represents a carbonyl group.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group may Selected by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1 -2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ₂₂ represents a carbonyl group.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are not present Exists, and R ₂₂ represents an optionally substituted adamantyl group, or R ₂₂ represents the structural formula of formula (II-1), wherein R _c is absent or represents an ethynylene group, a vinylene group, or a five-membered or six-membered heterozylidene group Ring base.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), when the R _c represents a five-membered or six-membered heterocyclylene, the five-membered or six-membered heterocyclylene includes But not limited to triazolylidene, azetidinylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, imidazolyl, pyrazolidinyl, pyrazolylidene, tetrahydrofuranyl, furylene Group, tetrahydropyranylene, tetrahydrothiophenylene, thienylene, tetrahydrothiophenylene, oxazolidinyl, oxazolylidene, isoxazolylidene, oxadiazolylidene, Thiazolidine, thiazolylidene, isothiazolylidene, thiadiazolylidene, piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholine Group, thiomorpholinyl or dioxanyl, wherein the five-membered or six-membered heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, Substituents substituted by halogen, C _1-3 alkoxy, alkylamino, halogenated C _1-3 alkyl, cyano, or any combination thereof.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), R ₂₂ represents the structural formula of formula (II-1), and the structural formula of formula (II-1) is also a combination of the following general structural formulas:

Where X represents CH ₂ or CO, R _c does not exist or represents N(R _c1 ), O, S, ethynylene, vinylene, or five- or six-membered heterocyclylene, where R _c1 and R _c2 are independent of each other地 denotes H or C _1-3 alkyl.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), R ₂₂ represents the structural formula of formula (II-2)

Where R _d represents H or methyl.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), R ₂₂ represents an adamantyl group, and the adamantyl group is adamantane-1-yl, adamantane-2-yl, or adamantane -3-yl, adamantane-4-yl, adamantane-5-yl, adamantane-6-yl, adamantane-7-yl, adamantane-8-yl, adamantane-9-yl or adamantane- 10-group, which is optionally selected from halogen, hydroxy, mercapto, oxo, cyano, C _1-3 alkyl, halo C _1-3 alkyl, C _1-3 alkoxy, C _{1 -3} alkylamino, C _1-3 alkyl-NHC(O)- or any combination thereof is one or more substituents (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or 9) substitution.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _1-30 alkylene group, and the substituent is selected from C ₁ -C ₃ Alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (E.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, such as trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The alkyl group is optionally substituted by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1- 3 or 1-2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted, wherein the substitution of _{C 2-30 alkylene and heterocyclylene} The groups are independently selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _{1 -6} alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the substituents are The number can be one or more (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 ).

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -, -(CH ₂ ) _n1 -(O (CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _a3 , R _a4 , R _a5 , R _a6 , R _a7 , R _a8 , R _a9 and R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _{5 to 14} aryl, especially C _6-10 aryl), alkoxy Group (for example, C _1-6 alkoxy), alkylamino (for example, C _1-6 alkylamino) or any combination thereof, wherein in the same LIN, R _a1 , R _a2 , R _a3 , R _a4 , or R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , and R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), LIN represents the following substituted or unsubstituted group:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) _2- (O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) _4- (O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH _2- (O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) _8- , -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) _4- , -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O (CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) _3- (O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) _8- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH ₂ -, -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH _2- O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -( O(CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH _2- O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl , Amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _{1- 6} alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group The alkyl group is optionally substituted by one or more (e.g. 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1- 3 or 1-2, or 1) optionally substituted heterocyclylene (especially five- or six-membered heterocyclylene) having heteroatoms selected from O, N and S interrupt, wherein C _{2- 30} Alkylene and heterocyclylene substituents are independently selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _5-14 aryl, especially C _6-10 Aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, such as trifluoromethyl), Cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19 or 20).

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), LIN represents -(CH ₂ ) _{n7 -heterocyclylene} -(CH ₂ ) _n8 -, wherein n7 and n8 each independently represent Integer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is not Substituted or substituted with a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof . In a sub-embodiment of the present disclosure, examples of the heterocyclylene include, but are not limited to, azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, Imidazolylidene, pyrazolidine, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, Tetrahydrothiopyranyl, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazole, Piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein The heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkyl Oxy group (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any of them The combined substituents are substituted.

In a sub-embodiment of x) of the present disclosure, in the compound of formula (II), when LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ None are present, and R ₂₂ represents an optionally substituted adamantyl group. In a sub-embodiment of the present disclosure, the adamantyl group is adamantane-1-yl, adamantane-2-yl, adamantane-3-yl, adamantane-4-yl, and adamantane-5-yl. , Adamantane-6-yl, adamantane-7-yl, adamantane-8-yl, adamantane-9-yl or adamantane-10-yl, which are optionally selected from halogen, hydroxyl, mercapto, oxygen Substitute, cyano, C _1-3 alkyl, halo C _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkylamino, C _1-3 alkyl -NHC(O)- One or more substituents (for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9) of a group consisting of any combination thereof.

In a sub-embodiment of x) of the present disclosure, R ₁₂ represents:

R ₂₂ represents an optionally substituted adamantyl group, formula (II-1) structural formula, or formula (II-2) structural formula:

Wherein A ₁₂ , LIN, A ₂₂ , X, n, R _c , R _c2 and _Rd are as defined in x) above, and include all sub-embodiments thereof.

In a sub-embodiment of x) of the present disclosure, R ₁₂ represents:

Where R _b means

Or N(R _b5 ), wherein R _b1 , R _b2 , R _b3 and R _{b4 are the} same or different and are each independently H or oxo group, and R _b5 represents H or C _1-3 alkyl;

R ₂₂ represents an optionally substituted adamantyl group, formula (II-1) structural formula, or formula (II-2) structural formula:

Wherein A ₁₂ , LIN, A ₂₂ , X, R _c , R _c2 and _Rd are as defined in x) above and include all sub-embodiments thereof.

In a sub-embodiment of x) of the present disclosure, wherein R ₁₂ represents any one of the following structural formulas:

R ₂₂ represents an optionally substituted adamantyl group, formula (II-1) structural formula, or formula (II-2) structural formula:

Wherein A ₁₂ , LIN, A ₂₂ , X, R _c , R _c2 and _Rd are as defined in x) above and include all sub-embodiments thereof.

In a sub-embodiment of x) of the present disclosure, R ₁₂ represents:

R ₂₂ represents an optionally substituted adamantyl group, formula (II-1) structural formula, or formula (II-2) structural formula:

Wherein A ₁₂ , LIN, A ₂₂ , X, R _c , R _c2 and _Rd are as defined in x) above and include all sub-embodiments thereof.

In a sub-embodiment of x) of the present disclosure, R ₁₂ represents:

R ₂₂ represents an optionally substituted adamantyl group, formula (II-1) structural formula, or formula (II-2) structural formula:

Wherein A ₁₂ , LIN, A ₂₂ , X, m, R _c , R _c2 and _Rd are as defined in x) above, and include all sub-embodiments thereof.

xi) The present disclosure further provides another embodiment of the compound of formula (II):

R ₁₂ -A ₁₂ -LIN-A ₂₂ -R ₂₂ (II)

Where R ₁₂ means:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12,}

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group;

R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1):

Where X represents CH ₂ or CO, and R _c represents a five-membered or six-membered heterocyclylene, and R _c2 represents H or C _1-3 alkyl (such as methyl, ethyl or propyl), and LIN is not present Or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1 -8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optionally substituted heterocyclylene or any combination thereof Interruption of the group, where in the absence of LIN, one of A ₁₂ and A ₂₂ does not exist and the other represents a carbonyl group or both A ₁₂ and A ₂₂ do not exist, or

R ₂₂ represents the structural formula of formula (II-1) wherein X represents CH ₂ or CO.'S, and R _c represents O, and R _c2 represents H or C _{1- 3} alkyl, LIN, and a substituted or unsubstituted straight or Branched alkylene, or

R ₂₂ represents the structural formula of formula (II-2):

Where R _d represents a methyl group, and LIN represents a substituted or unsubstituted linear or branched alkylene group, provided that A _{22 is} not present.

xi-1) This disclosure further provides a sub-implementation of xi):

Where R ₁₂ means:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12,}

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group;

R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1):

Where X represents CH ₂ or CO, and R _c represents a five-membered or six-membered heterocyclylene, and R _c2 represents H or C _1-3 alkyl (such as methyl, ethyl or propyl), and LIN is not present Or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1 -8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optionally substituted heterocyclylene or any combination thereof The groups of the group are interrupted, where in the absence of LIN, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are not present.

xi-2) This disclosure further provides a sub-implementation of xi):

Where R ₁₂ means:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12,}

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group;

R ₂₂ represents the structural formula of formula (II-1):

Wherein X represents CH ₂ or CO, and R _c represents O, and R _c2 represents H or C _1-3 alkyl, and LIN represents a substituted or unsubstituted linear or branched alkylene group.

xi-3) This disclosure further provides a sub-implementation of xi):

Where R ₁₂ means:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12,}

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist;

R ₂₂ represents the structural formula of formula (II-2):

Where R _d represents a methyl group, and LIN represents a substituted or unsubstituted linear or branched alkylene group.

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents a substituted or unsubstituted linear or branched alkylene Group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A _{22 is} not present.

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene Group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A _{22 is} not present.

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents a substituted or unsubstituted linear or branched alkylene Group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ₂₂ represents a carbonyl group.

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or branched alkylene Group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted; and A ₂₂ represents a carbonyl group.

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), LIN does not exist, one of A ₁₂ and A ₂₂ does not exist and the other represents a carbonyl group or Neither A ₁₂ nor A ₂₂ exist.

In a sub-embodiment of any one of xi), xi-1), xi-2) and xi-3) of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents substituted or unsubstituted A substituted linear or branched alkylene group; and A ₂₂ does not exist.

In a sub-embodiment of any one of xi), xi-1), xi-2) and xi-3) of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted A substituted linear or branched alkylene group; and A ₂₂ does not exist.

In a sub-embodiment of any one of xi), xi-1) and xi-2) of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents a substituted or unsubstituted linear or Branched alkylene; and A ₂₂ represents a carbonyl group.

In a sub-embodiment of any one of xi), xi-1) and xi-2) of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted linear or Branched alkylene; and A ₂₂ represents a carbonyl group.

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), when the R _c represents a five-membered or six-membered heterocyclylene, the five Member or six-membered heterocyclylene is triazolylidene, azetidinyl, pyrrolidinylene, pyrrolylene, imidazolidinylene, imidazolylidene, pyrazolidinylene, pyrazolylidene, Tetrahydrofuranyl, furanylene, tetrahydropyranyl, tetrahydrothiophenylene, thienylene, tetrahydrothiophenylene, oxazolidinylene, oxazolylidene, isoxazolylidene, sub Oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazolyl, piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyridinylene Azinyl, morpholinylene, thiomorpholinylene or dioxanyl, wherein the five-membered or six-membered heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, Substituents substituted by hydroxyl, amino, mercapto, halogen, C _1-3 alkoxy, alkylamino, halogenated C _1-3 alkyl, cyano, or any combination thereof.

In a sub-embodiment of any one of xi), xi-1) and xi-2) of the present disclosure, in the compound of formula (II), R ₂₂ represents the structural formula of formula (II-1), and formula (II) The structural formula of -1) is also a combination of the following general structural formulas:

Wherein X and R _c and R _c2 are as defined above.

In a sub-embodiment of any one of xi) and xi-3) of the present disclosure, in the compound of formula (II), R ₂₂ represents the structural formula of formula (II-2)

Wherein R _d represents H or methyl, and LIN represents a substituted or unsubstituted linear or branched alkylene group.

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), R ₂₂ represents an adamantyl group, and the adamantyl group is an adamantyl-1-yl group, Adamantane-2-yl, adamantane-3-yl, adamantane-4-yl, adamantane-5-yl, adamantane-6-yl, adamantane-7-yl, adamantane-8-yl, adamantane-8-yl, adamantane Alk-9-yl or adamantane-10-yl, which is optionally selected from halogen, hydroxyl, mercapto, oxo, cyano, C _1-3 alkyl, halo C _1-3 alkyl, C _{One or more substituents of the group consisting of 1-3} alkoxy, C _1-3 alkylamino, C _1-3 alkyl-NHC(O)- or any combination thereof (for example, 1, 2, 3 , 4, 5, 6, 7, 8, or 9) substitutions.

In a sub-embodiment of any one of xi), xi-1), xi-2) and xi-3) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or Branched C _1-30 alkylene, the substituent is selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (such as C _5-14 aryl, especially C _6-10 aryl ), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano Or any combination thereof, wherein the number of substituents can be one or more (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 , 17, 18, 19 or 20).

In a sub-embodiment of any one of xi), xi-1), xi-2) and xi-3) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted group group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group , Wherein the C _2-30 alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1 -5, 1-4, 1-3 or 1-2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof interrupted, wherein C _2-30 The substituents of the alkyl group and the heterocyclylene group are independently selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _5-14 aryl, especially C _6-10 aryl). ), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano Or any combination thereof, wherein the number of substituents can be one or more (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 , 17, 18, 19 or 20).

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -, -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -, -(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, Or -(CR _a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _a3 , R _a4 , R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino) or any combination thereof, wherein when in the same LIN, R _a1 , R _a2 , R _a3 , and R _{a4 are} not H at the same time, or R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , and R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), LIN represents the following substituted or unsubstituted group:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH _2- (O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) _4- (O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH _2- (O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) _8- , -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) _4- , -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O (CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) _3- (O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) _8- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH ₂ -, -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH _2- O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -( O(CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH _2- O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -,-(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl , Amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _{1- 6} alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group , Wherein the C _2-30 alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1 -5, 1-4, 1-3 or 1-2, or 1) optionally substituted heterocyclylene having heteroatoms selected from O, N and S (especially five-membered or six-membered heterocyclylene cycloalkyl group) interrupted, wherein C _{2- 30} alkylene and heterocyclyl substituents each independently selected from C ₁ -C ₃ alkyl group, a hydroxyl group, an amino group, a mercapto group, a halogen, an aryl group (e.g., C _5-14 Aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl) Group, such as trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), LIN represents -(CH ₂ ) _{n7 -heterocyclylene} -(CH ₂ ) _n8- , Where n7 and n8 respectively independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, And the heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano Group or any combination of substituents. In a sub-embodiment of the present disclosure, examples of the heterocyclylene include, but are not limited to, azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, Imidazolylidene, pyrazolidine, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, Tetrahydrothiopyranyl, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazole, Piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein The heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkyl Oxy group (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any of them The combined substituents are substituted.

In a sub-embodiment of any one of xi) and xi-1) of the present disclosure, in the compound of formula (II), when LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents The carbonyl group or both A ₁₂ and A ₂₂ are not present, and R ₂₂ represents an optionally substituted adamantyl group. In a sub-embodiment of the present disclosure, the adamantyl group is adamantane-1-yl, adamantane-2-yl, adamantane-3-yl, adamantane-4-yl, and adamantane-5-yl. , Adamantane-6-yl, adamantane-7-yl, adamantane-8-yl, adamantane-9-yl or adamantane-10-yl, which are optionally selected from halogen, hydroxyl, mercapto, oxygen Substitute, cyano, C _1-3 alkyl, halo C _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkylamino, C _1-3 alkyl -NHC(O)- One or more substituents (for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9) of a group consisting of any combination thereof.

xii) The present disclosure further provides another embodiment of the compound of formula (II):

R ₁₂ -A ₁₂ -LIN-A ₂₂ -R ₂₂ (II)

Where R ₁₂ means:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12;}

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group; and

R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1):

Where X represents CH ₂ or CO, R _c represents a five-membered or six-membered heterocyclylene or O, and R _c2 represents H or a C _1-3 alkyl group (such as methyl, ethyl or propyl), and LIN is not Exist or represent a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally composed of one or more selected from oxygen, optionally substituted heterocyclylene or any combination thereof The group of groups is interrupted, where in the absence of LIN, one of A ₁₂ and A ₂₂ is absent and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are absent, and R ₂₂ represents an optional substitution Or R ₂₂ represents the structural formula of formula (II-1), where R _c represents a five-membered or six-membered heterocyclylene,

or

R ₂₂ represents the structural formula of formula (II-1), where X represents CH ₂ or CO, and R _c represents vinylene or ethynylene, and R _c2 represents C _1-3 alkyl, and LIN does not exist or represents substitution Or an unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof Interrupt,

or

R ₂₂ represents the structural formula of formula (II-2), wherein R _d represents a methyl group, and LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted.

xii-1) This disclosure further provides a sub-implementation of xii):

Where R ₁₂ means:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12;}

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group; and

R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1):

Where X represents CH ₂ or CO, R _c represents a five-membered or six-membered heterocyclylene or O, and R _c2 represents H or a C _1-3 alkyl group (such as methyl, ethyl or propyl), and LIN is not Exist or represent a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally composed of one or more selected from oxygen, optionally substituted heterocyclylene or any combination thereof The group of groups is interrupted, where in the absence of LIN, one of A ₁₂ and A ₂₂ is absent and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are absent, and R ₂₂ represents an optional substitution Or R ₂₂ represents the structural formula of formula (II-1), wherein R _c represents a five-membered or six-membered heterocyclylene.

xii-2) This disclosure further provides a sub-implementation of xii):

Where R ₁₂ means:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12;}

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group; and

R ₂₂ represents the structural formula of formula (II-2):

Wherein R _d represents a methyl group, and LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more heterocyclic ring groups selected from oxygen and optionally substituted The group consisting of the group or any combination thereof is interrupted.

xii-3) This disclosure further provides a sub-implementation of xii):

Where R ₁₂ means:

Where R _x means

The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12;}

A ₁₂ does not exist or represents a carbonyl group;

A ₂₂ does not exist or represents a carbonyl group; and

R ₂₂ represents the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents vinylene or ethynylene, and R _c2 represents C _1-3 alkyl (such as methyl, ethyl or Propyl), and LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more heterocyclic ring groups selected from oxygen and optionally substituted The group consisting of the group or any combination thereof is interrupted.

In a sub-embodiment of any one of xii), xii-1), xii-2) and xii-3) of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents substituted or unsubstituted A substituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1- 7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted ; And A ₂₂ does not exist.

In a sub-embodiment of any one of xii), xii-1), xii-2) and xii-3) of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted A substituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1- 7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted ; And A ₂₂ does not exist.

In a sub-embodiment of any one of xii), xii-1), xii-2) and xii-3) of the present disclosure, in the compound of formula (II), A ₁₂ does not exist; LIN represents substituted or unsubstituted A substituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1- 7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted ; And A ₂₂ represents a carbonyl group.

In a sub-embodiment of any one of xii), xii-1), xii-2) and xii-3) of the present disclosure, in the compound of formula (II), A ₁₂ represents a carbonyl group; LIN represents a substituted or unsubstituted A substituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1- 7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted ; And A ₂₂ represents a carbonyl group.

In a sub-embodiment of any one of xii) and xii-1) of the present disclosure, in the compound of formula (II), in the absence of LIN, one of A ₁₂ and A ₂₂ is absent and the other One represents a carbonyl group or both A ₁₂ and A ₂₂ are absent, and R ₂₂ represents an optionally substituted adamantyl group, or R ₂₂ represents the structural formula of formula (II-1), wherein R _c represents five-membered or six-membered Heterocyclylene.

In a sub-embodiment of any one of xii) and xii-1) of the present disclosure, in the compound of formula (II), when the R _c represents a five-membered or six-membered heterocyclylene, the five Member or six-membered heterocyclylene is triazolylidene, azetidinyl, pyrrolidinylene, pyrrolylene, imidazolidinylene, imidazolylidene, pyrazolidinylene, pyrazolylidene, Tetrahydrofuranyl, furanylene, tetrahydropyranyl, tetrahydrothiophenylene, thienylene, tetrahydrothiophenylene, oxazolidinylene, oxazolylidene, isoxazolylidene, sub Oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazolyl, piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyridinylene Azinyl, morpholinylene, thiomorpholinylene or dioxanyl, wherein the five-membered or six-membered heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, Substituents substituted by hydroxyl, amino, mercapto, halogen, C _1-3 alkoxy, alkylamino, halogenated C _1-3 alkyl, cyano, or any combination thereof.

In a sub-embodiment of any one of xii), xii-1), and xii-3) of the present disclosure, in the compound of formula (II), R ₂₂ represents the structural formula of formula (II-1), and formula ( The structural formula of II-1) is also a combination of the following general structural formulas:

Wherein X and R _c and R _c2 are as defined above.

In a sub-embodiment of any one of xii) and xii-2) of the present disclosure, in the compound of formula (II), R ₂₂ represents the structural formula of formula (II-2)

Wherein R _d represents H or methyl, and LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more (e.g. 1-20, 1-15) , 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) selected from oxygen, optionally substituted The group consisting of heterocyclylene or any combination thereof is interrupted.

In a sub-embodiment of any one of xii) and xii-1) of the present disclosure, in the compound of formula (II), R ₂₂ represents an adamantyl group, and the adamantyl group is an adamantyl-1-yl group, Adamantane-2-yl, adamantane-3-yl, adamantane-4-yl, adamantane-5-yl, adamantane-6-yl, adamantane-7-yl, adamantane-8-yl, adamantane-8-yl, adamantane Alk-9-yl or adamantane-10-yl, which is optionally selected from halogen, hydroxyl, mercapto, oxo, cyano, C _1-3 alkyl, halo C _1-3 alkyl, C _{One or more substituents of the group consisting of 1-3} alkoxy, C _1-3 alkylamino, C _1-3 alkyl-NHC(O)- or any combination thereof (for example, 1, 2, 3 , 4, 5, 6, 7, 8, or 9) substitutions.

In a sub-embodiment of xii-3) of the present disclosure, in the compound of formula (II), R ₂₂ represents the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents vinylidene Or ethynylene, and R _c2 represents methyl, ethyl or propyl.

In a sub-embodiment of any one of xii), xii-1) and xii-2) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _{1 -30} alkylene, the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aryl (for example, C _5-14 aryl, especially C _6-10 aryl), alkoxy (E.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, The number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of any one of xii), xii-1) and xii-2) of the present disclosure, in the compound of formula (II), LIN represents the following substituted or unsubstituted group:

-CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of any one of xii), xii-1) and xii-3) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _{2 -30} alkylene group, wherein the C _2-30 alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) a group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted, wherein The substituents of C _2-30 alkylene and heterocyclylene are each independently selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (for example, C _{5 to 14} aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, such as trifluoromethyl Group), cyano group or any combination thereof, wherein the number of substituents can be one or more (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of any one of xii), xii-1) and xii-3) of the present disclosure, in the compound of formula (II), LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -,-(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _a3 , R _a4 , R _a5 , R _a6 , R _a7 , R _a8 , R _a9 , R _a10 each independently represent H, C _1-3 alkyl, hydroxyl, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl Group, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino) or any combination thereof, wherein the same In LIN, R _a1 , R _a2 , R _a3 , and R _{a4 are} not H at the same time, or R _a5 , R _a6 , R _a7 , _Ra8 , R _a9 , and R _{a10 are} not H at the same time;

n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

In a sub-embodiment of any one of xii), xii-1) and xii-3) of the present disclosure, in the compound of formula (II), LIN represents the following substituted or unsubstituted group:

-CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₄ -( O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -( O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₃ ) ₃ -,-(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH ₂ -, -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH _2- O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -( O(CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH _2- O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl , Amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _{1- 6} alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any combination thereof, the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

In a sub-embodiment of any one of xii), xii-1) and xii-3) of the present disclosure, in the compound of formula (II), LIN represents a substituted or unsubstituted linear or branched C _{2 -30} alkylene group, wherein the C _2-30 alkylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) optionally substituted heterocyclylene (especially five-membered) with heteroatoms selected from O, N and S Or six-membered heterocyclylene) interrupted, wherein _{the substituents of C 2-30} alkylene and heterocyclylene are independently selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aryl ( For example, C _5-14 aryl, especially C _6-10 aryl), alkoxy (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, such as trifluoromethyl), cyano or any combination thereof, wherein the number of substituents can be one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8 , 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20).

In a sub-embodiment of any one of xii), xii-1) and xii-3) of the present disclosure, in the compound of formula (II), LIN represents -(CH ₂ ) _{n7 -heterocyclylene-} ( CH 2) _n8 -, where n7 and n8 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, _{16, 17, 18} , 19 or 20, and the heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino , Haloalkyl, cyano or any combination of substituents. In a sub-embodiment of the present disclosure, examples of the heterocyclylene include, but are not limited to, azetidinyl, oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinyl, Imidazolylidene, pyrazolidine, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, Tetrahydrothiopyranyl, oxazolidinyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazole, Piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene or dioxanylene, wherein The heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl (e.g. C _5-14 aryl, especially C _6-10 aryl), alkyl Oxy group (e.g. C _1-6 alkoxy), alkylamino (e.g. C _1-6 alkylamino), haloalkyl (e.g. C _1-3 haloalkyl, e.g. trifluoromethyl), cyano or any of them The combined substituents are substituted.

In a sub-embodiment of any one of xii), xii-1) and xii-3) of the present disclosure, in the compound of formula (II), when LIN is not present, one of A ₁₂ and A ₂₂ is not Exist and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are absent, and R ₂₂ represents an optionally substituted adamantyl group. In a sub-embodiment of the present disclosure, the adamantyl group is adamantane-1-yl, adamantane-2-yl, adamantane-3-yl, adamantane-4-yl, and adamantane-5-yl. , Adamantane-6-yl, adamantane-7-yl, adamantane-8-yl, adamantane-9-yl or adamantane-10-yl, which are optionally selected from halogen, hydroxyl, mercapto, oxygen Substitute, cyano, C _1-3 alkyl, halo C _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkylamino, C _1-3 alkyl -NHC(O)- One or more substituents (for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9) of a group consisting of any combination thereof.

Particularly preferred are the compounds in Table 2 of the present invention and their salts (especially pharmaceutically acceptable salts), enantiomers, diastereomers, solvates, and polymorphs:

Table 2 Compounds of formula (II) of the present invention

It should be recognized that the compound of formula (I) or the compound of formula (II) of the present invention may have a stereo configuration and therefore can exist in more than one stereoisomer form. The present invention also relates to compounds having a stereoconfiguration in substantially pure isomeric form, such as greater than about 90% ee, such as about 95% ee or 97% ee, or greater than 99% ee, and mixtures thereof, including racemic mixtures. The purification and separation of these isomers can be performed by conventional methods well known to those of ordinary skill in the art (for example, column chromatography, preparative TLC, preparative HPLC, asymmetric synthesis (for example, by using chiral intermediates) and/or by chiral Split, etc.)) to achieve.

On the other hand, the present disclosure also provides a pharmaceutical composition comprising as an active ingredient the compound of formula (I), or compound of formula (II), or a pharmaceutically acceptable salt thereof, as an active ingredient of the present invention Racemates, enantiomers, diastereomers, solvates or polymorphs, and pharmaceutically acceptable carriers.

In one embodiment, the pharmaceutical composition of the present invention further includes at least one additional drug or therapeutic agent (for example, a drug or therapeutic agent for treating or preventing diseases related to BCL-2 family proteins or Hedgehog signaling pathway).

The pharmaceutical composition of the present invention can be prepared according to methods well known to those of ordinary skill in the art, and is conveniently presented in the form of a unit dosage form. The method includes making the compound of formula (I), or compound of formula (II), or a pharmaceutically acceptable salt thereof, optionally combined with other therapeutically valuable substances, together with pharmaceutical excipients (for example, therapeutically Compatible non-toxic inert suitable solid or liquid carrier materials) and (if necessary) common pharmaceutical adjuvants together form the desired formulation. In the pharmaceutical composition, the content of the compound of formula (I) or the compound of formula (II) as an active ingredient is sufficient to have a desired effect on the process or condition of the disease.

The pharmaceutical composition can be prepared into various dosage forms after sterilization based on methods known in the pharmaceutical field. The pharmaceutical composition according to the present invention containing the compound of formula (I) or the compound of formula (II) according to the present invention as an active ingredient may be in the form of enteral or parenteral administration, for example, according to appropriate administration Routes (including but not limited to nasal cavity administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural cavity administration, peritoneal administration, vaginal administration, intramuscular administration, subcutaneous administration Administration, transdermal administration, epidural administration, intrathecal administration and intravenous administration) are prepared into suitable spray formulations, patches, tablets (such as conventional tablets, dispersible tablets, orally disintegrates) Tablets), capsules (such as soft capsules, hard capsules, enteric-coated capsules), dragees, lozenges, powders, granules, powder injections, or liquid preparations (such as aqueous or oily suspensions, solutions, emulsions or syrups) , Tablets, pills, and injections (for example, sterile injections prepared with water, Ringer's solution or isotonic sodium chloride solution as a carrier or solvent according to known available methods), sprays or suppositories, etc. The form of preparation.

In another aspect of the present invention, the compound of formula (I), or compound of formula (II), or a pharmaceutically acceptable salt, racemate, enantiomer, or diastereomer of the present invention Isomers, solvates or polymorphs, which are used as medicaments.

In another aspect of the present invention, the compound of formula (I), or compound of formula (II), or a pharmaceutically acceptable salt, racemate, enantiomer, or diastereomer of the present invention Isomers, solvates or polymorphs, which prevent and/or treat diseases related to BCL-2 family proteins or Hedgehog signaling pathway (including tumors, and non-neoplastic diseases such as bone marrow fibrosis, renal fibrosis, liver Fibrosis, liver cirrhosis, etc.). In one embodiment, the tumor includes hematological tumors and solid tumors.

In one embodiment, the tumor is a tumor that depends on BCL-2 family proteins (for example, BCL-2, MCL-1, and/or BCL-XL), or a tumor that depends on the Hedgehog signaling pathway.

In one embodiment, the disease associated with the BCL-2 family protein or Hedgehog signaling pathway is selected from the group consisting of: myeloma, including multiple myeloma (MM); leukemia, including chronic lymphocytic leukemia (CLL) ), acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML); lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B-cell lymphoma; myelodysplastic syndrome; Myelofibrosis, renal fibrosis, liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer; prostate cancer; medulla Cell tumor; Basal cell carcinoma; Goering syndrome; Esophageal cancer; Colorectal cancer; Medulloblastoma; Rhabdomyosarcoma; Hepatoblastoma; Glioma; Astrocytoma; Liver cancer; Liver cirrhosis; Soft tissue sarcoma ; And pancreatic cancer.

Another aspect of the present invention provides a compound of formula (I), or a compound of formula (II), or a pharmaceutically acceptable salt, racemate, enantiomer, or diastereomer of the present invention The use of constructs, solvates or polymorphs for the prevention and/or treatment of diseases related to BCL-2 family proteins or Hedgehog signaling pathways (including tumors, and non-neoplastic diseases such as myelofibrosis) , Kidney fibrosis, liver fibrosis, liver cirrhosis, etc.). In one embodiment, the tumor includes hematological tumors and solid tumors. In one embodiment, the tumor is a tumor that depends on BCL-2 family proteins (for example, BCL-2, MCL-1, and/or BCL-XL), or a tumor that depends on the Hedgehog signaling pathway.

In one embodiment of the use, the disease related to the BCL-2 family protein or the Hedgehog signaling pathway is selected from the group consisting of: myeloma, including multiple myeloma (MM); leukemia, including chronic lymphocytes Leukemia (CLL), Acute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML); Lymphoma, including non-Hodgkin’s lymphoma, Anaplastic large cell lymphoma, Diffuse large B cell lymphoma; Myeloproliferation Abnormal syndrome; myelofibrosis, renal fibrosis, liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer; prostate Carcinoma; Medulloblastoma; Basal cell carcinoma; Goring syndrome; Esophageal cancer; Colorectal cancer; Medulloblastoma; Rhabdomyosarcoma; Hepatoblastoma; Glioma; Astrocytoma; Liver cancer; Liver Sclerosis; soft tissue sarcoma; and pancreatic cancer.

Another aspect of the present invention also provides treatment or prevention of diseases related to BCL-2 family proteins or Hedgehog signaling pathway in a subject (including tumors, and non-neoplastic diseases such as myelofibrosis, renal fibrosis, liver fibrosis) , Liver cirrhosis, etc.), which comprises administering to the subject a therapeutically effective amount of a compound of formula (I) or a compound of formula (II) of the present invention, or a pharmaceutically acceptable salt, racemic Isomers, enantiomers, diastereomers, solvates or polymorphs, or the pharmaceutical composition of the present invention. In one embodiment, the tumor is a tumor that depends on BCL-2 family proteins (for example, BCL-2 and/or MCL-1 and/or BCL-XL), or a tumor that depends on the Hedgehog signaling pathway.

In one embodiment of the treatment method, the disease associated with the BCL-2 family protein or Hedgehog signaling pathway is selected from the group consisting of: myeloma, including multiple myeloma (MM); leukemia, including chronic lymphoma Cellular Leukemia (CLL), Acute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML); Lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B cell lymphoma; bone marrow Dysplasia syndrome; myelofibrosis, renal fibrosis, liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer; Prostate cancer; Medulloblastoma; Basal cell carcinoma; Goring syndrome; Esophageal cancer; Colorectal cancer; Medulloblastoma; Rhabdomyosarcoma; Hepatoblastic carcinoma; Glioma; Astrocytoma; Liver cancer; Cirrhosis of the liver; soft tissue sarcoma; and pancreatic cancer.

In one embodiment of the treatment method, wherein at least one selected from the group consisting of nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural cavity administration, and peritoneal administration Drugs, vaginal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural administration, intrathecal administration and intravenous administration are administered to the subject.

definition

Unless otherwise specified, the following words, phrases, and symbols used in this specification generally have the meanings described below.

Generally, the nomenclature used herein and the laboratory procedures for cell culture, organic chemistry, analytical chemistry, and pharmacology described below are well-known and commonly used in the art. Unless defined otherwise, all scientific and technical terms used herein in conjunction with the present disclosure have the same meaning as commonly understood by those skilled in the art. In addition, in the claims and/or specification, when the term "a" or "an" is used in combination with the term "comprising" or a nominal term, its meaning can mean "a", but it can also be used with "one or more". ", "at least one" and "one or more than one" have the same meaning. Similarly, the term "another" or "other" can mean at least a second or more.

It should be understood that whenever the term "comprising" is used herein to describe various aspects, other similar aspects described with "consisting of" and/or "consisting essentially of" are also provided.

As used herein, the term "approximately" means approximately, approximately, approximately or approximately. When the term "about" is used in conjunction with a range of values, it modifies the range by extending boundaries above and below the stated value. For example, the term "approximately" as used herein may modify the value to be higher and lower than the stated value by, for example, ±20% or ±15%, or ±10%, ±5%, or ±1.

The term "absent" as used herein in combination with a substituent or group means that the substituent or group does not exist. In other words, when the substituent or group is not present, it becomes a bond or bond linker. For example, in the compound of formula (I) according to the present disclosure, when the A ¹ group is not present, the R ¹ group is directly covalently bonded (or connected) to LIN.

Herein, the compound of formula (I) and the compound of formula (II) of the present invention are also referred to as protein degrading agents (compounds) or PROTAD drugs, and they can be used interchangeably.

In this document, the terms "LIN" and "linker" are used interchangeably, and both represent the linking group in the compound of formula (I) and the compound of formula (II).

In this context, the term "intermediate LM" refers to ^{the intermediate compound used to construct the -A 1} -LIN-A ² -R ² part of the compound of formula (I) in the following schemes and examples, as well as to construct formula (II) The intermediate compound of the -A ₁₂ -LIN-A ₂₂ -R ₂₂ part of the compound.

In this context, the term "intermediate BINDER" refers to the intermediate compound used to construct the R ¹ _{group of the compound of formula (I) or the R 12} group of the compound of formula (II) in the following schemes and examples. The intermediate LM and the intermediate BINDER are coupled under appropriate conditions to synthesize the target protein degrading agent of the present invention.

In this article, the bond broken by the wavy line shows the connection point between the depicted group and the rest of the molecule. For example, the group represented by ^{R 2 shown below}

It means that the group is connected to the group A ^{2 of the} compound of formula (I).

In the present invention, the term "halogen atom" or "halogen" used alone or in combination means fluorine, chlorine, bromine or iodine, and is, for example, F, Cl or Br.

In the present invention, the term "alkyl" used alone or in combination refers to a linear or branched alkyl group. The term "C _x -C _y alkyl" or "C _xy alkyl" (x and y are each an integer) refers to a straight or branched chain alkyl group containing x to y carbon atoms. _{The term "C 1-10} alkyl group" used alone or in combination in the present invention refers to a straight or branched chain alkyl group containing 1 to 10 carbon atoms. _{The C 1-10} alkyl group of the present invention is _{preferably a C 1-9} alkyl group, more preferably a C _1-8 alkyl group, still more preferably a C _2-8 alkyl group, more preferably a C _1-7 alkyl group, and even More preferably, it is a C _1-6 alkyl group, a C _1-5 alkyl group, or a C _1-4 alkyl group. Representative examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, p-pentyl, hexyl , Heptyl, octyl, nonyl and decyl. The term "C _1-3 alkyl" in the present invention refers to an alkyl group containing 1 to 3 carbon atoms, and representative examples thereof include methyl, ethyl, n-propyl and isopropyl. In the present invention, the "alkyl" is optionally substituted, and the substituent is preferably one or more selected from halogen, cyano, C _1-3 alkyl, C _1-3 alkoxy, tri Substituents of fluoromethyl, heterocyclic group or any combination thereof.

In this article, the terms "alkylene" or "alkylene chain" (the two are used interchangeably), used alone or in combination, refer to a straight or branched divalent saturated hydrocarbon group composed of carbon and hydrogen atoms. . The term "C _x -C _y alkylene" or "C _xy alkylene" (x and y are each an integer) refers to a linear or branched alkylene group containing x to y carbon atoms. _{The C 1} -C ₃₀ alkylene group of the present invention is _{preferably a C 1} -C ₂₉ alkylene group, a C ₁ -C ₂₈ alkylene group, a C ₁ -C ₂₇ alkylene group, a C ₁ -C ₂₆ alkylene group, and C ₁ -C ₂₅ alkylene, C ₁ -C ₂₄ alkylene, C ₁ -C ₂₃ alkylene, C ₁ -C ₂₂ alkylene, C ₁ -C ₂₁ alkylene, C ₁ -C ₂₀ alkylene Alkyl, C ₁ -C ₁₉ alkylene, C ₁ -C ₁₈ alkylene, C ₁ -C ₁₇ alkylene, C ₁ -C ₁₆ alkylene, C ₁ -C ₁₅ alkylene, C ₁ -C ₁₄ alkylene, C ₁ -C ₁₃ alkylene, C ₁ -C ₁₂ alkylene, C ₁ -C ₁₁ alkylene, C ₁ -C ₁₀ alkylene, C ₁ -C ₉ alkylene Group, C ₁ -C ₈ alkylene, C ₁ -C ₇ alkylene, C ₁ -C ₆ alkylene, C ₁ -C ₅ alkylene, C ₁ -C ₄ alkylene, C _1- C ₃ alkylene, or C ₁ -C ₂ alkylene. Representative examples include, but are not limited to, methylene, ethylene, propylene, isopropylidene, butylene, isobutylene, sec-butylene, tert-butylene, pentylene, isopentylene , Neopentylene, terpentylene, hexylene, heptylene, octylene, nonylene, decylene, undecylene, dodecylene, tridecylene, decylene Tetraalkyl, pentadecylene, hexadecylene, heptadecylene, octadecylene, nonadecanyl, eicosylene, eicosylene, arachidylene Dialkyl, trichenylene, tetracosene, pentadecylene, hexadecylene, heptadecylene, octadecylene, and twenty-nine decylene Alkyl, and triaconylene. In the present disclosure, the "alkylene" is optionally substituted, and the substituent may be one or more selected from hydroxyl, amino, mercapto, halogen, cyano, C _1-3 alkyl, C _{1 -3} Substituents of alkoxy, trifluoromethyl, heterocyclyl or any combination thereof.

In this document, the terms "carbonyl", "CO", and "C=O" are used interchangeably.

As used herein, the expression "the alkylene group is interrupted by one or more groups" means that one or more (for example, 1-10 1, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1) groups as defined herein, namely Any one or more pairs of two adjacent carbon atoms in the carbon chain main chain structure of the linear or branched alkylene are covalently connected through the group. For example, the expression "the alkylene group is interrupted by one or more oxygens" means that one or more (for example, 1-10, 1- 8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1) oxygen atoms to form one or more (for example, 1 -10, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1) "-CH ₂ -O- The oxaalkylene group of the CH ₂ -" fragment.

As used herein, the term "aryl" used alone or in combination refers to an aromatic hydrocarbon group containing 5 to 14 carbon atoms (for example, 6-10 carbon atoms) and optionally one or more fused rings, such as Phenyl, naphthyl or fluorenyl. In this context, the "aryl group" is an optionally substituted aryl group. A substituted aryl group refers to an aryl group substituted 1-3 times with a substituent (that is, the aryl group is mono-substituted, di-substituted or tri-substituted with a substituent), wherein the substituent may be selected from _{, for example, a C 1-3} alkyl group, C _1-3 alkoxy, trifluoromethyl, mercapto, cyano, halogen, amino, hydroxyl or any combination thereof.

In this document, the term "alkoxy" used alone or in combination refers to a straight-chain or branched alkoxy group, the structural formula of which is -O-alkyl. Preferably, the alkyl portion of the alkoxy group may contain 1-10 carbon atoms. Representative examples of "alkoxy" include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentoxy, 2 -Pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, 2-hexyloxy, 3-hexyloxy, 3-methylpentyloxy, etc. The term "C ₁ -C ₃ alkoxy" or "C _1-3 alkoxy" refers to a straight or branched chain alkoxy group containing 1 to 3 carbon atoms. Representative examples of C _{1- 3} alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy and isopropoxy, methoxy and ethoxy, for example.

In this document, the term "alkylamino" used alone or in combination refers to a linear or branched alkylamino group, and its structural formula is -NH-alkyl. Preferably, the alkyl portion of the alkylamino group may contain 1-10 carbon atoms. Representative examples of "alkylamino" include, but are not limited to, methylamino, ethylamino, propylamino, isopropylamino, n-butylamino, isobutylamino, tert-butylamino, pentylamino, 2 -Pentylamino, isopentylamino, neopentylamino, hexylamino, 2-hexylamino, 3-hexylamino, 3-methylpentylamino, etc. The term "C ₁ -C ₃ alkylamino" or "C _1-3 alkylamino" refers to a linear or branched alkylamino group containing 1 to 3 carbon atoms. Representative examples of C _1-3 alkylamino include, but are not limited to, methylamino, ethylamino, n-propylamino, and isopropylamino. Preferably they are methylamino and ethylamino.

In this document, the term "haloalkyl" used alone or in combination refers to a straight or branched chain alkyl group substituted with one or more halogen atoms. The term "C _x -C _y haloalkyl" (x and y are each an integer) refers to a linear or branched haloalkyl group containing x to y carbon atoms. Preferably, the alkyl portion of the haloalkyl group may contain 1-10 carbon atoms, 1-8 carbon atoms, 1-5 carbon atoms, or 1-3 carbon atoms. Representative examples of "haloalkyl" include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl , 2-fluoroethyl, 2-chloroethyl, tetrafluoroethyl (CF ₃ CFH), pentafluoroethyl, 1,1,1-trifluoroprop-2-yl, etc.

In this document, the term "heterocyclylene" or "heterocyclylene" used alone or in combination means containing one or more (for example, containing 1 to 5 or 1 to 4, 1-3, 1-2 One or one) independently selected from 3 to 20 members of heteroatoms of sulfur, oxygen and nitrogen (e.g., 3 to 15, 3 to 12, 3 to 11, 3 to 10, 3 to 9, 3 to 8, 3 to 6-membered, or 3- to 5-membered) monocyclic, bicyclic or tricyclic saturated or unsaturated (that is, with one or more double bonds, conjugated or incompletely conjugated) divalent cyclic hydrocarbon group, which may include condensed Ring, bridge ring or spiro ring system. According to the definition herein, the term "heterocyclylene" may include an aromatic heterocyclic ring or a non-aromatic heterocyclic ring or an aliphatic heterocyclic ring having at least one heteroatom. In some embodiments, "heterocyclylene" may preferably refer to a 3- to 15-membered (for example, 3- to 8-membered or 3- to 6-membered) heteroatom containing one or more heteroatoms independently selected from sulfur, oxygen, and nitrogen Monocyclic, bicyclic or tricyclic saturated or unsaturated (that is, with one or more double bonds, conjugated or incompletely conjugated) divalent cyclic hydrocarbon group. Representative examples include, but are not limited to, azetidinyl, oxetanylene, pyrrolidinylene, imidazolidinyl, pyrazolidinylene, pyridinylene, triazolylidene, tetrahydrofuranyl , Tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyran, oxazolidinyl, thiazolidine, piperidinylene, piperazinylene, morpholinylene, thiosulfide Morpholinyl, dioxanyl, diazacycloheptane subunits (e.g. 1,4-diazepanylidene, 4,5-diazepanylidene, 1,3 -Diazabicycloheptane subunit), 3,8-diazabicyclo[3.2.1]octane subunit, 2,5-diazabicyclo[2.2.2]octane subunit, azo Spirocyclic group (e.g. 3-azaspiro[5.5]undecylidene), furanylene, oxazolylidene, isoxazolylidene, oxadiazolylidene, thienylene, thiazolylidene, sub Isothiazolyl, thiadiazole, pyrrolylene, imidazolylidene, pyrazolylidene, triazolylidene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene , Isoindolylene, benzofuranyl, isobenzofuranyl, benzothienylene, indazolylidene, benzimidazolylidene, benzoxazolylidene, benzisoxazole Group, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazole subunit, benzo[2,1,3]thiadiazole subunit Group, benzo[1,2,3]thiadiazolylidene, quinolinylene, isoquinolinylene, naphthyridinylene, cinolinylene, quinazolinylene, quinoxalinylene, Subphthalazinyl, pyrazolo[1,5-a]pyridine subunit, pyrazolo[1,5-a]pyrimidin subunit, imidazo[1,2-a]pyridine subunit, 1H-pyrrolo [3,2-b]pyridine subunit, 1H-pyrrolo[2,3-b]pyridine subunit, 4H-fluoro[3,2-b]pyrrol subunit, pyrrolo[2,1-b]thiazole Subunits and imidazo[2,1-b]thiazol subunits. The heterocyclylene may be unsubstituted or substituted as clearly defined, for example, having 1 to 3 identical or different substituents, and the substituents may for example be selected from C ₁ -C ₃ alkyl, hydroxyl, amino, Mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof.

In this context, the term "heterocyclic group" used alone or in combination means containing one or more (for example, containing 1 to 5 or 1 to 4, 1-3, 1-2 or 1) independently selected From 3 to 20 members of heteroatoms of sulfur, oxygen, and nitrogen (e.g., 3 to 15, 3 to 12, 3 to 11, 3 to 10, 3 to 9, 3 to 8, 3 to 6, or 3 to 5 ) Monocyclic, bicyclic or tricyclic saturated or unsaturated (that is, having one or more double bonds, conjugated or incompletely conjugated) divalent cyclic hydrocarbon group, which may include fused ring, bridged ring or spiro ring system . According to the definition herein, the term "heterocyclic group" may include an aromatic heterocyclic group or a non-aromatic heterocyclic group or an aliphatic heterocyclic group having at least one heteroatom. In some embodiments, "heterocyclyl" may preferably refer to a 3 to 15 membered (e.g., 3 to 8 membered or 3 to 6 membered) monomer containing one or more heteroatoms independently selected from sulfur, oxygen, and nitrogen. Cyclic, bicyclic or tricyclic saturated or unsaturated (ie, with one or more double bonds, conjugated or incompletely conjugated) divalent cyclic hydrocarbon group. Representative examples include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, pyridinyl, triazolyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyranyl Hydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, diazacycloheptanyl (E.g. 1,4-diazepanyl, 4,5-diazepanyl, 1,3-diazepanyl), 3,8-diazabicyclo [3.2. 1]octyl, 2,5-diazabicyclo[2.2.2]octyl, azaspirocyclic group (e.g. 3-azaspiro[5.5]undecyl), furyl, oxazolyl , Isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, Pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl , Benzothiazolyl, benzoisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1 ,2,3]thiadiazolyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a ]Pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2, 3-b]pyridyl, 4H-fluoro[3,2-b]pyrrolyl, pyrrolo[2,1-b]thiazolyl and imidazo[2,1-b]thiazolyl. The heterocyclic group may be unsubstituted or substituted as clearly defined, for example, having 1-3 identical or different substituents, and the substituents may be selected from, for example, C ₁ -C ₃ alkyl, hydroxyl, amino, and mercapto groups. , Halogen, aryl, C _1-3 alkoxy, alkylamino, haloalkyl, cyano or any combination thereof.

In this article, "adamantane" (also known as Tricyclo[3.3.1.1 ^3,7 ]decane) has a definition known to those skilled in the art, and its structural formula is for example as follows:

As used herein, "adamantyl" refers to a monovalent group of adamantane, that is, the group remaining after any hydrogen in the adamantane is removed. Representative examples include, but are not limited to, 1-adamantyl, 2-adamantyl, 3-adamantyl, 4-adamantyl, 5-adamantyl, 6-adamantyl, 7-adamantyl, 8 -Adamantyl, 9-adamantyl or 10-adamantyl.

The salts or pharmaceutically acceptable salts, enantiomers, stereoisomers, solvates, and polymorphs of the compounds of formula I and the compounds of formula II described in the present disclosure are also encompassed within the scope of the present disclosure.

In all embodiments of the present disclosure, the salt or pharmaceutically acceptable salt of the compound of formula I and the compound of formula II refers to non-toxic inorganic or organic acid and/or base addition salts. Examples include: sulfate, hydrochloride, citrate, maleate, sulfonate, citrate, lactate, tartrate, fumarate, phosphate, dihydrophosphate, pyrophosphate Salt, metaphosphate, oxalate, malonate, benzoate, mandelate, succinate, glycolate or p-toluenesulfonate, etc.

"Pharmaceutically acceptable carrier" refers to pharmaceutically acceptable materials, such as fillers, stabilizers, dispersants, suspending agents, diluents, excipients, thickeners, solvents, or encapsulating materials. The compounds useful in the invention are carried or transported into the patient's body or administered to the patient so that it can perform its intended function. Generally, such constructs are carried or transported from one organ or part of the body to another organ or part of the body. The carrier is compatible with the other ingredients of the formulation (including the compounds useful in this disclosure) and is not harmful to the patient, the carrier must be "acceptable." Some examples of materials that can be used as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose, and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl acetate Base cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository wax; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil And soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffers, such as magnesium hydroxide And aluminum hydroxide; surfactant phosphate buffer solution; and other non-toxic compatible substances used in pharmaceutical preparations.

The term "treatment" or "treatment" refers to the administration of a compound of formula (I) or a compound of formula II, or a pharmaceutically acceptable salt thereof, according to the present disclosure, or a compound of formula I or formula II as an active ingredient. A pharmaceutical composition of a compound or a pharmaceutically acceptable salt thereof to slow down (alleviate) the development of undesirable diseases or conditions. The beneficial or desired clinical results of the present disclosure include, but are not limited to: alleviating symptoms, reducing the severity of the disease, stabilizing the state of the disease, delaying or delaying the progression of the disease, improving or alleviating the disease, and alleviating the disease.

The "therapeutically effective amount" of the compound of the present disclosure depends on a variety of factors, including the activity of the particular compound used, the metabolic stability and duration of action of the compound, the patient's age, sex and weight, the patient's general medical condition, and administration Method and time, excretion rate, combination medication, and disease or disease progression of the patient being treated. Those skilled in the art can determine the appropriate dosage based on these and other factors. The dosing and dosing regimen should be within the capabilities of those skilled in the art, and the appropriate dosage depends on many factors including the level of knowledge and ability of general technical doctors, veterinarians or researchers (see, for example, Wells et al.eds., Pharmacotherapy Handbook, 2nd Edition, Appleton and Lange, Stamford, Conn. (2000); PDR Pharmacopoeia, Tarascon Pocket Pharmacopoeia 2000, Deluxe Edition, Tarascon Publishing, Loma Linda, Calif. (2000)).

The patients or subjects treated above refer to animals, such as mammals, including but not limited to primates (such as humans), cattle, sheep, goats, horses, dogs, cats, rabbits, guinea pigs, rats, and mice Wait.

The term "room temperature" in the present disclosure refers to the ambient temperature, for example, a temperature of 20-30°C.

Example

In the following description, many specific details are proposed in order to provide a thorough understanding of the present disclosure. The present disclosure may be implemented without some or all of these specific details. In other cases, in order not to cause unnecessary confusion to the present disclosure, well-known process operations are not described in detail. Although the present disclosure will be described in conjunction with specific embodiments, it should be understood that this is not intended to limit the present disclosure to these embodiments.

The following abbreviations are used throughout the specification and examples:

Boc tert-Butoxycarbonyl

Bipy Bipyridine

BnCl Benzyl chloride

DCM Dichloromethane

DIPEA N,N-Diisopropylethylamine

DMF N,N-Dimethylformamide

DMAP 4-Dimethylaminopyridine

EDCI Carbodiimide

ESI Electrospray ionization

equiv Equivalent

ETOH Ethanol

HATU O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-Tetramethyluronium hexafluorophosphate

HOAT 1-hydroxy-7-azobenzotriazole

HPLC High Performance Liquid Chromatography

HRMS High-resolution mass spectrometry

LC-MS Liquid chromatography-mass spectrometry

LRMS Low-resolution mass spectrometry

LC Liquid chromatography

Me Methyl

MS Mass spectrometry

MsCl Methanesulfonyl chloride

OMs or MsO Methanesulfonyloxy

NMP N-methylpyrrolidone

¹ H NMR Proton Nuclear Magnetic Resonance Spectroscopy

rt or RT Room temperature

t-BuOH tert-Butanol

t-BuONO tert-butyl nitrite

TEA Triethylamine

TFA Trifluoroacetic acid

TLC Thin layer chromatography

TMS Trimethylsilyl

In this disclosure, the ¹ H NMR spectrum is measured with a Bruker-500MHz nuclear magnetic resonance instrument, using CD ₃ OD containing 0.1% TMS as a solvent, and the ¹ H NMR spectrum uses CD ₃ OD (δ=3.31 ppm) as an internal standard; _{Or use CDCl 3} containing 0.1% TMS as the solvent, in which the ¹ H NMR spectrum uses CDCl ₃ (δ=7.26 ppm) as the internal standard; or use DMSO-d ₆ containing 0.03% TMS as the solvent, in which the ¹ H NMR spectrum is based on DMSO-d ₆ (δ=2.50ppm) is used as internal standard; LRMS spectrum is measured on AB Triple 4600 mass spectrometer, HPLC preparation is measured on SHIMADZU LC-20AP instrument, HPLC purity is measured on SHIMADZU LC-30AP or Waters 1525 instrument The above determination; the product is prepared and separated by column chromatography (silica gel: 200-300 mesh), C18 reverse phase column (100g). All reactions were carried out under air atmosphere without special instructions; the reactions were followed by TLC or LC-MS.

Solvents and reagents are handled as follows:

The solvents used in the reaction such as DCM, DMF, NMP, anhydrous EtOH, anhydrous MeOH, etc. are all purchased from Sinopharm;

HPLC preparation uses preparative CH ₃ CN and deionized water;

The starting materials for the synthesis of intermediate Binder, such as 4-fluoro-3-nitrobenzenesulfonamide, and the starting materials for the synthesis of intermediate LM, such as pomalidomide, can be directly purchased.

Other reagents and medicines can be purchased directly from commercial sources without special instructions.

Preparation

The compounds described herein and/or pharmaceutically acceptable salts thereof can be synthesized by methods known in the art using commercially available raw materials. The synthesis scheme described below exemplifies the preparation of most compounds. Generally, the compound of formula (I) and the compound of formula (II) of the present invention can be prepared by coupling (constructing R ¹ group or R ₁₂ ) intermediate BINDER and intermediate LM under appropriate conditions, including the following methods and implementations Examples of suitable variants or alternative forms. Those skilled in the art can prepare the salt, racemate, enantiomer, carbamate, phosphate, sulfate, salt of the compound of formula (I) or compound of formula (II) of the present invention according to conventional techniques in the art Salt and prodrug forms.

General preparation method of intermediate LM

Scheme 1. General preparation method of intermediate LM (Poma-N-Linker-COOH) (refer to patent CN 109912655 A, the content of which is incorporated herein by reference in its entirety):

plan 1

Wherein n is an integer from 0-20.

Scheme 2. General preparation method of intermediate LM (Len-NC _n -COOH) (refer to patent CN 109912655 A, the content of which is incorporated herein by reference in its entirety):

Scenario 2

Wherein n is an integer of 1-20.

Scheme 3. General preparation method of intermediate LM (Po-NC _{n -I):}

Scheme 3

Wherein n is an integer from 0-20.

Scheme 4. General preparation method of intermediate LM (Len/Poma-CC-linker-OMs):

Scheme 4

Wherein n is an integer from 0-20.

Scheme 5. General preparation method of intermediate LM (Len/Poma-CC _{n -OMs):}

Scheme 5

Wherein n is an integer from 0-20.

Scheme 6. General preparation method of intermediate LM (Poma-SC _{n -COOH):}

Scheme 6

Wherein n is an integer of 1-20.

Scheme 7. General preparation method of sulfur substituted pomalidomide PEG chain carboxylic acid series compounds:

Scheme 7

Wherein n is an integer of 1-20.

Scheme 8. General preparation method of intermediate LM (Len-SC _{n -COOH):}

Scheme 8

Wherein n is an integer of 1-20.

Scheme 9. General preparation method of thiol substituted lenalidomide PEG chain carboxylic acid series compound:

Scheme 9

Wherein n is an integer of 1-20.

Scheme 10. General preparation method of intermediate LM (Len-S-Cn-Br):

Scheme 10

Wherein n is an integer of 1-20.

Scheme 11. General preparation method of intermediate LM (Len-OC _{n -Br):}

Scheme 11

Wherein n is an integer of 1-20.

Scheme 12. General preparation method of intermediate LM (VHL-CO-Linker-COOH) (refer to patent CN 109912655 A, the content of which is incorporated herein by reference in its entirety):

Scheme 12

Wherein n is an integer of 1-20.

Scheme 13. General preparation method of intermediate LM (VHL-CO-Linker-Br) (refer to patent KR20170132934(A), the content of which is incorporated herein by reference in its entirety)

Scheme 13

Wherein n is an integer of 1-20.

Scheme 14. General preparation method of intermediate LM (VHL-Linker-OTs/I)

Scheme 14

Wherein n is an integer of 1-20.

General preparation method of the compound of the present invention

Scheme 15. Method for synthesizing the PROTAC compound of the present invention by condensation reaction

Scheme 15

POI shows the reactive group of the intermediate BINDER, and the E3 ligand corresponds to R ² or R ₂₂ in the compound of the present invention.

Scheme 16. Method for synthesizing the PROTAC compound of the present invention by substitution reaction:

Scheme 16

POI shows the reactive group of the intermediate BINDER, and the E3 ligand corresponds to R ² or R ₂₂ in the compound of the present invention.

Scheme 17. Method for synthesizing the PROTAC compound of the present invention by Click reaction:

Scheme 17

POI shows the reactive group of the intermediate BINDER, and the E3 ligand corresponds to R ² or R ₂₂ in the compound of the present invention.

The compounds obtained in the above scheme can be further modified by substituents and the like according to methods well known to those skilled in the art to obtain other target compounds.

Preparation examples

Preparation example of intermediate BINDER

Preparation of intermediate BINDER Example 1: Synthesis of compound SIAIS230138

first step

Dissolve 4-Fluoro-3-nitrobenzenesulfonamide (1.0g, 4.5mmol) in 20mL tetrahydrofuran, add 1-tert-butoxycarbonyl-4-aminomethylpiperidine in sequence (1-Boc-4-(aminomethyl)piperidine) (0.97g, 4.5mmol) and triethylamine (0.68g, 6.8mmol, 0.93mL) were reacted at room temperature for 12h, and the reaction was complete. Distill under reduced pressure, remove the solvent, and perform column chromatography (silica gel, PE/EA=1/1-EA). Obtained SIAIS230121, yellow powder, m=1.7g, yield (yield)=90%. ¹ H NMR(500MHz,DMSO-d ₆ )δ8.58(t,J=6.1Hz,1H), 8.47(d,J=2.3Hz,1H), 7.82(dd,J=9.2,2.3Hz,1H) ,7.38–7.25(m,3H),3.36(t,J=6.6Hz,2H),2.68(s,2H),1.84(m,1H),1.68(dd,J=13.6,3.5Hz,2H), 1.39 (s, 9H), 1.09 (qd, J = 12.3, 4.3 Hz, 2H).

Second step

2-[(1H-pyrrolo[2,3-B]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl ring Hex-1-enyl]methyl]piperazin-1-yl]benzoic acid (0.78g, 1.36mmol) and SIAIS230121 (0.56g, 1.36mmol) were added to 20mL of dichloromethane, and EDCI (0.40g, 2.04 mmol) and DMAP (0.24g, 2.04mmol), the reaction system became clear. After 12 hours of reaction, the raw material reacted completely. Add 30mL of dichloromethane to dilute, wash with saturated brine, distill under reduced pressure to remove the solvent, and column chromatography to obtain SIAIS230126, yellow powder, m=1.17g, yield=89%.

third step

Dissolve SIAIS230126 (1.17g, 1.21mmol) in 20mL of dichloromethane, add 5mL of trifluoroacetic acid, and react for 30min at room temperature. After the reaction was completed, the organic solvent and trifluoroacetic acid were removed by distillation under reduced pressure, and the powder was lyophilized to obtain compound SIAIS230138, a yellow solid, m=1.05g, yield=100%. ¹ H NMR(500MHz,DMSO-d6)δ11.79(s,1H), 11.70(s,1H), 10.78(s,1H), 9.01(s,1H), 8.73(s,1H), 8.69(J =6.2Hz,1H),8.57(d,J=2.3Hz,1H),8.06(d,J=2.6Hz,1H),7.81(dd,J=9.2,2.3Hz,1H),7.59(d,J =2.6Hz,1H),7.56–7.49(m,2H),7.42–7.36(m,2H),6.72(dd,J＝9.0,2.4Hz,1H), 6.42(dd,J＝3.4,1.8Hz, 1H), 6.26 (d, J = 2.4 Hz, 1H), 3.62 (d, J = 13.2 Hz, 2H), 3.53 (d, J = 4.9 Hz, 2H), 3.38-3.22 (m, 8H), 2.81 ( q,J=11.9Hz,2H),2.76–2.61(m,2H),2.36(s,2H),2.01(s,2H), 1.97–1.89(m,1H),1.85(d,J=13.8Hz ,2H),1.43(q,J=8.5,7.4Hz,4H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₄₅ H ₅₂ ClN ₈ O ₆ S ⁺ [M+H] ⁺ ,867.3414; measured value,867.3410.

Preparation of intermediate BINDER Example 2: Synthesis of compound SIAIS255123

The compound SIAIS255123 was synthesized by referring to the synthesis method of the preparation example 1 of the intermediate BINDER.

Compound SIAIS155122, yellow powder.

¹ H NMR(500MHz,DMSO-d ₆ )δ8.56(s,1H), 8.48(d,J=2.3Hz,1H), 7.84(dd,J=9.2,2.3Hz,1H), 7.33(s, 2H), 7.28 (d, J = 9.2 Hz, 1H), 3.71 (d, J = 13.1 Hz, 1H), 3.35 (t, J = 6.5 Hz, 2H), 2.84 (ddd, J = 13.4, 10.6, 3.1 Hz, 1H), 2.68 (s, 1H), 1.81 (dt, J = 8.5, 4.1 Hz, 2H), 1.63 (dt, J = 12.9, 3.9 Hz, 1H), 1.46-1.15 (m, 12H).

Compound SIAIS255123, yellow powder, total yield 94%, m=1.30g.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.73(t,J=2.2Hz,1H), 11.69(s,1H), 9.45(s,1H), 8.70(t,J=6.3Hz,1H) ,8.65(s,1H),8.58(d,J=2.3Hz,1H),8.23(s,1H),8.05(d,J=2.7Hz,1H),7.85(dd,J=9.3,2.3Hz, 1H), 7.57(d,J=2.7Hz,1H),7.55-7.51(m,2H),7.43-7.37(m,2H),7.16(d,J=9.4Hz,1H),7.12-7.06(m , 2H), 6.72 (dd, J = 9.0, 2.3 Hz, 1H), 6.41 (dd, J = 3.4, 1.9 Hz, 1H), 6.26 (d, J = 2.4 Hz, 1H), 3.67 (d, J = 13.0Hz, 2H), 3.58 (s, 2H), 3.39 (q, J = 7.9, 7.2 Hz, 2H), 3.25 (dd, J = 35.3, 12.2 Hz, 4H), 3.02 (s, 2H), 2.84- 2.61 (m, 4H), 2.20 (s, 2H), 2.02 (s, 2H), 1.82 (t, J = 15.4 Hz, 2H), 1.59 (t, J = 13.2 Hz, 1H), 1.45 (t, J =6.4Hz,2H),1.28–1.17(m,1H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₄₅ H ₅₂ ClN ₈ O ₆ S ⁺ [M+H] ⁺ , 867.3414; measured value, 867.3414.

Preparation of intermediate BINDER Example 3: Synthesis of compound SIAIS268193

first step

Dissolve 4-Fluoro-3-nitrobenzenesulfonamide (1.0g, 4.5mmol) in 20mL tetrahydrofuran, add propynylamine (0.30g, 5.5mmol) and triethylamine in sequence (0.91g, 9.0mmol, 1.25mL), react at room temperature for 12h, the reaction is complete. Distill under reduced pressure to remove the solvent, add 5 mL of methanol, stir, and add 30 mL of water to precipitate the product SIAIS268192. Yellow powder, m=1.0g, yield=90%.

Second step

2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl ring Hex-1-enyl]methyl]piperazin-1-yl]benzoic acid (1.00g, 1.75mmol) and SIAIS268192 (0.45g, 1.75mmol) were added to 20mL of dichloromethane, and EDCI (0.50g, 2.63 mmol) and DMAP (0.32g, 2.63mmol), the reaction system became clear. After 12 hours of reaction, the raw material reacted completely. Add 30 mL of dichloromethane to dilute, wash with saturated brine, distill off the solvent under reduced pressure, and column chromatography to obtain yellow powder. SIAIS268193, m=1.29g, yield=91%.

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.70 (s, 1H), 11.35 (s, 1H), 8.79 (t, J = 5.9 Hz, 1H), 8.60 (d, J = 2.3 Hz, 1H) ,8.06(d,J=2.6Hz,1H),7.93(dd,J=9.1,2.3Hz,1H),7.57(d,J=2.6Hz,1H),7.54–7.48(m,2H),7.38– 7.31 (m, 2H), 7.13 (d, J = 9.3 Hz, 1H), 7.04 (d, J = 8.4 Hz, 2H), 6.67 (dd, J = 9.1, 2.4 Hz, 1H), 6.40 (dd, J ＝3.4,1.9Hz,1H),6.18(d,J＝2.4Hz,1H), 5.76(s,1H), 4.27(dd,J＝5.9,2.5Hz,2H), 3.27(s,1H),3.07 (s,4H),2.76(s,2H),2.21(s,4H),2.14(s,2H),1.95(s,2H),1.38(t,J=6.5Hz,2H),0.92(s, 6H). MS (ESI) m/z: calculated value C ₄₂ H ₄₃ ClN ₇ O ₆ S ⁺ [M+H] ⁺ , 808.27; actually measured value, 808.62.

Preparation of intermediate BINDER Example 4: Synthesis of compound SIAIS268115

first step

Dissolve 2-bromo-6-hydroxybenzaldehyde (1.0g, 5.0mmol) in 10mL DMF, cool to 0℃, add NaH(1.5equiv), stir at room temperature for 15min, add 3-(iodomethyl)aza Butane-1-carboxylic acid tert-butyl ester (1.5equiv), react at 50°C overnight, quench the reaction with saturated ammonium chloride, extract twice with EA, wash with saturated brine three times, dry with sodium sulfate, and distill the solvent under reduced pressure. Column chromatography (PE-PE/EA=1/1) gave SIAIS268118 as a white solid with a yield of 54%.

Dissolve SIAIS268118 (1.07g, 2.9mmol) in a mixed solvent (DMF/H ₂ O = 10/1, 10mL), add p-chlorophenylboronic acid (0.54g, 3.5mmol), Pd(PPh ₃ ) ₂ Cl ₂ (102mg, 0.15mmol) and K ₂ CO ₃ (1.2g, 8.7mmol), bubbling Ar gas for 5 min, heating to 110° C., reacting for 8 h, and the reaction is complete. The reaction was quenched by adding water, extracted with DCM (50 mL×3), washed with saturated brine (50 mL×3), the organic solvent was distilled off under reduced pressure, and column chromatography (silica gel, PE/EA=1/1). Obtained SIAIS268129, light yellow oil, m=1.07g, w=92%.

Second step

Dissolve SIAIS268129 (1.07g, 2.7mmol) in 50mL methanol, reduce the temperature to 0℃, and add 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-( Piperazin-1-yl) methyl benzoate (0.94 g, 2.7 mmol), NaBH ₃ CN (0.25 g, 4.1 mmol), ZnCl ₂ (0.37 g, 2.7 mmol). Slowly warm up to room temperature and react overnight. The reaction was quenched by adding water, extracted with DCM (50 mL×3), washed with saturated brine (50 mL×3), and the organic solvent was distilled off under reduced pressure.

The obtained crude product was dissolved in 50 mL of a mixed solvent of MeOH/THF=1/1, 2.0 equivalents of 1M sodium hydroxide aqueous solution was added, the temperature was raised to 50° C., and the reaction was carried out for 48 hours. The ester is completely hydrolyzed and cooled to room temperature. Adjust PH=5-6 with 5% dilute hydrochloric acid, extract with EA (50mL×3), wash with saturated brine (50mL×3), distill off the organic solvent under reduced pressure, column chromatography (silica gel, DCM/MeOH=10/ 1). A white solid SIAIS268138 was obtained, m=1.54g, w=80%. MS (ESI) m/z: calculated value C ₄₀ H ₄₃ ClN ₅ O ₆ ⁺ [M+H] ⁺ , 724.29; measured value, 724.41.

third step

Dissolve compound SIAIS268138 (0.54g, 0.75mmol) in 20mL dichloromethane, and add 3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide in sequence (0.24g, 0.75mmol), EDCI (0.22g, 1.13mmol) and DMAP (138mg, 1.13mmol), react overnight at room temperature, quench the reaction by adding water, extract with DCM (50mL×3), wash with saturated brine (50mL× 3), the organic solvent is removed by distillation under reduced pressure. Column chromatography (silica gel, DCM/MeOH=10/1).

The obtained product was dissolved in 10 mL of dichloromethane, 2 mL of trifluoroacetic acid was added, and the reaction was carried out for 2 h, and the reaction was monitored. When the reaction is complete, dichloromethane and trifluoroacetic acid are removed by distillation under reduced pressure. Obtain SIAIS268115, yield = 90%.

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.50 (s, 1H), 8.64 (s, 2H), 8.36 (d, J = 2.2 Hz, 1H), 8.32 (t, J = 5.9 Hz, 1H) ,7.90(d,J=2.7Hz,1H),7.63-7.55(m,2H),7.50(d,J=8.4Hz,2H),7.45(d,J=8.4Hz,2H),7.40(t, J = 2.9 Hz, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.22 (d, J = 2.6 Hz, 1H), 7.05 (d, J = 8.3 Hz, 1H), 6.86 (d, J = 7.6Hz, 1H), 6.77 (d, J = 9.1Hz, 1H), 6.62 (dd, J = 8.8, 2.4 Hz, 1H), 6.34-6.21 (m, 2H), 4.14 (d, J = 5.6 Hz, 2H), 4.10–4.00 (m, 2H), 3.90 (dd, J = 10.5, 7.1 Hz, 2H), 3.84 (dd, J = 11.0, 3.2 Hz, 2H), 3.29–3.20 (m, 5H), 2.98 (s, 4H), 2.31 (s, 4H), 1.85 (ddd, J = 11.3, 7.6, 4.0 Hz, 1H), 1.60 (d, J = 11.1 Hz, 2H), 1.31-1.18 (m, 4H). MS (ESI) m/z: calculated value for C ₄₇ H ₅₀ ClN ₈ O ₈ S ⁺ [M+H] ⁺ , 921.32; found value, 921.77.

Preparation of intermediate BINDER Example 5: Synthesis of compound SIAIS346181

first step

Dissolve SIAIS268115 (0.34g, 0.37mmol) in 10mL methanol, add N-tert-butoxycarbonyl-2-aminoacetaldehyde (88mg, 0.56mmol), 0.25mL acetic acid and sodium cyanoborohydride (70mg, 1.12 mmol) and react overnight. Column chromatography (DCM-DCM/MeOH=10/1) yielded yellow powder, which was directly put into the next reaction.

Second step

Dissolve the product of the first step in 10 mL of dichloromethane, add 1 mL of trifluoroacetic acid, and react for 2 hours. The solvent and trifluoroacetic acid were removed by rotary evaporation and lyophilized to obtain SIAIS346181 as a yellow powder. m=0.30g, yield=84%. ¹ H NMR(500MHz, methanol-d ₄ )δ8.65(d,J=2.3Hz,1H), 8.09(d,J=2.5Hz,1H), 7.87( dd,J=9.3,2.3Hz,1H),7.76(d,J=2.4Hz,1H), 7.62(d,J=8.9Hz,1H), 7.57–7.53(m,2H),7.48(d,J ＝8.4Hz,2H),7.33(d,J＝8.4Hz,2H),7.25(d,J＝8.3Hz,1H),7.03-6.97(m,2H),6.78(dd,J＝9.0,2.4Hz ,1H),6.54(d,J=3.5Hz,1H),6.43(d,J=2.3Hz,1H),4.56(d,J=13.5Hz,1H),4.52-4.46(m,2H),4.47 –4.42(m,1H), 4.41–4.37(m,1H), 4.03–3.92(m,5H), 3.57(s,3H), 3.50–3.39(m,10H), 3.00(h,J=5.4Hz ,1H),2.95(s,1H),2.85(s,1H),1.96(ddt,J=11.5,7.9,4.0Hz,1H),1.71(d,J=14.6Hz,2H),1.44-1.33( m, 3H). MS (ESI) m/z: calculated value C ₄₉ H ₅₅ ClN ₉ O ₈ S ⁺ [M+H] ⁺ , 964.3577; found value, 964.3613.

Preparation of intermediate BINDER Example 6: Synthesis of compound SIAIS346012

first step

The compound SIAIS230121 (5.0 g, 12.1 mmol) was dissolved in 50 mL of dichloromethane, 5 mL of trifluoroacetic acid was added, and the reaction was carried out for 3 hours until the reaction of the raw materials was complete. Rotate to remove the solvent and trifluoroacetic acid. Add 50 mL of water and 10 mL of acetonitrile to dissolve the product, add saturated NaHCO ₃ aqueous solution dropwise until no bubbles are generated, at this time PH=8-9, and the product precipitates. Filter, wash with water, and suck dry to obtain a yellow solid powder. Yield = 98%.

Second step

Compound SIAIS255056 (1.0g, 3.18mmol) was dissolved in 50mL methanol, added N-tert-butoxycarbonyl-4-piperidone (0.95g, 4.77mmol), stirred for 30min, added 1mL AcOH, stirred for 30min, added NaBH ₃ CN (0.60g, 9.54mmol), react at room temperature for 12h. The reaction was quenched with saturated sodium bicarbonate, extracted with dichloromethane, the solvent was removed by rotary evaporation, and column chromatography was performed. DCM/MeOH=10/1, yield=70%. MS (ESI) m/z: calculated value C ₂₂ H ₃₆ N ₅ O ₆ S ⁺ [M+H] ⁺ , 498.24; measured value, 498.50.

third step

Using SIAIS315187 as the raw material, the compound SIAIS346012 was synthesized by referring to the synthesis method of Preparation Example 1 of the intermediate BINDER. ¹ H NMR (500MHz, DMSO-d ₆ ) δ11.50 (s, 1H), 8.36 (d, J = 2.1 Hz, 1H), 8.32 (t, J = 5.4 Hz, 1H), 7.90 (d, J = 2.6Hz,1H),7.59(d,J=8.8Hz,2H),7.42-7.38(m,1H),7.35(d,J=8.4Hz,2H),7.24(d,J=2.6Hz,1H) ,7.05(d,J=8.4Hz,2H), 6.78(d,J=9.2Hz,1H), 6.61(dd,J=8.8,2.3Hz,1H), 6.28(dd,J=3.4,1.8Hz, 1H), 6.25(d,J=2.4Hz,1H), 3.27–3.20(m,4H), 3.00(s,3H), 2.83(s,4H), 2.73(s,2H), 2.18(d,J = 20.0Hz, 6H), 2.09 (t, J = 10.9Hz, 2H), 1.96 (s, 2H), 1.79 (d, J = 12.3Hz, 2H), 1.68 (d, J = 12.3Hz, 2H), 1.62–1.50(m,3H),1.39(t,J=6.4Hz,2H),1.25–1.13(m,2H),0.93(s,6H).MS(ESI)m/z: calculated value C ₅₀ H ₆₁ ClN ₉ O ₆ S ⁺ [M+H] ⁺ , 950.4149; found value, 950.4180.

Preparation of intermediate BINDER Example 7: Synthesis of compound SIAIS363080

first step

SIAIS230138 (0.50g, 0.58mmol) was dissolved in 10mL NMP, potassium carbonate (2.0equiv), sodium iodide (2.0equiv) and bromide (2.0equiv) were added in sequence, heated at 50℃ overnight, reversed phase column separation and purification (CH ₃ CN/H ₂ O) to obtain the compound SIAIS363080A. MS (ESI) m/z: calculated value C ₅₄ H ₆₉ ClN ₉ O ₈ S ⁺ [M+H] ⁺ , 1038.47; measured value, 1039.52.

Second step

The obtained SIAIS363080A was dissolved in 10 mL of dichloromethane, 1 mL of trifluoroacetic acid was added, and the reaction was carried out for 2 hours. The solvent and trifluoroacetic acid were removed by rotary evaporation to obtain the trifluoroacetic acid salt of SIAIS363080. m=0.30g, yield=55%. ¹ H NMR(500MHz, methanol-d ₄ )δ8.63(d,J=2.3Hz,1H), 8.14(s,1H), 7.93(d,J=2.1Hz,1H), 7.89(dd,J= 9.2,2.3Hz,1H), 7.64–7.57(m,2H), 7.35(d,J=8.0Hz,2H), 7.10(d,J=8.1Hz,2H), 7.07(d,J=9.3Hz, 1H), 6.82 (d, J = 10.1 Hz, 1H), 6.62 (d, J = 3.5 Hz, 1H), 6.50 (s, 1H), 3.76 (d, J = 13.8 Hz, 2H), 3.71-3.64 ( m, 4H), 3.43 (dd, J = 18.8, 9.3 Hz, 4H), 3.29–3.20 (m, 4H), 3.12 (t, J = 7.7 Hz, 2H), 3.09–3.00 (m, 2H), 2.80 (t,J=11.7Hz,2H),2.74(s,3H),2.35(t,J=4.5Hz,2H),2.25-2.17(m,2H),2.11(s,3H),2.07(s, 2H), 1.72 (q, J = 13.3 Hz, 2H), 1.57 (t, J = 6.3 Hz, 2H), 1.01 (s, 6H). MS (ESI) m/z: calculated value C ₄₉ H ₆₁ ClN ₉ O ₆ S ⁺ [M+H] ⁺ , 938.4149; found value, 938.4173.

Preparation of intermediate BINDER Example 8: Synthesis of compound SIAIS363102

first step

SIAIS230138 (0.25g, 0.29mmol) was dissolved in 10mL of methanol, and N-tert-butoxycarbonyl-(methylamino)acetaldehyde (60mg, 0.34mmol), 0.25mL of acetic acid and sodium cyanoborohydride (55mg, 0.88mmol) were added , React overnight. Column chromatography (DCM-DCM/MeOH=10/1) gave SIAIS363098 (yellow powder, yield=70%). MS (ESI) m/z: calculated value for C ₅₃ H ₆₇ ClN ₉ O ₈ S ⁺ [M+H] ⁺ , 1024.45; found value, 1024.87.

Second step

The above product was dissolved in 10 mL of dichloromethane, 1 mL of trifluoroacetic acid was added, and the reaction was completed for 2 hours. The solvent and trifluoroacetic acid were removed by rotary evaporation and lyophilized to obtain SIAIS363102 as a yellow powder. ¹ H NMR(500MHz, methanol-d ₄ )δ8.64(d,J=2.3Hz,1H), 8.12(s,1H), 7.91-7.85(m,2H), 7.65-7.59(m,2H), 7.36(d,J=8.3Hz,2H), 7.10(d,J=8.4Hz,2H), 7.05(d,J=9.3Hz,1H), 6.82(dd,J=9.0,2.2Hz,1H), 6.59 (d, J = 3.5 Hz, 1H), 6.48 (d, J = 2.3 Hz, 1H), 3.74 (t, J = 12.2 Hz, 3H), 3.69 (s, 2H), 3.53 (dd, J = 14.0 ,5.4Hz,4H),3.47–3.38(m,4H), 3.23(t,J=12.5Hz,2H),3.10(t,J=12.6Hz,2H),2.82-2.78(m,2H),2.80 (s,3H),2.33(s,2H),2.15-2.05(m,5H),1.82-1.75(m,2H),1.57(t,J=6.3Hz,2H),1.01(s,6H). MS (ESI) m/z: calculated value for C ₄₈ H ₅₉ ClN ₉ O ₆ S ⁺ [M+H] ⁺ , 924.3992; found value, 924.4006.

Preparation of intermediate BINDER Example 9: Synthesis of compound SIAIS363101

The compound SIAIS363101 was synthesized by referring to the preparation method of the intermediate BINDER in Example 1. ¹ H NMR (500MHz, methanol-d ₄ )δ8.64(d,J=2.3Hz,1H), 8.06(d,J=2.5Hz ,1H), 7.86(dd,J=9.2,2.3Hz,1H),7.73(d,J=2.5Hz,1H), 7.60(d,J=8.9Hz,1H),7.53(d,J=3.5Hz ,1H),7.33(d,J=8.4Hz,2H), 7.08(d,J=8.4Hz,2H), 6.97(d,J=9.3Hz,1H), 6.77(dd,J=9.0,2.4Hz ,1H), 6.51(d,J=3.5Hz,1H), 6.39(d,J=2.4Hz,1H), 3.72(d,J=13.2Hz,2H), 3.68(s,2H), 3.43(d ,J = 10.6Hz, 2H), 3.29 (d, J = 6.9 Hz, 2H), 3.23 (t, J = 11.8 Hz, 2H), 3.10 (tt, J = 11.9, 3.9 Hz, 1H), 2.81 (q ,J = 12.3, 10.7 Hz, 2H), 2.36-2.30 (m, 2H), 2.10 (s, 4H), 1.98 (d, J = 12.0 Hz, 2H), 1.75-1.70 (m, 1H), 1.56 ( t,J=6.3Hz,2H),1.43(td,J=12.5,3.5Hz,2H),1.22(qd,J=13.3,3.3Hz,2H),1.00(s,6H).MS(ESI)m /z: Calculated value C ₄₆ H ₅₄ ClN ₈ O ₆ S ⁺ [M+H] ⁺ , 881.3570; measured value, 881.3556.

Preparation of intermediate BINDER Example 10: Synthesis of compound SIAIS363103

The compound SIAIS363103 was synthesized by referring to the synthesis method of Preparation Example 1 of the intermediate BINDER. ¹ H NMR(500MHz, methanol-d ₄ )δ8.65(d,J=2.3Hz,1H), 8.05(d,J=2.6Hz,1H), 7.88(dd,J=9.2,2.3Hz,1H) ,7.72(d,J=2.5Hz,1H), 7.60(d,J=8.9Hz,1H), 7.53(d,J=3.5Hz,1H), 7.33(d,J=8.4Hz,2H), 7.08 (d,J=8.4Hz,2H), 7.00(d,J=9.3Hz,1H), 6.77(dd,J=9.0,2.4Hz,1H), 6.50(d,J=3.5Hz,1H), 6.38 (d,J=2.4Hz,1H), 3.71(d,J=13.8Hz,2H), 3.68(s,2H), 3.47–3.34(m,5H), 3.22(t,J=12.6Hz,2H) ,2.81(q,J=12.7,11.2Hz,2H),2.38–2.29(m,2H),2.10(s,2H),1.09–1.93(m,1H),1.85–1.80(m,4H),1.77 –1.73(m,2H),1.64–1.55(m,4H),1.00(s,6H).MS(ESI)m/z: calculated value C ₄₆ H ₅₄ ClN ₈ O ₆ S ⁺ [M+H] ⁺ , 881.3570; Measured value, 881.3582.

Preparation of intermediate BINDER Example 11: Synthesis of compound SIAIS364025

first step

The compound SIAIS363101 (100mg, 0.11mmol) was dissolved in 10mL methanol, and 2-hydroxymorpholine-4-carboxylic acid tert-butyl ester (28mg, 0.136mmol), 100uL acetic acid and sodium cyanoborocyanide (21mg.0.33mmol) were added ), reacted at 40°C overnight to obtain SIAIS363130, a yellow powder. Yield=92%. MS (ESI) m/z: calculated value C ₅₅ H ₇₁ ClN ₉ O ₉ S ⁺ [M+H] ⁺ , 1068.48; measured value, 1068.71.

Second step

SIAIS363130 (100mg, 0.094mmol) was dissolved in 5mL DMF, added triphenylphosphine (49mg, 0.19mmol), cooled to 0°C, added DIAD (37uL, 0.19mmol). Reacted overnight, column chromatography (PE-EA- DCM/MeOH=10/1). MS (ESI) m/z: calculated value C ₅₅ H ₆₉ ClN ₉ O ₈ S ⁺ [M+H] ⁺ , 1050.47; found value, 1050.49.

third step

The above product was dissolved in 5 mL of dichloromethane, 0.5 mL of trifluoroacetic acid was added, and the reaction was carried out for 2 hours. The solvent and trifluoroacetic acid were removed by rotary evaporation and lyophilized to obtain SIAIS364025. Yellow powder, yield=59%. ¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.04(d,J=2.6Hz,1H), 7.87(dd,J=9.3,2.3Hz,1H) ,7.70–7.62(m,2H),7.50(d,J=3.4Hz,1H), 7.36(d,J=8.4Hz,2H), 7.08(d,J=8.4Hz,2H), 6.97(d, J = 9.4 Hz, 1H), 6.79 (dd, J = 9.0, 2.4 Hz, 1H), 6.48 (d, J = 3.4 Hz, 1H), 6.39 (d, J = 2.4 Hz, 1H), 3.70-3.50 ( m,12H), 3.48–3.36(m,3H),3.32-3.25(m,2H),3.21–3.11(m,2H), 2.86–2.72(m,2H),2.32-2.25(m,4H), 2.11(s,2H),2.07(d,J=13.0Hz,2H),1.76(t,J=3.5Hz,1H),1.70–1.59(m,2H),1.57(t,J=6.3Hz,2H ),1.27-1.22(m,2H),1.00(s,6H).MS(ESI)m/z: calculated value C ₅₀ H ₆₁ ClN ₉ O ₆ S ⁺ [M+H] ⁺ ,950.4149; measured value, 950.4209.

Preparation of intermediate BINDER Example 12: Synthesis of compound SIAIS364043

^{The compound SIAIS364043. 1} H NMR (500MHz, methanol-d ₄ ) δ8.65 (d, J = 2.3 Hz, 1H), 7.98 (d, J = 2.6 Hz) was synthesized by referring to the preparation method of the intermediate BINDER in Example 11 ,1H),7.83(dd,J=9.2,2.3Hz,1H),7.59(d,J=8.9Hz,1H),7.55(d,J=2.5Hz,1H),7.44(d,J=3.4Hz ,1H), 7.31(d,J=8.4Hz,2H), 7.06(d,J=8.4Hz,2H), 6.95(d,J=9.5Hz,1H), 6.70(dd,J=9.0,2.4Hz ,1H), 6.40(d,J=3.4Hz,1H), 6.28(d,J=2.3Hz,1H), 3.84–3.80(m,3H),3.75-3.55(m,5H),3.42(d, J = 7.6Hz, 2H), 3.37–3.34 (m, 2H), 3.17 (dd, J = 6.2, 4.3 Hz, 4H), 2.99 (s, 1H), 2.86 (s, 1H), 2.26 (t, J =6.6Hz,2H),2.08(s,3H),2.02-1.95(m,2H),1.92-1.85(m,4H),1.72(dt,J=15.8,7.5Hz,2H),1.53(t, J=6.4Hz,2H),1.34-1.26(m,2H),0.98(s,6H).MS(ESI)m/z: calculated value C ₅₀ H ₆₁ ClN ₉ O ₆ S ⁺ [M+H] ⁺ , 950.4149; Measured value, 950.4176.

Preparation of intermediate BINDER Example 13: Synthesis of compound SIAIS360129

first step

Dissolve 3-(trifluoromethanesulfonyl)-4-fluorobenzenesulfonamide (1.0g, 3.3mmol) in 20 methylene chloride, and add L-aspartic acid-4-methyl ester (0.72g, 5.0 mmol) and DIPEA (1.09mL, 6.6mmol), react for 8h at room temperature, the reaction is complete, the solvent is removed by distillation under reduced pressure, NaHCO ₃ (aq.) is added, the impurities are removed by ether extraction, 5% HCl (aq.) is acidified, and filtered, sucked dry to give SIAIS346151, white powder, yield = 76% .MS (ESI) m / z: Calcd _{12 F 3 N 2 O 8 S} 2 C 12 H - [MH] -, 433.00; found, 433.28.

Second step

Dissolve SIAIS346151 (0.50g, 1.15mmol) in 10mL THF, cool to 0°C, add borane-tetrahydrofuran solution (3.45mmol), react at room temperature for 6h, the reaction is complete, methanol quench the reaction, add sodium bicarbonate aqueous solution, Dichloromethane extraction 3 times, saturated brine washing once, anhydrous sodium sulfate drying, reduced pressure distillation to remove the solvent, column chromatography (PE-PE/EA = 1/3) to obtain SIAIS346153, yield = 74%. MS (ESI) m/z: calculated value for C ₁₂ H ₁₆ F ₃ N ₂ O ₇ S ₂ ⁺ [M+H] ⁺ , 421.03; found value, 421.24.

third step

Dissolve SIAIS346153 (0.89g, 2.1mmol) in a mixed solvent of DCM/THF=4/1, cool to 0°C, add triethylamine (0.35mL, 2.5mmol) and methylsulfonyl chloride (0.20mL, 2.5 mmol), react for 2.5h, the reaction is complete, the reaction is quenched with sodium bicarbonate (aq.), extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, column chromatography (PE-PE / EA = 1 /1), to give SIAIS360123, yield = 64% .MS (ESI) m / z: calculated for _{C 13 H 16 F 3 N 2} O 9 S 3 - [MH] -, 497.00 ; Measured value, 497.18.

the fourth step

Dissolve SIAIS360123 (0.68g, 1.36mmol) in 15mL methanol, bubbling nitrogen for 5min, add thiophenol (0.23g, 2.05mmol) and triethylamine (0.68mL) in sequence, react for 12h, the reaction is complete, sodium bicarbonate (aq.) Quench the reaction, extract with dichloromethane 3 times, wash with saturated brine once, dry with anhydrous sodium sulfate, distill under reduced pressure to remove the solvent, and column chromatography (PE-PE/EA=1/1) to obtain SIAIS360124, m = 0.36g, yield = 51% .MS (ESI) m / z: Calcd _{18 F 3 N 2 O 6 S} 3 C 18 H - [MH] -, 511.02; found, 511.22.

the fifth step

Dissolve SIAIS360123 (0.35g, 0.68mmol) in 15mL of dichloromethane, cool to -78°C, add 1.5M DIBAL-H toluene solution (1.4mL, 2.05mmol), react for 1.5h, and complete the reaction of the raw materials. The reaction was quenched with methanol, potassium sodium tartrate solution was added, extracted with dichloromethane three times, washed with saturated brine once, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Column chromatography (PE-PE/EA=1/ 1), to give SIAIS360125, m = 0.25g, yield = 76% .MS (ESI) m / z: calculated for _{C 17 H 16 F 3 N 2} O 5 S 3 - [MH] -, 481.02; Found, 481.26.

Sixth step

The compound SIAIS360125 (0.25g, 0.52mmol) was dissolved in 10mL methanol, 1-tert-butoxycarbonylpiperazine (0.14g, 0.78mmol), 0.14mL acetic acid and sodium cyanoborocyanide (98mg.1.56mmol) were added, After 12 hours of reaction, the reaction was complete, the reaction was quenched with sodium bicarbonate (aq.), extracted with dichloromethane three times, washed with saturated brine once, dried with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, column chromatography (DCM-DCM /MeOH=10/1) to obtain SIAIS360126, m=0.31g, yield=92%. MS(ESI) m/z: calculated value C ₂₆ H ₃₆ F ₃ N ₄ O ₆ S ₃ ⁺ [M+H] ⁺ ,653.17; measured value, 653.37.

In the following steps, the compound SIAIS360129 was synthesized by referring to the synthesis method of the preparation example 1 of the intermediate BINDER. ¹ H NMR (500MHz, DMSO-d ₆ ) δ9.00 (s, 1H), 8.17 (d, J=2.3Hz, 1H ),8.00(dd,J=9.4,2.3Hz,1H),7.77(d,J=8.7Hz,2H),7.42(d,J=8.4Hz,2H),7.32-7.28(m,2H),7.23 (dd,J=8.5,6.8Hz,2H), 7.19–7.13(m,4H), 7.01(d,J=9.2Hz,1H), 6.97(d,J=8.9Hz,2H), 4.19–4.10( m, 2H), 3.93(s, 2H), 3.60(s, 2H), 3.45–3.35(m, 4H), 3.21(s, 5H), 3.00–2.60(m, 8H), 2.28(s, 2H) ,2.04(s,3H),1.95(s,1H),1.48(t,J=6.5Hz,2H),1.00(s,6H).MS(ESI)m/z: calculated value C ₄₇ H ₅₇ ClF ₃ N ₆ O ₅ S ₃ ⁺ [M+H] ⁺ , 973.3188; found value, 973.3204.

Preparation of intermediate BINDER Example 13: Synthesis of compound SIAIS360149

The compound SIAIS360149 was synthesized by referring to the synthesis method of Preparation Example 1 of the intermediate BINDER. ¹ H NMR(500MHz,DMSO-d ₆ )δ9.28(s,1H), 8.24(d,J=2.3Hz,1H), 8.07(dd,J=9.2,2.4Hz, 1H), 7.76(d, J = 8.9 Hz, 2H), 7.52 (t, J = 6.0 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 9.5 Hz, 1H), 7.17 (d, J = 8.4Hz, 2H), 6.96 (d, J = 9.2 Hz, 2H), 3.93 (s, 2H), 3.60 (s, 2H), 3.47 (d, J = 6.5 Hz, 3H), 3.45-3.11 (m, 13H),3.02(s,3H),2.81(s,2H),2.29(s,2H),2.05(s,2H),1.89(t,J=7.5Hz,2H),1.48(t,J=6.4 Hz, 2H), 1.00 (s, 6H). MS (ESI) m/z: calculated value C ₄₀ H ₅₁ ClF ₃ N ₆ O ₅ S ₂ ⁺ [M+H] ⁺ , 851.2997; measured value, 851.2974.

Intermediate LM preparation example

Intermediate LM Preparation Example 1: 2-(2,6-dioxopiperidin-3-yl)-4-((2-iodoethyl)amino)isoindoline-1,3-dione ( SIAIS268006) preparation

With reference to the method similar to Step 1 of Scheme 3, the 2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione (16.8mmol, 1equiv) Dissolve in 25mL NMP, add 2-(tert-butyldimethylsiloxy)ethylamine (16.8mmol, 1.0equiv) and N,N-diisopropylethylamine (25.2mmol, 1.5equiv), 90 The reaction was completed by heating at ℃ for 4h. The reaction solution was cooled to room temperature, poured into saturated brine, extracted with ethyl acetate (4x 50mL), combined the organic phases, washed with water (2x 30mL), washed with saturated brine (50mL), dried with anhydrous Na ₂ SO ₄ , and evaporated under reduced pressure The solvent is removed, and the crude product is purified by column chromatography (eluent (v/v): petroleum ether/ethyl acetate=1:1) to obtain an intermediate. The intermediate was dissolved in 50 mL of tetrahydrofuran, tetrabutylammonium fluoride (16.8 mmol) was added, and the mixture was stirred at room temperature for 2 hours, and the reaction was complete. Add 200mL of saturated brine, extract with ethyl acetate (4x 50mL), combine the organic phases, wash with water (2x 30mL), wash with saturated brine (50mL), dry with anhydrous Na ₂ SO ₄ , and evaporate the solvent under reduced pressure to obtain crude SIAIS255178 ( 2-(2,6-dioxopiperidin-3-yl)-4-((2-hydroxyethyl)amino)isoindoline-1,3-dione), m=1.0g, put in Next step.

Refer to the method of Step 2 of Scheme 3, dissolve SIAIS255178 in 40mL mixed solvent (DCM/pyridine=3/1), add triethylamine (0.52mL, 3.8mmol) and methanesulfonyl chloride (0.30mL, 3.8mmol) ), heat to 40°C, react for 2h, and the reaction is complete. Wash with saturated brine, evaporate the solvent under reduced pressure, and column chromatography to obtain SIAIS255180(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-isoindoline-4 -Amino) ethyl methanesulfonate), yellow powder, m=0.80 g.

With reference to the method in step 3 of Scheme 3, SIAIS255180 was dissolved in 10 mL of acetone, sodium iodide (3.0 equiv) was added, and the reaction was heated to 60° C. for 24 hours to complete the conversion. It was cooled to room temperature, diluted with 40 mL of ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the solvent to obtain the crude product SIAIS268006 as a yellow solid, which was directly put into use.

¹ H NMR (500MHz, DMSO-d ₆ ) δ11.10 (s, 1H), 7.60 (dd, J = 8.6, 7.1 Hz, 1H), 7.19 (dd, J = 18.6, 8.6 Hz, 1H), 7.08 ( d,J=7.0Hz,1H), 6.81(t,J=6.3Hz,1H), 5.06(dd,J=12.8,5.4Hz,1H), 3.81(t,J=6.1Hz,1H), 3.75- 3.64 (m, 2H), 3.39 (t, J = 6.3 Hz, 2H), 2.89 (ddd, J = 16.9, 13.8, 5.5 Hz, 1H), 2.64-2.53 (m, 1H), 2.04 (m, 1H) .

Intermediate LM Preparation Example 2: 2-(2,6-dioxopiperidin-3-yl)-4-((3-iodopropyl)amino)isoindoline-1,3-dione ( SIAIS268007) preparation

According to Scheme 3, in step 1, dissolve 2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione (16.8mmol, 1equiv) In 25 mL of NMP, 3-aminopropanol (16.8 mmol, 1.0 equiv) and N,N-diisopropylethylamine (25.2 mmol, 1.5 equiv) were sequentially added, and the reaction was heated at 90° C. for 4 hours, and the reaction was complete. The reaction solution was cooled to room temperature, poured into saturated brine, extracted with ethyl acetate (4x 50mL), combined the organic phases, washed with water (2x 30mL), washed with saturated brine (50mL), dried with anhydrous Na ₂ SO ₄ , and evaporated under reduced pressure The solvent was removed, and the crude product was purified by column chromatography (eluent (v/v): petroleum ether/ethyl acetate=1:1) to obtain the intermediate 2-(2,6-dioxopiperidin-3-yl) -4-((3-hydroxypropyl)amino)isoindoline-1,3-dione (2-(2,6-dioxopiperidin-3-yl)-4-((3-hydroxypropyl)amino)isoindoline -1,3-dione).

The following steps refer to the steps 2 and 3 of the intermediate LM preparation example 1 to prepare SIAIS268007. The difference is that in step 2, dichloromethane is used as the solvent instead of the mixed solvent, and the final product uses DCM/EA= 5/1 column chromatography.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.09(s,1H), 7.60(dd,J=8.5,7.0Hz,1H), 7.14(d,J=8.5Hz,1H), 7.04(d, J = 7.0Hz, 1H), 6.68 (t, J = 6.2 Hz, 1H), 5.05 (dd, J = 12.8, 5.4 Hz, 1H), 3.39 (q, J = 6.6 Hz, 2H), 3.31 (t, J = 6.9 Hz, 2H), 2.88 (ddd, J = 16.9, 13.8, 5.4 Hz, 1H), 2.62-2.52 (m, 1H), 2.12-2.01 (m, 3H).

Intermediate LM Preparation Example 3: 2-(2,6-dioxopiperidin-3-yl)-4-((4-iodobutyl)amino)isoindoline-1,3-dione ( SIAIS255191) preparation

According to the method of preparation example 2 of intermediate LM, SIAIS255191 was prepared, except that 4-aminobutanol was used instead of 2-(tert-butyldimethylsiloxy)ethylamine as the starting material. In step 2, SIAIS255191 was prepared. Dichloromethane replaces the mixed solvent as the solvent.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.05(s,1H),7.83-7.68(m,1H),7.56(dd,J=8.6,6.9Hz,1H),7.11(dd,J=7.7 ,6.0Hz,2H),5.06(dd,J=12.8,5.4Hz,1H), 3.35–3.26(m,1H), 2.97–2.81(m,2H), 2.65–2.53(m,2H), 2.18( t,J=8.1Hz,1H), 2.11–1.97(m,2H), 1.96–1.85(m,4H).

Intermediate LM Preparation Example 4: 2-(2,6-dioxopiperidin-3-yl)-4-((5-iodopentyl)amino)isoindoline-1,3-dione ( SIAIS264016) preparation

According to the method of preparation example 2 of intermediate LM, SIAIS264016 was prepared. The difference is that 5-aminopentanol was used instead of 2-(tert-butyldimethylsiloxy)ethylamine as the starting material. In step 2, SIAIS264016 was prepared. Dichloromethane replaces the mixed solvent as the solvent.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.09(s,1H), 7.58(dd,J=8.6,7.0Hz,1H), 7.11(d,J=8.7Hz,1H), 7.02(d, J = 7.0Hz, 1H), 5.05 (dd, J = 12.8, 5.4 Hz, 1H), 3.29 (t, J = 6.9 Hz, 4H), 2.88 (ddd, J = 16.6, 13.6, 5.2 Hz, 1H), 2.64–2.55(m,1H),2.07–1.99(m,1H),1.86–1.75(m,2H),1.68(s,1H),1.59(q,J=7.4Hz,2H),1.43(dd, J = 8.5, 6.3Hz, 2H).

Intermediate LM Preparation Example 5: 2-(2,6-dioxopiperidin-3-yl)-4-((6-iodohexyl)amino)isoindoline-1,3-dione (SIAIS264018 ) Preparation

Refer to the method of preparing the intermediate LM in Example 2 to prepare SIAIS264018. The difference is that 6-aminohexanol is used instead of 2-(tert-butyldimethylsiloxy)ethylamine as the starting material. In step 2, Dichloromethane replaces the mixed solvent as the solvent.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.09(s,1H), 7.58(dd,J=8.5,7.0Hz,1H), 7.10(d,J=8.6Hz,1H), 7.02(d, J = 7.0Hz, 1H), 6.54 (t, J = 5.9 Hz, 1H), 5.05 (dd, J = 12.7, 5.4 Hz, 1H), 3.28 (q, J = 6.7 Hz, 4H), 2.95-2.83 ( m,1H), 2.63–2.55(m,1H),2.08(d,J=4.9Hz,1H),2.06–1.99(m,1H),1.77(t,J=7.0Hz,2H),1.57(t ,J=7.1Hz,2H),1.38(p,J=5.0Hz,4H).

Intermediate LM Preparation Example 6: 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yne-1- Preparation of Mesylate (SIAIS255120)

According to Scheme 4, in step 1, 3-(4-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione (0.50g, 1.5mmol) was dissolved in 5mL DMF In the medium, Ar gas was bubbled for 5 minutes, and 3-alkynyl butanol (0.21 g, 3.0 mmol), Pd(PPh ₃ ) ₂ Cl ₂ (0.10 g, 0.15 mmol) and CuI (57 mg, 0.30 mmol) were added in sequence. Stir for 5 min, add 2.5 mL of triethylamine, heat to 80°C, and react overnight. Cool to room temperature, quench the reaction with 50mL water, extract with ethyl acetate (3x 50mL), combine the organic phases, wash with water (2x 30mL), wash with saturated brine (50mL), dry with anhydrous Na ₂ SO ₄ , and evaporate the solvent under reduced pressure The crude product was subjected to column chromatography (DCM/MeOH=5/1) to obtain an alcohol intermediate. Light yellow solid, m=0.50g.

In step 2, the above-mentioned intermediate was dissolved in 15mL DCM, and triethylamine (0.44g, 4.4mmol) and methanesulfonyl chloride (0.25g, 2.2mmol) were added in sequence. The system became clear and reacted overnight. The reaction solution was washed with saturated brine, the solvent was evaporated under reduced pressure, and column chromatography (DCM/MeOH=5/1) was used to obtain SIAIS255120. Light yellow solid, m=0.35g.

¹ H NMR(500MHz,DMSO-d6)δ11.01(s,1H), 7.74(dd,J=7.6,1.0Hz,1H), 7.67(dd,J=7.6,1.0Hz,1H), 7.54(t ,J=7.6Hz,1H), 5.16(dd,J=13.4,5.1Hz,1H), 4.52–4.27(m,4H), 3.24(s,3H), 3.02–2.87(m,3H), 2.67– 2.57 (m, 1H), 2.42 (qd, J = 13.3, 4.4 Hz, 1H), 2.03 (m, 1H).

Intermediate LM Preparation Example 7: 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yne-1- Preparation of Mesylate (SIAIS255121)

According to the method of preparing intermediate LM in Example 6, SIAIS255121 was prepared, except that 4-ynylpentanol was used as the starting material instead of 3-ynylbutanol.

¹ H NMR(500MHz, DMSO-d ₆ )δ11.00(s,1H), 7.72(dd,J=7.6,1.0Hz,1H), 7.66(dd,J=7.8,1.0Hz,1H), 7.53( t,J=7.6Hz,1H), 5.15(dd,J=13.3,5.1Hz,1H), 4.48(d,J=17.8Hz,1H), 4.38–4.28(m,3H), 3.20(s,3H) ), 3.00–2.86 (m, 1H), 2.61m, 3H), 2.45 (dd, J = 13.1, 4.5 Hz, 1H), 2.00 (m, 3H).

Intermediate LM Preparation Example 8: 6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yne-1- Preparation of Mesylate (SIAIS255119)

According to the method of preparing intermediate LM in Example 6, SIAIS255119 was prepared, except that 5-alkynylhexanol was used as the starting material instead of 3-alkynylbutanol.

¹ H NMR(500MHz, DMSO-d ₆ )δ10.99(s,1H), 7.71(dd,J=7.6,1.1Hz,1H), 7.65(dd,J=7.7,1.0Hz,1H), 7.52( t, J = 7.6Hz, 1H), 5.14 (dd, J = 13.4, 5.1 Hz, 1H), 4.46 (d, J = 17.7 Hz, 1H), 4.31 (d, J = 17.7 Hz, 1H), 4.27 ( t,J=6.4Hz,2H),3.17(s,3H),2.91(m,1H),2.55(m,3H), 2.48–2.42(m,1H),2.01(m,1H),1.88–1.80 (m, 2H), 1.67 (m, 2H).

Intermediate LM Preparation Example 9: 7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yne-1- Preparation of Mesylate (SIAIS292017)

Referring to the method of preparing intermediate LM in Example 6, SIAIS292017 was prepared, except that 6-alkynylheptanol was used as the starting material instead of 3-ynylbutanol.

¹ H NMR(500MHz,DMSO)δ10.99(s,1H), 7.71(dd,J=7.6,0.8Hz,1H), 7.64(dd,J=7.6,0.9Hz,1H), 7.52(t,J =7.6Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.45 (d, J = 17.7 Hz, 1H), 4.31 (d, J = 17.7 Hz, 1H), 4.22 (t, J ＝6.4Hz,2H),3.15(d,J＝1.4Hz,3H),2.90(tt,J＝18.3,5.0Hz,1H),2.62–2.56(m,1H),2.51(t,J＝4.0Hz ,2H),2.48–2.41(m,1H),2.05–1.98(m,1H),1.72(dd,J=14.6,6.7Hz,2H),1.61(dd,J=13.9,6.5Hz,2H), 1.54-1.48 (m, 2H).

Intermediate LM Preparation Example 10: 8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yne-1- Preparation of Mesylate (SIAIS292020)

According to the method of preparing the intermediate LM in Example 6, SIAIS292020 was prepared, except that 7-alkynyl octanol was used as the starting material instead of 3-alkynyl butanol.

¹ H NMR(500MHz,DMSO)δ10.99(s,1H), 7.70(dd,J=7.6,0.7Hz,1H), 7.63(dd,J=7.6,0.9Hz,1H), 7.51(dd,J ＝9.7,5.5Hz,1H), 5.14(dd,J＝13.3,5.1Hz,1H), 4.45(d,J＝17.7Hz,1H), 4.31(d,J＝17.6Hz,1H), 4.18(dt ,J=6.5,4.1Hz,2H), 2.90(tt,J=19.0,5.4Hz,1H), 2.60(d,J=17.6Hz,1H), 2.49–2.46(m,2H), 2.46–2.40( m,1H),2.05–1.98(m,1H),1.68(dd,J=14.3,6.8Hz,2H),1.58(dd,J=14.7,7.2Hz,2H),1.48–1.38(m,4H) .

Intermediate LM Preparation Example 11: 9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yne-1- Preparation of Mesylate (SIAIS255127)

According to the method of preparing intermediate LM in Example 6, SIAIS255127 was prepared, except that 8-alkynylnonanol was used as the starting material instead of 3-alkynylbutanol.

¹ H NMR(500MHz,DMSO)δ11.00(s,1H), 7.70(d,J=7.4Hz,1H), 7.63(d,J=7.0Hz,1H), 7.52(t,J=7.6Hz, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.44 (d, J = 17.6 Hz, 1H), 4.30 (d, J = 17.6 Hz, 1H), 4.18 (t, J = 6.5 Hz, 2H), 3.15 (s, 3H), 2.91 (ddd, J = 17.5, 13.7, 5.4 Hz, 1H), 2.63-2.57 (m, 1H), 2.47 (d, J = 7.1 Hz, 2H), 2.46-2.40 (m,1H),2.02(ddd,J=10.3,5.1,3.1Hz,1H),1.66(dd,J=13.5,6.6Hz,2H),1.61–1.53(m,2H),1.47–1.40(m ,2H),1.40-1.33(m,4H).

Intermediate LM Preparation Example 12: 5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yne Preparation of -1-yl methanesulfonate (SIAIS292006)

According to the method of preparing the intermediate LM in Example 6, SIAIS292006 was prepared, except that 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3- Diketone instead of 3-(4-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione, and 4-ynylpentanol instead of 3-ynylbutanol Starting materials.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.13(s,1H),8.00-7.80(m,3H), 5.16(dd,J=12.9,5.4Hz,1H), 4.36(t,J=6.1 Hz, 2H), 3.21 (s, 3H), 2.89 (ddd, J = 18.1, 13.8, 5.4 Hz, 1H), 2.64 (t, J = 7.0 Hz, 2H), 2.61-2.50 (m, 2H), 2.10 -2.02(m,1H),1.99(p,J=6.6Hz,2H).

Intermediate LM Preparation Example 13: 6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yne Preparation of -1-yl methanesulfonate (SIAIS292007)

According to the method of preparing the intermediate LM in Example 12, SIAIS292007 was prepared, except that 5-alkynylhexanol was used as the starting material instead of 4-alkynylpentanol.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.14(s,1H),8.00-7.80(m,3H), 5.16(dd,J=12.9,5.4Hz,1H), 4.27(t,J=6.3 Hz, 2H), 3.18 (s, 3H), 2.89 (ddd, J = 18.1, 13.9, 5.5 Hz, 1H), 2.66-2.53 (m, 4H), 2.13-2.02 (m, 1H), 1.85 (p, J = 6.5Hz, 2H), 1.68 (p, J = 7.1Hz, 2H).

Intermediate LM Preparation Example 14: 7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hept-6-yne Preparation of -1-yl methanesulfonate (SIAIS292016)

According to the method of preparing intermediate LM in Example 12, SIAIS292016 was prepared, except that 6-alkynylheptanol was used as the starting material instead of 4-ynylpentanol.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.13(s,1H),7.92-7.73(m,3H), 5.16(dd,J=12.9,5.4Hz,1H), 4.23(t,J=6.4 Hz, 2H), 3.17 (s, 3H), 2.89 (ddd, J = 17.8, 14.1, 5.3 Hz, 1H), 2.65-2.50 (m, 2H), 2.54 (d, J = 6.5 Hz, 2H), 2.11 –2.03(m,1H),1.73(p,J=6.8Hz,2H),1.63(p,J=7.1Hz,2H),1.57–1.49(m,2H).

Intermediate LM Preparation Example 15: 8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-yne Preparation of -1-yl methanesulfonate (SIAIS292008)

Referring to the method of preparing intermediate LM in Example 12, SIAIS292008 was prepared, except that 7-ynyloctanol was used as the starting material instead of 4-ynylpentanol.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.13(s,1H),8.00-7.80(m,3H), 5.15(dd,J=12.8,5.3Hz,1H), 4.20(t,J=6.4 Hz, 2H), 3.16 (s, 3H), 2.89 (ddd, J = 18.0, 14.4, 5.4 Hz, 1H), 2.60-2.50 (m, 4H), 2.06 (dt, J = 10.0, 4.6 Hz, 1H) ,1.70(p,J=6.6Hz,2H), 1.59(q,J=7.0Hz,2H), 1.52-1.44(m,2H), 1.40(p,J=7.0Hz,2H).

Intermediate LM Preparation Example 16: 9-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)non-8-yne Preparation of -1-yl methanesulfonate (SIAIS292009)

According to the method of preparing the intermediate LM in Example 12, SIAIS292009 was prepared, except that 8-alkynylnonanol was used as the starting material instead of 4-ynylpentanol.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.13(s,1H),8.00-7.80(m,3H), 5.15(dd,J=12.9,5.4Hz,1H), 4.19(t,J=6.4 Hz, 2H), 3.16 (s, 3H), 2.89 (ddd, J = 17.8, 14.4, 5.3 Hz, 1H), 2.65-2.50 (m, 4H), 2.12-2.03 (m, 1H), 1.67 (p, J = 6.6 Hz, 2H), 1.59 (p, J = 7.2 Hz, 2H), 1.45 (p, J = 6.9, 6.3 Hz, 2H), 1.41-1.31 (m, 4H).

Intermediate LM Preparation Example 17: 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)pent-4-yne-1- Preparation of Mesylate (SIAIS292111)

According to the method of preparing the intermediate LM in Example 6, SIAIS292111 was prepared, except that 3-(5-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione was substituted 3-(4-Bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione, and 4-ynylpentanol instead of 3-ynylbutanol as starting materials.

¹ H NMR(500MHz,DMSO-d ₆ )δ10.99(s,1H),7.75-7.59(m,2H),7.53(d,J=7.8Hz,1H), 5.11(dd,J=13.3,5.1 Hz, 1H), 4.45 (d, J = 17.4 Hz, 1H), 4.39-4.29 (m, 3H), 3.21 (s, 3H), 2.91 (ddd, J = 17.9, 13.5, 5.3 Hz, 1H), 2.65 --2.57 (m, 3H), 2.48 - 2.33 (m, 1H), 2.05-1.95m, 3H).

Intermediate LM Preparation Example 18: 6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)hex-5-yne-1- Preparation of methyl methanesulfonate (SIAIS292112)

According to the method of preparing the intermediate LM in Example 17, SIAIS292112 was prepared, except that 5-alkynylhexanol was used as the starting material instead of 4-alkynylpentanol.

¹ H NMR(500MHz,DMSO-d ₆ )δ10.99(s,1H), 7.69(d,J=7.8Hz,1H), 7.64(s,1H), 7.51(d,J=7.9Hz,1H) ,5.11(dd,J＝13.3,5.1Hz,1H), 4.44(d,J＝17.4Hz,1H), 4.32(d,J＝17.4Hz,1H), 4.27(t,J＝6.3Hz,2H) , 3.18 (s, 3H), 2.91 (ddd, J = 18.1, 13.6, 5.4 Hz, 1H), 2.60 (d, J = 17.6 Hz, 1H), 2.54 (t, J = 6.9 Hz, 2H), 2.39 ( qd, J = 13.2, 4.6 Hz, 1H), 2.01 (dd, J = 12.4, 5.9 Hz, 1H), 1.83 (q, J = 7.0 Hz, 2H), 1.66 (p, J = 7.3 Hz, 2H).

Intermediate LM Preparation Example 19: 5-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)pent-4-yne-1- Preparation of methyl methanesulfonate (SIAIS292104)

According to the method of preparation example 6 of intermediate LM, SIAIS292104 was prepared, except that 3-(7-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione was substituted 3-(4-Bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione, and 4-ynylpentanol instead of 3-ynylbutanol as starting materials.

¹ H NMR(500MHz,DMSO-d ₆ )δ10.99(s,1H), 7.58(d,J=7.3Hz,2H), 7.49(d,J=6.7 Hz,1H), 5.06(dd,J= 13.2, 5.1 Hz, 1H), 4.49 (t, J = 6.3 Hz, 2H), 4.40 (s, 1H), 4.31 (d, J = 17.4 Hz, 1H), 3.20 (s, 3H), 2.90 (ddd, J = 18.0, 13.5, 5.4 Hz, 1H), 2.62 (t, J = 6.8 Hz, 3H), 2.46–2.36 (m, 1H), 2.05-1.95 (m, 3H).

Intermediate LM Preparation Example 20: 6-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)hex-5-yne-1- Preparation of Mesylate (SIAIS292105)

Referring to the method of preparing intermediate LM in Example 19, SIAIS292105 was prepared, except that 5-alkynylhexanol was used as the starting material instead of 4-alkynylpentanol.

¹ H NMR(500MHz,DMSO-d ₆ )δ10.99(s,1H), 7.60-7.52(m,2H), 7.47(d,J=6.9Hz,1H), 5.07(dd,J=13.2,5.1 Hz, 1H), 4.41 (d, J = 17.4 Hz, 1H), 4.33-4.25 (m, 3H), 3.18 (s, 3H), 2.90 (ddd, J = 18.1, 13.5, 5.4 Hz, 1H), 2.61 (d,J=18.0Hz,1H),2.54(t,J=6.9Hz,2H),2.45-2.33(m,1H),2.00(dt,J=11.6,5.6Hz,1H),1.92(p, J = 6.7Hz, 2H), 1.67 (p, J = 7.0Hz, 2H).

Intermediate LM Preparation Example 21: 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl methanesulfonate (SIAIS255130) preparation

According to Scheme 5, in step 1, 3-(4-(4-hydroxybut-1-yn-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6- Diketone (0.11g, 0.35mmol) was dissolved in 10mL ethanol, 10% Pd/C (5mg) and PtO ₂ (5mg) were added as catalysts, reacted under hydrogen atmosphere at normal pressure at 50℃ for 12h, filtered, and evaporated under reduced pressure. The solvent was removed to obtain the intermediate 3-(4-(4-hydroxybutyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione. Light yellow solid, m=0.11g.

In step 2, refer to step 2 of the preparation of intermediate SIAIS255120 to prepare SIAIS255130 as a pale yellow solid with m=0.11 g.

¹ H NMR(500MHz,DMSO-d ₆ )δ11.00(s,1H), 7.65–7.53(m,2H), 7.50–7.46(m,2H), 5.14(dd,J=13.3,5.2Hz,1H ), 4.47 (d, J = 17.1 Hz, 1H), 4.31 (d, J = 17.1 Hz, 1H), 4.24 (t, J = 5.9 Hz, 2H), 3.16 (s, 3H), 2.93 (ddd, J = 17.4, 13.7, 5.4 Hz, 1H), 2.69 (t, J = 7.3 Hz, 2H), 2.66–2.58 (m, 1H), 2.42 (m, 1H), 2.02 (m, 1H), 1.71 (dt, J = 10.5, 4.9 Hz, 4H).

Intermediate LM Preparation Example 22: 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)acetic acid (SIAIS151045) Preparation

The compound SIAIS151045 was prepared according to the method of Scheme 6.

Preparation of 2-(2,6-dioxopiperidin-3-yl)-4-mercaptoisoindoline-1,3-dione (SIAIS151014):

The compound 2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione (20g, 72.4mmol) was added to a 250mL egg-shaped flask, and then Anhydrous N,N-dimethylformamide (150 mL) was added, and while stirring at room temperature, sodium sulfide nonahydrate (28 g, 108.6 mmol) was added in batches, and after the addition, the mixture was stirred at room temperature for 6 hours. Subsequently, the reaction solution was slowly poured into 400 mL of ice-water mixture, and the pH of the reaction solution was slowly adjusted with 6N hydrochloric acid aqueous solution under stirring to pH=2–3. The color of the solution changed from blood red to pale yellow, and a large amount of off-white solid was precipitated. , Stirred at room temperature for 0.5h, filtered with suction, and the filter cake was washed 3 times with water; then the filter cake was slurried with 100 mL of anhydrous acetone, filtered with suction, the filter cake was washed with acetone 3 times, and dried under reduced pressure to obtain the intermediate compound (SIAIS151014) ( Off-white solid, 14g, yield 67%).

¹ H NMR(500MHz,DMSO)δ11.16(s,1H), 7.79(d,J=7.8Hz,1H), 7.69(t,J=7.6Hz,1H), 7.64(d,J=7.1Hz, 1H), 6.30 (s, 1H), 5.14 (dd, J = 12.9, 5.4 Hz, 1H), 2.93-2.84 (m, 1H), 2.62-2.52 (m, 2H), 2.09-2.02 (m, 1H) .HRMS(ESI)m/z: calculated value C ₁₃ H ₁₁ N ₂ O ₄ S ⁺ [M+H] ⁺ , 291.0434; measured value, 291.0119.

The intermediate compound SIAIS151014 (3.4mmol, 1equiv) was added to a 100mL egg-shaped flask, and then anhydrous N,N-dimethylformamide (10mL) and anhydrous potassium carbonate (6.8mmol, 2equiv) were added, and stirred at room temperature Add tert-butyl 2-bromoacetate (4.1 mmol, 1.2 equiv) slowly, and stir at room temperature for 0.5h after dropping. After the raw materials have reacted, pour 50mL of water into the reaction mixture, extract with ethyl acetate (2x 50mL), combine the organic phases, wash with water (3x 20mL), wash with saturated brine (50mL), dry with anhydrous sodium sulfate, and evaporate under reduced pressure. The solvent was removed, and the crude product was purified by column chromatography (eluent (v/v): dichloromethane/ethyl acetate = 20:1) and evaporated to dryness to obtain the corresponding tert-butyl ester intermediate product; The intermediate compound was added to a 25 mL egg-shaped flask, followed by 88% formic acid (10 mL), and stirred at room temperature for 12 h. The solvent was evaporated under reduced pressure, and the target intermediate LM (SIAIS151045) (light yellow solid, 0.69 g, yield 80%) was obtained by adding water and lyophilizing.

¹ H NMR (500MHz, DMSO) δ 13.06 (s, 1H), 11.15 (s, 1H), 7.80 (dd, J = 8.1, 7.3 Hz, 1H), 7.66 (t, J = 7.9 Hz, 2H), 5.13(dd,J=12.9,5.4Hz,1H),4.09(s,2H),2.92–2.85(m,1H),2.66–2.51(m,2H),2.08–2.03(m,1H).HRMS( ESI) m/z: calculated value C ₁₅ H ₁₃ N ₂ O ₆ S ⁺ [M+H] ⁺ , 349.0489; measured value, 349.0297.

Intermediate LM Preparation Example 23: Preparation of 3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl) Propionic acid (SIAIS151138)

The compound SIAIS151138 was prepared by referring to the intermediate LM preparation method in Example 22 under appropriate conditions understandable in the art, except that tert-butyl 3-bromopropionate was used instead of tert-butyl 2-bromoacetate as the starting point. Starting materials. Obtain the target compound SIAIS151138 (light yellow solid, 0.64g, yield 74%)

¹ H NMR(500MHz,DMSO)δ11.12(s,1H),7.81-7.76(m,2H),7.64(d,J=6.7Hz,1H), 5.11(dd,J=12.9,5.4Hz,1H ), 3.32(t,J=7.0Hz,2H), 2.92–2.84(m,1H), 2.66(t,J=7.0Hz,2H), 2.62–2.51(m,2H),2.07–2.00(m, 1H).HRMS(ESI)m/z: calculated value C ₁₆ H ₁₅ N ₂ O ₆ S ⁺ [M+H] ⁺ , 363.0645; measured value, 363.0802.

Intermediate LM Preparation Example 24: Preparation of 4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl) Butyric acid (SIAIS151139)

The compound SIAIS151139 was prepared by referring to the intermediate LM preparation method in Example 22 under appropriate conditions understandable in the art, except that tert-butyl 4-bromobutyrate was used instead of tert-butyl 2-bromoacetate as the starting point. Starting materials. The target compound SIAIS151139 (light yellow solid, 0.71 g, yield 82%) was obtained.

¹ H NMR(500MHz,DMSO)δ12.24(s,1H),11.12(s,1H),7.86-7.74(m,2H),7.63(d,J=6.2Hz,1H), 5.11(dd,J = 12.9, 5.4 Hz, 1H), 3.15 (t, J = 7.2 Hz, 2H), 2.92-2.84 (m, 1H), 2.64-2.51 (m, 2H), 2.42 (t, J = 7.2 Hz, 2H) ,2.09–2.02(m,1H),1.93–1.83(m,2H).HRMS(ESI)m/z: calculated value C ₁₇ H ₁₇ N ₂ O ₆ S ⁺ [M+H] ⁺ ,377.0802; measured value , 377.0962.

Intermediate LM Preparation Example 25: Preparation of 5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl) Valeric acid (SIAIS151140)

The compound SIAIS151140 was prepared by referring to the intermediate LM preparation method of Example 22 under appropriate conditions understandable in the art, except that tert-butyl 5-bromopentanoate was used instead of tert-butyl 2-bromoacetate as the starting point. Starting materials. The target compound SIAIS151140 (light yellow solid, 0.9g, yield 74%) was obtained.

¹ H NMR(500MHz,DMSO)δ11.12(s,1H),7.83-7.71(m,2H),7.62(d,J=6.9Hz,1H), 5.11(dd,J=12.9,5.4Hz,1H ), 3.13(t,J=6.6Hz,2H), 2.92–2.85(m,1H), 2.64–2.52(m,2H), 2.28(t,J=6.6Hz,2H), 2.08–2.02(m, 1H),1.72–1.65(m,4H).HRMS(ESI)m/z: calculated value C ₁₈ H ₁₉ N ₂ O ₆ S ⁺ [M+H] ⁺ , 391.0958; measured value, 391.1109.

Intermediate LM Preparation Example 26: Preparation of 6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl) Caproic acid (SIAIS151141)

The compound SIAIS151141 was prepared by referring to the method of intermediate LM in the preparation of Example 22 under appropriate conditions understandable in the art, except that tert-butyl 6-bromohexanoate was used instead of tert-butyl 2-bromoacetate as the starting point. Starting materials. The target compound SIAIS151141 (light yellow solid, 0.71 g, yield 74%) was obtained.

¹ H NMR(500MHz,DMSO)δ12.01(s,1H),11.12(s,1H),7.82-7.70(m,2H),7.62(d,J=7.1Hz,1H), 5.11(dd,J = 12.9, 5.4 Hz, 1H), 3.12 (t, J = 7.2 Hz, 2H), 2.92-2.85 (m, 1H), 2.62-2.48 (m, 2H), 2.22 (t, J = 7.2 Hz, 2H) ,2.08-2.03(m,1H),1.71-1.63(m,2H),1.59-1.51(m,2H),1.49-1.40(m,2H).HRMS(ESI)m/z: calculated value C ₁₉ H ₂₁ N ₂ O ₆ S ⁺ [M+H] ⁺ , 405.1115; measured value, 405.1268.

Intermediate LM Preparation Example 27: Preparation of 7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl) Enanthic acid (SIAIS151142)

The compound SIAIS151142 was prepared by referring to the intermediate LM preparation method of Example 22 under appropriate conditions understandable in the art, except that tert-butyl 7-bromoheptanoate was used instead of tert-butyl 2-bromoacetate as the starting point. Starting materials. The target compound SIAIS151142 (light yellow solid, 0.7g, yield 80%) was obtained.

¹ H NMR(500MHz,DMSO)δ11.12(s,1H), 7.80–7.71(m,2H), 7.62(d,J=6.9Hz,1H), 5.11(dd,J=12.9,5.4Hz,1H ), 3.12 (t, J = 7.3Hz, 2H), 2.92-2.85 (m, 1H), 2.62-2.52 (m, 2H), 2.20 (t, J = 7.3 Hz, 2H), 2.07-2.00 (m, 1H), 1.69-1.62 (m, 2H), 1.53--1.47 (m, 2H), 1.46-1.41 (m, 2H), 1.36-1.27 (m, 2H).HRMS (ESI) m/z: calculated value C ₂₀ H ₂₃ N ₂ O ₆ S ⁺ [M+H] ⁺ , 419.1271; measured value, 419.1432.

Intermediate LM Preparation Example 28: Preparation of 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl) (Thio)ethoxy)acetic acid (SIAIS1204137)

According to the method of Scheme 7, the intermediate compound SIAIS151014 (0.724mmol, 1 equiv) was added to a 50 mL egg-shaped flask, and then anhydrous N,N-dimethylformamide (10mL) and anhydrous potassium carbonate (1.448mmol) , 2equiv), slowly drip tert-butyl 2-(2-(toluenesulfonyloxy)ethoxy) acetate (0.869mmol, 1.2equiv) under stirring at room temperature, and stir at room temperature for 0.5h after dropping. After the reaction of the raw materials, filter to remove the insoluble matter and directly load the sample on a C18 reversed phase column for separation. Eluent: 10%-100% (v1:v2) acetonitrile: water, remove the solvent under reduced pressure to obtain the corresponding tert-butanol ester intermediate Product; the corresponding tert-butanol ester intermediate compound was added to a 25 mL egg-shaped flask, followed by addition of dichloromethane (1 mL) and trifluoroacetic acid (3 mL), and the reaction was stirred at room temperature for 1 h. The solvent was evaporated under reduced pressure, and water was added to freeze-dry to obtain the target compound SIAIS1204137 (light yellow solid, 185 mg, yield 69%). ¹ H NMR(500MHz,DMSO)δ11.12(s,1H),7.83-7.73(m,2H),7.64(d,J=6.6Hz,1H), 5.12(dd,J=12.8,5.4Hz,1H ),4.08(s,2H),3.77(t,J=6.4Hz,2H),3.14-3.07(m,2H),2.94-2.82(m,1H),2.66-2.55(m,2H),2.09- 2.01(m,1H).HRMS(ESI)m/z: calculated value C ₁₇ H ₁₇ N ₂ O ₇ S ⁺ [M+H] ⁺ , 393.0751; measured value, 393.0763.

Intermediate LM Preparation Example 29: Preparation of 2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindoline-4 -Yl)thio)ethoxy)ethoxy)acetic acid (SIAIS1204139)

The compound SIAIS1204139 was prepared by referring to the method of the intermediate LM in the preparation of Example 28 and under the appropriate conditions understandable in the art, except that tert-butyl 2-(2-(2-(tosyloxy)ethoxy group was used. )Ethoxy)acetate replaces tert-butyl 2-(2-(tosyloxy)ethoxy)acetate as the starting material. The target compound SIAIS1204139 (light yellow solid, 190 mg, yield 63%) was obtained. ¹ H NMR(500MHz,DMSO)δ11.12(s,1H),7.83-7.76(m,2H),7.63(dd,J=6.4,1.3Hz,1H), 5.12(dd,J=12.9,5.4Hz ,1H),4.02(s,2H),3.72(t,J=6.3Hz,2H),3.59(s,4H),3.39–3.30(m,2H),3.13-3.06(m,1H),2.64- 2.52(m,2H),2.09-2.02(m,1H).HRMS(ESI)m/z: calculated value C ₁₉ H ₂₁ BN ₂ O ₈ S ⁺ [M+H] ⁺ ,437.1013; measured value, 437.1032.

Intermediate LM Preparation Example 30: Preparation of 2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindole (Alkolin-4-yl)thio)ethoxy)ethoxy)ethoxy)acetic acid (SIAIS1204141)

The compound SIAIS1204141 was prepared by referring to the method of the intermediate LM in the preparation of Example 28 under appropriate conditions understandable in the art, except that tert-butyl 2-(2-(2-(2-(tosyloxy) Ethoxy)ethoxy)ethoxy)acetate replaces tert-butyl 2-(2-(toluenesulfonyloxy)ethoxy)acetate as the starting material. The target compound SIAIS1204141 (light yellow solid, 246 mg, yield 74%) was obtained. ¹ H NMR(500MHz,DMSO)δ11.12(s,1H),7.85-7.73(m,2H),7.63(dd,J=6.1,1.9Hz,1H), 5.12(dd,J=12.9,5.4Hz ,1H),4.02(s, 2H),3.71(t,J=6.3Hz,2H),3.62-3.48(m,8H),3.35(t,J=6.3Hz,2H),2.94-2.84(m, 1H),2.63-2.52(m,2H),2.11–1.99(m,1H).HRMS(ESI)m/z: calculated value C ₂₁ H ₂₅ N ₂ O ₉ S ⁺ [M+H] ⁺ ,481.1275; Measured value, 481.1273.

Intermediate LM Preparation Example 31: Preparation of 14-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl) -3,6,9,12-Tetraoxatetradecanoic acid (SIAIS1204147)

The compound SIAIS1204147 was prepared with reference to the intermediate LM preparation method in Example 28 and under appropriate conditions understandable in the art, except that tert-butyl 14-(tosyloxy)-3,6,9,12- Tetraoxatetradecanoate replaces tert-butyl 2-(2-(toluenesulfonyloxy)ethoxy)acetate as the starting material. The target compound SIAIS1204147 (light yellow solid, 228 mg, yield 63%) was obtained. ¹ H NMR(500MHz,DMSO)δ11.12(s,1H),7.83-7.73(m,2H),7.63(dd,J=6.2,1.7Hz,1H), 5.12(dd,J=12.9,5.4Hz ,1H),4.01(s,2H),3.71(t,J=6.3Hz,2H),3.59–3.54(m,4H),3.54–3.49(m,8H),3.35(t,J=6.3Hz, 2H), 2.94–2.84(m,1H), 2.64–2.56(m,1H), 2.55–2.51(m,1H), 2.08-2.02(m,1H).HRMS(ESI)m/z: calculated value C ₂₃ H ₂₉ N ₂ O ₁₀ S ⁺ [M+H] ⁺ , 525.1537; measured value, 525.1536.

Intermediate LM Preparation Example 32: Preparation of 17-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl) -3,6,9,12,15-pentaoxahexadecanoic acid (SIAIS1204149)

The compound SIAIS1204149 was prepared by referring to the method of intermediate LM in the preparation of Example 28 under appropriate conditions understandable in the art, except that tert-butyl 17-(tosyloxy)-3,6,9,12 was used. 15-Pentoxahexadecanoate replaced tert-butyl 2-(2-(toluenesulfonyloxy)ethoxy)acetate as a starting material. The target compound SIAIS1204149 (light yellow solid, 259 mg, yield 66%) was obtained. ¹ H NMR(500MHz,DMSO)δ11.12(s,1H),7.83-7.74(m,2H),7.63(dd,J=6.2,1.8Hz,1H), 5.12(dd,J=12.9,5.4Hz ,1H),4.01(s,2H),3.71(t,J=6.3Hz,2H),3.60–3.55(m,4H),3.55–3.47(m,12H),3.35(t,J=6.3Hz, 2H), 2.93-2.84(m,1H), 2.64-2.56(m,1H), 2.55-2.51(m,1H), 2.08-2.02(m,1H).HRMS(ESI)m/z: calculated value C ₂₅ H ₃₃ N ₂ O ₁₁ S ⁺ [M+H] ⁺ , 569.1800; measured value, 569.1814.

Intermediate LM Preparation Example 33: Preparation of 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)acetic acid (SIAIS171090 )

Step 1: Prepare 3-(4-(benzylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS171088) according to Scheme 8:

Add sodium thiosulfate pentahydrate (53.7g, 216.3mmol), benzyl chloride (27.4g, 216.3mmol), copper sulfate pentahydrate (77.4mg, 0.31mmol) and bipyridine (0.72g, 4.6mmol) together. In a 500 mL egg-shaped flask containing methanol (120 mL) and water (120 mL), the temperature was slowly raised to 80° C. and stirred for 2 h. Then the reaction solution was cooled to room temperature, and 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione (namely lenalidomide) (8.0g, 30.9 mmol), and finally tert-butyl nitrite (4.78g, 46.4mmol) was slowly added dropwise, after the dropping, the temperature was raised to 80°C again and stirred for 8h. After the reaction, the reaction solution was cooled to room temperature, water (200mL) was added, ethyl acetate extracted (2x 200mL), the organic phases were combined, washed with water (2x 50mL), saturated brine (50mL), dried with anhydrous sodium sulfate, and reduced pressure The solvent was evaporated, and the crude product was purified by column chromatography (eluent (v/v): petroleum ether/ethyl acetate=1:2) to obtain the compound (SIAIS171088) (white solid, 6.8 g, yield 60%). ¹ H NMR(500MHz,CDCl ₃ )δ8.07(s,1H),7.75(t,J=7.3Hz,1H),7.55(dd,J=7.4,6.8Hz,1H),7.49–7.41(m, 1H), 7.27–7.17(m,5H), 5.20–5.17(m,1H), 4.22(d,J=16.5Hz,1H), 4.15–4.04(m,2H), 3.92(d,J=16.5Hz ,1H),2.95-2.74(m,2H),2.32-2.22(m,1H),2.17-2.11(m,1H).HRMS(ESI)m/z: calculated value C ₂₀ H ₁₉ N ₂ O ₃ S ⁺ [M+H] ⁺ ,367.1111; measured value,367.1402.

Step 2: Prepare 3-(4-mercapto-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS171095) according to Scheme 8:

Add anhydrous aluminum trichloride (2.61g, 19.6mmol) and anhydrous toluene (70mL) into a 250mL egg-shaped flask, and slowly add the compound (SIAIS171088) (1.8g, 4.9mmol) under stirring. After the addition, 35 Stir overnight at °C. After the reaction, a 20% aqueous solution of citric acid was slowly added under stirring, and a large amount of solids precipitated, followed by suction filtration, the filter cake was washed with water and ethyl acetate, and the filter cake was dried to obtain the compound (SIAIS171095) (white solid, 1.15) g, yield 85%). ¹ H NMR(500MHz,DMSO)δ11.01(s,1H), 7.82-7.39(m,3H), 5.73(s,1H), 5.21-5.04(m,1H), 4.40-4.20(m,2H) ,2.99–2.85(m,1H),2.67–2.56(m,1H),2.47–2.30(m,1H),2.05–1.95(m,1H).HRMS(ESI)m/z: calculated value C ₁₃ H ₁₃ N ₂ O ₃ S ⁺ [M+H] ⁺ , 277.0641; measured value, 276.8348.

Step 3: Preparation of 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)acetic acid ( SIAIS171090)

Add compound SIAIS171095 (0.36mmol, 1equiv), tert-butyl 2-bromoacetate (0.43mmol, 1.2equiv) and anhydrous potassium carbonate (0.72mmol, 2equiv) together into a 10mL egg-shaped bottle, and then add anhydrous N,N-dimethylformamide (2mL), stirred at room temperature for 2h. After the reaction, it was poured into 50mL of water, extracted with ethyl acetate (2x 50mL), combined the organic phases, washed with water (2x 30mL), washed with saturated brine (50mL), dried over anhydrous sodium sulfate, evaporated under reduced pressure to remove the solvent, and the crude product was washed with water (2x 30mL) and saturated brine (50mL). Reverse phase C18 column separation, eluent (v/v): acetonitrile/(water+0.05%TFA)=10%-100%, to obtain the corresponding tert-butanol ester intermediate product; then the corresponding tert-butanol ester The intermediate product was added to a 10 mL egg-shaped flask, 88% formic acid (3 mL) was added, and the mixture was stirred at room temperature for 12 hours. The reaction solvent was evaporated under reduced pressure, and water was added to freeze-dry to obtain the target compound SIAIS171090 (white solid, 77 mg, the total yield of step 3 was 64%). ¹ H NMR(500MHz,DMSO)δ12.88(s,1H), 11.00(s,1H), 7.68–7.45(m,3H), 5.15–5.13(m,1H), 4.32(dd,J=56.2, 17.3Hz, 2H), 3.94 (s, 2H), 2.95-2.91 (m, 1H), 2.63-2.59 (m, 1H), 2.49-2.39 (m, 1H), 2.08-1.92 (m, 1H).HRMS (ESI) m/z: calculated value C ₁₅ H ₁₅ N ₂ O ₅ S ⁺ [M+H] ⁺ , 335.0696; measured value, 334.8134.

Intermediate LM Preparation Example 34: Preparation of 3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propionic acid ( SIAIS171086)

The compound SIAIS171086 was prepared by referring to the intermediate LM preparation method in Example 33 under appropriate conditions understandable in the art, except that in step 3, tert-butyl 3-bromopropionate was used instead of tert-butyl 2-bromoethyl Acid ester. The target compound SIAIS171086 was obtained (white solid, 40 mg, the total yield of step 3 was 32%). ¹ H NMR(500MHz,DMSO)δ10.99(s,1H), 7.70–7.55(m,3H), 5.13(dd,J=13.3,5.1Hz,1H), 4.40–4.18(m,2H), 3.24 (t,J=7.0Hz,2H), 2.95–2.87(m,1H), 2.63–2.53(m,3H), 2.47–2.34(m,1H), 2.05–1.95(m,1H).HRMS(ESI )m/z: calculated value C ₁₆ H ₁₇ N ₂ O ₅ S ⁺ [M+H] ⁺ , 349.0853; measured value, 348.8166.

Intermediate LM Preparation Example 35: Preparation of 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butanoic acid ( SIAIS171089)

The compound SIAIS171089 was prepared by referring to the intermediate LM preparation method of Example 33 under appropriate conditions understandable in the art, except that in step 3, tert-butyl 4-bromobutyrate was used instead of tert-butyl 2-bromoethyl. Acid ester. The target compound SIAIS171089 (white solid, 50 mg, step 3 total yield 38%) was obtained. ¹ H NMR (500MHz, DMSO) δ 12.15 (s, 1H), 10.99 (s, 1H), 7.71-7.49 (m, 3H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.41-4.18 (m,2H),3.10(t,J=7.3Hz,2H), 2.92–2.88(m,1H), 2.61–2.59(m,1H), 2.49–2.42(m,1H), 2.38(t,J =7.2Hz,2H),2.05–1.96(m,1H),1.84–1.74(m,2H).HRMS(ESI)m/z: calculated value C ₁₇ H ₁₉ N ₂ O ₅ S ⁺ [M+H] ⁺ ,363.1009; measured value, 362.8160.

Intermediate LM Preparation Example 36: Preparation of 5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentanoic acid ( SIAIS171079)

The compound SIAIS171079 was prepared with reference to the method of intermediate LM to prepare Example 33 under appropriate conditions understandable in the art, except that in step 3, tert-butyl 5-bromopentanoate was used instead of tert-butyl 2-bromoethyl Acid ester. The target compound SIAIS171079 (white solid, 30 mg, 22% total yield in step 3) was obtained. ¹ H NMR (500MHz, DMSO) δ 12.01 (s, 1H), 10.98 (s, 1H), 7.66-7.55 (m, 3H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.37-4.18 (m, 2H), 3.10-3.05 (m, 2H), 2.95-2.84 (m, 1H), 2.65-2.61 (m, 1H), 2.48-2.38 (m, 1H), 2.27-2.20 (m, 3H) ,1.63–1.59(m,4H).HRMS(ESI)m/z: calculated value C ₁₈ H ₂₁ N ₂ O ₅ S ⁺ [M+H] ⁺ , 377.1166; measured value, 376.8981.

Intermediate LM Preparation Example 37: Preparation of 6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexanoic acid ( SIAIS171091)

The compound SIAIS171091 was prepared with reference to the method of intermediate LM in the preparation of Example 33 under appropriate conditions understandable in the art, except that in step 3, tert-butyl 6-bromohexanoate was used instead of tert-butyl 2-bromoethyl Acid ester. The target compound SIAIS171091 was obtained (white solid, 75 mg, the total yield of step 3 was 53%). ¹ H NMR(500MHz,DMSO)δ11.98(s,1H),10.98(s,1H),7.59–7.52(m,3H), 5.12(dd,J=13.4,5.1Hz,1H), 4.26(dd ,J=40.9,20.5Hz,2H),3.07(t,J=7.3Hz,2H), 2.96–2.84(m,1H), 2.64–2.60(m,1H), 2.48–2.39(m,1H), 2.19–2.15(m,2H),2.02–2.00(m,1H),1.70–1.35(m,6H).HRMS(ESI) m/z: calculated value C ₁₉ H ₂₃ N ₂ O ₅ S ⁺ (M+ H] ⁺ , 391.1322; measured value, 390.8150.

Intermediate LM Preparation Example 38: Preparation of 7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptanoic acid ( SIAIS171092)

The compound SIAIS171092 was prepared by referring to the method of intermediate LM to prepare Example 33 under appropriate conditions understandable in the art. The difference is that in step 3, tert-butyl 7-bromoheptanoate was used instead of tert-butyl 2-bromoethyl. Acid ester. The target compound SIAIS171092 (white solid, 79 mg, step 3 total yield 54%) was obtained. ¹ H NMR (500MHz, DMSO) δ 11.99 (s, 1H), 10.98 (s, 1H), 7.66-7.45 (m, 3H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.26 (dd ,J=40.9,20.5Hz,2H),3.07(t,J=7.3Hz,2H), 2.97–2.83(m,1H), 2.63–2.60(m,1H), 2.47–2.35(m,1H), 2.18(t,J=7.3Hz,2H),2.06–1.93(m,1H),1.65–1.20(m,8H).HRMS (ESI)m/z: calculated value C ₂₀ H ₂₅ N ₂ O ₅ S ⁺ [M+H] ⁺ ,405.1479; measured value,404.8155.

Intermediate LM Preparation Example 39: Preparation of 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl) Ethoxy) acetic acid (SIAIS1213129)

According to the method of Scheme 9, the intermediate compound SIAIS171095 (0.724mmol, 1equiv) was added to a 50mL egg-shaped flask, and then anhydrous N,N-dimethylformamide (10mL) and anhydrous potassium carbonate (1.448mmol) , 2equiv), slowly drip tert-butyl 2-(2-(toluenesulfonyloxy)ethoxy) acetate (0.869mmol, 1.2equiv) under stirring at room temperature, and stir at room temperature for 0.5h after dropping. After the reaction of the raw materials, filter to remove the insoluble matter and directly load the sample on a C18 reversed phase column for separation. Eluent: 10%-100% (v1:v2) acetonitrile: water, remove the solvent under reduced pressure to obtain the corresponding tert-butanol ester intermediate The product; the corresponding tert-butanol ester intermediate compound was added to a 25mL egg-shaped flask, followed by dichloromethane (1mL) and trifluoroacetic acid (3mL), stirred at room temperature for 1h. The solvent was evaporated under reduced pressure, and water was added to lyophilize to obtain the corresponding target compound SIAIS1213129 (pale yellow solid, 148 mg, yield 54%).

¹ H NMR(500MHz, CDCl ₃ )δ8.90(s,1H), 7.81(d,J=7.5Hz,1H), 7.68(d,J=7.7Hz,1H), 7.54(t,J=7.7Hz ,1H),5.33(dd,J＝13.4,5.1Hz,1H), 4.60(d,J＝17.2Hz,1H), 4.47(d,J＝17.2Hz,1H),4.11(s,2H),3.78 -3.73(m,1H),3.72-3.66(m,1H),3.22(t,J=6.2Hz,2H),2.98-2.93(m,1H),2.90–2.82(m,1H),2.53-2.43 (m,1H),2.32-2.25(m,1H).HRMS(ESI)m/z: calculated value C ₁₇ H ₁₉ N ₂ O ₆ S ⁺ [M+H] ⁺ , 379.0958; measured value, 379.0963.

Intermediate LM Preparation Example 40: Preparation of 2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl) (Thio)ethoxy)ethoxy)acetic acid (SIAIS1213131)

The compound SIAIS1213131 was prepared by referring to the method of intermediate LM in the preparation of Example 39 under appropriate conditions understandable in the art, except that tert-butyl 2-(2-(2-(tosyloxy)ethoxy group was used. )Ethoxy)acetate replaces tert-butyl 2-(2-(tosyloxy)ethoxy)acetate as the starting material. The target compound SIAIS1213131 (light yellow oil, 158 mg, yield 52%) was obtained.

¹ H NMR(500MHz,CDCl ₃ )δ8.77(s,1H), 7.68(d,J=7.5Hz,1H), 7.53(d,J=7.7Hz,1H), 7.42(t,J=7.7Hz ,1H),5.21(dd,J＝13.4,5.1Hz,1H), 4.41(d,J＝17.1Hz,1H), 4.32(d,J＝17.1Hz,1H),4.06(s,2H),3.65 –3.59(m,4H),3.54(t,J=4.1Hz,2H), 3.11(t,J=6.1Hz,2H), 2.88–2.83(m,1H), 2.81–2.76(m,1H), 2.42–2.34(m,1H),2.20–2.14(m,1H).HRMS (ESI) m/z: calculated value C ₁₉ H ₂₃ BN ₂ O ₇ S ⁺ [M+H] ⁺ ,423.1200; measured value, 423.1205.

Intermediate LM Preparation Example 41: Preparation of 2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-4 -Yl)thio)ethoxy)ethoxy)ethoxy)acetic acid (SIAIS1213133)

The compound SIAIS1213133 was prepared by referring to the intermediate LM preparation method in Example 39 under appropriate conditions understandable in the art, except that tert-butyl 2-(2-(2-(2-(tosyloxy) Ethoxy)ethoxy)ethoxy)acetate replaces tert-butyl 2-(2-(toluenesulfonyloxy)ethoxy)acetate as the starting material. The target compound SIAIS1213133 (light yellow oil, 149 mg, yield 44%) was obtained.

¹ H NMR(500MHz,CDCl ₃ )δ8.91(s,1H), 7.75(d,J=7.5Hz,1H), 7.61(d,J=7.6Hz,1H), 7.50(t,J=7.7Hz ,1H), 5.29(dd,J=13.4,5.1Hz,1H), 4.49(d,J=17.0Hz,1H), 4.39(d,J=17.1Hz,1H), 4.17–4.15(m,2H) ,3.72–3.63(m,10H), 3.20(t,J=6.3Hz,2H), 2.96-2.90(m,1H), 2.90–2.82(m,1H), 2.50-2.44(m,1H), 2.28 –2.22(m,1H).HRMS(ESI)m/z: calculated value C ₂₁ H ₂₇ N ₂ O ₈ S ⁺ [M+H] ⁺ , 467.1483; measured value, 467.1467.

Intermediate LM Preparation Example 42: Preparation of 14-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-3, 6,9,12-Tetraoxatetradecanoic acid (SIAIS1213135)

The compound SIAIS1213135 was prepared with reference to the intermediate LM preparation method of Example 39 under appropriate conditions understandable in the art, except that tert-butyl 14-(tosyloxy)-3,6,9,12- Tetraoxatetradecanoate replaces tert-butyl 2-(2-(toluenesulfonyloxy)ethoxy)acetate as the starting material. The target compound SIAIS1213135 (light yellow oil, 181 mg, yield 49%) was obtained. ¹ H NMR(500MHz, CDCl ₃ )δ8.61(s,1H), 7.78(dd,J=7.6,0.7Hz,1H), 7.63(dd,J=7.8,0.8Hz,1H), 7.50(t, J = 7.0Hz, 1H), 5.29 (dd, J = 13.3, 5.1 Hz, 1H), 4.50 (d, J = 17.0 Hz, 1H), 4.40 (d, J = 16.9 Hz, 1H), 4.15 (s, 2H), 3.72–3.66(m,14H), 3.19(t,J=6.6Hz,2H), 2.95-2.93(m,1H), 2.91–2.86(m,1H), 2.52–2.46(m,1H) ,2.28–2.24(m,1H).HRMS(ESI)m/z: calculated value C ₂₃ H ₃₁ N ₂ O ₉ S ⁺ [M+H] ⁺ , 511.1745; measured value, 511.1749.

Intermediate LM Preparation Example 43: Preparation of 17-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-3, 6,9,12,15-pentaoxahexadecanoic acid (SIAIS1213137)

The compound SIAIS1213137 was prepared by referring to the intermediate LM preparation method in Example 39 under appropriate conditions understandable in the art, except that tert-butyl 17-(tosyloxy)-3,6,9,12 was used. 15-Pentoxahexadecanoate replaced tert-butyl 2-(2-(toluenesulfonyloxy)ethoxy)acetate as a starting material. The target compound SIAIS1213137 (light yellow oil, 209 mg, yield 52%) was obtained. ¹ H NMR(500MHz, CDCl ₃ )δ8.71(s,1H), 7.77(d,J=7.0Hz,1H), 7.64(dd,J=7.7,0.7Hz,1H), 7.54–7.49(m, 1H), 5.31 (dd, J = 13.4, 5.1 Hz, 1H), 4.50 (d, J = 17.0 Hz, 1H), 4.40 (d, J = 17.0 Hz, 1H), 4.17 (s, 2H), 3.76- 3.74(m, 2H), 3.70–3.66(m, 12H), 3.64–3.61(m, 4H), 3.20(t, J=6.5Hz, 2H), 2.98–2.94(m, 1H), 2.90–2.85( m,1H),2.53-2.43(m,1H),2.30-2.25(m,1H).HRMS(ESI) m/z: calculated value C ₂₅ H ₃₅ N ₂ O ₁₀ S ⁺ [M+H] ⁺ , 569.1800; measured value, 569.1814.

Intermediate LM Preparation Example 44: 3-(4-(4-Bromobutoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1222171):

Refer to Scheme 11, dissolve 3-(4-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione (1.0g, 3.8mmol) in 20mL DMF, add K ₂ CO ₃ (0.27g, 1.9mmol), stir for 15min, add 1,4-dibromobutane (1.64g, 7.6mmol), heat to 80℃, react for 12h, pour the reaction solution into 50mL water, and extract with dichloromethane Twice, the organic phase was washed with saturated brine, the solvent was distilled off under reduced pressure, and silica gel column chromatography (DCM-DCM/MeOH=10/1) was used to obtain SIAIS1222171, a yellow powder, with a yield of 30%. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 10.97 (s, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.31 (d, J = 7.5 Hz, 1H), 7.24 (d, J = 8.1Hz, 1H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.38 (d, J = 17.4 Hz, 1H), 4.23 (d, J = 17.4 Hz, 1H), 4.16 (t, J = 6.2Hz,2H),3.62(t,J=6.6Hz,2H),2.96-2.85(m,1H),2.58(d,J=17.1Hz,1H), 2.44(td,J=13.3,4.6Hz, 1H), 1.99 (dq, J = 12.4, 6.5 Hz, 3H), 1.92-1.83 (m, 2H).

Intermediate LM Preparation Example 45: 3-(4-((5-Bromopentyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1222169) :

The compound SIAIS1222169 was prepared by referring to the method of intermediate LM to prepare Example 44 under appropriate conditions understandable in the art, except that 1,5-dibromopentane was used instead of 1,4-dibromobutane as the starting material SIAIS1222169 was obtained as a light yellow powder. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 10.97 (s, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.31 (d, J = 7.4 Hz, 1H), 7.24 (d, J = 8.2Hz, 1H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.37 (d, J = 17.3 Hz, 1H), 4.23 (d, J = 17.4 Hz, 1H), 4.13 (t, J = 6.3Hz, 2H), 3.56 (t, J = 6.7 Hz, 2H), 2.91 (ddd, J = 17.3, 13.7, 5.4 Hz, 1H), 2.60 (t, J = 17.9 Hz, 1H), 2.43 (td, J = 13.2, 4.5 Hz, 1H), 1.99 (dtd, J = 12.7, 5.3, 2.3 Hz, 1H), 1.88 (p, J = 6.9 Hz, 2H), 1.77 (p, J = 6.5 Hz, 2H), 1.61-1.52 (m, 2H).

Intermediate LM Preparation Example 46: 3-(4-(4-(3-iodopropyl)-1H-1,2,3-triazol-1-yl)-1-oxoisoindoline-2 -Base) piperidine-2,6-dione (SIAIS315194):

first step

Dissolve 3-(4-azido-1-oxoisoindolin-2-yl)piperidine-2,6-dione (0.20g, 0.70mmol) in DMF/H ₂ O=1/1 Add 5-chloro-1-pentyne (79mg, 0.77mmol), copper sulfate (11mg, 0.070mmol) and sodium ascorbate (14mg, 0.070mmol) in order to the mixed solvent of, and react at room temperature overnight. When the reaction is complete, add water The product was separated out, washed with ether, and drained to obtain SIAIS315193 (purple powder, m=0.22g, yield 79%). ¹ H NMR (500MHz, DMSO-d ₆ )δ11.02(s, 1H), 8.75( s, 1H), 8.08 (dd, J = 8.0, 1.0 Hz, 1H), 7.92-7.81 (m, 1H), 7.77 (t, J = 7.7 Hz, 1H), 5.18 (dd, J = 13.3, 5.1 Hz ,1H),4.77(d,J=18.2Hz,1H), 4.67(d,J=18.3Hz,1H), 3.75(t,J=6.5Hz,2H), 2.93(dd,J=13.6,5.3Hz ,1H), 2.89(t,J=7.5Hz,2H),2.66-2.57(m,1H),2.46(dd,J=13.3,4.4Hz,1H), 2.15(p,J=6.7Hz,2H) ,2.02(dtd,J=12.8,5.4,2.2Hz,1H).LRMS(ESI)m/z: calculated value C ₁₈ H ₁₉ ClN ₅ O ₃ ⁺ [M+H] ⁺ ,388.12; measured value, 388.33.

Second step

Dissolve SIAIS315193 (125mg, 0.32mmol) in 10mL of acetone, add sodium iodide (0.24g, 1.61mmol), heat to 60°C, react for 24h, cool to room temperature, distill the solvent under reduced pressure, wash with water, and filter to obtain SIAIS315194 (gray powder, 129mg, yield 84%) LRMS (ESI) m/z: calculated value C ₁₈ H ₁₉ IN ₅ O ₃ ⁺ [M+H] ⁺ , 480.05; measured value, 480.30.

Intermediate LM Preparation Example 47: Preparation of 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindol-4-yl)pent-4-ynoic acid (SIAIS364068 )

The reaction raw material 3-(4-(5-hydroxyhex-1-yn-1-yl)-1-oxoisoindol-2-yl)piperidine-2,6-dione is the intermediate LM Preparation Example Intermediate in 7. Take 3-(4-(5-hydroxyhex-1-yn-1-yl)-1-oxoisoindol-2-yl)piperidine-2,6-dione (200mg, 0.61mmol) and dissolve In 20 mL of acetone, cool to 0°C, add Jones' reagent, slowly rise to room temperature, and react for 6 hours. Add 100 mL of ethyl acetate, separate the layers, wash the organic phase with water until it is colorless, dry with anhydrous sodium sulfate, and distill off the solvent under reduced pressure to obtain the crude product of SIAIS364068, m=51mg, yield=24%.LRMS(ESI)m/ z: Calculated value C ₁₈ H ₁₇ N ₂ O ₅ ⁺ [M+H] ⁺ , 341.11; measured value, 341.41.

Intermediate LM Preparation Example 48: (2S,4R)-4-hydroxy-1-((S)-2-((6-iodohexyl)amino)-3,3-dimethylbutyryl)-N- (4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363013)

Referring to Scheme 14, the raw material (2S,4R)-1-((S)-2-amino-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazole- 5-yl)benzyl)pyrrolidine-2-carboxamide (0.25g, 0.58mmol) was dissolved in 10mL acetonitrile, and NaI (0.18g, 1.16mmol), Cs ₂ CO ₃ (0.30g, 1.16mmol) and 1,6-Dibromohexane (1.16mmol), heated to 80°C, reacted for 12h, and the reaction was complete. The reaction solution was poured into 50 mL water, extracted with dichloromethane twice, the organic phase was washed with saturated brine, the solvent was distilled off under reduced pressure, and silica gel column chromatography (DCM-DCM/MeOH=10/1) was performed to obtain a white solid. Yield=60% (contains a small amount of difficult-to-separate by-products, but does not affect the nucleophilic substitution reaction in the next step). LRMS(ESI) m/z: calculated value C ₂₈ H ₄₂ IN ₄ O ₃ S ⁺ [M+H] ⁺ , 641.20; measured value, 641.67.

Intermediate LM Preparation Example 49: (2S,4R)-4-hydroxy-1-((S)-2-((7-iodoheptyl)amino)-3,3-dimethylbutyryl)-N -(4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363039)

The compound SIAIS363039 was prepared by referring to the method of intermediate LM to prepare Example 48 under appropriate conditions understandable in the art, except that 1,7-dibromoheptane was used instead of 1,6-dibromohexane as the starting material , The target compound SIAIS363039 (white solid, 200 mg, yield 57%) was obtained. LRMS(ESI)m/z: calculated value C ₂₉ H ₄₄ IN ₄ O ₃ S ⁺ [M+H] ⁺ , 655.22; measured value, 655.67.

Intermediate LM Preparation Example 50: (2S,4R)-4-hydroxy-1-((S)-2-((8-iodooctyl)amino)-3,3-dimethylbutyryl)-N -(4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363040)

The compound SIAIS363040 was prepared by referring to the method of intermediate LM to prepare Example 48 under appropriate conditions understandable in the art, except that 1,8-dibromooctane was used instead of 1,6-dibromohexane as the starting material , The target compound SIAIS363040 (white solid, 220 mg, yield 61%) was obtained. LRMS(ESI)m/z: calculated value C ₃₀ H ₄₆ IN ₄ O ₃ S ⁺ [M+H] ⁺ , 669.23; measured value, 669.87.

Intermediate LM Preparation Example 51: (2S,4R)-4-hydroxy-1-((S)-2-((9-iodononyl)amino)-3,3-dimethylbutyryl)-N -(4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363033)

The compound SIAIS363033 was prepared by referring to the method of intermediate LM to prepare Example 48 under appropriate conditions understandable in the art, except that 1,9-dibromononane was used instead of 1,6-dibromohexane as the starting material , The target compound SIAIS363040 (white solid, 220 mg, yield 69%) was obtained. LRMS(ESI) m/z: calculated value C ₃₁ H ₄₈ IN ₄ O ₃ S ⁺ [M+H] ⁺ , 683.25; measured value, 683.68.

Intermediate LM Preparation Example 52: (2S,4R)-4-hydroxy-1-((S)-2-((10-iododecyl)amino)-3,3-dimethylbutyryl)-N -(4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363041)

The compound SIAIS363041 was prepared by referring to the intermediate LM preparation method of Example 48 under appropriate conditions understandable in the art, except that 1,10-dibromodecane was used instead of 1,6-dibromohexane as the starting material , The target compound SIAIS363040 (white solid, 240 mg, yield 64%) was obtained. LRMS(ESI)m/z: calculated value C ₃₂ H ₅₀ IN ₄ O ₃ S ⁺ [M+H] ⁺ , 697.26; measured value, 697.87.

Intermediate LM Preparation Example 53: (2S,4R)-4-hydroxy-1-((S)-2-((2-(2-(2-iodoethoxy)ethoxy)ethyl)amino )-3,3-Dimethylbutyryl)-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363110)

The compound SIAIS363110 was prepared by referring to the method of intermediate LM to prepare Example 48 under appropriate conditions understandable in the art, except that triethylene glycol di-p-toluenesulfonate was used instead of 1,6-dibromohexane as the starting point. The starting material was used to obtain the target compound SIAIS363110 (white solid, 159 mg, yield 41%). LRMS(ESI)m/z: calculated value C ₂₈ H ₄₂ IN ₄ O ₅ S ⁺ [M+H] ⁺ , 673.19; measured value, 673.60.

Intermediate LM Preparation Example 54: (2S,4R)-1-((S)-2-(tert-butyl)-14-iodo-6,9,12-trioxa-3-azatetradecane Acyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363111)

The compound SIAIS363111 was prepared by referring to the method of intermediate LM to prepare Example 48 under appropriate conditions understandable in the art, except that tetraethylene glycol di-p-toluenesulfonate was used instead of 1,6-dibromohexane as the starting point. The starting material was used to obtain the target compound SIAIS363111 (white solid, 186 mg, yield 45%). LRMS(ESI)m/z: calculated value C ₃₀ H ₄₆ IN ₄ O ₆ S ⁺ [M+H] ⁺ , 717.22; measured value, 717.56.

Intermediate LM Preparation Example 55: (2S,4R)-1-((S)-2-(tert-butyl)-17-iodo-6,9,12,15-tetraoxa-3-azadecade Heptaalkanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363112)

The compound SIAIS363112 was prepared by referring to the method of intermediate LM to prepare Example 48 under appropriate conditions understandable in the art. The difference is that pentaethylene glycol di-p-toluenesulfonate was used instead of 1,6-dibromohexane as the starting point. The starting material was used to obtain the target compound SIAIS363112 (white solid, 170 mg, yield 39%). LRMS(ESI)m/z: Calculated value C ₃₂ H ₅₀ IN ₄ O ₇ S ⁺ [M+H] ⁺ ,761.24; measured value, 761.57.

Intermediate LM Preparation Example 56: (2S,4R)-1-((S)-2-(tert-butyl)-20-iodo-6,9,12,15,18-pentaoxa-3-nitrogen Heteroeicosanyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363119)

The compound SIAIS363119 was prepared with reference to the method of intermediate LM to prepare Example 48 under appropriate conditions understandable in the art, except that hexaethylene glycol di-p-toluenesulfonate was used instead of 1,6-dibromohexane as the starting point. The starting material was used to obtain the target compound SIAIS363119 (white solid, 145 mg, yield 31%). LRMS (ESI) m/z: calculated value C ₃₄ H ₅₄ IN ₄ O ₈ S ⁺ [M+H] ⁺ , 805.27; actual value, 805.72. Intermediate LM preparation example 57: (2S,4R)-1- ((S)-2-(5-Bromopentanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl) Pyrrolidine-2-carboxamide (SIAIS360137)

According to Scheme 13. Refer to the reaction conditions of patent KR20170132934(A), SIAIS360137 was synthesized with 5-bromovaleryl chloride as a raw material (white solid, yield 87%). LRMS(ESI)m/z: calculated value C ₂₇ H ₃₈ BrN ₄ O ₄ S ⁺ [M+H] ⁺ ,593.18; measured value,593.41.

Intermediate LM Preparation Example 58: (2S,4R)-1-((S)-2-(6-bromohexanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( 4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS360131)

The compound SIAIS360131 was prepared by referring to the intermediate LM method in Example 57 under appropriate conditions understandable in the art, except that 6-bromohexanoyl chloride was used instead of 5-bromovaleryl chloride as the starting material to obtain the target compound SIAIS360131. (White solid, 71% yield). LRMS(ESI)m/z: calculated value C ₂₈ H ₄₀ BrN ₄ O ₄ S ⁺ [M+H] ⁺ , 607.19; measured value, 607.41.

Intermediate LM Preparation Example 59: (2S,4R)-1-((S)-2-(7-bromoheptanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( 4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS360135)

The compound SIAIS360135 was prepared by referring to the intermediate LM preparation method in Example 57 under appropriate conditions understandable in the art, except that 7-bromoheptanoyl chloride was used instead of 5-bromovaleryl chloride as the starting material to obtain the target compound SIAIS360135. (White solid, 87% yield). LRMS(ESI)m/z: calculated value C ₂₉ H ₄₂ BrN ₄ O ₄ S ⁺ [M+H] ⁺ ,621.21; measured value,621.50.

Intermediate LM Preparation Example 60: (2S,4R)-1-((S)-2-(8-bromooctanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( 4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS360138)

The compound SIAIS360138 was prepared by referring to the intermediate LM preparation method in Example 57 under appropriate conditions understandable in the art, except that 8-bromooctanoyl chloride was used instead of 5-bromovaleryl chloride as the starting material to obtain the target compound SIAIS360138. (White solid, yield 60%). LRMS(ESI)m/z: calculated value C ₃₀ H ₄₄ BrN ₄ O ₄ S ⁺ [M+H] ⁺ , 635.23; measured value, 635.54.

Intermediate LM Preparation Example 61: (2S,4R)-1-((S)-2-(9-bromononanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( 4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS360139)

The compound SIAIS360139 was prepared by referring to the intermediate LM method in Example 57 under appropriate conditions understandable in the art, except that 9-bromononanoyl chloride was used instead of 5-bromovaleryl chloride as the starting material to obtain the target compound SIAIS360139. (White solid, yield 55%). LRMS(ESI)m/z: calculated value C ₃₁ H ₄₆ BrN ₄ O ₄ S ⁺ [M +H] ⁺ ,649.24; measured value, 649.50.

Intermediate LM Preparation Example 62: (2S,4R)-1-((S)-2-(10-bromodecanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( 4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS360140)

The compound SIAIS360140 was prepared with reference to the intermediate LM preparation method in Example 57 under appropriate conditions understandable in the art, except that 10-bromodecanoyl chloride was used instead of 5-bromovaleryl chloride as the starting material to obtain the target compound SIAIS360140. (White solid, yield 75%). LRMS(ESI)m/z: calculated value C ₃₂ H ₄₈ BrN ₄ O ₄ S ⁺ [M+H] ⁺ , 663.26; measured value, 663.50.

Intermediate LM Preparation Example 63: (2(2S,4R)-1-((S)-2-(11-bromoundecanoylamino)-3,3-dimethylbutyryl)-4-hydroxy -N-(4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS360141)

The compound SIAIS360140 was prepared by referring to the method of intermediate LM to prepare Example 57 under appropriate conditions understandable in the art, except that 11-bromoundecanoyl chloride was used instead of 5-bromopentanoyl chloride as the starting material to obtain the target compound SIAIS360141. (white solid, yield 91%). LRMS(ESI)m/z: calculated value C ₃₃ H ₅₀ BrN ₄ O ₄ S ⁺ [M+H] ⁺ , 677.27; measured value, 677.59.

Intermediate Preparation Example 64: Preparation of 3-(4-(3-bromopropylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS213132)

According to the method of Scheme 10, the compound SIAIS171095 (1equiv) was added to a 25mL reaction flask, followed by adding anhydrous N,N-dimethylformamide (10mL) and anhydrous potassium carbonate (2equiv), stirring at room temperature Add 1,3-dibromopropane (1.2equiv) slowly, and stir at room temperature for 1h after dropping. After the raw materials are reacted, they are quenched with water, extracted with ethyl acetate, and the organic phase is concentrated. The crude product is separated by a reversed-phase C18 column. Eluent (v/v): acetonitrile/water=10%-100%, evaporated under reduced pressure The solvent was lyophilized to obtain the target compound SIAIS213132 (light yellow solid, 130 mg, yield 30.1%). ¹ H NMR (500 MHz, CDCl ₃ ) δ8.01 (s, 1H), 7.76 (t, J = 11.2Hz, 1H), 7.57-7.43 (m, 2H), 5.28-5.18 (m, 1H), 4.46 –4.25(m,2H),3.62–3.50(m,2H),3.16(t,J=7.0Hz,2H),2.98–2.77(m,2H),2.46–2.33(m,1H),2.28–2.13 (m,3H).LCMS(ESI)m/z: calculated value C ₁₆ H ₁₈ BrN ₂ O ₃ S ⁺ [M+H] ⁺ , 397.0216\399.0196; measured value, 397.15\399.11.

Intermediate Preparation Example 65: Preparation of 3-(4-(4-bromobutylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS213134)

According to the method of Scheme 10 and referring to Intermediate Preparation Example 64, the compound SIAIS213134 was prepared under appropriate conditions understandable in the art. The difference is that the brominated substrate used as the linker is 1,4-dibromobutane. alkyl. The target compound SIAIS213134 (light yellow solid, 170 mg, yield 38.1%) was obtained. ¹ H NMR(500MHz,CDCl ₃ )δ8.00(s,1H),7.74(t,J=8.7Hz,1H),7.55-7.44(m,2H),5.23(dt,J=20.5,10.3Hz, 1H),4.33(ddd,J=33.1,25.9,11.5Hz,2H),3.48–3.35(m,2H),3.01(dd,J=20.7,13.5Hz,2H),2.97–2.81(m,2H) ,2.41(ddd,J=26.6,13.3,4.8Hz,1H),2.28–2.19(m,1H),2.09–1.96(m,2H),1.89–1.86(m,2H).LCMS(ESI)m/ z: Calculated value C ₁₇ H ₂₀ BrN ₂ O ₃ S ⁺ [M+H] ⁺ ,411.0373\413.0352; measured value, 411.10\413.11.

Intermediate Preparation Example 66: Preparation of 3-(4-(5-bromopentylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS213135)

According to the method of Scheme 10 and referring to Intermediate Preparation Example 64, the compound SIAIS213135 was prepared under appropriate conditions understandable in the art. The difference is that the brominated substrate used as the linker is 1,5-dibromopentane alkyl. The target compound SIAIS213135 (light yellow solid, 190 mg, yield 41.1%) was obtained. ¹ H NMR(500MHz, CDCl ₃ )δ8.05(d,J=28.3Hz,1H), 7.76–7.69(m,1H), 7.52–7.41(m,2H), 5.26–5.18(m,1H), 4.47–4.24 (m, 2H), 3.41 (t, J = 6.6 Hz, 2H), 2.99 (dd, J = 17.3, 10.1 Hz, 2H), 2.95–2.79 (m, 2H), 2.39 (tdd, J = 22.4, 15.4, 7.4Hz, 1H), 2.31–2.19(m,1H), 1.93–1.84(m,2H), 1.73–1.70(m,2H), 1.69–1.63(m,2H).LCMS(ESI) m/z: Calculated value C ₁₈ H ₂₂ BrN ₂ O ₃ S ⁺ [M+H] ⁺ ,425.0529\427.0509; measured value, 425.10\427.10.

Intermediate LM Preparation Example 67: 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yne-1- Preparation of Mesylate (SIAIS268191)

Dissolve SIAIS255121 (50mg, 0.12mol) in 1mL DMF, cool to 0°C, add NaH (1.2equiv), stir for 5min, add methyl iodide (25mg, 0.18mmol), and react at room temperature for 1h. After the reaction was complete, the reaction was quenched with saturated ammonium chloride, extracted with dichloromethane, washed with saturated brine, and the solvent was distilled off under reduced pressure. The column chromatography (DCM-DCM/MeOH=20/1) gave the target product SIAIS268191 (m=36mg). , w% = 70%). LCMS (ESI) m/z: calculated value C ₂₀ H ₂₃ N ₂ O ₆ S ⁺ [M+H] ⁺ , 419.13; measured value, 419.20.

Compound preparation example

Example 1: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)aminoacetyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide (SIAIS230148)

According to the synthetic strategy of Scheme 15, the intermediate BINDER (SIAIS230138) (25mg, 0.029mmol) was dissolved in 2mL DMF, and the intermediate LM (SIAIS151025) (2-(2,6-dioxo) prepared according to Scheme 1 was added in sequence. Piperidin-3-yl)-1,3-dioxo-isoindolin-4-yl)glycine (9.5mg, 0.029mmol), HATU (16.5mg, 0.044mmol) and DIPEA (11.4mg, 0.088 mmol), react overnight at room temperature. Add 0.10mL of water to quench the reaction, HPLC preparation and separation (eluent (v/v): acetonitrile/(water+0.05%HCl)=10%-100%), evaporate most of the water of acetonitrile under reduced pressure, and freeze-dry The final target compound (SIAIS230148) was obtained. Yellow powder, m=15mg, yield=44%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.67 (s, 1H), 11.10 (s, 1H), 8.67 (t, J = 5.9 Hz, 1H), 8.58 (d, J = 2.3Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 9.2, 2.4 Hz, 1H), 7.61 (dd, J = 8.5, 7.0 Hz, 1H), 7.56 ( d,J=2.6Hz,1H),7.53(dd,J=5.7,2.7Hz,2H),7.39(d,J=8.3Hz,2H),7.18-7.05(m,5H),6.72(dd,J ＝9.0,2.3Hz,1H), 6.40(dd,J＝3.4,1.9Hz,1H), 6.25(d,J＝2.3Hz,1H), 5.07(dd,J＝12.8,5.4Hz,1H), 4.41 (d,J=12.8Hz,1H), 4.18(q,J=16.5Hz,2H), 3.92(d,J=13.5Hz,1H), 3.70-3.40(m,4H), 3.37-3.31(m, 2H), 3.26 (d, J = 10.5 Hz, 2H), 3.23–3.07 (m, 2H), 3.02 (t, J = 11.9 Hz, 1H), 2.95–2.83 (m, 1H), 2.78–2.54 (m ,4H),2.25(s,2H),2.03(d,J=16.1Hz,4H),1.84-1.72(m,2H),1.45(t,J=5.8Hz,2H),1.25(d,J= 11.0Hz,2H),1.18-1.04(m,1H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₀ H ₆₃ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ ,1180.4112 ; Measured value, 1180.4120.

Example 2: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propionyl)piperidin-4-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230149) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS151026) 3-((2-(2,6-dioxo) were prepared according to Scheme 1 under appropriate conditions understood in the art. Piperidin-3-yl)-1,3-dioxo-isoindolin-4-yl)amino)propionic acid was prepared to obtain the target compound (SIAIS230149). Yellow powder, m=15mg, yield=44%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.71 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 9.70 (s, 1H), 8.63 (t, J = 5.6 Hz, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 9.2, 2.2 Hz, 1H), 7.64–7.47 (m, 4H), 7.39(d,J=8.4Hz,2H),7.16-7.06(m,4H),7.03(d,J=7.0Hz,1H),6.40(s,1H),6.25(s,1H),5.04(dd ,J=12.8,5.4Hz,1H), 4.42(d,J=12.9Hz,1H), 3.87(d,J=13.4Hz,1H), 3.70-3.40(m,4H), 3.35-3.20(m, 6H), 3.11(t, J=12.6Hz, 2H), 3.01–2.82(m, 2H), 2.79–2.59(m, 6H), 2.25(s, 2H), 2.01(s, 3H), 1.88(s ,1H),1.71(d,J=12.6Hz,2H),1.45(t,J=6.4Hz,2H),1.19-1.00(m,3H),0.94(s,6H).HRMS(ESI)m/ z: Calculated value C ₆₁ H ₆₅ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ , 1194.4269; measured value, 1194.4271.

Example 3: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyryl)piperidin-4-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230150) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS151019) 4-((2-(2,6-dioxo) were prepared according to Scheme 1 under appropriate conditions understood in the art. Piperidin-3-yl)-1,3-dioxo-isoindolin-4-yl)amino)butyric acid was prepared to obtain the target compound (SIAIS230150). Yellow powder, m=14mg, yield=40%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.71 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 8.64 (s, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.04(d,J=2.6Hz,1H), 7.81(dd,J=9.2,2.3Hz,1H), 7.67–7.47(m,4H),7.48–7.35(m,2H), 7.17(d ,J=8.6Hz,1H), 7.13(d,J=9.4Hz,1H), 7.08(d,J=7.9Hz,2H), 7.02(d,J=7.0Hz,1H), 6.72(dd,J ＝8.9,2.3Hz,1H),6.67(s,1H),6.40(dd,J＝3.5,1.9Hz,1H), 6.25(d,J＝2.2Hz,1H), 5.05(dd,J＝12.7, 5.4Hz, 1H), 4.42 (d, J = 13.0 Hz, 1H), 3.87 (d, J = 13.4 Hz, 1H), 3.70-3.50 (m, 4H), 3.36-3.23 (m, 6H), 3.10 ( d, J = 13.0Hz, 3H), 2.99–2.82 (m, 2H), 2.72 (d, J = 6.3 Hz, 2H), 2.66–2.56 (m, 2H), 2.43–2.34 (m, 2H), 2.24 (s,2H),2.01(s,3H),1.89(s,1H),1.83-1.67(m,4H),1.45(t,J=6.4Hz,2H),1.17-1.00(m,3H), 0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₂ H ₆₇ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ , 1208.4425; measured value, 1208.4438.

Example 4: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentanoyl)piperidin-4-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230151) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS151020) 5-((2-(2,6-dioxo) were prepared according to Scheme 1 under appropriate conditions understood in the art. Piperidin-3-yl)-1,3-dioxo-isoindolin-4-yl)amino)pentanoic acid was prepared to obtain the target compound (SIAIS230151). Yellow powder, m=11mg, yield=31%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.67 (s, 1H), 11.09 (s, 1H), 8.63 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3Hz, 1H), 8.05 (t, J = 2.5 Hz, 1H), 7.81 (dd, J = 9.2, 2.3 Hz, 1H), 7.61-7.54 (m, 2H), 7.55-7.50 (m, 2H) ),7.43–7.37(m,2H),7.16–7.05(m,4H), 7.02(d,J=7.0Hz,1H), 6.71(dd,J=9.0,2.3Hz,1H), 6.56(s, 1H), 6.40 (dd, J = 3.3, 1.9 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.05 (dd, J = 12.7, 5.4 Hz, 1H), 4.39 (d, J = 12.9 Hz,1H), 3.88(d,J=13.4Hz,1H), 3.70–3.50(m,4H), 3.35–3.23(m,6H), 3.21–3.08(m,2H), 3.00–2.83(m, 2H), 2.72 (d, J = 10.9 Hz, 2H), 2.66-2.54 (m, 2H), 2.40-2.35 (m, 2H), 2.28 (d, J = 20.4 Hz, 2H), 2.10-2.00 (m ,3H), 1.88(s, 1H), 1.77-1.66(m, 2H), 1.58(s, 4H), 1.45(s, 2H), 1.18-0.98(m, 3H), 0.94(s, 6H). HRMS(ESI) m/z: calculated value C ₆₃ H ₆₉ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ , 1222.4582; measured value, 1222.4581.

Example 5: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)piperidin-4-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230152) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS151027) 6-((2-(2,6-dioxo) were prepared according to Scheme 1 under appropriate conditions understood in the art. Piperidin-3-yl)-1,3-dioxo-isoindolin-4-yl)amino)hexanoic acid was prepared to obtain the target compound (SIAIS230152). Yellow powder, m=14mg, yield=39%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.67 (s, 1H), 11.09 (s, 1H), 8.63 (t, J = 6.1 Hz, 1H), 8.57 (d, J = 2.4Hz, 1H), 8.05 (t, J = 2.8 Hz, 1H), 7.81 (dd, J = 9.2, 2.4 Hz, 1H), 7.58 (dd, J = 8.6, 7.0 Hz, 2H), 7.55- 7.49(m,2H),7.39(dd,J=8.4,1.8Hz,2H),7.16-7.06(m,4H),7.02(d,J=7.0Hz,1H),6.71(d,J=11.0Hz ,1H), 6.53 (s, 1H), 6.40 (d, J = 3.6 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.05 (dd, J = 12.8, 5.4 Hz, 1H), 4.39 (d,J=12.9Hz,1H), 3.87(d,J=13.4Hz,1H), 3.70-3.50(m,4H), 3.35–3.22(m,6H), 3.15(d,J=12.0Hz, 2H), 2.99–2.82(m,2H), 2.70(s,2H), 2.64–2.51(m,2H), 2.30(t,J=7.4Hz,4H),2.06–1.98(m,3H),1.88 (s,1H),1.71(t,J=14.9Hz,2H),1.63-1.48(m,4H),1.44(s,2H),1.36(m,2H),1.17-0.97(m,3H), 0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₁ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ , 1236.4738; measured value, 1236.4729.

Example 6: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoyl)piperidin-4-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230153) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS151086) 7-((2-(2,6-dioxo) prepared according to Scheme 1 were used under appropriate conditions. Piperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoic acid was prepared to obtain the target compound (SIAIS230153). Yellow powder, m=15mg, yield=41%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.74 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 8.63 (t, J = 5.8 Hz, 1H), 8.57 (s, 1H), 8.04 (s, 1H), 7.81 (dd, J = 9.2, 2.3 Hz, 1H), 7.61-7.54 (m, 2H), 7.52 (dd, J = 5.9, 2.8 Hz, 2H), 7.39 (d ,J=7.9Hz,2H), 7.13(d,J=9.4Hz,1H), 7.09(dt,J=8.5,2.6Hz,3H), 7.02(d,J=7.0Hz,1H), 6.71(d ,J=8.6Hz,1H),6.53(s,1H),6.40(s,1H),6.25(d,J=2.3Hz,1H),5.05(dd,J=12.8,5.4Hz,1H), 4.39 (d,J=12.9Hz,1H), 3.86(d,J=13.5Hz,1H), 3.70-3.50(m,4H), 3.30(m,6H), 3.20-3.10(m,2H),3.01– 2.83(m, 2H), 2.72(s, 2H), 2.65-2.55(m, 2H), 2.30-2.20(m, 4H), 2.10-2.00(m, 3H), 1.88(s, 1H), 1.71( t,J=15.3Hz,2H),1.60-1.55(m,2H),1.53-1.41(m,4H),1.35-1.30(m,4H),1.17-0.98(m,3H),0.94(s, 6H).HRMS(ESI)m/z: calculated value C ₆₅ H ₇₃ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ , 1250.4895; measured value, 1250.4894.

Example 7: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)propionyl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230159) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS230159) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS151138). Yellow powder, m=17mg, yield=48%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.67 (s, 1H), 11.12 (s, 1H), 8.64 (t, J = 5.8 Hz, 1H), 8.57 (s, 1H), 8.04(d,J=2.5Hz,1H),7.84-7.75(m,3H),7.64(d,J=6.7Hz,1H),7.56(s,1H),7.54-7.49(m,2H ), 7.39 (d, J = 8.4 Hz, 2H), 7.10 (dd, J = 17.7, 8.9 Hz, 3H), 6.72 (dd, J = 8.9, 1.9 Hz, 1H), 6.40 (dd, J = 3.4, 1.9Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.12 (dd, J = 12.9, 5.4 Hz, 1H), 4.41 (d, J = 12.9 Hz, 1H), 3.80-3.50 (m, 4H) 3.36-3.22(m, 6H), 3.20-3.10(m, 2H), 2.99-2.83(m, 2H), 2.82-2.65(m, 4H), 2.67-2.56(m, 3H), 2.28(s ,2H),2.06-2.00(m,3H),1.89(s,1H),1.72(d,J=12.7Hz,2H),1.45(t,J=6.4Hz,2H),1.25-1.00(m, 3H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₁ H ₆₄ ClN ₁₀ O ₁₁ S ₂ ⁺ [M+H] ⁺ , 1211.3880; measured value, 1211.3885.

Example 8: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)pentanoyl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230160) preparation

With reference to the method of Example 1, the target compound (SIAIS230160) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS151140) under appropriate conditions understandable in the art. Yellow powder, m=17mg, yield=47%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.67 (s, 1H), 11.12 (s, 1H), 8.64 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3Hz, 1H), 8.05 (dd, J = 2.7, 1.2 Hz, 1H), 7.86–7.72 (m, 3H), 7.63 (dd, J = 6.7, 1.3 Hz, 1H), 7.56 (s, 1H) ), 7.54–7.49 (m, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 9.5 Hz, 1H), 7.09 (d, J = 8.2 Hz, 2H), 6.72 (dd ,J=9.0,2.3Hz,1H),6.42–6.39(m,1H), 6.25(d,J=2.4Hz,1H), 5.11(dd,J=12.8,5.4Hz,1H), 4.40(d, J = 12.8Hz, 1H), 3.89 (d, J = 13.6Hz, 1H), 3.80–3.50(m, 4H), 3.37–3.23(m, 4H), 3.22-3.10(m, 4H), 3.00–2.83 (m, 2H), 2.71 (s, 2H), 2.65-2.52 (m, 2H), 2.36 (s, 2H), 2.29 (s, 2H), 2.08-1.99 (m, 3H), 1.90 (s, 1H) ),1.74-1.60(m,6H),1.44(t,J=6.4Hz,2H),1.23-0.98(m,3H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₆₈ ClN ₁₀ O ₁₁ S ₂ ⁺ [M+H] ⁺ , 1239.4193; found value, 1239.4192.

Example 9: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)heptanoyl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230161) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS230161) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS151142). Yellow powder, m=16mg, yield=43%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 11.12 (s, 1H), 8.64 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3Hz, 1H), 8.08–8.03 (m, 1H), 7.83–7.72 (m, 3H), 7.62 (d, J = 6.9 Hz, 1H), 7.56 (d, J = 3.1 Hz, 1H), 7.52 (dd, J = 5.7, 2.7 Hz, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.11 (dd, J = 20.6, 8.8 Hz, 3H), 6.72 (dd, J = 9.0, 2.3 Hz ,1H), 6.40 (s, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.11 (dd, J = 12.9, 5.4 Hz, 1H), 4.39 (d, J = 12.9 Hz, 1H), 3.87 (d,J=13.6Hz,1H), 3.70–3.50(m,4H), 3.34–3.22(m,4H), 3.12(t,J=7.3Hz,4H), 2.99–2.83(m,2H), 2.71(s,2H),2.66-2.52(m,3H),2.30-2.20(m,4H),2.10-1.98(m,3H),1.88(s,1H),1.77-1.62(m,4H), 1.54–1.39(m,6H),1.32(t,J=7.5Hz,2H),1.20–0.97(m,3H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₅ H ₇₂ ClN ₁₀ O ₁₁ S ₂ ⁺ [M+H] ⁺ , 1267.4506; found value, 1267.4506.

Example 10: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)acetyl)piperidin-4-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide (SIAIS230162) preparation

With reference to the method of Example 1, the target compound (SIAIS230162) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS171090) under appropriate conditions understandable in the art. Yellow powder, m=13mg, yield=38%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.67 (s, 1H), 11.00 (s, 1H), 8.65 (t, J = 5.7 Hz, 1H), 8.57 (s, 1H), 8.04 (s, 1H), 7.82 (d, J = 11.4 Hz, 1H), 7.72 (dd, J = 7.8, 2.3 Hz, 1H), 7.62-7.50 (m, 5H), 7.39 (d, J ＝8.1Hz,2H),7.14(d,J＝9.4Hz,1H), 7.09(d,J＝8.0Hz,2H), 6.72(dd,J＝9.0,2.3Hz,1H), 6.42–6.38(m ,1H), 6.25(d,J=2.2Hz,1H),5.19–5.10(m,1H), 4.41(d,J=17.4Hz,1H),4.33(d,J=12.8Hz,1H), 4.26 (d, J = 17.4 Hz, 1H), 4.13 (dd, J = 11.6, 3.5 Hz, 2H), 3.96 (d, J = 13.3 Hz, 1H), 3.70-3.50 (m, 4H), 3.35-3.23 ( m,4H), 3.20-3.10(m,2H), 3.02(t,J=12.8Hz,1H), 2.97–2.86(m,1H), 2.71(s,2H), 2.65–2.56(m,2H) ,2.26(s,2H),2.01(s,3H),1.90(s,1H),1.73(t,J=11.4Hz,2H),1.45(s,2H),1.30-0.99(m,3H), 0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₀ H ₆₄ ClN ₁₀ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1183.3931; measured value, 1183.3931.

Example 11: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)butyryl)piperidin-4-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide (SIAIS230163) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS230163) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS171089). Yellow powder, m=14mg, yield=40%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.74 (s, 1H), 11.67 (s, 1H), 10.99 (s, 1H), 8.63 (s, 1H), 8.57 (d, J = 2.2 Hz, 1H), 8.05 (t, J = 1.9 Hz, 1H), 7.81 (dd, J = 9.2, 2.3 Hz, 1H), 7.68 (d, J = 7.4 Hz, 1H), 7.59–7.50 (m, 5H), 7.39 (d, J = 8.1 Hz, 2H), 7.11 (dd, J = 18.3, 8.8 Hz, 3H), 6.72 (dd, J = 9.0, 2.3 Hz, 1H), 6.40 (d, J = 3.2 Hz, 1H ), 6.25 (d, J = 2.2 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.40-4.30 (m, 2H), 4.22 (d, J = 17.4 Hz, 1H), 3.83 (d,J=13.3Hz,1H),3.63(d,J=13.3Hz,1H), 3.60-3.40(m,4H), 3.35-3.20(m,6H), 3.11(t,J=7.3Hz, 2H), 2.93-2.87(m, 2H), 2.71(s, 2H), 2.67–2.56(m, 1H), 2.45(d, J=5.0Hz, 2H), 2.30(s, 2H), 2.01(s ,3H),1.93-1.77(m,3H),1.70(s,2H),1.44(s,2H),1.20-0.96(m,3H),0.94(s,6H).HRMS(ESI)m/z : Calculated value C ₆₂ H ₆₈ ClN ₁₀ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1211.4244; measured value, 1211.4252.

Example 12: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)hexanoyl)piperidin-4-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide (SIAIS230164) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS230164) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS171091). Yellow powder, m=14mg, yield=39%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.67 (s, 1H), 10.99 (s, 1H), 8.63 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3Hz, 1H), 8.05 (q, J = 2.4 Hz, 1H), 7.81 (dd, J = 9.3, 2.3 Hz, 1H), 7.63 (dd, J = 7.6, 1.2 Hz, 1H), 7.61- 7.49 (m, 4H), 7.39 (dd, J = 8.3, 1.6 Hz, 2H), 7.18-7.06 (m, 3H), 6.71 (dd, J = 9.0, 2.3 Hz, 1H), 6.40 (dd, J = 3.6, 1.8 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.40-4.34 (m, 2H), 4.22 (d, J = 17.4 Hz, 1H), 4.00-3.50 (m, 6H), 3.35-3.10 (m, 6H), 3.07 (t, J = 7.2 Hz, 2H), 2.93-2.89 (m, 2H), 2.70 (s, 2H) ,2.65-2.56(m,1H),2.27(t,J=7.3Hz,4H),2.10-1.90(m,3H),1.88(s,1H),1.72(d,J=14.1Hz,2H), 1.60(t,J=7.3Hz,2H),1.54-1.37(m,6H),1.20-1.00(m,3H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₂ ClN ₁₀ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1239.4557; found value, 1239.4551.

Example 13: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)aminoacetyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide (SIAIS255044) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS230138) and the intermediate prepared according to Scheme 2 (2-(2,6-dioxopiperidin-3-yl) -1-oxoisoindolin-4-yl)aminoacetic acid (SIAIS1204057) was prepared to obtain the target compound (SIAIS255044). Yellow powder, m=12mg, yield=35%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.71 (s, 1H), 11.67 (s, 1H), 11.00 (s, 1H), 9.54 (s, 1H), 8.66 (t, J = 6.1Hz, 1H), 8.58 (d, J = 2.4 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 9.2, 2.4 Hz, 1H), 7.58–7.50 (m, 3H), 7.39 (d, J = 8.1 Hz, 2H), 7.29 (t, J = 7.7 Hz, 1H), 7.15 (d, J = 9.5 Hz, 1H), 7.08 (d, J = 8.2 Hz, 2H), 6.99 ( d, J = 7.4 Hz, 1H), 6.78 (d, J = 8.2 Hz, 1H), 6.72 (dd, J = 9.0, 2.3 Hz, 1H), 6.40 (dd, J = 3.4, 1.9 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.12 (dd, J = 13.2, 5.1 Hz, 1H), 4.38 (d, J = 12.8 Hz, 1H), 4.31 (d, J = 16.8 Hz, 1H), 4.18(dd,J=16.8,3.2Hz,1H),4.09–3.96(m,2H),3.66(d,J=13.4Hz,2H),3.57(s,2H),3.35-3.20(m,4H) ,3.14–2.89(m,4H),2.73(d,J=9.7Hz,2H), 2.65–2.59(m,2H),2.42–2.34(m,1H),2.23(s,2H),2.10-1.90 (m,4H),1.81-1.71(m,2H),1.45(s,2H),1.32-1.03(m,3H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₀ H ₆₅ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1166.4320; measured value, 1166.4320.

Example 14: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)propionyl)piperidin-4-yl)methyl)amino)- Preparation of 3-nitrophenyl)sulfonyl)benzamide (SIAIS255045)

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS230138) and the intermediate intermediate LM (SIAIS1204059) prepared according to Scheme 2 were used as 3-((2-(2,6-二) Oxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)propionic acid was prepared to obtain the target compound (SIAIS255045). Yellow powder, m=8mg, yield=23%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.67 (s, 1H), 11.00 (s, 1H), 8.63 (t, J = 5.9 Hz, 1H), 8.57 (d, J = 2.4Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 9.2, 2.4 Hz, 1H), 7.56 (d, J = 2.6 Hz, 1H), 7.54–7.49 ( m, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.30 (t, J = 7.7 Hz, 1H), 7.14-7.07 (m, 3H), 6.96 (d, J = 7.5 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 6.71 (dd, J = 9.0, 2.3 Hz, 1H), 6.40 (dd, J = 3.4, 1.8 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H) ), 5.11 (dd, J = 13.3, 5.2 Hz, 1H), 4.42 (d, J = 12.9 Hz, 1H), 4.21 (d, J = 17.1 Hz, 1H), 4.11 (d, J = 17.1 Hz, 1H ),3.92-3.88(m,1H),3.64(d,J=13.2Hz,2H),3.55(s,2H),3.39(t,J=7.0Hz,2H),3.31-3.25(m,5H) ,3.17(s,2H),3.02-2.83(m,2H),2.76-2.57(m,5H),2.29(s,2H),2.01(s,3H),1.88(s,1H),1.71(d ,J=12.5Hz,2H),1.44(t,J=6.1Hz,2H),1.19–1.00(m,3H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₁ H ₆₇ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1180.4476; found value, 1180.4477.

Example 15: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)butyryl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide (SIAIS255046) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS230138) and the intermediate LM 4-((2-(2,6-dioxopiperidine- 3-yl)-1-oxoisoindolin-4-yl)amino)butyric acid (SIAIS1204085) was prepared to obtain the target compound (SIAIS255046). Yellow powder, m=12mg, yield=35%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.71 (s, 1H), 11.66 (s, 1H), 11.00 (s, 1H), 9.46 (s, 1H), 8.64 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 9.2, 2.3 Hz, 1H), 7.55 (d, J = 2.7 Hz, 1H), 7.54–7.49 (m, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.28 (t, J = 7.7 Hz, 1H), 7.12 (d, J = 9.4 Hz, 1H), 7.08 ( d,J=8.3Hz,2H), 6.93(d,J=7.4Hz,1H), 6.78(d,J=8.1Hz,1H), 6.72(dd,J=9.0,2.3Hz,1H), 6.41– 6.38 (m, 1H), 6.26 (d, J = 2.2 Hz, 1H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.42 (d, J = 12.9 Hz, 1H), 4.23 (d, J = 17.1Hz, 1H), 4.13 (d, J = 17.1Hz, 1H), 3.88 (d, J = 13.3Hz, 1H), 3.66 (d, J = 13.3Hz, 2H), 3.57 (s, 2H), 3.34–3.22 (m, 5H), 3.15 (t, J = 7.1 Hz, 2H), 3.08 (t, J = 12.6 Hz, 2H), 2.99-2.88 (m, 2H), 2.73 (d, J = 11.1 Hz ,2H),2.65-2.58(m,1H),2.43(s,2H),2.23(s,2H),2.04-1.97(m,3H),1.92-1.85(m,1H),1.80(t,J =7.1Hz,2H),1.72(s,2H),1.45(t,J=6.5Hz,2H),1.16-1.00(m,3H),0.94(s,6H).HRMS(ESI)m/z: Calculated value C ₆₂ H ₆₉ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1194.4633; measured value, 1194.4627.

Example 16: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentanoyl)piperidin-4-yl)methyl)amino)- Preparation of 3-nitrophenyl)sulfonyl)benzamide (SIAIS255047)

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS230138) and 5-((2-(2,6-dioxopiperidin-3-yl )-1-oxoisoindolin-4-yl)amino)pentanoic acid (SIAIS1210133) was prepared to obtain the target compound (SIAIS255047). Yellow powder, m=13mg, yield=37%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 11.01 (s, 1H), 10.15 (s, 1H), 8.63 (t, J = 6.1Hz, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 9.2, 2.4 Hz, 1H), 7.55 (d, J = 2.7 Hz, 1H), 7.54–7.49 (m, 2H), 7.39 (d, J = 8.3 Hz, 2H), 7.28 (t, J = 7.7 Hz, 1H), 7.11 (dd, J = 19.0, 8.9 Hz, 3H), 6.92(d,J=7.4Hz,1H), 6.78–6.69(m,2H), 6.42–6.38(m,1H), 6.25(d,J=2.2Hz,1H), 5.11(dd,J＝13.2, 5.1Hz, 1H), 4.39 (d, J = 13.0 Hz, 1H), 4.23 (d, J = 17.1 Hz, 1H), 4.13 (d, J = 17.1 Hz, 1H), 3.88 (d, J = 13.4 Hz ,1H),3.63(d,J=13.2Hz,2H),3.54(d,J=5.1Hz,2H),3.35-3.23(m,4H),3.23-3.09(m,5H),3.00-2.90( m,2H), 2.71(d,J=11.0Hz,2H), 2.65–2.58(m,1H), 2.40-2.25(m,4H), 2.08–1.95(m,3H), 1.89(s,1H) ,1.71(t,J=14.0Hz,2H),1.59(s,4H),1.44(t,J=6.4Hz,2H),1.20-1.00(m,3H),0.94(s,6H).HRMS( ESI) m/z: calculated value C ₆₃ H ₇₁ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1208.4789; measured value, 1208.4789.

Example 17: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)hexanoyl)piperidin-4-yl)methyl)amino)- Preparation of 3-nitrophenyl)sulfonyl)benzamide (SIAIS255048)

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS230138) and the intermediate LM 6-((2-(2,6-dioxopiperidine- 3-yl)-1-oxoisoindolin-4-yl)amino)hexanoic acid (SIAIS1204061) was prepared to obtain the target compound (SIAIS255048). Yellow powder, m=15mg, yield=42%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.67 (s, 1H), 11.01 (s, 1H), 9.84 (s, 1H), 8.63 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 9.2, 2.3 Hz, 1H), 7.56 (d, J = 2.6 Hz, 1H), 7.55–7.49 (m, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.28 (t, J = 7.7 Hz, 1H), 7.13 (d, J = 9.4 Hz, 1H), 7.09 ( d, J = 8.3 Hz, 2H), 6.93 (d, J = 7.4 Hz, 1H), 6.78–6.69 (m, 2H), 6.40 (t, J = 2.6 Hz, 1H), 6.25 (d, J = 2.2 Hz, 1H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.39 (d, J = 12.9 Hz, 1H), 4.24 (d, J = 17.1 Hz, 1H), 4.13 (d, J = 17.1 Hz, 1H), 3.86 (d, J = 13.3 Hz, 1H), 3.70–3.50 (m, 5H), 3.33–3.22 (m, 4H), 3.19–3.07 (m, 4H), 2.99–2.86 (m, 2H) ),2.78–2.67(m,2H),2.67–2.57(m,1H),2.40-2.20(m,,4H),2.02(d,J=4.1Hz,3H),1.88(s,1H),1.78 –1.65(m,2H),1.56(dt,J=32.1,7.4Hz,4H),1.45(t,J=6.4Hz,2H),1.38(t,J=7.6Hz,2H),1.07(dd, J = 49.2, 11.1 Hz, 3H), 0.94 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₄ H ₇₃ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ ,1222.4946; measured value, 1222.4955 .

Example 18: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)heptanoyl)piperidin-4-yl)methyl)amino)- Preparation of 3-nitrophenyl)sulfonyl)benzamide (SIAIS255049)

With reference to the method of Example 1, the intermediate BINDER (SIAIS230138) and the intermediate LM 7-((2-(2,6-dioxopiperidine- 3-yl)-1-oxoisoindolin-4-yl)amino)heptanoic acid (SIAIS1204063) was prepared to obtain the target compound (SIAIS255049). Yellow powder, m=14mg, yield=39%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 11.01 (s, 1H), 9.80 (s, 1H), 8.64 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 9.2, 2.3 Hz, 1H), 7.59–7.49 (m, 3H), 7.39(d,J=8.2Hz,2H), 7.28(t,J=7.7Hz,1H), 7.11(dd,J=21.0,8.8Hz,3H), 6.93(d,J=7.4Hz,1H), 6.79–6.69 (m, 2H), 6.40 (t, J = 2.6 Hz, 1H), 6.25 (d, J = 2.2 Hz, 1H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.39 (d ,J=12.9Hz,1H), 4.23(d,J=17.1Hz,1H), 4.13(d,J=17.1Hz,1H), 3.86(d,J=13.4Hz,1H), 3.65(d,J = 13.3Hz, 2H), 3.57-3.53(m, 2H), 3.33-3.23(m, 4H), 3.20-3.07(m, 4H), 2.99-2.86(m, 2H), 2.77-2.68(m, 2H) ),2.66-2.56(m,1H),2.30-2.20(m,4H),2.10-2.00(m,3H),,1.89(s,1H),1.71(t,J=15.2Hz,2H),1.58 (t,J=7.3Hz,2H),1.53-1.41(m,4H),1.39–1.28(m,4H),1.07(dd,J=50.1,11.2Hz,3H),0.94(s,6H). HRMS (ESI) m/z: calculated value C ₆₄ H ₇₃ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1236.5102; measured value, 1236.5069.

Example 19: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)aminoacetyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide (SIAIS255144) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151025) prepared according to Scheme 1 (2-(2,6-dioxopiperidine) -3-yl)-1,3-dioxo-isoindolin-4-yl)glycine was prepared to obtain the target compound (SIAIS255144). Yellow powder, m=16mg, yield=47%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.75 (s, 1H), 11.67 (d, J = 5.6 Hz, 1H), 11.10 (s, 1H), 10.46 (s, 1H), 8.75-8.51 ( m, 2H), 8.05 (s, 1H), 7.85-7.80 (m, 1H), 7.67-7.44 (m, 4H), 7.39 (d, J = 8.1 Hz, 2H), 7.22-7.00 (m, 6H) ,6.71(dd,J=9.1,2.2Hz,1H), 6.41(dd,J=3.5,1.9Hz,1H), 6.25(d,J=2.3Hz,1H), 5.15–5.02(m,1H), 4.20-4.10(m,1H),3.85-3.72(m,1H),3.62(d,J=13.1Hz,2H),3.53(s,2H),3.38-3.30(m,2H),3.30-3.20( m,4H),3.14(t,J=10.9Hz,1H),3.01–2.84(m,2H), 2.82–2.64(m,3H), 2.63–2.55(m,2H), 2.32(s,2H) ,2.07–1.93(m,4H),1.84(s,2H),1.79–1.64(m,1H),1.48-1.40(m,2H),1.40-1.10(m,2H),0.94(s,6H) .HRMS(ESI)m/z: calculated value C ₆₀ H ₆₃ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ , 1180.4112; measured value, 1180.4103.

Example 20: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propionyl)piperidin-3-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255138) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151026) prepared according to Scheme 2 were used as 3-((2-(2,6-dioxo) The target compound (SIAIS255138) was prepared by the preparation of piperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propionic acid. Yellow powder, m=12mg, yield=35%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.67 (s, 1H), 11.09 (d, J = 3.8 Hz, 1H), 8.75-8.51 (m, 2H), 8.05 ( s, 1H), 7.90–7.76 (m, 1H), 7.65–7.48 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.20–7.06 (m, 4H), 7.00 (dd, J = 10.7,7.1Hz,1H),6.84-6.66(m,2H),6.40(s,1H),6.25(s,1H),5.04(ddd,J=12.7,5.5,2.6Hz,1H), 4.20(d ,J=12.9Hz,1H),3.70-3.62(m,3H),3.53(s,4H),3.38–3.15(m,6H),3.06(t,J=11.7Hz,1H),2.94–2.81( m,2H),2.77–2.54(m,5H),2.32(s,2H),2.04–1.96(m,4H),1.82(s,2H),1.65(s,1H),1.44(t,J= 6.4Hz,2H),1.30-1.10(m,2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₁ H ₆₅ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ ,1194.4269 ; Measured value, 1194.4271.

Example 21: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyryl)piperidin-3-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255139) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151019) 4-((2-(2,6-dioxo) prepared according to Scheme 1 were used under appropriate conditions understood in the art. Piperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butanoic acid was prepared to obtain the target compound (SIAIS255139). Yellow powder, m=10mg, yield=28%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.71 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 8.77-8.52 (m, 2H), 8.04 (d, J = 2.6 Hz,1H),7.90–7.80(m,1H), 7.64–7.48(m,4H), 7.47–7.35(m,2H), 7.26–7.04(m,4H), 7.00(dd,J=7.0,4.7 Hz,1H), 6.77–6.59(m,2H), 6.40(s,1H), 6.33–6.15(m,1H), 5.12–4.93(m,1H), 4.14(t,J=16.3Hz,1H) ,3.70-3.40(m,4H),3.32-3.25(m,6H),3.21-3.06(m,3H),2.90-2.86m,2H),2.75-2.62(m,3H),2.58(d,J =18.9Hz,1H),2.42-2.35(m,2H),2.27(s,2H),2.01(s,4H),1.85-1.72(m,4H),1.66(s,1H),1.45(t, J=6.3Hz,2H),1.30-1.10(m,2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₂ H ₆₇ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ ,1208.4425; measured value,1208.4416.

Example 22: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)piperidin-3-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255141) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151027) 6-((2-(2,6-dioxo) prepared according to Scheme 1 were used. Piperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoic acid was prepared to obtain the target compound (SIAIS255141). Yellow powder, m=12mg, yield=34%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 10.17 (s, 1H), 8.70-8.52 (m, 2H), 8.04(d,J=2.6Hz,1H), 7.85–7.80(m,1H), 7.62–7.48(m,4H), 7.39(d,J=8.5Hz,2H), 7.19–6.97(m,5H) ,6.71(d,J=7.9Hz,1H),6.51(d,J=21.5Hz,1H),6.40(d,J=1.5Hz,1H),6.29–6.20(m,1H),5.04(dd, J = 12.7, 5.4 Hz, 1H), 4.13 (t, J = 13.7 Hz, 1H), 3.80-3.60 (m, 3H), 3.54 (s, 2H), 3.34-3.13 (m, 8H), 2.97-2.82 (m,2H),2.77-2.54(m,4H),2.34-2.21(m,4H),2.01(s,4H),1.81(s,1H),1.75-1.42(m,7H),1.40-1.19 (m,4H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₁ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ , 1236.4738; measured value, 1236.4701.

Example 23: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoyl)piperidin-3-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255142) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151086) 7-((2-(2,6-dioxo) prepared according to Scheme 1 were used under appropriate conditions. Piperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoic acid was prepared to obtain the target compound (SIAIS255142). Yellow powder, m=12mg, yield=33%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 8.72-8.51 (m, 2H), 8.04 (s, 1H), 7.88–7.77(m,1H), 7.63–7.48(m,4H), 7.42–7.32(m,2H), 7.21–6.96(m,6H), 6.71(d,J=8.9Hz,1H), 6.51( s, 1H), 6.40 (s, 1H), 6.29-6.21 (m, 1H), 5.04 (dd, J = 12.8, 5.4 Hz, 1H), 4.13 (t, J = 15.1 Hz, 1H), 3.80-3.60 (m, 3H), 3.54 (s, 2H), 3.32-3.04 (m, 8H), 2.95-2.83 (m, 2H), 2.78-2.55 (m, 4H), 2.35-2.15 (m, 4H), 2.06 –1.94(m,4H),1.81(s,1H),1.71(d,J=47.2Hz,2H),1.60–1.18(m,12H),0.94(s,6H).HRMS(ESI)m/z : Calculated value C ₆₅ H ₇₃ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ , 1250.4895; measured value, 1250.4885.

Example 24: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)octanoyl)piperidin-3-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255143) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151183) 8-((2-(2,6-dioxo) prepared according to Scheme 1 were used under appropriate conditions. Piperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)octanoic acid was prepared to obtain the target compound (SIAIS255143). Yellow powder, m=12mg, yield=33%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 10.21 (s, 1H), 8.75-8.47 (m, 2H), 8.05(d,J=2.6Hz,1H), 7.85–7.80(m,1H), 7.60–7.45(m,4H), 7.39(d,J=8.5Hz,2H), 7.20–6.94(m,5H) ,6.71(d,J=8.9Hz,1H),6.40(dd,J=3.4,1.9Hz,1H),6.25(s,1H),5.04(dd,J=12.8,5.4Hz,1H), 4.20- 3.90 (m, 3H), 3.65-3.60 (m, 3H), 3.54 (s, 2H), 3.30-3.15 (m, 8H), 2.94-2.81 (m, 2H), 2.76-2.54 (m, 4H), 2.33-2.25(m,4H),2.01(s,4H),1.81(s,1H),1.76-1.61(m,2H),1.60-1.12(m,14H),0.94(s,6H).HRMS( ESI) m/z: calculated value C ₆₆ H ₇₅ ClN ₁₁ O ₁₁ S ⁺ [M+H] ⁺ , 1264.5051; measured value, 1264.5049.

Example 25: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)acetyl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255145) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS255145) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151045). Yellow powder, m=10mg, yield=29%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.74 (s, 1H), 11.66 (s, 1H), 11.13 (s, 1H), 10.42 (s, 1H), 8.64 (s, 1H), 8.56 ( t,J=2.4Hz,1H),8.05(s,1H),7.89–7.71(m,3H), 7.67–7.46(m,4H),7.45–7.34(m,2H), 7.09(d,J= 8.1Hz,3H), 6.78–6.66(m,1H), 6.43–6.36(m,1H), 6.25(d,J=2.3Hz,1H), 5.12(dd,J=12.9,5.4Hz,1H), 4.25(d,J=9.2Hz,2H),4.20-3.80(m,2H),3.63(d,J=13.2Hz,2H),3.54(s,2H),3.37–3.19(m,6H),3.04 --2.84(m,2H),2.77–2.65(m,3H), 2.65–2.55(m,1H), 2.32(s,2H), 2.10–1.96(m,4H), 1.89–1.72(m,2H) ,1.44(t,J=6.4Hz,3H),1.32(s,2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₀ H ₆₂ ClN ₁₀ O ₁₁ S ₂ ⁺ [M +H] ⁺ ,1197.3724; measured value,1197.3711.

Example 26: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)propionyl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255146) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS255146) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151138). Yellow powder, m=13mg, yield=37%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.67 (s, 1H), 11.12 (s, 1H), 10.32 (s, 1H), 8.74-8.54 (m, 2H), 8.05(dd,J=6.5,2.6Hz,1H), 7.84–7.70(m,3H), 7.68–7.46(m,4H), 7.39(d,J=8.4Hz,2H), 7.22–7.05(m, 3H), 6.71(dd,J=9.1,2.8Hz,1H), 6.46–6.37(m,1H), 6.25(d,J=2.5Hz,1H), 5.11(dd,J=12.9,5.4Hz,1H ), 4.15(t,J=14.7Hz,1H),3.73-3.58(m,3H),3.54(d,J=5.0Hz,2H),3.37–3.18(m,8H),2.96–2.83(m, 2H), 2.80--2.64(m,5H), 2.61-2.57(m,1H), 2.31(s,2H), 2.12--1.95(m,4H), 1.87--1.72(m,2H), 1.66(d, J = 11.7Hz, 1H), 1.50-1.39 (m, 2H), 1.35-1.20 (m, 2H), 0.94 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₁ H ₆₄ ClN ₁₀ O ₁₁ S ₂ ⁺ [M+H] ⁺ ,1211.3880; measured value,1211.3874.

Example 27: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)butyryl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255147) preparation

With reference to the method of Example 1, the target compound (SIAIS255147) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151139) under appropriate conditions understandable in the art. Yellow powder, m=15mg, yield=42%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.75 (s, 1H), 11.67 (s, 1H), 11.12 (s, 1H), 10.48 (s, 1H), 8.73-8.53 (m, 2H), 8.05(d,J=2.6Hz,1H), 7.93–7.75(m,3H), 7.66–7.48(m,4H), 7.43–7.34(m,2H), 7.19–7.07(m,3H), 6.71( dd, J = 8.9, 2.2 Hz, 1H), 6.41 (dd, J = 3.4, 1.9 Hz, 1H), 6.26 (d, J = 2.6 Hz, 1H), 5.11 (dd, J = 12.9, 5.4 Hz, 1H) ), 4.20-4.10 (m, 2H), 3.71-3.58 (m, 3H), 3.54 (d, J = 5.0 Hz, 2H), 3.30-3.20 (m, 6H), 3.18-3.06 (m, 3H), 2.96–2.83(m,2H),2.75-2.65(m,3H), 2.63–2.56(m,1H), 2.33(s,2H), 2.11–1.95(m,4H),1.90-1.80(m,4H) ), 1.72-1.64 (m, 1H), 1.48-1.42 (m, 2H), 1.35-1.25 (m, 2H), 0.94 (s, 6H).HRMS (ESI) m/z: calculated value C ₆₂ H ₆₆ ClN ₁₀ O ₁₁ S ₂ ⁺ [M+H] ⁺ , 1225.4037; measured value, 1225.4044.

Example 28: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)pentanoyl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255148) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS255148) is prepared by using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151140). Yellow powder, m=15mg, yield=42%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.74 (s, 1H), 11.66 (s, 1H), 11.12 (s, 1H), 10.36 (s, 1H), 8.70-8.55 (m, 2H), 8.05(d,J=2.4Hz,1H), 7.85–7.66(m,3H), 7.63–7.47(m,4H), 7.39(d,J=8.5Hz,2H), 7.25–7.04(m,3H) ,6.71(dt,J=9.4,3.0Hz,1H), 6.40(dd,J=3.4,1.9Hz,1H), 6.25(dd,J=6.5,2.3Hz,1H), 5.11(dd,J=12.8 ,5.5Hz,1H), 4.20-4.10 (m, 2H), 3.80-3.60 (m, 3H), 3.54 (s, 2H), 3.30-3.20 (m, 6H), 3.18-3.06 (m, 3H), 2.94-2.85(m, 2H), 2.70- 2.65(m, 3H), 2.64-2.56(m, 1H), 2.42-2.34(m, 2H), 2.34-2.24(m, 2H), 2.10-1.95(m ,4H),1.85-1.79(m,1H),1.74-1.59(m,6H),1.44(t,J=6.4Hz,2H),1.29-1.23(m,2H),0.94(s,6H). HRMS (ESI) m/z: calculated value C ₆₃ H ₆₈ ClN ₁₀ O ₁₁ S ₂ ⁺ [M+H] ⁺ , 1239.4193; measured value, 1239.4200.

Example 29: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)hexanoyl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255149) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS255149) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151141). Yellow powder, m=16mg, yield=44%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.66 (s, 1H), 11.12 (s, 1H), 10.28 (s, 1H), 8.72-8.54 (m, 2H), 8.05(d,J=2.5Hz,1H), 7.89–7.68(m,3H), 7.64–7.49(m,4H), 7.39(d,J=8.1Hz,2H), 7.20–7.02(m,3H) , 6.71 (dd, J = 8.9, 2.2 Hz, 1H), 6.40 (dd, J = 3.4, 1.8 Hz, 1H), 6.25 (t, J = 2.8 Hz, 1H), 5.11 (dd, J = 12.9, 5.4 Hz,1H),4.13(t,J=12.8Hz,2H),3.70-3.60(m,3H),3.54(s,2H),3.32-3.20(m,6H),3.16-3.03(m,3H) ,2.94-2.83(m,2H),2.76-2.65(m,3H),2.63-2.56(m,1H),2.37-2.23(m,4H),2.09-1.96(m,4H),1.81(s, 1H),1.70-1.58(m,4H),1.56--1.25(m,8H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₀ ClN ₁₀ O ₁₁ S ₂ ⁺ [ M+H] ⁺ ,1253.4350; measured value,1253.4356.

Example 30: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)heptanoyl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255150) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS255150) was prepared by using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS151142). Yellow powder, m=12mg, yield=33%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 11.12 (s, 1H), 10.00 (s, 1H), 8.72-8.51 (m, 2H), 8.04(d,J=2.6Hz,1H),7.92-7.70(m,3H),7.66-7.48(m,4H),7.39(d,J=8.3Hz,2H),7.22-7.05(m,3H) ,6.71(dd,J=8.9,2.2Hz,1H),6.40(dd,J=3.4,1.9Hz,1H),6.33-6.20(m,1H),5.11(dd,J=12.9,5.4Hz,1H ), 4.13 (t, J = 14.8 Hz, 1H), 3.80-3.60 (m, 5H), 3.55 (s, 2H), 3.35-3.04 (m, 8H), 2.92-2.85 (m, 2H), 2.76- 2.64(m,3H),2.63-2.56(m,1H),2.33-2.21(m,4H),2.09-1.97(m,4H),1.82(s,1H),1.73-1.57(m,4H), 1.54–1.29(m,10H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₅ H ₇₂ ClN ₁₀ O ₁₁ S ₂ ⁺ [M+H] ⁺ ,1267.4506; measured value, 1267.4503 .

Example 31: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)acetyl)piperidin-3-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide (SIAIS255151) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS255151) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS171090). Yellow powder, m=18mg, yield=52%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.76 (s, 1H), 11.67 (s, 1H), 10.99 (s, 1H), 10.52 (s, 1H), 8.63 (t, J = 5.4 Hz, 1H),8.61–8.52(m,1H),8.06(t,J=2.7Hz,1H),7.85-7.80(m,1H),7.74-7.45(m,6H),7.39(d,J=8.0Hz ,2H), 7.24–7.05(m,3H), 6.75–6.63(m,1H), 6.41(dd,J=3.3,1.8Hz,1H), 6.25(dd,J=7.7,2.2Hz,1H), 5.13 (dd, J = 13.2, 4.7 Hz, 1H), 4.44–4.07 (m, 5H), 3.84 (dd, J = 65.9, 13.5 Hz, 1H), 3.63 (d, J = 13.4 Hz, 2H), 3.53 (s, 2H), 3.35-3.24 (m, 6H), 2.98-2.86 (m, 2H), 2.76-2.64 (m, 3H), 2.64-2.55 (m, 1H), 2.33 (s, 2H), 2.05 –1.94(m,4H),1.86–1.64(m,3H),1.44(t,J=6.4Hz,2H),1.35-1.20(m,2H),0.94(s,6H).HRMS(ESI)m /z: Calculated value C ₆₀ H ₆₄ ClN ₁₀ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1183.3931; measured value, 1183.3932.

Example 32: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)propionyl)piperidin-3-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide (SIAIS255152) preparation

With reference to the method of Example 1, the target compound (SIAIS255152) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS171086) under appropriate conditions understandable in the art. Yellow powder, m=15mg, yield=43%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.75 (s, 1H), 11.67 (s, 1H), 10.99 (s, 1H), 10.40 (s, 1H), 8.69-8.54 (m, 2H), 8.06(q,J=2.7Hz,1H), 7.84–7.77(m,1H), 7.70–7.46(m,6H), 7.41–7.35(m,2H), 7.17–7.07(m,3H), 6.71( td,J=6.9,3.5Hz,1H), 6.46–6.39(m,1H), 6.31–6.20(m,1H), 5.12(dd,J＝13.3,5.1Hz,1H), 4.38–4.12(m, 3H),3.62(d,J=13.2Hz,3H),3.53(s,2H),3.39–3.17(m,8H),3.10–2.82(m,2H),2.75-2.65(m,5H),2.59 (d,J=17.8Hz,1H),2.32(s,2H),2.04–1.94(m,4H),1.86–1.71(m,2H),1.69–1.61(m,1H),1.44(t,J =6.4Hz, 2H), 1.27 (t, J = 10.6Hz, 2H), 0.94 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₁ H ₆₆ ClN ₁₀ O ₁₀ S ₂ ⁺ [M+ H] ⁺ ,1197.4088; measured value, 1197.4093.

Example 33: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)butyryl)piperidin-3-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide (SIAIS255153) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS255153) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS171089). Yellow powder, m=11mg, yield=31%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.74 (s, 1H), 11.66 (s, 1H), 10.99 (s, 1H), 10.34 (s, 1H), 8.73-8.52 (m, 2H), 8.05(d,J=2.6Hz,1H), 7.85–7.80(m,1H), 7.71–7.59(m,1H), 7.60–7.47(m,5H), 7.43–7.37(m,2H), 7.20– 7.07 (m, 3H), 6.70 (ddd, J = 8.5, 6.1, 2.2 Hz, 1H), 6.40 (dd, J = 3.4, 1.8 Hz, 1H), 6.31-6.23 (m, 1H), 5.22-5.06 ( m, 1H), 4.35 (dd, J = 17.4, 3.8 Hz, 1H), 4.25-4.15 (m, 2H), 3.63 (d, J = 13.2 Hz, 3H), 3.53 (s, 2H), 3.26 (q ,J=13.0,12.2Hz,6H),3.15-3.05(m,2H),2.95-2.84(m,2H),2.68(dt,J=23.0,7.6Hz,3H),2.64-2.54(m,1H) ),2.47–2.41(m,2H),2.32(s,2H),2.05–1.95(m,4H),1.85-1.75(m,4H),1.64(s,1H),1.44(t,J=6.4 Hz, 2H), 1.27 (d, J = 9.7 Hz, 2H), 0.94 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₂ H ₆₈ ClN ₁₀ O ₁₀ S ₂ ⁺ [M+H] ⁺ ,1211.4244; measured value,1211.4270.

Example 34: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)pentanoyl)piperidin-3-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide (SIAIS255154) preparation

With reference to the method of Example 1, the target compound (SIAIS255154) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS171079) under appropriate conditions understandable in the art. Yellow powder, m=15mg, yield=42%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.75 (s, 1H), 11.67 (s, 1H), 10.99 (s, 1H), 10.52 (d, J = 81.4 Hz, 1H), 8.75-8.54 ( m, 2H), 8.05 (d, J = 2.4 Hz, 1H), 7.85-7.80 (m, 1H), 7.67-7.45 (m, 6H), 7.44-7.35 (m, 2H), 7.21-7.06 (m, 3H), 6.70 (ddd, J = 8.9, 6.3, 2.3 Hz, 1H), 6.41 (dd, J = 3.4, 1.9 Hz, 1H), 6.35-6.19 (m, 1H), 5.12 (dd, J = 13.3, 5.1Hz, 1H), 4.47--4.14 (m, 3H), 3.65-3.54 (m, 5H), 3.35-3.20 (m, 6H), 3.12-3.00 (m, 2H), 2.92-2.88 (m 1H), 2.74–2.63(m,3H), 2.63–2.55(m,1H), 2.49–2.41(m,1H), 2.38-2.25(m,4H), 2.05-1.95(m,4H), 1.81(s,1H) ),1.72-1.53(m,6H),1.44(t,J=6.4Hz,2H),1.30-1.20(m,2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₇₀ ClN ₁₀ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1225.4401; found value, 1225.4410.

Example 35: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)hexanoyl)piperidin-3-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide (SIAIS255155) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS255155) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS171091). Yellow powder, m=15mg, yield=42%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.76 (s, 1H), 11.67 (s, 1H), 10.99 (s, 1H), 10.42 (s, 1H), 8.71-8.54 (m, 2H), 8.06(t,J=2.6Hz,1H),7.85-7.80(m,1H),7.66-7.50(m,6H),7.39(d,J=8.2Hz,2H),7.21-7.03(m,3H) ,6.78–6.67(m,1H),6.41(dd,J＝3.4,1.9Hz,1H), 6.25 (dd,J＝4.7,2.3Hz,1H), 5.12(dd,J＝13.3,5.1Hz,1H) ), 4.40-4.20 (m, 3H), 3.80-3.50 (m, 3H), 3.53 (s, 2H), 3.41--3.20 (m, 6H), 3.10-3.00 (m, 2H), 2.95-2.85 (m ,1H), 2.75–2.63(m,3H), 2.59(d,J=17.9,1H), 2.49–2.41(m,1H), 2.38–2.19(m,4H), 2.05–1.94(m,J= 2.8,2.3Hz,4H),1.81(s,1H),1.74-1.56(m,3H),1.56-1.24(m,9H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₂ ClN ₁₀ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1239.4557; found value, 1239.4564.

Example 36: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)heptanoyl)piperidin-3-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide (SIAIS255156) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS255156) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS171092). Yellow powder, m=13mg, yield=36%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 10.98 (s, 1H), 9.96 (s, 1H), 8.70-8.43 (m, 2H), 8.04(d,J=2.6Hz,1H), 7.85–7.80(m,1H), 7.68–7.46(m,6H), 7.45–7.33(m,2H), 7.19–7.05(m,3H), 6.71( dd,J=9.0,2.5Hz,1H), 6.40(dd,J=3.4,1.8Hz,1H), 6.28–6.15(m,1H), 5.12(dd,J=13.3,5.1Hz,1H), 4.34 (dd,J=17.4,2.1Hz,1H),4.22(s,1H),4.12(t,J=15.5Hz,1H), 3.76(d,J=13.2Hz,2H),3.55(s,2H) ,3.34-3.22(m,4H), 3.20-3.15(m,2H), 3.10-3.00(m,3H), 2.92-2.88(m,1H), 2.72-2.65(m,3H), 2.63-2.56( m,1H), 2.50-2.42(m,1H), 2.30-2.20(m,4H), 2.04-1.94(m,4H), 1.81(s,1H), 1.73-1.52(m,4H), 1.48-- 1.23(m,10H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₅ H ₇₄ ClN ₁₀ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1253.4714; measured value, 1253.4762.

Example 37: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)aminoacetyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide (SIAIS255157) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS1204057) prepared according to Scheme 2 (2-(2,6-dioxopiperidine- 3-yl)-1-oxoisoindolin-4-yl)aminoacetic acid was prepared to obtain the target compound (SIAIS255157). Yellow powder, m=10mg, yield=30%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.74 (s, 1H), 11.66 (s, 1H), 10.99 (s, 1H), 10.29 (s, 1H), 8.72-8.54 (m, 2H), 8.05(t,J=2.3Hz,1H),7.85-7.80(m,1H),7.63-7.46(m,3H),7.39(d,J=8.0Hz,2H),7.32-7.17(m,2H) ,7.10(t,J=7.8Hz,3H), 6.97(d,J=7.4Hz,1H), 6.74(dd,J=36.9,8.2Hz,2H), 6.48–6.38(m,1H), 6.25( d, J = 2.2Hz, 1H), 5.11 (dd, J = 13.2, 5.1 Hz, 1H), 4.29 (d, J = 17.0 Hz, 1H), 4.24-3.75 (m, 6H), 3.63 (d, J = 13.4Hz, 2H), 3.54(s, 2H), 3.35–3.17(m, 6H), 2.99–2.87(m, 1H), 2.73(dd, J = 12.6, 9.2Hz, 3H), 2.64–2.56( m,1H), 2.41–2.25(m,2H), 2.05–1.93(m,4H), 1.89–1.66(m,3H), 1.44(t,J=6.5Hz,2H), 1.36–1.26(m, 2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₀ H ₆₅ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1166.4320; measured value, 1166.4388.

Example 38: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)butyryl)piperidin-3-yl)methyl)amino)- Preparation of 3-nitrophenyl)sulfonyl)benzamide (SIAIS255158)

With reference to the method of Example 1, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS1204085) 4-((2-(2,6-dioxo) prepared according to Scheme 2 were used under appropriate conditions understandable in the art. Piperidin-3-yl)-1-oxoisoindolin-4-yl)amino)butyric acid was prepared to obtain the target compound (SIAIS255158). Yellow powder, m=12mg, yield=35%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.74 (s, 1H), 11.67 (s, 1H), 11.00 (s, 1H), 10.30 (s, 1H), 8.71-8.53 (m, 2H), 8.05(d,J=2.5Hz,1H),7.94–7.73(m,1H),7.57–7.47(m,3H),7.43–7.35(m,2H),7.33–7.25(m,1H),7.10( t,J=7.9Hz,3H),6.94(s,1H),6.85-6.67(m,2H),6.41(q,J=1.9,1.4Hz,1H),6.31-6.23(m,1H),5.11 (dd,J=13.2,4.9Hz,1H), 4.28–4.08(m,4H), 3.82–3.61(m,3H),3.54(s,2H), 3.35–3.06(m,8H),2.96-2.85 (m,1H), 2.76–2.58(m,4H), 2.47–2.39(m,2H), 2.35–2.26(m,2H), 2.08–1.94(m,4H), 1.79(dd,J=17.3, 9.9Hz,4H),1.66(s,1H),1.44(t,J=6.4Hz,2H),1.28(d,J=9.3Hz,2H),0.94(s,6H).HRMS(ESI)m/ z: Calculated value C ₆₂ H ₆₉ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1194.4633; measured value, 1194.4645.

Example 39: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentanoyl)piperidin-3-yl)methyl)amino)- Preparation of 3-nitrophenyl)sulfonyl)benzamide (SIAIS255159)

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS1210133) prepared according to Scheme 2 were used to 5-((2-(2,6-dioxo) Piperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentanoic acid was prepared to obtain the target compound (SIAIS255159). Yellow powder, m=13mg, yield=37%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.77 (s, 1H), 11.68 (s, 1H), 11.01 (s, 1H), 10.44 (s, 1H), 8.70-8.53 (m, 2H), 8.07 (dt, J = 4.8, 2.3 Hz, 1H), 7.83 (ddd, J = 17.5, 9.1, 2.3 Hz, 1H), 7.62-7.49 (m, 3H), 7.45-7.34 (m, 2H), 7.29 ( d,J=8.0Hz,1H),7.25-7.08(m,3H),6.96(s,1H),6.80(s,1H),6.70(td,J=9.0,2.2Hz,1H),6.42(ddd ,J=5.1,3.4,1.7Hz,1H), 6.31–6.17(m,1H), 5.11(dd,J=13.2,5.1Hz,1H), 4.25(d,J=16.6Hz,1H), 4.15( d, J = 15.1Hz, 2H), 3.84–3.58 (m, 3H), 3.53 (s, 2H), 3.27 (dd, J = 17.0, 9.0 Hz, 6H), 3.18–3.02 (m, 3H), 2.92 (ddd,J=17.6,13.7,5.5Hz,1H), 2.74–2.58(m,4H), 2.38–2.27(m,4H), 2.06–1.95(m,4H), 1.82(s,1H), 1.74 –1.51(m,6H),1.44(t,J=6.5Hz,2H),1.31-1.25(m,2H),0.94(s,6H).HRMS(ESI) m/z: calculated value C ₆₃ H ₇₁ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1208.4789; measured value, 1208.4811.

Example 40: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)hexanoyl)piperidin-3-yl)methyl)amino)- Preparation of 3-nitrophenyl)sulfonyl)benzamide (SIAIS255160)

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS1204061) 6-((2-(2,6-dioxo) prepared according to Scheme 2 were used. Piperidin-3-yl)-1-oxoisoindolin-4-yl)amino)hexanoic acid was prepared to obtain the target compound (SIAIS255160). Yellow powder, m=13mg, yield=37%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.84 (s, 1H), 11.69 (s, 1H), 11.01 (s, 1H), 10.79 (s, 1H), 8.71-8.51 (m, 2H), 8.10–8.01 (m, 1H), 7.83 (ddd, J = 18.3, 9.2, 2.3 Hz, 1H), 7.65–7.57 (m, 1H), 7.57–7.49 (m, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.31 (s, 1H), 7.20-7.07 (m, 3H), 7.01 (d, J = 18.0 Hz, 1H), 6.83 (s, 1H), 6.75-6.67 (m, 1H), 6.42 (s, 1H), 6.27 (s, 1H), 5.11 (dd, J = 13.2, 5.1 Hz, 1H), 4.35-4.09 (m, 3H), 3.80-3.58 (m, 3H), 3.53 (s, 2H) ), 3.27(dd,J=17.7,9.3Hz,6H), 3.16–3.03(m,3H), 2.98–2.81(m,1H), 2.76–2.56(m,4H), 2.40-2.20(m,4H) ),2.06–1.93(m,4H),1.86–1.20(m,13H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₃ ClN ₁₁ O ₁₀ S ⁺ (M+ H] ⁺ ,1222.4946; measured value,1222.4974.

Example 41: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)heptanoyl)piperidin-3-yl)methyl)amino)- Preparation of 3-nitrophenyl)sulfonyl)benzamide (SIAIS255161)

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS1204063) 7-((2-(2,6-dioxo) prepared according to Scheme 2 were used under appropriate conditions. Piperidin-3-yl)-1-oxoisoindolin-4-yl)amino)heptanoic acid was prepared to obtain the target compound (SIAIS255161). Yellow powder, m=13mg, yield=36%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.81 (s, 1H), 11.69 (s, 1H), 11.01 (s, 1H), 10.70 (s, 1H), 8.68-8.53 (m, 2H), 8.07(s,1H),7.82(ddd,J=17.7,9.2,2.3Hz,1H), 7.63–7.47(m,3H),7.44–7.35(m,2H),7.30(s,1H),7.19– 7.05 (m, 3H), 7.00 (s, 1H), 6.83 (s, 1H), 6.71 (dt, J = 9.1, 2.8 Hz, 1H), 6.49-6.39 (m, 1H), 6.26 (s, 1H) , 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.29 (d, J = 16.4 Hz, 1H), 4.23-4.06 (m, 2H), 3.83-3.58 (m, 3H), 3.53 (d, J =4.8Hz,2H), 3.35-3.20(m,6H),3.15-3.08(m,3H),2.99–2.86(m,1H),2.75–2.57(m,4H),2.38–2.15(m,4H) ),2.08–1.92(m,4H),1.87–1.19(m,15H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₅ H ₇₅ ClN ₁₁ O ₁₀ S ⁺ (M+ H] ⁺ , 1236.5102; measured value, 1236.5119.

Example 42: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-4-yl)pent-4-yn-1-yl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255124) preparation

According to the synthetic strategy of Scheme 16: Intermediate BINDER (SIAIS230138) (25mg, 0.029mmol) was dissolved in 2mL DMF, and intermediate LM (SIAIS255121) (11.7mg, 0.029mmol), NaI (8.7mg, 0.058mmol) were added in sequence And K ₂ CO ₃ (8.0 mg, 0.058 mmol), heat to 50° C., and react overnight. Add 0.10mL of water to quench the reaction, HPLC preparation and separation (eluent (v/v): acetonitrile/(water+0.05%HCl)=10%-100%), evaporate acetonitrile and most of water under reduced pressure, and freeze-dry Then the final target compound (SIAIS255124) was obtained. Yellow powder, m=12mg, yield=35%

¹ H NMR(500MHz, methanol-d ₄ )δ8.63(d,J=2.3Hz,1H), 8.17(s,1H), 7.96(d,J=2.3Hz,1H), 7.89(dd,J= 9.2,2.3Hz,1H),7.72(dd,J=7.7,1.0Hz,1H),7.66-7.56(m,3H),7.48(t,J=7.7Hz,1H),7.39-7.32(m,2H ), 7.15–7.02 (m, 3H), 6.80 (dd, J = 8.9, 2.3 Hz, 1H), 6.63 (d, J = 3.5 Hz, 1H), 6.49 (d, J = 2.3 Hz, 1H), 5.15 (dd,J=13.3,5.1Hz,1H), 4.62–4.45(m,2H), 3.81–3.62(m,6H), 3.48-3.38(m,4H), 3.29–3.17(m,3H), 3.04 (t,J=12.9Hz,2H), 2.95–2.73(m,4H), 2.66(t,J=6.8Hz,2H), 2.60–2.48(m,1H), 2.33(s,2H), 2.24– 1.99(m,7H),1.68(t,J=13.2Hz,2H),1.57(t,J=6.3Hz,2H),1.37–1.28(m,2H),1.01(s,6H).HRMS(ESI ) m/z: calculated value C ₆₃ H ₆₈ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1175.4574; measured value, 1175.4577.

Example 43: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255126) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS255126) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS255119). Yellow powder, m=4.0mg, yield=12%

¹ H NMR(500MHz, methanol-d ₄ )δ8.65(d,J=2.2Hz,1H),8.11(s,1H),7.89(dd,J=9.1,2.3Hz,1H),7.82(d, J = 2.0Hz, 1H), 7.72 (dd, J = 7.6, 0.9 Hz, 1H), 7.65–7.59 (m, 2H), 7.56 (d, J = 3.2 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.35 (d, J = 7.9 Hz, 2H), 7.06 (dd, J = 17.4, 8.6 Hz, 3H), 6.79 (d, J = 8.7 Hz, 1H), 6.55 (d, J = 3.4 Hz, 1H), 6.43 (s, 1H), 5.15 (dd, J = 13.2, 5.1 Hz, 1H), 4.50 (q, J = 17.5 Hz, 2H), 3.74-3.60 (m, 6H), 3.47–3.37 (m,4H), 3.24–3.14(m,3H),3.03–2.95(m,2H), 2.92–2.72(m,4H), 2.60(t,J=6.7Hz,2H), 2.57–2.47(m ,1H),2.32(s,2H),2.24-2.14(m,1H),2.14-2.02(m,4H),2.02-1.96(m,2H),1.71(t,J=7.5Hz,2H), 1.64(d,J=13.2Hz,2H),1.56(t,J=6.3Hz,2H),1.36--1.30(m,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₀ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1189.4731; found value, 1189.4725.

Example 44: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)piperidin-4-yl)methyl)amino)-3-nitro Phenyl)sulfonyl)benzamide (SIAIS255132) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS255132) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS255130). Yellow powder, m=7.0mg, yield=21%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.09(d,J=2.5Hz,1H), 7.91(dd,J=9.3,2.3Hz,1H) ,7.78(d,J=2.3Hz,1H),7.69–7.61(m,2H),7.59–7.54(m,1H),7.53–7.46(m,2H),7.40–7.35(m,2H),7.14 –7.03(m,3H), 6.81(dd,J=9.0,2.4Hz,1H), 6.54(d,J=3.5Hz,1H), 6.44(d,J=2.4Hz,1H), 5.18(dd, J = 13.4, 5.1 Hz, 1H), 4.59–4.42(m, 2H), 3.78–3.64(m, 4H), 3.64–3.56(m, 2H), 3.47–3.38(m, 4H), 3.21–3.08( m, 4H), 2.97–2.86 (m, 3H), 2.86–2.72 (m, 4H), 2.52 (dd, J = 13.1, 4.6 Hz, 1H), 2.30 (s, 2H), 2.22–2.15 (m, 1H), 2.12 (s, 2H), 2.06 (d, J = 14.1Hz, 2H), 1.78 (s, 4H), 1.57 (t, J = 6.4 Hz, 4H), 1.35-1.25 (m, 2H), 1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₂ H ₇₀ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1165.4731; measured value, 1165.4732.

Example 45: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)piperidin-3-yl)methyl)amino)-3-nitro Phenyl)sulfonyl)benzamide (SIAIS255134) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS255134) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS255130). Yellow powder, m=9mg, yield=27%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.70–8.64 (m, 1H), 8.12 (d, J = 2.3 Hz, 1H), 7.93 (dd, J = 9.2, 2.3 Hz, 1H), 7.88 ( d, J = 2.5Hz, 1H), 7.65–7.58 (m, 3H), 7.48–7.42 (m, 2H), 7.41–7.35 (m, 2H), 7.09 (dd, J = 8.7, 6.5 Hz, 3H) ,6.79(dd,J=9.3,2.0Hz,1H), 6.59(d,J=3.5Hz,1H), 6.46(d,J=2.3Hz,1H),5.22–5.06(m,1H),4.56– 4.38 (m, 2H), 3.80-3.68 (m, 4H), 3.65 - 3.50 (m, 2H), 3.48 - 3.40 (m, 4H), 3.24 - 3.10 (m, 4H), 2.95 - 2.85 (m, 2H) ), 2.83--2.72(m,5H),2.56-2.48(m,1H),2.35-2.25(m,3H),2.23-2.14(m,1H),2.11(s,2H),2.00(t,J =14.0Hz,2H),1.88–1.71(m,5H),1.57(t,J=6.3Hz,2H),1.36-1.28(m,2H),1.01(s,6H).HRMS(ESI)m/ z: Calculated value C ₆₂ H ₇₀ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1165.4731; measured value, 1165.4734.

Example 46: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255135) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS255135) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS255121). Yellow powder, m=10mg, yield=29%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68–8.58(m,1H), 8.10(s,1H), 7.93(ddd,J=9.3,2.3, 1.2Hz,1H), 7.80(s,1H) ), 7.72(dd,J=7.7,1.0Hz,1H),7.65–7.54(m,3H),7.46(t,J=7.6Hz,1H),7.38–7.35(m,2H),7.11–7.05( m, 3H), 6.79 (dt, J = 9.0, 2.4 Hz, 1H), 6.55 (d, J = 3.6 Hz, 1H), 6.44 (s, 1H), 5.15 (dd, J = 13.3, 5.3 Hz, 1H) ), 4.56–4.42(m,2H), 3.76–3.60(m,6H), 3.47-3.40(m,4H), 3.22–3.12(m,2H), 3.00–2.73(m,7H), 2.67–2.61 (m,2H),2.60–2.49(m,1H),2.31(s,2H),2.21–1.98(m,8H),1.91–1.82(m,1H),1.57(t,J=6.4Hz,2H ),1.38–1.30(m,2H),1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₆₈ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ ,1175.4574; measured value, 1175.4599.

Example 47: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS255136) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS255136) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS255119). Yellow powder, m=8.0mg, yield=23%

¹ H NMR(500MHz, methanol-d ₄ )δ8.64(dd,J=2.3,1.5Hz,1H), 8.10(s,1H), 7.98–7.89(m,1H), 7.88–7.74(m,1H ), 7.69(dd,J=7.6,1.1Hz,1H), 7.63(dd,J=8.8,1.2Hz,1H), 7.59–7.55(m,2H),7.45(td,J=7.7,1.6Hz, 1H), 7.36(d,J=8.4Hz,2H), 7.11–7.04(m,3H), 6.79(dd,J=9.0,2.3Hz,1H), 6.56(d,J=3.5Hz,1H), 6.45(s,1H), 5.14(ddd,J=12.8,7.2,5.1Hz,1H), 4.48(dd,J=10.1,4.1Hz,2H),3.73-3.67(m,4H),3.61(dd, J=21.0, 12.1Hz, 2H), 3.48–3.39(m,4H), 3.23–3.14(m,4H), 2.94–2.85(m,2H), 2.84–2.74(m,3H), 2.58(t, J = 6.8Hz, 2H), 2.56–2.46(m,1H), 2.30(s,3H), 2.22–2.15(m,1H), 2.11(s,2H), 2.06–1.95(m,4H), 1.87 (t,J=13.8Hz,1H),1.70(q,J=7.2Hz,2H),1.57(t,J=6.3Hz,2H),1.37–1.28(m,2H),1.01(s,6H) .HRMS(ESI)m/z: calculated value C ₆₄ H ₇₀ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1189.4731; measured value, 1189.4728.

Example 48: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propionyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide (SIAIS255162) preparation

With reference to the method of Example 1, the intermediate BINDER (SIAIS255123) and the intermediate LM (3-(2-(2,6-dioxopiperidin-3-yl)- 1-oxoisoindolin-4-yl)propionic acid) (CAS No. 2229976-18-3) was prepared to obtain the target compound (SIAIS255162). Yellow powder, m=13.0mg, yield=38%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.74 (s, 1H), 11.67 (s, 1H), 10.99 (d, J = 9.4 Hz, 1H), 10.29 (s, 1H), 8.77-8.50 ( m, 2H), 8.05 (dd, J = 5.1, 2.5 Hz, 1H), 7.88–7.71 (m, 1H), 7.53 (tdd, J = 15.1, 13.4, 7.2, 3.2 Hz, 5H), 7.45–7.34 ( m,3H),7.19–7.05(m,3H),6.75–6.66(m,1H), 6.40(dt,J=3.5,1.9Hz,1H), 6.25(dd,J=6.2,2.3Hz,1H) ,5.11(dd,J=13.1,5.1Hz,1H),4.56–4.42(m,1H), 4.34(d,J=17.1Hz,1H), 4.17–3.77(m,2H),3.666-3.60(m ,3H),3.54(s,2H),3.32-3.22(m,6H),2.93-2.83(m,3H),2.76-2.55(m,5H),2.48-2.39(m,1H),2.32(s ,2H),2.05-1.92(m,4H),1.90-1.56(m,3H),1.44(t,J=6.3Hz,2H),1.31-1.22(m,2H),0.94(s,6H). HRMS (ESI) m/z: calculated value C ₆₁ H ₆₆ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1165.4367; measured value, 1165.4365.

Example 49: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)piperidin-4-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS268024) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS268024) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS268007). Yellow powder, m=6.8mg, yield=20%

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(s,1H), 8.07(s,1H), 7.89(d,J=9.0Hz,1H), 7.75(s,1H), 7.62(d, J = 8.7Hz, 1H), 7.57 (t, J = 7.8Hz, 1H), 7.54 (d, J = 3.2Hz, 1H), 7.36 (d, J = 7.8Hz, 2H), 7.14-7.01 (m, 6H), 6.79 (d, J = 8.9 Hz, 1H), 6.52 (d, J = 3.4 Hz, 1H), 6.42 (s, 1H), 5.05 (dd, J = 12.8, 5.4 Hz, 1H), 3.75 3.65 (m, 4H), 3.63 (d, J = 12.1Hz, 2H), 3.48 (t, J = 6.7 Hz, 2H), 3.45-3.37 (m, 4H), 3.25-3.15 (m, 4H), 2.98 (t,J=12.7Hz,2H),2.90–2.64(m,6H),2.31(s,2H),2.16–2.00(m,7H),1.67–1.54(m,4H),1.01(s,6H) ). HRMS (ESI) m/z: calculated value C ₆₁ H ₆₇ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1180.4476; measured value, 1180.4475.

Example 50: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)piperidin-4-yl)methyl) (Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS268027) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS268027) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS264016). Yellow powder, m=5.1mg, yield=15%

¹ H NMR(500MHz, methanol-d ₄ )δ8.69(s,1H),7.99(s,1H),7.90(d,J=9.3Hz,1H), 7.65(d,J=8.8Hz,1H) ,7.58–7.52(m,2H),7.45(d,J=3.4Hz,1H),7.36(d,J=7.3Hz,2H),7.15-6.97(m,6H),6.76(d,J=8.9 Hz, 1H), 6.42 (d, J = 3.5 Hz, 1H), 6.32 (s, 1H), 5.04 (dd, J = 12.7, 5.4 Hz, 2H), 3.75-3.60 (m, 4H), 3.60 (d ,J=12.5Hz,2H), 3.38(d,J=6.2Hz,6H), 3.18–3.06(m,4H), 2.94(t,J=12.7Hz,2H), 2.87–2.67(m,6H) ,2.28(s,2H),2.15-2.00(m,5H),1.85-1.69(m,4H),1.60-1.50(m,6H),1.00(s,6H).HRMS(ESI)m/z: Calculated value C ₆₃ H ₇₁ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1208.4789; measured value, 1208.4822.

Example 51: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS268178) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS268178) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS292020). Yellow powder, m=8.7mg, yield=25%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.08(d,J=2.4Hz,1H), 7.77(d,J=2.4Hz,1H), 7.72 (dd,J=7.6,1.0Hz,1H), 7.64(d,J=8.9Hz,1H), 7.60(dd,J=7.6,1.1Hz,1H), 7.55(d,J=3.4Hz,1H) ,7.49(t,J=7.6Hz,1H),7.36(d,J=8.4Hz,2H),7.12-7.03(m,3H),6.80(dd,J=8.9,2.2Hz,1H),6.53( d, J = 3.5Hz, 1H), 6.43 (d, J = 2.3 Hz, 1H), 5.16 (dd, J = 13.3, 5.1 Hz, 1H), 4.57-4.39 (m, 2H), 3.72 (d, J = 13.9Hz, 2H), 3.68 (s, 2H), 3.60 (d, J = 12.3Hz, 2H), 3.41 (t, J = 11.0Hz, 4H), 3.22-3.14 (m, 2H), 3.09 (d ,J=16.5Hz,2H),2.99–2.85(m,3H), 2.85–2.74(m,3H), 2.51(dt,J=9.0,5.7Hz,3H), 2.30(s,2H), 2.11( s, 2H), 2.06 (d, J = 14.2 Hz, 3H), 1.79 (dd, J = 10.3, 6.3 Hz, 2H), 1.67 (q, J = 7.1 Hz, 2H), 1.57 (t, J = 6.3 Hz,6H),1.51–1.42(m,2H),1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₄ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ ,1217.5044; Measured value, 1217.5123.

Example 52: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS268179) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS268179) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS255127). Yellow powder, m=10mg, yield=28%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.09(d,J=2.3Hz,1H), 7.92(dd,J=9.2,2.3Hz,1H) ,7.79(d,J=2.5Hz,1H), 7.71(dd,J=7.6,1.1Hz,1H), 7.63(d,J=8.8Hz,1H), 7.59(dd,J=7.7,1.0Hz, 1H), 7.56 (d, J = 3.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 8.3 Hz, 2H), 7.10-7.07 (m, 2H), 7.04 ( d, J = 9.3 Hz, 1H), 6.80 (dd, J = 8.9, 2.2 Hz, 1H), 6.55 (d, J = 3.5 Hz, 1H), 6.44 (d, J = 2.2 Hz, 1H), 5.17 ( dd,J＝13.3,5.2Hz,1H),4.55-4.40(m,2H),3.72(d,J＝13.6Hz,2H),3.68(s,2H),3.56(t,J＝11.7Hz,2H ), 3.40 (dd, J = 19.6, 9.0 Hz, 4H), 3.23–3.15 (m, 2H), 3.09–3.02 (m, 2H), 2.89 (ddd, J = 20.8, 10.3, 3.6 Hz, 3H), 2.84–2.73(m,3H), 2.50(dd,J=8.0,5.5Hz,3H), 2.31(s,2H),2.21–2.15(m,1H),2.11(s,2H),2.02(t, J = 12.3 Hz, 3H), 1.76 (d, J = 8.6 Hz, 2H), 1.69-1.61 (m, 2H), 1.56 (q, J = 8.0, 7.2 Hz, 6H), 1.44 (s, 4H), 1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₆ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1231.5200; measured value, 1231.5247.

Example 53: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS268180) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS268180) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS292020). Yellow powder, m=9.0mg, yield=25%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.07(d,J=2.5Hz,1H), 7.93(dd,J=9.2,2.2Hz,1H) ,7.75(d,J=2.5Hz,1H),7.71(dt,J=7.7,1.3Hz,1H),7.65-7.61(m,1H),7.57(d,J=7.1Hz,1H),7.53( d, J = 3.4 Hz, 1H), 7.47 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.07 (dd, J = 12.2, 8.9 Hz, 3H), 6.78 ( dd, J = 8.9, 2.3 Hz, 1H), 6.52 (d, J = 3.5 Hz, 1H), 6.41 (d, J = 2.3 Hz, 1H), 5.15 (dd, J = 13.3, 5.3 Hz, 1H), 4.57–4.40(m,2H), 3.68(d,J=9.4Hz,4H), 3.64–3.53(m,2H), 3.46–3.38(m,4H), 3.20–3.08(m,4H), 2.95– 2.84 (m, 2H), 2.84–2.70 (m, 4H), 2.49 (t, J = 6.8 Hz, 3H), 2.29 (d, J = 6.6 Hz, 3H), 2.18 (ddd, J = 12.7, 5.2, 2.3Hz, 1H), 2.11 (s, 2H), 2.02 (d, J = 11.1Hz, 2H), 1.85-1.75 (m, 2H), 1.69-1.62 (m, 2H), 1.56 (q, J = 10.0 ,8.1Hz,4H),1.44(q,J=7.6Hz,2H),1.38–1.27(m,2H),1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₄ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ ,1217.5044; measured value,1217.5096.

Example 54: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS268181) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS268181) was prepared using the intermediate BINDER (SIAIS255123) and the intermediate LM (SIAIS255127). Yellow powder, m=6.3mg, yield=18%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.73-8.67 (m, 1H), 8.04 (d, J = 2.4 Hz, 1H), 7.94 (dd, J = 9.1, 2.3 Hz, 1H), 7.72 ( ddd, J = 7.7, 2.8, 1.0 Hz, 1H), 7.67 (t, J = 2.2 Hz, 1H), 7.65 (dd, J = 8.9, 0.7 Hz, 1H), 7.58 (dt, J = 7.8, 1.3 Hz ,1H),7.51–7.45(m,2H),7.36(d,J=8.4Hz,2H), 7.07(d,J=8.4Hz,2H), 7.04(d,J=9.3Hz,1H), 6.78 (dd,J=8.9,2.3Hz,1H), 6.48(d,J=3.5Hz,1H), 6.38(d,J=2.3Hz,1H), 5.16(dt,J=13.3,4.9Hz,1H) ,4.47(q,J=17.4Hz,2H),3.69(d,J=16.2Hz,4H),3.62–3.50(m,2H),3.47–3.36(m,4H),3.18–3.05(m,4H) ), 2.94–2.70(m,6H),2.55 2.45(m,3H),2.32-2.21(m,3H),2.21–2.15(m,1H),2.11(s,2H),2.05-1.95(m, 2H), 1.70-1.70 (m, 2H), 1.63 (p, J = 6.9 Hz, 2H), 1.57 (t, J = 6.4 Hz, 2H), 1.51 (t, J = 7.5 Hz, 2H), 1.46- 1.38(m,4H),1.34-1.26(m,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₆ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1231.5200; measured value, 1231.5198.

Example 55: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( 2-(1-Methyl-2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperidine-3 -Yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS268194) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS268194) was prepared using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS268191), yellow powder, m=16mg, yield=46 %

¹ H NMR(500MHz, methanol-d ₄ )δ8.63(s,1H), 8.06(s,1H), 7.90(d,J=9.2Hz,1H), 7.78–7.68(m,2H), 7.62( d,J=8.8Hz,1H),7.57(d,J=7.6Hz,1H),7.51(s,1H),7.45(t,J=7.5Hz,1H),7.36(d,J=8.0Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.5 Hz, 1H), 6.76 (d, J = 8.7 Hz, 1H), 6.50 (s, 1H), 6.39 (s, 1H), 5.15 (dd, J = 13.5, 5.1 Hz, 1H), 4.54-4.40 (m, 2H), 3.69 (d, J = 5.9 Hz, 5H), 3.61 (d, J = 12.3 Hz, 1H), 3.42(dq,J=13.8,8.3,7.5Hz,4H), 3.15(q,J=8.7,6.5Hz,2H), 3.10(d,J=5.9Hz,3H), 2.99–2.75(m,6H) ,2.68–2.60(m,2H),2.51(dt,J=13.0,6.4Hz,1H),2.30(s,3H),2.07(d,J=43.1Hz,8H),1.88(q,J=18.4 ,16.0Hz,1H),1.57(t,J=6.4Hz,2H),1.42-1.27(m,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₀ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ ,1189.4731; measured value,1189.4722.

Example 56: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)-1H-1,2,3-tri (Azol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292021) preparation

first step

Intermediate LM (SIAIS268006) (200 mg, 0.47 mmol) was dissolved in 2 mL of DMF, sodium azide (91 mg, 1.41 mmol) was added, and reacted overnight at room temperature to obtain azide intermediate (74 mg, 46%).

Second step

According to Scheme 17, under appropriate conditions understandable in the art, the target compound (SIAIS292021) was prepared by Click reaction using the intermediate BINDER (SIAIS268193) and the azide intermediate from the previous step, yellow powder, m=20mg, yield= 56%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.74 (s, 1H), 11.67 (s, 1H), 11.09 (s, 1H), 10.31 (s, 1H), 9.00 (t, J = 5.9 Hz, 1H), 8.59 (d, J = 2.3 Hz, 1H), 8.10 (s, 1H), 8.08-8.02 (m, 1H), 7.84 (dd, J = 9.2, 2.3 Hz, 1H), 7.56 (d, J =2.7Hz,1H),7.55–7.46(m,2H),7.44–7.34(m,3H),7.18(d,J＝9.5Hz,1H), 7.09(d,J＝8.3Hz,2H), 6.96 (d,J=7.0Hz,1H), 6.90(d,J=8.6Hz,1H), 6.76(s,1H), 6.70(dd,J=9.0,2.3Hz,1H), 6.40(dd,J= 3.4, 1.8 Hz, 1H), 6.24 (d, J = 2.2 Hz, 1H), 5.04 (dd, J = 12.8, 5.4 Hz, 1H), 4.67 (d, J = 5.9 Hz, 2H), 4.57 (t, J = 5.9Hz, 2H), 3.78 (d, J = 5.8Hz, 2H), 3.62 (d, J = 12.9Hz, 2H), 3.53 (s, 2H), 3.33–3.18 (m, 4H), 2.93– 2.81 (m, 1H), 2.71 (t, J = 11.3 Hz, 2H), 2.62-2.54 (m, 1H), 2.37-2.27 (m, 2H), 2.01 (s, 4H), 1.44 (t, J = 6.4Hz,2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₅₇ H ₅₇ ClN ₁₃ O ₁₀ S ⁺ [M+H] ⁺ ,1150.3755; measured value,.

Example 57: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)-1H-1,2,3-tri (Azol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292024) preparation

With reference to the method of Example 56, under appropriate conditions understandable in the art, the target compound (SIAIS292024) was prepared using intermediate BINDER (SIAIS268193) and intermediate LM (SIAIS268007), yellow powder, m=8.6mg, yield= 39%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 10.15 (s, 1H), 9.03 (t, J = 5.9 Hz, 1H), 8.59 (d, J = 2.3 Hz, 1H), 8.12 (s, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.84 (dd, J = 9.2, 2.4 Hz, 1H), 7.58- 7.49 (m, 4H), 7.39 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 9.4 Hz, 1H), 7.09 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 7.2 Hz, 2H), 6.70 (dd, J = 9.0, 2.4 Hz, 2H), 6.40 (dd, J = 3.4, 1.9 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H), 5.05 (dd, J = 12.8, 5.4 Hz, 1H), 4.71 (d, J = 5.7 Hz, 2H), 4.43 (t, J = 6.9 Hz, 2H), 3.63 (d, J = 12.8 Hz, 2H), 3.55 (d, J =5.1Hz, 2H), 3.34–3.16(m, 6H), 2.94–2.83(m, 1H), 2.71(d, J = 10.9Hz, 2H), 2.65–2.53(m, 1H), 2.29(s, 2H), 2.10(t,J=6.9Hz,2H),2.01(s,4H),1.44(t,J=6.3Hz,2H),0.94(s,6H).HRMS(ESI)m/z: calculation Value C ₅₈ H ₅₉ ClN ₁₃ O ₁₀ S ⁺ [M+H] ⁺ , 1164.3912; measured value, 1164.3959.

Example 58: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)-1H-1,2,3-tri (Azol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292025) preparation

With reference to the method of Example 56, under appropriate conditions understandable in the art, the target compound (SIAIS292025) was prepared using intermediate BINDER (SIAIS268193) and intermediate LM (SIAIS264016), yellow powder, m=10mg, yield=44 %

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 10.16 (s, 1H), 9.03 (t, J = 5.9 Hz, 1H), 8.59 (d, J = 2.3 Hz, 1H), 8.07 (s, 1H), 8.05 (d, J = 2.7 Hz, 1H), 7.84 (dd, J = 9.2, 2.3 Hz, 1H), 7.60- 7.49(m,4H),7.39(d,J=8.5Hz,2H),7.17(d,J=9.4Hz,1H),7.13-7.04(m,4H),7.02(dd,J=7.1,4.8Hz ,1H), 6.70(dd,J=9.0,2.3Hz,1H),6.53(s,1H),6.40(dd,J=3.4,1.9Hz,1H), 6.25(d,J=2.3Hz,1H) ,5.04(dd,J=12.8,5.5Hz,1H),4.70(d,J=5.8Hz,2H),4.33(t,J=7.1Hz,2H),3.63(d,J=13.3Hz,2H) ,3.55(d,J=5.2Hz,2H), 3.30–3.16(m,6H), 2.88(ddd,J=16.4,13.7,5.3Hz,1H), 2.70(d,J=11.2Hz,2H), 2.59(d,J=15.4Hz,1H),2.30(s,2H),2.06–1.94(m,4H),1.83(p,J=7.3Hz,2H),1.58(q,J=7.3Hz,2H ), 1.44(t,J=6.4Hz,2H),1.33-1.25(m,2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₀ H ₆₃ ClN ₁₃ O ₁₀ S ⁺ [M+H] ⁺ ,1192.4225; measured value, 1192.4272.

Example 59: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hepta-6-yn-1-yl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292026) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292017) to prepare the target compound (SIAIS292026), yellow powder, m=8.3mg, yield= twenty four%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.10(s,1H), 7.79(s,1H), 7.73(d,J=7.6Hz,1H) ,7.64(d,J=8.9Hz,1H),7.60(d,J=7.6Hz,1H),7.55(d,J=3.4Hz,1H),7.49(t,J=7.6Hz,1H),7.36 (d,J=8.4Hz,2H), 7.08(d,J=8.3Hz,2H), 7.05(d,J=9.4Hz,1H), 6.81(dd,J=8.9,2.0Hz,1H), 6.54 (d, J = 3.4 Hz, 1H), 6.44 (d, J = 1.8 Hz, 1H), 5.16 (dd, J = 13.3, 5.1 Hz, 1H), 4.48 (q, J = 17.5 Hz, 2H), 3.75 -3.68(m,4H),3.61(d,J=12.0Hz,2H), 3.47–3.37(m,4H), 3.24–3.08(m,4H), 3.00–2.85(m,3H), 2.85–2.74 (m,3H), 2.59--2.49(m,3H), 2.30(s,2H), 2.23--2.14(m,1H), 2.11(s,2H), 2.09--1.99(m,3H),1.86-1.78 (m, 2H), 1.71 (p, J = 7.0 Hz, 2H), 1.60-1.50 (m, 6H), 1.01 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₅ H ₇₂ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ ,1203.4887; measured value,1203.4902.

Example 60: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hepta-6-yn-1-yl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292027) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS292017) to prepare the target compound (SIAIS292027), yellow powder, m=8.1mg, yield= twenty three%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.67 (s, 1H), 8.09 (s, 1H), 7.93 (dd, J = 9.2, 2.3 Hz, 1H), 7.73 (s, 1H), 7.71 ( d,J=7.5Hz,1H), 7.64(d,J=8.8Hz,1H), 7.57(d,J=7.1Hz,1H), 7.52(d,J=3.4Hz,1H),7.46(t, J = 7.6 Hz, 1H), 7.36 (d, J = 8.1 Hz, 2H), 7.08 (d, J = 8.2 Hz, 2H), 7.05 (d, J = 9.3 Hz, 1H), 6.77 (d, J = 10.2Hz, 1H), 6.52 (d, J = 3.4 Hz, 1H), 6.39 (s, 1H), 5.15 (ddd, J = 13.2, 5.1, 2.4 Hz, 1H), 4.55-4.40 (m, 2H), 3.75-3.65(m,4H),3.59(t,J=13.2Hz,2H), 3.48–3.36(m,4H), 3.20-3.10(m,4H), 2.87(t,J=13.5Hz,2H) , 2.82-2.75 (m, 4H), 2.56-2.46 (m, 3H), 2.29 (s, 2H), 2.22-2.14 (m, 1H), 2.11 (s, 2H), 2.06-2.00 (m, 2H) ,1.86-1.80(m,3H),1.69(p,J=6.9Hz,2H),1.63-1.52(m,4H),1.36-1.30(m,2H),1.00(s,6H).HRMS(ESI) )m/z: Calculated value C ₆₅ H ₇₂ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1203.4887; measured value, 1203.4908.

Example 61: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292030) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292006) to prepare the target compound (SIAIS292030), yellow powder, m=4.9mg, yield= 14%

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(s,1H), 8.08(s,1H), 7.91(dd,J=14.7,7.9Hz,1H), 7.83(d,J=9.0Hz, 2H), 7.75 (s, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.54 (t, J = 3.6 Hz, 1H), 7.36 (d, J = 7.6 Hz, 2H), 7.07 (dd, J = 18.2, 8.4 Hz, 3H), 6.78 (d, J = 7.7 Hz, 1H), 6.53 (s, 1H), 6.42 (s, 1H), 5.13 (dd, J = 12.9, 5.4 Hz, 1H), 3.69 (d, J = 9.7 Hz, 6H), 3.40 (d, J = 5.8 Hz, 4H), 3.18 (t, J = 10.1 Hz, 3H), 3.05 (t, J = 12.6 Hz, 2H), 2.91- 2.63(m,7H),2.31(s,2H),2.22-1.96(m,9H),1.66-1.54(m,4H),1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₆₆ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1189.4367; found value, 1189.4345.

Example 62: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292031) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292007) to prepare the target compound (SIAIS292031), yellow powder, m=3.4mg, yield= 10%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.68 (d, J = 2.3 Hz, 1H), 8.01 (s, 1H), 7.90 (dd, J = 9.2, 2.4 Hz, 1H), 7.84–7.78 ( m, 3H), 7.64 (d, J = 8.9 Hz, 1H), 7.60 (d, J = 2.5 Hz, 1H), 7.47 (d, J = 3.4 Hz, 1H), 7.36 (d, J = 8.2 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 9.3 Hz, 1H), 6.77 (dd, J = 8.9, 2.4 Hz, 1H), 6.44 (d, J = 3.4 Hz, 1H), 6.35 (d, J = 2.4 Hz, 1H), 5.13 (dd, J = 12.9, 5.4 Hz, 1H), 3.66 (d, J = 14.4 Hz, 5H), 3.45–3.37 (m, 4H), 3.22–3.07(m,4H), 3.00(t,J=12.8Hz,2H), 2.92–2.66(m,5H), 2.61(t,J=6.8Hz,2H), 2.29(s,2H), 2.22 –1.92(m,9H),1.73(q,J=7.4Hz,2H),1.65-1.52(m,4H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₆₈ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1203.4524; measured value, 1203.4586.

Example 63: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hept-6-yn-1-yl)piperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292032) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292016) to prepare the target compound (SIAIS292032), yellow powder, m=6.8mg, yield= 19%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.67 (d, J = 2.3 Hz, 1H), 8.07 (s, 1H), 7.90 (dd, J = 9.2, 2.4 Hz, 1H), 7.86–7.76 ( m, 3H), 7.74 (s, 1H), 7.63 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 3.3 Hz, 1H), 7.36 (d, J = 8.2 Hz, 2H), 7.08 ( d, J = 8.1 Hz, 2H), 7.04 (d, J = 9.4 Hz, 1H), 6.79 (dd, J = 9.0, 2.3 Hz, 1H), 6.52 (d, J = 3.4 Hz, 1H), 6.41 ( d, J = 2.3Hz, 1H), 5.13 (dd, J = 12.8, 5.4 Hz, 1H), 3.76–3.58 (m, 6H), 3.41 (t, J = 9.9 Hz, 4H), 3.22–3.09 (m ,4H),2.97(t,J=12.6Hz,2H),2.92–2.66(m,5H),2.55(t,J=6.8Hz,2H),2.30(s,2H),2.23–2.00(m, 8H), 1.87–1.79(m,2H), 1.71(q,J=7.2Hz,2H),1.65–1.53(m,4H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₅ H ₇₀ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1217.4680; found value, 1217.4706.

Example 64: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292033) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS292033) was prepared using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292008), yellow powder, m=5.9mg, yield= 17%

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(d,J=2.3Hz,1H),8.13(s,1H),7.92(dd,J=9.2,2.3Hz,1H),7.87(d, J = 2.4Hz, 1H), 7.84–7.77 (m, 3H), 7.63 (d, J = 8.9 Hz, 1H), 7.59 (d, J = 3.5 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.08 (dd, J = 10.5, 9.0 Hz, 3H), 6.81 (dd, J = 8.9, 2.3 Hz, 1H), 6.59 (d, J = 3.5 Hz, 1H), 6.48 (d, J = 2.4 Hz, 1H), 5.13 (dd, J = 12.8, 5.4 Hz, 1H), 3.74 (d, J = 14.0 Hz, 2H), 3.68 (s, 2H), 3.62 (d, J = 12.4 Hz, 2H), 3.47–3.38(m,4H), 3.26–3.16(m,2H), 3.14–3.06(m,2H), 2.96(t,J=12.1Hz,2H), 2.87(dd,J=5.5,3.7Hz, 1H), 2.85–2.68(m,5H), 2.52(t,J=6.8Hz,2H), 2.31(t,J=5.8Hz,2H), 2.16–2.00(m,7H), 1.79(dq,J ＝6.9,3.6,2.9Hz,2H),1.72–1.64(m,2H),1.62–1.54(m,4H),1.50–1.41(m,2H),1.01(s,6H).HRMS(ESI)m /z: Calculated value C ₆₆ H ₇₂ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1231.4837; measured value, 1231.4835.

Example 65: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292034) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292009) to prepare the target compound (SIAIS292034), yellow powder, m=6.0mg, yield= 17%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(s,1H), 8.04(s,1H), 7.91(d,J=9.0Hz,1H), 7.80(q,J=9.5,8.5Hz, 3H), 7.72–7.61 (m, 3H), 7.50 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 7.5 Hz, 2H), 7.08 (d, J = 7.6 Hz, 2H), 7.03 ( d,J=9.2Hz,1H), 6.78(d,J=8.7Hz,1H), 6.48(d,J=2.9Hz,1H), 6.38(s,1H), 5.13(ddd,J=12.5,5.5 ,1.4Hz,1H), 3.69(d,J=17.2Hz,4H),3.59(d,J=12.3Hz,2H),3.41(d,J=14.1Hz,4H),3.14(d,J=13.0 Hz, 2H), 3.09 (d, J = 8.2 Hz, 2H), 2.99-2.89 (m, 2H), 2.89-2.67 (m, 6H), 2.51 (t, J = 6.8 Hz, 2H), 2.29 (s ,2H),2.22-1.99(m,7H),1.77(s,2H),1.66(t,J=7.2Hz,2H),1.62-1.50(m,4H),1.50-1.40(m,4H), 1.06–0.97(m,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₄ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1245.4993; measured value, 1245.4997.

Example 66: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-3-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292035) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS292006) to prepare the target compound (SIAIS292035), yellow powder, m=4.4mg, yield= 13%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.61 (dd, J = 2.3, 1.0 Hz, 1H), 8.03 (s, 1H), 7.89 (dd, J = 9.2, 2.3 Hz, 1H), 7.71 ( dd, J = 17.2, 2.1 Hz, 3H), 7.67 (dd, J = 2.6, 1.3 Hz, 1H), 7.60 (d, J = 8.9 Hz, 1H), 7.48 (dd, J = 3.4, 1.6 Hz, 1H) ), 7.34 (d, J = 8.0 Hz, 2H), 7.10-7.04 (m, 3H), 6.73 (d, J = 8.7 Hz, 1H), 6.47 (d, J = 5.0 Hz, 1H), 6.37 (s ,1H), 5.12(dd,J=12.7,5.5Hz,1H), 3.75–3.63(m,6H), 3.50–3.39(m,4H), 3.22–3.12(m,2H),3.01–2.60(m ,10H),2.31(s,2H),2.21–1.97(m,8H),1.90-1.82(m,1H),1.57(d,J=6.2Hz,2H),1.35-1.30(m,2H), 1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₆₆ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1189.4367; measured value, 1189.4332.

Example 67: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-3-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292036) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS292007) to prepare the target compound (SIAIS292036), yellow powder, m=2.7mg, yield= 7.7%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.65 (t, J = 2.1Hz, 1H), 8.01 (s, 1H), 7.93 (dd, J = 2.3, 1.2 Hz, 1H), 7.83–7.72 ( m,3H),7.70–7.58(m,2H),7.46(d,J=3.4Hz,1H), 7.36(d,J=8.4Hz,2H), 7.08(d,J=8.3Hz,2H), 7.04(d,J=9.1Hz,1H), 6.75(ddd,J=8.9,4.3,2.3Hz,1H), 6.45(dd,J=3.5,1.0Hz,1H), 6.35(d,J=2.3Hz ,1H), 5.15–5.07(m,1H), 3.66(d,J=12.7Hz, 6H), 3.47–3.37(m,4H), 3.23–3.08(m,4H), 2.99–2.66(m,8H) ), 2.59(t,J=6.8Hz,2H),2.29(s,2H),2.15-2.10(m,3H),2.08–1.91(m,5H),1.90–1.80(m,1H),1.75– 1.67(m,2H),1.56(t,J=6.3Hz,2H),1.39-1.31(m,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₆₈ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ ,1203.4524; measured value,1203.4547.

Example 68: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hept-6-yn-1-yl)piperidin-3-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292037) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS292016) to prepare the target compound (SIAIS292037), yellow powder, m=9.3mg, yield= 26%

¹ H NMR(500MHz, methanol-d ₄ )δ8.63(d,J=2.2Hz,1H), 8.12(s,1H), 7.91(dd,J=9.1,2.3Hz,1H), 7.88(s, 1H), 7.76 (dd, J = 17.9, 8.0 Hz, 3H), 7.64–7.56 (m, 2H), 7.35 (d, J = 7.9 Hz, 2H), 7.08 (dd, J = 8.6, 5.3 Hz, 3H ), 6.77 (d, J = 9.1Hz, 1H), 6.58 (d, J = 3.5Hz, 1H), 6.44 (s, 1H), 5.12 (dd, J = 12.8, 5.4 Hz, 1H), 3.79–3.55 (m,6H), 3.50–3.40(m,4H), 3.27–3.13(m,4H), 2.96–2.63(m,8H), 2.52(t,J=6.8Hz,2H), 2.32(s,2H) ), 2.16–2.09(m,3H),2.05-1.98(m,2H),1.91–1.79(m,2H),1.68(q,J=7.2Hz,2H),1.56(t,J=6.7Hz, 4H),1.38–1.31(m,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₅ H ₇₀ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ ,1217.4680; measured value ,1217.4698.

Example 69: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-3-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292038) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS292008) to prepare the target compound (SIAIS292038), yellow powder, m=3.9mg, yield= 11%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.66 (dt, J = 2.3, 1.1 Hz, 1H), 8.05 (s, 1H), 7.92 (dd, J = 9.2, 2.3 Hz, 1H), 7.79 ( d, J = 8.1 Hz, 1H), 7.77–7.72 (m, 2H), 7.70 (d, J = 2.5 Hz, 1H), 7.62 (d, J = 8.9 Hz, 1H), 7.51 (d, J = 3.4 Hz, 1H), 7.35 (d, J = 8.3 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.05 (d, J = 9.3 Hz, 1H), 6.76 (dd, J = 8.9, 2.3 Hz, 1H), 6.49 (d, J = 3.4 Hz, 1H), 6.37 (d, J = 2.3 Hz, 1H), 5.12 (dd, J = 12.8, 5.5 Hz, 1H), 3.72–3.56 (m, 6H ),3.42(q,J=9.6,8.1Hz,4H),3.22–3.10(m,4H), 2.95–2.63(m,8H), 2.50(t,J=6.8Hz,2H), 2.30(s, 2H), 2.15–2.09(m,3H),2.05-1.98(m,2H),1.86–1.75(m,2H),1.69–1.61(m,2H),1.56(h,J=6.6Hz,4H) ,1.44(q,J =7.2,6.7Hz,2H),1.37–1.32(m,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₂ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1231.4837; measured value, 1231.4860.

Example 70: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-3-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292039) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS292009) to prepare the target compound (SIAIS292039), yellow powder, m=8.3mg, yield= twenty three%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.09(d,J=2.5Hz,1H), 7.94(dd,J=9.2,2.4Hz,1H) ,7.82-7.78(m,2H),7.76(dt,J=4.2,2.1Hz,2H),7.62(d,J=8.9Hz,1H),7.55(d,J=3.4Hz,1H),7.36( d,J=8.3Hz,2H), 7.08(dd,J=8.9,7.0Hz,3H), 6.78(dd,J=8.9,2.3Hz,1H), 6.54(d,J=3.5Hz,1H), 6.42(d,J=2.4Hz,1H),5.12(dd,J=12.8,5.4Hz,1H),3.72-3.65(m,4H),3.64-3.54(m,2H),3.49–3.38(m, 4H), 3.23–3.15(m,2H), 3.14–3.08(m,2H), 2.92–2.64(m,8H), 2.49(t,J=6.9Hz,2H), 2.30(d,J=6.5Hz ,2H),2.16–2.09(m,3H),2.07–1.97(m,2H),1.83–1.73(m,2H),1.63(q,J=7.1Hz,2H),1.56(t,J=6.4 Hz,2H),1.52(q,J=6.1,5.4Hz,2H),1.45-1.40(m,4H),1.38-1.31(m,2H),1.00(s,6H).HRMS(ESI)m/ z: Calculated value C ₆₇ H ₇₄ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1245.4993; measured value, 1245.4954.

Example 71: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)-1H-1,2,3-triazole -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292040) preparation

With reference to the method of Example 56, under appropriate conditions understandable in the art, the target compound (SIAIS292040) was prepared using intermediate BINDER (SIAIS268193) and intermediate LM (SIAIS264018), yellow powder, m=13mg, yield=57 %

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.66 (s, 1H), 11.09 (s, 1H), 9.02 (t, J = 5.9 Hz, 1H), 8.58 (d, J = 2.3Hz, 1H), 8.07 (s, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 9.2, 2.3 Hz, 1H), 7.59-7.54 (m, 2H), 7.53–7.50 (m, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 9.4 Hz, 1H), 7.09 (d, J = 8.4 Hz, 2H), 7.06 (d, J ＝8.7Hz,1H), 7.01(d,J＝7.0Hz,1H), 6.71(dd,J＝9.0,2.3Hz,1H), 6.51(s,1H), 6.40(dd,J＝3.4,1.9Hz ,1H), 6.25 (d, J = 2.3 Hz, 1H), 5.04 (dd, J = 12.8, 5.4 Hz, 1H), 4.70 (d, J = 5.8 Hz, 2H), 4.31 (t, J = 7.1 Hz , 2H), 3.63 (d, J = 13.1Hz, 2H), 3.54 (s, 2H), 3.25 (t, J = 7.4 Hz, 6H), 2.92-2.83 (m, 1H), 2.70 (d, J = 10.9Hz, 2H), 2.58 (dt, J = 17.8, 3.4 Hz, 1H), 2.30 (s, 2H), 2.01 (d, J = 2.4 Hz, 4H), 1.79 (p, J = 7.2 Hz, 2H) ,1.53(p,J=7.3 Hz,2H),1.44(t,J=6.5Hz,2H),1.33(q,J=7.4Hz,2H),1.28–1.22(m,2H),0.94(s, 6H).HRMS(ESI)m/z: calculated value C ₆₁ H ₆₅ ClN ₁₃ O ₁₀ S ⁺ [M+H] ⁺ , 1206.4381; measured value, 1206.4372.,

Example 72: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)-1H-1,2,3- Triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292041) preparation

With reference to the method of Example 56, under appropriate conditions understandable in the art, the target compound (SIAIS292041) was prepared using intermediate BINDER (SIAIS268193) and intermediate LM (SIAIS255121), yellow powder, m=5.2mg, yield= twenty four%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.76 (s, 1H), 11.67 (s, 1H), 10.99 (s, 1H), 10.74 (s, 1H), 9.02 (t, J = 5.9 Hz, 1H), 8.58 (d, J = 2.3 Hz, 1H), 8.14 (s, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.84 (dd, J = 9.2, 2.3 Hz, 1H), 7.70 ( dd,J=7.5,1.0Hz,1H),7.63(dd,J=7.6,1.0Hz,1H),7.58(d,J=2.5Hz,1H),7.51(dt,J=7.6,3.3Hz,3H ), 7.39 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 9.4 Hz, 1H), 7.09 (d, J = 8.4 Hz, 2H), 6.70 (dd, J = 9.0, 2.4 Hz, 1H) ), 6.41 (dd, J = 3.4, 1.9 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.70 (d, J = 5.8 Hz ,2H),4.52–4.48(m,2H),4.46(s,1H),4.33(d,J=17.7Hz,1H),3.65-3.55(m,2H),3.52(s,2H),3.32- 3.25 (m, 4H), 2.91 (ddd, J = 17.3, 13.7, 5.4 Hz, 1H), 2.68 (q, J = 11.2 Hz, 2H), 2.62-2.55 (m, 1H), 2.48 (d, J = 6.7Hz, 2H), 2.35 (s, 2H), 2.12 (p, J = 7.0 Hz, 2H), 2.05-1.97 (m, 4H), 1.44 (t, J = 6.4 Hz, 2H), 0.94 (s, 6H).HRMS(ESI)m/z: calculated value C ₆₀ H ₆₀ ClN ₁₂ O ₉ S ⁺ [M+H] ⁺ , 1159.4010; measured value, 1159.4039.

Example 73: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)-1H-1,2,3- Triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292042) preparation

With reference to the method of Example 56, under appropriate conditions understandable in the art, the target compound (SIAIS292042) was prepared by using intermediate BINDER (SIAIS268193) and intermediate LM (SIAIS255119), yellow powder, m=4.7mg, yield= twenty one%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.75 (s, 1H), 11.66 (s, 1H), 10.99 (s, 1H), 10.61 (s, 1H), 9.03 (t, J = 5.9 Hz, 1H), 8.58 (d, J = 2.3 Hz, 1H), 8.10 (s, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.84 (dd, J = 9.2, 2.3 Hz, 1H), 7.71 ( d,J=7.5Hz,1H), 7.62(d,J=7.4Hz,1H), 7.57(d,J=2.6Hz,1H),7.56–7.47(m,3H),7.39(d,J=8.5 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 7.09 (d, J = 8.4 Hz, 2H), 6.70 (dd, J = 9.0, 2.3 Hz, 1H), 6.41 (dd, J = 3.4 ,1.9Hz,1H), 6.25(d,J=2.3Hz,1H), 5.15(dd,J=13.3,5.1Hz,1H), 4.70(d,J=5.7Hz,2H), 4.49–4.37(m ,3H), 4.30(d,J=17.7Hz,1H),3.61(s,2H),3.53(s,2H), 3.25(d,J=11.7Hz,4H), 2.92(ddd,J=17.2, 13.6, 5.4 Hz, 1H), 2.69 (q, J = 10.7, 9.9 Hz, 2H), 2.60 (d, J = 17.7 Hz, 1H), 2.55-2.45 (m, 2H), 2.34 (s, 2H), 2.07–1.93(m,6H),1.52(p,J=7.1Hz,2H),1.47–1.40(m,2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₁ H ₆₂ ClN ₁₂ O ₉ S ⁺ [M+H] ⁺ , 1173.4166; found value, 1173.4166.

Example 74: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)-1H-1,2,3- Triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292043) preparation

With reference to the method of Example 56, under appropriate conditions understandable in the art, the target compound (SIAIS292043) was prepared using intermediate BINDER (SIAIS268193) and intermediate LM (SIAIS292017), yellow powder, m=9.0mg, yield= 40%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.66 (s, 1H), 10.99 (s, 1H), 10.03 (s, 1H), 9.01 (t, J = 5.9 Hz, 1H), 8.58 (s, 1H), 8.08 (s, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.84 (dd, J = 9.2, 2.1 Hz, 1H), 7.69 (d, J = 7.5 Hz,1H), 7.63–7.58(m,1H), 7.56(d,J=2.3Hz,1H), 7.55–7.48(m,3H), 7.39(d,J=8.4Hz,2H), 7.15(d ,J=9.4Hz,1H),7.09(d,J=8.4Hz,2H), 6.70(d,J=11.0Hz,1H), 6.40(s,1H), 6.24(s,1H), 5.14(dd ,J = 13.3, 5.1 Hz, 1H), 4.68 (d, J = 5.9 Hz, 2H), 4.44 (d, J = 17.7 Hz, 1H), 4.37-4.27 (m, 3H), 3.65 (s, 2H) , 3.55 (s, 2H), 3.26 (d, J = 11.6 Hz, 2H), 3.18 (d, J = 7.8 Hz, 2H), 2.97-2.86 (m, 1H), 2.68 (s, 2H), 2.60 ( s, 1H), 2.45 (t, J = 7.0 Hz, 2H), 2.28 (s, 2H), 2.00 (d, J = 8.4 Hz, 4H), 1.84 (p, J = 7.2 Hz, 2H), 1.57 ( p,J=7.1Hz,2H),1.45(t,J=6.1Hz,2H),1.37(p,J=7.7Hz,2H),0.94(s,6H).HRMS(ESI)m/z: calculation Value C ₆₂ H ₆₄ ClN ₁₂ O ₉ S ⁺ [M+H] ⁺ , 1187.4323; measured value, 1187.4333.

Example 75: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)-1H-1,2,3- Triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292044) preparation

With reference to the method of Example 56, under appropriate conditions understandable in the art, the target compound (SIAIS292044) was prepared using intermediate BINDER (SIAIS268193) and intermediate LM (SIAIS292020), yellow powder, m=8.8mg, yield= 39%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.66 (s, 1H), 10.99 (s, 1H), 10.04 (s, 1H), 9.03 (t, J = 5.9 Hz, 1H), 8.58 (d, J = 2.3 Hz, 1H), 8.07 (s, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.83 (dd, J = 9.2, 2.3 Hz, 1H), 7.70 ( dd, J = 7.6, 1.0 Hz, 1H), 7.62 (dd, J = 7.6, 1.1 Hz, 1H), 7.56 (d, J = 2.7 Hz, 1H), 7.54–7.49 (m, 3H), 7.39 (d ,J=8.4Hz,2H), 7.16(d,J=9.4Hz,1H), 7.09(d,J=8.5Hz,2H), 6.71(dd,J=9.0,2.3Hz,1H), 6.40(dd ,J=3.4,1.8Hz,1H), 6.25(d,J=2.3Hz,1H), 5.14(dd,J=13.3,5.2Hz,1H), 4.70(d,J=5.8Hz,2H), 4.44 (d,J=17.6Hz,1H), 4.35-4.27(m,3H), 3.64(d,J=13.5Hz,2H), 3.55(s,2H), 3.26(d,J=11.2Hz,2H) , 3.17 (t, J = 11.5 Hz, 2H), 2.90 (ddd, J = 17.2, 13.6, 5.4 Hz, 1H), 2.71 (d, J = 10.3 Hz, 2H), 2.58 (d, J = 17.4 Hz, 1H), 2.50-2.40 (m, 2H), 2.28 (s, 2H), 2.00 (d, J = 11.0 Hz, 4H), 1.80 (p, J = 7.2 Hz, 2H), 1.57-1.48 (m, 2H ), 1.43 (dt, J = 15.7, 6.9 Hz, 4H), 1.31-1.24 (m, 2H), 0.94 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₃ H ₆₆ ClN ₁₂ O ₉ S ⁺ [M+H] ⁺ ,1201.4479; measured value,1201.4513.

Example 76: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)-1H-1,2,3- Triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292045) preparation

With reference to the method of Example 56, under appropriate conditions understandable in the art, the target compound (SIAIS292045) was prepared using intermediate BINDER (SIAIS268193) and intermediate LM (SIAIS255127), yellow powder, m=10mg, yield=43 %

¹ H NMR(500MHz,DMSO-d ₆ )δ11.73(s,1H),11.66(s,1H),11.00(s,1H),10.02(s,1H),9.03(t,J=5.9Hz, 1H), 8.58 (d, J = 2.3 Hz, 1H), 8.06 (s, 1H), 8.04 (d, J = 2.5 Hz, 1H), 7.83 (dd, J = 9.2, 2.3 Hz, 1H), 7.70 ( dd, J = 7.6, 1.0 Hz, 1H), 7.61 (dd, J = 7.6, 1.1 Hz, 1H), 7.56 (d, J = 2.6 Hz, 1H), 7.54-7.48 (m, 3H), 7.39 (d ,J=8.4Hz,2H),7.16(d,J=9.5Hz,1H), 7.09(d,J=8.3Hz,2H), 6.71(dd,J=9.0,2.3Hz,1H),6.40(dd ,J=3.3,1.9Hz,1H), 6.25(d,J=2.3Hz,1H), 5.14(dd,J=13.4,5.1Hz,1H), 4.70(d,J=5.8Hz,2H), 4.44 (d,J=17.6Hz,1H), 4.37–4.23(m,3H), 3.70-3.60(m,2H),3.55(s,2H), 3.26(d,J=11.9Hz,2H), 3.18( d, J = 12.2Hz, 2H), 2.91 (ddd, J = 17.2, 13.6, 5.4 Hz, 1H), 2.71 (d, J = 11.3 Hz, 2H), 2.59 (d, J = 16.7 Hz, 1H), 2.45(t,J=7.1Hz,2H),2.28(s,2H),2.00(d,J=11.2Hz,4H),1.78(p,J=7.1Hz,2H),1.52(q,J=7.2 Hz, 2H), 1.44 (t, J = 6.2 Hz, 2H), 1.42-1.35 (m, 2H), 1.30 (p, J = 6.8 Hz, 2H), 1.25-1.18 (m, 2H), 0.94 (s ,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₆₈ ClN ₁₂ O ₉ S ⁺ [M+H] ⁺ ,1215.4636; measured value, 1215.4626.

Example 77: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)pent-4-yn-1-yl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292113) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292111) to prepare the target compound (SIAIS292113), yellow powder, m=6.5mg, yield= 19%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.69 (s, 1H), 11.00 (s, 1H), 10.25 (s, 1H), 10.00 (s, 1H), 8.71 ( t,J=6.1Hz,1H),8.57(s,1H),8.04(s,1H),7.82(d,J=9.3Hz,1H),7.70(d,J=7.7Hz,1H),7.66( s, 1H), 7.58–7.49 (m, 4H), 7.39 (d, J = 7.9 Hz, 2H), 7.15 (d, J = 9.6 Hz, 1H), 7.09 (d, J = 7.9 Hz, 2H), 6.72(d,J＝8.9Hz,1H),6.41(s,1H),6.25(s,1H),5.11(dd,J＝13.3,5.1Hz,1H), 4.45(d,J＝17.5Hz,1H ), 4.32(d,J=17.4Hz,1H),3.66-3.50(m,6H), 3.37(d,J=17.5Hz,2H),3.31-3.18(m,5H),3.13(s,2H) ,2.96-2.90(m,3H),2.70(d,J=9.6Hz,2H),2.65-2.55(m,3H),2.44-2.34(m,1H),2.30(s,2H),2.01(s ,4H),1.92(d,J=11.1Hz,3H),1.63-1.51(m,2H),1.44(t,J=6.4Hz,2H),0.94(s,6H).HRMS(ESI)m/ z: Calculated value C ₆₃ H ₆₈ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1175.4574; measured value, 1175.4589.

Example 78: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)hex-5-yn-1-yl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292114) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292111) to prepare the target compound (SIAIS292114), yellow powder, m=8.4mg, yield= twenty four%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.69 (s, 1H), 11.00 (s, 1H), 10.26 (s, 1H), 9.78 (s, 1H), 8.70 ( t,J=6.2Hz,1H),8.57(s,1H),8.04(s,1H),7.82(d,J=9.5Hz,1H),7.69(d,J=7.8Hz,1H),7.65( s, 1H), 7.58–7.48 (m, 4H), 7.39 (d, J = 7.9 Hz, 2H), 7.14 (d, J = 9.5 Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 6.72(d,J＝8.9Hz,1H),6.41(s,1H),6.25(s,1H),5.11(dd,J＝13.3,5.1Hz,1H), 4.44(d,J＝17.4Hz,1H ), 4.32(d,J=17.5Hz,1H), 3.70–3.60(m,6H), 3.35(s,2H), 3.31–3.15(m,5H),3.03(s,2H),2.95-2.85( m,3H),2.70(d,J=10.8Hz,2H),2.65-2.57(m,2H),2.43-2.38(m,1H),2.31(s,2H),2.01(s,3H),1.94 -1.85(m,5H),1.61-1.55(m,4H),1.44(t,J=6.4Hz,2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₀ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1189.4731; measured value, 1189.4751.

Example 79: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292115) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292104) to prepare the target compound (SIAIS292115), yellow powder, m=8.0mg, yield= twenty three%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.70 (s, 1H), 11.52 (s, 1H), 11.01 (s, 1H), 9.41 (s, 1H), 8.69 (s, 1H), 8.58 ( s, 1H), 8.04 (d, J = 2.4 Hz, 1H), 7.83 (d, J = 9.2 Hz, 1H), 7.61-7.54 (m, 3H), 7.54-7.47 (m, 3H), 7.35 (d ,J=8.1Hz,2H),7.15(d,J=9.3Hz,1H),7.05(d,J=7.7Hz,2H),6.69(d,J=9.1Hz,1H),6.40(s,1H ), 6.19 (s, 1H), 4.97 (dd, J = 13.3, 5.2 Hz, 1H), 4.44 (d, J = 17.5 Hz, 1H), 4.35 (d, J = 17.5 Hz, 1H), 3.57 (d ,J=11.7Hz,2H),3.41-3.35(m,4H),3.08(s,4H),2.98–2.80(m,4H),2.73(s,1H),2.65-2.59(m,4H), 2.47–2.33(m,2H),2.17(s,4H), 2.03–1.88(m,8H), 1.50(d,J=13.4Hz,2H),1.39(s,2H),0.92(s,6H) .HRMS(ESI)m/z: calculated value C ₆₃ H ₆₈ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1175.4574; measured value, 1175.4576.

Example 80: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS292116) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS292105) to prepare the target compound (SIAIS292116), yellow powder, m=8.0mg, yield= twenty three%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.68 (s, 1H), 11.01 (s, 1H), 10.17 (s, 1H), 9.52 (s, 1H), 8.68 ( t,J=6.0Hz,1H),8.58(s,1H),8.04(s,1H),7.83(d,J=9.0Hz,1H),7.63-7.46(m,6H),7.39(d,J =8.0Hz, 2H), 7.14 (d, J = 9.4 Hz, 1H), 7.09 (d, J = 7.9 Hz, 2H), 6.71 (d, J = 9.1 Hz, 1H), 6.41 (s, 1H), 6.25 (s, 1H), 4.99 (dd, J = 13.2, 5.2 Hz, 1H), 4.42 (d, J = 17.4 Hz, 1H), 4.32 (d, J = 17.6 Hz, 1H), 3.65-3.55 (m , 6H), 3.35 (s, 2H), 3.26-3.20 (m, 5H), 3.07 (s, 2H), 2.89-2.83 (m, 3H), 2.773-3.67 (m, 2H), 2.61 (d, J = 21.7Hz, 2H), 2.45–2.36(m, 1H), 2.30(s, 2H), 2.05–1.86(m, 8H), 1.61(t, J = 7.3Hz, 2H), 1.56–1.41(m, 4H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₀ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ ,1189.4731; measured value, 1189.4719.

Example 81: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethoxy)acetyl)piperidine -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230165) preparation

With reference to the method of Example 1, the target compound (SIAIS230165) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS1204137) under appropriate conditions understandable in the art. Yellow powder, m=15mg, yield=53%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 11.12 (s, 1H), 8.64 (s, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.05 (t, J = 2.3 Hz, 1H), 7.83–7.76 (m, 3H), 7.63 (dd, J = 7.0, 1.1 Hz, 1H), 7.59–7.55 (m, 1H), 7.54–7.50 (m, 2H), 7.39 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 9.5 Hz, 1H), 7.09 (d, J = 8.2 Hz, 2H), 6.71 (dd, J = 9.0, 2.3Hz, 1H), 6.40 (dd, J = 3.4, 1.9 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.11 (dd, J = 12.8, 5.4 Hz, 1H), 4.33 (d, J = 12.8Hz, 1H), 4.27–4.13(m, 2H), 3.79–3.73(m, 2H), 3.38(t, J = 6.3Hz, 2H), 3.34–3.23(m, 4H), 3.14(d ,J＝13.1Hz,2H),2.97–2.84(m,2H),2.71(t,J＝9.2Hz,2H), 2.65–2.55(m,2H),2.27(s,2H),2.09–1.98( m, 3H), 1.88 (s, 1H), 1.71 (d, J = 12.7 Hz, 2H), 1.45 (s, 2H), 1.17 (s, 1H), 1.04 (d, J = 12.9 Hz, 1H), 0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₂ H ₆₆ ClN ₁₀ O ₁₂ S ₂ ⁺ [M+H] ⁺ , 1241.3986; measured value, 1241.3989.

Example 82: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( 2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethoxy )Ethoxy)ethoxy)acetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230166) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS230166) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS1204141). Yellow powder, m=12mg, yield=39%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 11.12 (s, 1H), 9.62 (s, 1H), 8.63 (t, J = 5.9 Hz, 1H), 8.56 (d, J = 2.3 Hz, 1H), 8.04 (d, J = 2.5 Hz, 1H), 7.85–7.73 (m, 3H), 7.61 (dd, J = 6.1, 1.9 Hz, 1H), 7.55(d,J=2.7Hz,1H),7.55-7.50(m,2H),7.39(d,J=8.1Hz,2H),7.12(d,J=9.5Hz,1H),7.08(d,J =8.4Hz, 2H), 6.71 (dd, J = 9.0, 2.3 Hz, 1H), 6.40 (dd, J = 3.4, 1.9 Hz, 1H), 6.25 (d, J = 2.2 Hz, 1H), 5.11 (dd ,J=12.9,5.4Hz,1H), 4.32(d,J=13.0Hz,1H), 4.20–4.04(m,2H), 3.86–3.52(m,14H), 3.37–3.23(m,6H), 3.11(s,2H), 2.96–2.83(m,2H), 2.72(s,2H), 2.67–2.56(m,2H), 2.25(s,2H), 2.09–1.98(m,3H), 1.88( s, 1H), 1.71 (d, J = 12.8 Hz, 2H), 1.45 (s, 2H), 1.17 (d, J = 13.3 Hz, 1H), 1.05 (d, J = 12.1 Hz, 1H), 0.94 ( s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₄ ClN ₁₀ O ₁₄ S ₂ ⁺ [M+H] ⁺ , 1329.4510; measured value, 1329.4503.

Example 83: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(17-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)-3,6,9,12,15-penta Oxaheptadecanoyl) piperidin-4-yl) methyl) amino)-3-nitrophenyl) sulfonyl) benzamide (SIAIS230167) preparation

With reference to the method of Example 1, and under appropriate conditions understandable in the art, the target compound (SIAIS230167) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS1204149). Yellow powder, m=14mg, yield=43%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.67 (s, 1H), 11.12 (s, 1H), 10.18 (s, 1H), 8.63 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.05 (d, J = 2.5 Hz, 1H), 7.84–7.74 (m, 3H), 7.62 (dd, J = 5.9, 2.1 Hz, 1H), 7.57(s,1H),7.55-7.49(m,2H),7.39(d,J=8.4Hz,2H),7.13(d,J=9.5Hz,1H),7.09(d,J=8.4Hz,2H ), 6.71 (dd, J = 9.0, 2.3 Hz, 1H), 6.40 (dd, J = 3.2, 1.7 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.11 (dd, J = 12.9, 5.4Hz,1H), 4.32(d,J=12.9Hz,1H), 4.20–4.05(m,2H), 3.71(d,J=6.4Hz,2H), 3.66–3.61(m,2H), 3.60– 3.44(m,20H), 3.37–3.14(m,8H), 2.98–2.82(m,2H), 2.70(d,J=10.9Hz,2H), 2.65–2.53(m,2H), 2.30(s, 2H), 2.11–1.97 (m, 3H), 1.89 (s, 1H), 1.72 (d, J = 11.9 Hz, 2H), 1.44 (t, J = 6.4 Hz, 2H), 1.17 (d, J = 12.5 Hz,1H),1.05(d,J=11.5Hz,1H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₇₀ H ₈₂ ClN ₁₀ O ₁₆ S ₂ ⁺ [M+H] ⁺ ,1417.5035; measured value,1417.5039.

Example 84: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethoxy)ethoxy)acetyl (Yl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230168) preparation

With reference to the method of Example 1, the target compound (SIAIS230168) was prepared using the intermediate BINDER (SIAIS230138) and the intermediate LM (SIAIS1213131) under appropriate conditions understandable in the art. Yellow powder, m=10mg, yield=34%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 10.99 (s, 1H), 9.58 (s, 1H), 8.63 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.04 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 9.2, 2.4 Hz, 1H), 7.68 (d, J = 8.3 Hz, 1H), 7.59–7.54(m,2H), 7.55–7.49(m,3H), 7.39(d,J=7.8Hz,2H), 7.12(d,J=9.5Hz,1H), 7.08(d,J =8.4Hz, 2H), 6.71 (dd, J = 9.0, 2.3 Hz, 1H), 6.40 (dd, J = 3.4, 1.9 Hz, 1H), 6.25 (d, J = 2.2 Hz, 1H), 5.12 (dd ,J=13.3,5.1Hz,1H), 4.37(d,J=17.5Hz,1H), 4.32(d,J=12.5Hz,1H), 4.23(d,J=17.4Hz,1H), 4.17-4.05 (m, 2H), 3.80–3.57 (m, 12H), 3.27 (dt, J = 21.4, 6.4 Hz, 6H), 3.11 (s, 2H), 2.90 (ddd, J = 17.8, 12.5, 5.3 Hz, 2H ), 2.72(t,J=9.2Hz,2H),2.65-2.56(m,2H),2.25(s,2H),2.05-1.94(m,3H),1.88(s,1H),1.71(d, J = 12.6Hz, 2H), 1.45 (s, 2H), 1.16 (d, J = 12.0 Hz, 1H), 1.05 (d, J = 12.8 Hz, 1H), 0.94 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₄ H ₇₂ ClN ₁₀ O ₁₂ S ₂ ⁺ [M+H] ⁺ , 1271.4456; measured value, 1271.4460.

Example 85: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(14-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)-3,6,9,12-tetraoxatetradecane (Acyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS230169) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS230169) was prepared using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS1213135). Yellow powder, m=11mg, yield=35%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.66 (s, 1H), 10.99 (s, 1H), 10.19 (s, 1H), 8.63 (t, J = 6.1Hz, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.81 (dd, J = 9.2, 2.3 Hz, 1H), 7.67 (dd, J = 7.7, 1.0 Hz,1H), 7.60–7.54(m,2H), 7.54–7.48(m,3H), 7.39(d,J=8.4Hz,2H), 7.13(d,J=9.5Hz,1H), 7.09(d ,J=8.4Hz,2H), 6.71(dd,J=9.0,2.3Hz,1H), 6.40(dd,J=3.4,1.9Hz,1H), 6.25(d,J=2.3Hz,1H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.37 (d, J = 17.5 Hz, 1H), 4.32 (d, J = 13.0 Hz, 1H), 4.23 (d, J = 17.4 Hz, 1H), 4.18 –4.04(m,2H),3.79(d,J=13.4Hz,1H),3.62(q,J＝8.7,6.4Hz,5H),3.57–3.49(m,14H),3.34–3.15(m,8H ), 2.96–2.86 (m, 2H), 2.70 (d, J = 10.9 Hz, 2H), 2.65–2.56 (m, 2H), 2.30 (s, 2H), 2.01 (q, J = 2.4 Hz, 3H) , 1.89 (s, 1H), 1.71 (d, J = 12.5 Hz, 2H), 1.44 (t, J = 6.4 Hz, 2H), 1.17 (d, J = 12.7 Hz, 1H), 1.05 (d, J = 12.2Hz,1H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₆₈ H ₈₀ ClN ₁₀ O ₁₄ S ₂ ⁺ [M+H] ⁺ ,1359.4980; measured value, 1359.4986.

Example 86: (2S,4R)-1-((S)-2-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-4-oxobutyrylamino )-3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS230170)

Referring to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS074011) 4-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy (Oxybut-2-yl)amino)-4-oxobutanoic acid was prepared to obtain the target compound (SIAIS230170). Yellow powder, m=12mg, yield=38%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.77 (s, 1H), 11.68 (s, 1H), 10.45 (s, 1H), 9.02 (s, 1H), 8.65 (s, 1H), 8.60-- 8.49 (m, 2H), 8.06 (d, J = 2.6 Hz, 1H), 7.90 (d, J = 9.3 Hz, 1H), 7.81 (dd, J = 9.2, 2.3 Hz, 1H), 7.58 (d, J ＝2.6Hz,1H),7.54–7.50(m,2H),7.45–7.37(m,6H),7.13(d,J＝9.5Hz,1H), 7.09(d,J＝8.4Hz,2H), 6.72 (dd,J=9.0,2.3Hz,1H), 6.42(dd,J=3.4,1.9Hz,1H), 6.26(d,J=2.3Hz,1H), 4.52(dd,J=9.4,2.4Hz, 1H), 4.43 (dd, J = 9.5, 6.7 Hz, 2H), 4.35 (dt, J = 5.2, 2.5 Hz, 3H), 3.89 (d, J = 13.3 Hz, 1H), 3.71–3.59 (m, 4H ), 3.54 (d, J = 4.9 Hz, 2H), 3.36–3.20 (m, 6H), 2.95 (t, J = 12.7 Hz, 1H), 2.70 (q, J = 11.2 Hz, 2H), 2.55-2.48 (m,4H),2.45(s,3H),2.42–2.35(m,1H),2.32(s,2H),2.02(d,J=13.1Hz,3H),1.95-1.85(m,,2H) ,1.72(dd,J＝23.0,13.1Hz,2H),1.44(t,J＝6.4Hz,2H),1.16(d,J＝12.4Hz,1H),1.04(d,J＝13.1Hz,1H) ,1.00-0.90(m,15H).HRMS(ESI)m/z: calculated value C ₇₁ H ₈₄ ClN ₁₂ O ₁₁ S ₂ ⁺ [M+H] ⁺ ,1379.5507; measured value, 1379.5502.

Example 87: (2S,4R)-1-((S)-2-(6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-6-oxohexanamido )-3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS230171)

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS074013) 6-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy (Oxybut-2-yl)amino)-6-oxohexanoic acid was prepared to obtain the target compound (SIAIS230171). Yellow powder, m=10mg, yield=31%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.67 (s, 1H), 10.03 (s, 1H), 8.99 (s, 1H), 8.64 (t, J = 6.0 Hz, 1H), 8.62–8.53 (m, 2H), 8.05 (d, J = 2.5 Hz, 1H), 7.85 (d, J = 9.4 Hz, 1H), 7.81 (dd, J = 9.2, 2.3 Hz, 1H), 7.56(d,J=2.6Hz,1H),7.55-7.50(m,2H),7.45-7.37(m,6H),7.13(d,J=9.4Hz,1H),7.09(d,J=8.4Hz , 2H), 6.71 (dd, J = 9.0, 2.3 Hz, 1H), 6.40 (dd, J = 3.4, 1.8 Hz, 1H), 6.25 (d, J = 2.2 Hz, 1H), 4.54 (d, J = 9.4Hz, 1H), 4.48–4.32 (m, 4H), 4.21 (dd, J = 15.9, 5.5 Hz, 1H), 3.87 (d, J = 13.9 Hz, 1H), 3.73-3.50 (m, 6H), 3.35–3.23(m,4H), 3.18(d,J=12.1Hz,2H), 2.94(t,J=12.7Hz,1H), 2.71(d,J=11.6Hz,2H), 2.60-2.48(m , 2H), 2.44 (s, 3H), 2.28 (t, J = 7.0 Hz, 4H), 2.13 (dd, J = 14.3, 7.4 Hz, 1H), 2.01 (s, 3H), 1.90 (ddd, J = 12.8,8.6,4.7Hz,2H),1.77–1.65(m,2H), 1.47(dd,J=16.4,7.2Hz,7H), 1.13(d,J=12.2Hz,1H), 1.09–0.99(m ,1H),0.94(d,J=3.1Hz,15H).HRMS(ESI)m/z: calculated value C ₇₃ H ₈₈ ClN ₁₂ O ₁₁ S ₂ ⁺ [M+H] ⁺ ,1407.5820; measured value, 1407.5819 .

Example 88: (2S,4R)-1-((S)-2-(8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-8-oxooctanoylamino )-3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS230172)

Referring to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS074015) 8-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy The target compound (SIAIS230172) was prepared by the preparation of (but-2-yl)amino)-8-oxooctanoic acid. Yellow powder, m=11mg, yield=33%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.67 (s, 1H), 10.05 (s, 1H), 9.00 (s, 1H), 8.64 (t, J = 6.0 Hz, 1H),8.61–8.52(m,2H),8.05(d,J=2.6Hz,1H),7.88–7.79(m,2H),7.56(d,J=2.6Hz,1H),7.55–7.49(m ,2H),7.45–7.36(m,6H),7.13(d,J=9.4Hz,1H), 7.09(d,J=8.4Hz,2H), 6.72(dd,J=9.0,2.3Hz,1H) ,6.40(dd,J=3.4,1.9Hz,1H),6.25(d,J=2.3Hz,1H),4.54(d,J=9.4Hz,1H),4.47–4.33(m,4H),4.22( dd,J=15.9,5.5Hz,1H),3.86(d,J=13.7Hz,1H),3.70-3.60(m,4H),3.58-3.51(m,2H),3.35-3.24(m,4H) , 3.17 (t, J = 12.4 Hz, 2H), 2.94 (t, J = 12.8 Hz, 1H), 2.72 (t, J = 7.8 Hz, 2H), 2.55-2.48 (m, 1H), 2.44 (s, 3H), 2.31-2.21(m, 5H), 2.16-2.07(m, 1H), 2.01(s, 3H), 1.95-1.85(m, 2H), 1.76-1.66(m, 2H), 1.52-1.40( m,6H),1.25(s,4H),1.13(d,J=12.2Hz,1H),1.09–1.00(m,1H),0.94(d,J=3.2Hz,15H).HRMS(ESI)m /z: Calculated value C ₇₅ H ₉₂ ClN ₁₂ O ₁₁ S ₂ ⁺ [M+H] ⁺ , 1435.6133; measured value, 1435.6135.

Example 89: (2S,4R)-1-((S)-2-(10-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-10-oxodecanoylamino )-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS230173)

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS074019) 10-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy (But-2-yl)amino)-10-oxodecanoic acid was prepared to obtain the target compound (SIAIS230173). Yellow powder, m=10mg, yield=30%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.66 (s, 1H), 9.80 (s, 1H), 8.99 (s, 1H), 8.64 (t, J = 6.0 Hz, 1H), 8.61–8.54(m,2H), 8.04(d,J=2.5Hz,1H),7.88–7.77(m,2H),7.56(s,1H),7.55-7.50(m,2H),7.46 –7.35(m,6H),7.13(d,J=9.4Hz,1H), 7.09(d,J=8.3Hz,2H), 6.72(dd,J=9.0,2.3Hz,1H), 6.40(dd, J = 3.4, 1.8 Hz, 1H), 6.25 (d, J = 2.2 Hz, 1H), 4.54 (d, J = 9.4 Hz, 1H), 4.49–4.33 (m, 4H), 4.21 (dd, J = 15.9 ,5.5Hz,1H),3.86(d,J=14.0Hz,1H),3.75-3.55(s,6H),3.34-3.22(m,4H),3.18-3.10(m,2H),2.94(t, J = 12.7Hz, 1H), 2.75-2.65 (m, 2H), 2.55-2.48 (m, 1H), 2.44 (s, 3H), 2.25 (dt, J = 14.1, 7.5Hz, 5H), 2.17-2.08 (m,1H),2.01(s,3H),1.95-1.85(m,2H),1.79-1.66(m,2H),1.50-1.40(m,6H),1.24(s,8H),1.13(d ,J=12.7Hz,1H),1.04(d,J=12.2Hz,1H),0.93(d,J=4.3Hz,15H).HRMS(ESI)m/z: calculated value C ₇₇ H ₉₆ ClN ₁₂ O ₁₁ S ₂ ⁺ [M+H] ⁺ , 1463.6446; measured value, 1435.6456.

Example 90: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-methylnitrogen Etan-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4- (((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268174) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS268115) and the intermediate LM (SIAIS151025) prepared according to Scheme 1 (2-(2,6-dioxopiperidine) -3-yl)-1,3-dioxo-isoindolin-4-yl)glycine was prepared to obtain the target compound (SIAIS268174). Yellow powder, m=14mg, yield=52%

¹ H NMR(500MHz,DMSO-d ₆ )δ11.69(d,J=13.0Hz,2H),11.10(s,1H),9.33(s,1H),8.62(t,J=6.0Hz,1H) ,8.56(d,J=2.3Hz,1H),8.02(d,J=2.6Hz,1H),7.79(dd,J=9.2,2.3Hz,1H),7.58(dd,J=8.5,7.1Hz, 1H), 7.55–7.48 (m, 6H), 7.35 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 9.4 Hz, 1H), 7.07 ( d,J=7.0Hz,1H), 6.99(d,J=8.6Hz,1H), 6.92(d,J=7.6Hz,1H), 6.87(s,1H), 6.68(dd,J=9.1,2.3 Hz, 1H), 6.38 (dd, J = 3.4, 1.9 Hz, 1H), 6.26 (d, J = 2.3 Hz, 1H), 5.07 (dd, J = 12.8, 5.5 Hz, 1H), 4.37 (t, J ＝8.5Hz,1H),4.31(d,J＝6.5Hz,2H), 4.28–3.89(m,6H), 3.85(ddd,J＝11.5,4.5,1.8Hz,2H),3.55(d,J＝ 11.8Hz, 2H), 3.34–3.23(m, 4H), 3.21–3.14(m, 1H), 3.07(s, 4H), 2.88(ddd, J = 16.4, 13.4, 5.2Hz, 3H), 2.65–2.54 (m,2H),2.08–1.98(m,1H),1.88(ddt,J=11.3,7.8,3.9Hz,1H),1.66–1.57(m,2H),1.30-1.20(m,3H).HRMS (ESI) m/z: calculated value C ₆₂ H ₆₁ ClN ₁₁ O ₁₃ S ⁺ [M+H] ⁺ , 1234.3854; measured value, 1234.3850.

Example 91: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3- ((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propionyl)azetidin-3-yl )Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H- Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268163) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS268115) and the intermediate LM (SIAIS151026) prepared according to Scheme 1 were used as 3-((2-(2,6-dioxo) Piperidin-3-yl)-1,3-dioxo-isoindolin-4-yl)amino)propionic acid was prepared to obtain the target compound (SIAIS268163). Yellow powder, m=9mg, yield=33%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.69 (s, 1H), 11.67 (s, 1H), 11.09 (d, J = 4.4 Hz, 1H), 8.98 (s, 1H), 8.62 (t, J = 6.0 Hz, 1H), 8.56 (d, J = 2.4 Hz, 1H), 8.03 (d, J = 2.7 Hz, 1H), 7.80 (dd, J = 9.3, 2.4 Hz, 1H), 7.62–7.54 ( m, 1H), 7.54–7.47 (m, 6H), 7.34 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.4 Hz, 1H), 7.12 (d, J = 9.5 Hz, 2H), 7.03(d,J=7.1Hz,1H), 6.91(d,J=7.7Hz,1H), 6.72(s,1H), 6.69(dd,J=9.0,2.3Hz,1H), 6.38(dd,J = 3.4, 1.9 Hz, 1H), 6.26 (s, 1H), 5.03 (dd, J = 12.8, 5.4 Hz, 1H), 4.22 (dd, J = 25.0, 11.3 Hz, 5H), 4.00 (t, J = 9.2Hz, 2H), 3.89-3.79 (m, 4H), 3.60-3.50 (m, 4H), 3.36-3.21 (m, 4H), 3.10-2.95 (m, 5H), 2.95-2.79 (m, 3H) ,2.67–2.55(m,1H),2.38(q,J=6.2,5.6Hz,2H),2.05–1.96(m,1H),1.95-1.85(m,1H),1.61(d,J=12.9Hz ,2H),1.30–1.20(m,3H).HRMS(ESI)m/z: calculated value C ₆₃ H ₆₃ ClN ₁₁ O ₁₃ S ⁺ [M+H] ⁺ ,1248.4011; measured value, 1248.4013.

Example 92: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4- ((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyryl)azetidin-3-yl )Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H- Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268164) preparation

Referring to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS268115) and intermediate LM (SIAIS151019) 4-((2-(2,6-dioxo) prepared according to Scheme 1 were used under appropriate conditions understood in the art. The target compound (SIAIS268164) was prepared by using piperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid. Yellow powder, m=16mg, yield=58%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.71 (s, 1H), 11.68 (s, 1H), 11.09 (s, 1H), 9.49 (s, 1H), 8.62 (t, J = 6.0 Hz, 1H), 8.56 (d, J = 2.3 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 9.2, 2.4 Hz, 1H), 7.56 (dd, J = 8.6, 7.1 Hz, 1H), 7.53–7.49 (m, 6H), 7.35 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 1H), 7.13 (dd, J = 10.4, 9.0 Hz, 2H ), 7.01 (d, J = 7.0 Hz, 1H), 6.91 (d, J = 7.7 Hz, 1H), 6.69 (dd, J = 9.0, 2.3 Hz, 1H), 6.63 (s, 1H), 6.38 (dd ,J=3.4,1.9Hz,1H), 6.26(d,J=2.3Hz,1H), 5.05(dd,J=12.7,5.4Hz,1H), 4.30-4.15(m,5H),4.05-3.95( m,2H),3.89–3.77(m,3H),3.55(d,J=13.3Hz,2H), 3.35–3.21(m,6H),3.07(d,J=13.0Hz,5H),2.93-2.85 (m,3H),2.58(d,J=18.7Hz,1H),2.13(t,J=7.1Hz,2H),2.05-1.98(m,1H),1.92-1.85(m,1H),1.82– 1.73(m,2H),1.61(d,J=12.1Hz,2H),1.30-1.20(m,3H).HRMS(ESI) m/z: calculated value C ₆₄ H ₆₅ ClN ₁₁ O ₁₃ S ⁺ (M +H] ⁺ , 1262.4167; measured value, 1262.4167.

Example 93: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5- ((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentanoyl)azetidin-3-yl)methoxy Yl)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran- 4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268165) preparation

Referring to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS268115) and the intermediate 5-((2-(2,6-dioxopiperidine-3) prepared according to Scheme 2 were used. -Yl)-1-oxoisoindolin-4-yl)amino)pentanoic acid (SIAIS1210133) was prepared to obtain the target compound (SIAIS268165). Yellow powder, m=10mg, yield=36%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.69 (s, 1H), 11.01 (s, 1H), 9.61 (s, 1H), 8.61 (t, J = 6.0 Hz, 1H), 8.56 (d, J = 2.3 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 9.1, 2.3 Hz, 1H), 7.58–7.46 (m, 6H), 7.35 (d, J = 8.0 Hz, 2H), 7.27 (t, J = 7.7 Hz, 1H), 7.18 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 9.4 Hz, 1H), 6.92 ( dd, J = 13.5, 7.5 Hz, 2H), 6.74 (d, J = 8.3 Hz, 1H), 6.70 (dd, J = 8.9, 2.2 Hz, 1H), 6.43-6.35 (m, 1H), 6.26 (d ,J=2.2Hz,1H),5.11(dd,J=13.2,5.1Hz,1H),4.31–4.10(m,7H),4.05–3.74(m,6H),3.54(d,J=13.3Hz, 2H), 3.34–3.22(m,4H), 3.18-3.00(m,6H), 2.99–2.79(m,3H), 2.62(d,J=19.8Hz,1H), 2.34–2.21(m,1H) ,2.12-1.98(m,3H),1.88(ddd,J=11.2,7.4,3.9Hz,1H),1.66-1.52(m,5H),1.30-1.20(m,3H).HRMS(ESI)m/ z: Calculated value C ₆₅ H ₆₉ ClN ₁₁ O ₁₂ S ⁺ [M+H] ⁺ , 1262.4531; measured value, 1262.4530.

Example 94: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6- ((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)azetidin-3-yl )Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H- Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268166) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS268115) and the intermediate LM (SIAIS151027) 6-((2-(2,6-dioxo) prepared according to Scheme 1 were used under appropriate conditions. Piperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoic acid was prepared to obtain the target compound (SIAIS268166). Yellow powder, m=12mg, yield=42%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.70 (s, 1H), 11.68 (s, 1H), 11.09 (s, 1H), 9.29 (s, 1H), 8.61 (t, J = 5.9 Hz, 1H), 8.56 (d, J = 2.3 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 9.0, 2.3 Hz, 1H), 7.56 (dd, J = 8.6, 7.1 Hz, 1H), 7.54-7.49 (m, 6H), 7.35 (d, J = 7.9 Hz, 2H), 7.20 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 9.4 Hz, 1H), 7.07(d,J=8.6Hz,1H), 7.01(d,J=7.0Hz,1H), 6.94–6.88(m,1H), 6.70(dd,J=9.0,2.3Hz,1H), 6.52(s ,1H), 6.38(dd,J=3.4,1.9Hz,1H), 6.26(d,J=2.2Hz,1H), 5.05(dd,J=12.8,5.5Hz,1H), 4.30–4.17(m, 4H), 4.02-3.95(m, 2H), 3.88-3.82(m, 2H), 3.79(s, 1H), 3.75-3.50(m, 6H), 3.33-3.21(m, 6H), 3.15-3.00( m,4H),2.95-2.80(m,3H),2.60(t,J=18.5Hz,1H),2.03(q,J=7.6Hz,3H),1.92-1.85(m,1H),1.60-1.45 (m,5H),1.37–1.20(m,4H).HRMS(ESI)m/z: calculated value C ₆₆ H ₆₉ ClN ₁₁ O ₁₃ S ⁺ [M+H] ⁺ , 1290.4480; measured value, 1290.4478.

Example 95: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(7- ((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoyl)azetidin-3-yl )Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H- Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268167) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS268115) and intermediate LM (SIAIS151086) 7-((2-(2,6-dioxo) prepared according to Scheme 1 were used under appropriate conditions. The target compound (SIAIS268167) was prepared by using piperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoic acid. Yellow powder, m=12mg, yield=42%

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.69 (s, 1H), 11.09 (s, 1H), 9.64 (s, 1H), 8.61 (d, J = 6.0 Hz, 1H), 8.56 (d, J = 2.3 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.80 (dd, J = 9.2, 2.4 Hz, 1H), 7.59–7.54 (m, 1H), 7.54–7.46 (m, 6H), 7.36 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 9.5 Hz, 1H), 7.07 (d, J ＝8.7Hz,1H), 7.01(d,J＝6.9Hz,1H), 6.90(d,J＝7.6Hz,1H), 6.70(dd,J＝9.0,2.3Hz,1H), 6.51(s,1H ), 6.39 (dd, J = 3.4, 1.9 Hz, 1H), 6.26 (d, J = 2.3 Hz, 1H), 5.05 (dd, J = 12.8, 5.4 Hz, 1H), 4.31–4.15 (m, 5H) ,4.09–3.94(m,3H), 3.83–3.75(m,2H), 3.55(d,J=13.2Hz,2H), 3.32–3.22(m,6H), 3.20–2.99(m,6H), 2.93 -2.83(m,3H), 2.59(d,J=18.3Hz,1H),2.02(t,J=7.3Hz,3H),1.94-1.84(m,1H),1.65-1.51(m,4H), 1.46(t,J=7.3Hz,2H),1.42–1.24(m,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₁ ClN ₁₁ O ₁₃ S ⁺ [M+H] ⁺ ,1304.4637; Measured value, 1304.4630.

Example 96: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)azetidine-3- Yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H -Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268168) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS268115) and the intermediate LM (SIAIS255121) were used to react to prepare the target compound (SIAIS268168), yellow powder, m=6.8mg, yield Rate = 20%

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(d,J=2.3Hz,1H), 8.02(s,1H), 7.85(dd,J=9.3,2.3Hz,1H), 7.72(q, J = 5.6Hz, 1H), 7.65–7.58 (m, 3H), 7.54 (q, J = 6.2, 4.0 Hz, 1H), 7.48 (dd, J = 8.0, 5.4 Hz, 4H), 7.31 (dd, J = 10.4, 7.7 Hz, 2H), 7.20 (dd, J = 38.4, 8.5 Hz, 1H), 7.00 (dd, J = 11.8, 7.6 Hz, 1H), 6.95 (d, J = 9.4 Hz, 1H), 6.71 (d,J=8.8Hz,1H),6.46(s,1H),6.34(s,1H), 5.17(d,J=13.4Hz,1H),4.58-4.34(m,8H), 4.30-4.20( m, 2H), 4.00--3.92 (m, 2H), 3.60 - 3.37 (m, 7H), 3.32-3.25 (m, 3H), 3.20 (s, 2H), 2.94-2.85 (m, 3H), 2.74 ( d,J=18.3Hz,1H), 2.69–2.62(m,2H), 2.61–2.48(m,1H), 2.20–2.11(m,1H), 2.01–1.89(m,3H), 1.70(d, J = 13.1Hz, 2H), 1.43-1.31 (m, 3H). HRMS (ESI) m/z: calculated value C ₆₅ H ₆₆ ClN ₁₀ O ₁₁ S ⁺ [M+H] ⁺ ,1229.4316; measured value, 1229.4316 .

Example 97: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)azetidine-3- Yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H -Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268169) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS268115) and the intermediate LM (SIAIS255119) were used to react to prepare the target compound (SIAIS268169), yellow powder, m=3.6mg, yield Rate = 11%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H),8.00(s,1H),7.85(dd,J=9.3,2.3Hz,1H),7.68(d, J = 7.6Hz, 1H), 7.62 (s, 0H), 7.60 (d, J = 7.4 Hz, 2H), 7.54 (d, J = 7.5 Hz, 1H), 7.51 (d, J = 2.5 Hz, 1H) ,7.47(d,J=8.4Hz,3H),7.44(d,J=3.6Hz,2H),7.33-7.27(m,2H),7.20(dd,J=39.5,8.5Hz,1H),7.00( t,J=7.7Hz,1H), 6.94(d,J=9.3Hz,1H), 6.67(d,J=8.8Hz,1H), 6.41(d,J=3.5Hz,1H), 6.27(s, 1H), 5.17(dd,J=13.3,5.0Hz,1H),4.57–4.42(m,5H),4.37(s,3H),4.22(t,J=10.0Hz,1H),4.18–4.08(m ,1H),3.99–3.91(m,2H),3.47(s,2H),3.45–3.37(m,4H), 3.27(d,J=7.0Hz,3H),3.16(s,2H), 2.87( s, 3H), 2.75 (t, J = 14.2 Hz, 1H), 2.57 (t, J = 6.6 Hz, 3H), 2.18 (d, J = 7.7 Hz, 1H), 2.00-1.90 (m, 1H), 1.81(s,2H),1.70(d,J=13.7Hz,5H),1.45-1.35(m,3H).HRMS(ESI) m/z: calculated value C ₆₆ H ₆₈ ClN ₁₀ O ₁₁ S ⁺ (M +H] ⁺ ,1243.4473; measured value,1243.4470

Example 98: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(8- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)azetidine-3- Yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H -Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268170) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS268115) and the intermediate LM (SIAIS292020) were used to react to prepare the target compound (SIAIS268170), yellow powder, m=5.7mg, yield Rate = 16%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.06(s,1H), 7.87(dd,J=9.1,2.3Hz,1H), 7.69(dd, J = 7.4, 2.3 Hz, 1H), 7.67 (d, J = 2.4 Hz, 1H), 7.62 (d, J = 8.9 Hz, 1H), 7.57 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 6.5Hz, 1H), 7.50 (d, J = 3.0 Hz, 1H), 7.47 (dd, J = 7.9, 3.1 Hz, 3H), 7.31 (dd, J = 8.3, 5.0 Hz, 2H), 7.20 ( dd, J = 32.4, 8.4 Hz, 1H), 7.00 (t, J = 7.5 Hz, 1H), 6.97 (d, J = 9.3 Hz, 1H), 6.74 (d, J = 9.0 Hz, 1H), 6.48 ( d, J = 3.4 Hz, 1H), 6.37 (d, J = 2.3 Hz, 1H), 5.16 (dd, J = 13.3, 5.2 Hz, 1H), 4.54-4.30 (m, 8H), 4.19 (t, J = 10.1Hz, 1H), 4.11 (t, J = 9.8Hz, 1H), 3.99–3.91 (m, 2H), 3.54 (d, J = 13.6Hz, 2H), 3.47–3.38 (m, 4H), 3.29 –3.26(m,3H), 3.25–3.18(m,2H), 2.95–2.83(m,3H), 2.76(d,J=16.9Hz,1H), 2.50(dd,J=8.0,5.4Hz,3H ),2.22–2.13(m,1H),2.00-1.90(m,1H),1.73-1.59(m,7H),1.55(s,2H),1.46(t,J=7.2 Hz,2H),1.42– 1.32(m,3H).HRMS(ESI)m/z: calculated value C ₆₈ H ₇₂ ClN ₁₀ O ₁₁ S ⁺ [M+H] ⁺ , 1271.4786; measured value, 1271.4780

Example 99: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(9- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)azetidine-3- Yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H -Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS268171) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS268115) and the intermediate LM (SIAIS255127) were used to react to prepare the target compound (SIAIS268171), yellow powder, m=6.6mg, yield Rate = 19%

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(d,J=2.3Hz,1H), 8.06(d,J=2.5Hz,1H), 7.86(dd,J=9.3,2.3Hz,1H) ,7.73–7.67(m,2H),7.62(d,J=8.9Hz,1H),7.59–7.50(m,3H),7.50–7.45(m,3H),7.31(ddd,J=8.5,4.6, 2.2Hz, 2H), 7.26-7.15 (m, 1H), 7.01 (d, J = 7.3 Hz, 1H), 6.97 (d, J = 9.4 Hz, 1H), 6.75 (ddd, J = 8.9, 4.3, 2.3 Hz, 1H), 6.50 (d, J = 3.4 Hz, 1H), 6.39 (s, 1H), 5.16 (dd, J = 13.3, 5.2 Hz, 1H), 4.56-4.29 (m, 8H), 4.17 (t ,J=9.3Hz,1H),4.10(t,J=9.9Hz,1H),4.00–3.92(m,2H),3.55(d,J=14.6Hz,3H),3.47–3.37(m,3H) , 3.28(d,J=7.0Hz,4H), 3.24–3.18(m,2H), 2.95–2.83(m,3H), 2.80–2.74(m,1H), 2.48(td,J=6.9,2.6Hz ,3H),2.21–2.13(m,1H),2.00-1.90(m,1H),1.70(d,J=13.1Hz,2H),1.62(q,J=8.0,7.4Hz,4H),1.52( s,2H),1.46–1.31(m,7H).HRMS(ESI)m/z: calculated value C ₆₈ H ₇₂ ClN ₁₀ O ₁₁ S ⁺ [M+H] ⁺ ,1285.4942; measured value, 1285.4936

Example 100: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(7- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)azetidine-3- Yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H -Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS292028) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS268115) and the intermediate LM (SIAIS292017) were used to react to prepare the target compound (SIAIS292028), yellow powder, m=5.1mg, yield Rate = 15%

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(d,J=2.2Hz,1H), 8.07(s,1H), 7.87(dd,J=9.2,2.3Hz,1H), 7.74–7.68( m, 2H), 7.60 (ddd, J = 11.2, 8.2, 2.5 Hz, 2H), 7.57-7.51 (m, 2H), 7.47 (dt, J = 7.7, 2.6 Hz, 3H), 7.31 (dd, J = 8.1,5.8Hz,2H),7.20(dd,J=32.3,8.4Hz,1H),7.03-6.95(m,2H),6.74(d,J=9.1Hz,1H),6.51(s,1H), 6.39(s,1H), 5.16(d,J=13.3Hz,1H),4.54-4.30(m,8H),4.21(t,J=10.0Hz,1H),4.15(s,1H),4.02-3.91 (m,2H),3.54(s,3H),3.48–3.38(m,3H), 3.29–3.15(m,5H), 2.95–2.82(m,3H), 2.76(d,J=17.1Hz,1H ), 2.58–2.46(m,3H), 2.23–2.10(m,1H), 2.00–1.92(m,1H), 1.75-1.65(m,5H), 1.65-1.55(m,4H), 1.43– 1.32 (m,3H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₀ ClN ₁₀ O ₁₁ S ⁺ [M+H] ⁺ , 1257.4629; measured value, 1257.4623.

Example 101: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)-(1,4'-linked (Piperidin)-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS346014) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS255121) to prepare the target compound (SIAIS346014), yellow powder, m=10mg, yield=30 %

¹ H NMR(500MHz, methanol-d ₄ )δ8.65(d,J=2.2Hz,1H), 8.10(d,J=2.3Hz,1H), 7.90(dd,J=9.2,2.3Hz,1H) ,7.83(d,J=2.4Hz,1H),7.75(d,J=7.5Hz,1H),7.63(t,J=7.2Hz,2H),7.58(d,J=3.4Hz,1H),7.50 (t,J=7.6Hz,1H), 7.35(d,J=8.2Hz,2H), 7.09(d,J=8.2Hz,2H), 7.06(d,J=9.3Hz,1H), 6.80(d ,J=7.8Hz,1H),6.57(d,J=3.5Hz,1H),6.45(s,1H), 5.18(dd,J=13.2,5.1Hz,1H), 4.65–4.47(m,2H) , 3.85–3.54(m,10H), 3.48–3.38(m,4H), 3.26–3.07(m,6H), 2.95–2.85(m,1H), 2.84–2.74(m,3H), 2.73–2.56( m, 3H), 2.45 (d, J = 13.6 Hz, 2H), 2.29 (dd, J = 28.1, 6.0 Hz, 4H), 2.23–2.00 (m, 9H), 1.76-1.68 (m, 2H), 1.56 (t,J=6.3Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₈ H ₇₇ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1258.5309; measured value, 1258.5338.

Example 102: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(6- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)-(1,4'-linked (Piperidin)-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS346015) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS255119) to prepare the target compound (SIAIS346015), yellow powder, m=11mg, yield=33 %

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.07(d,J=2.5Hz,1H), 7.91(dd,J=9.3,2.3Hz,1H) ,7.77–7.71(m,2H),7.67–7.61(m,2H),7.54(d,J=3.4Hz,1H),7.50(t,J=7.6Hz,1H),7.35(d,J=8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.05 (d, J = 9.4 Hz, 1H), 6.80 (dd, J = 9.0, 2.4 Hz, 1H), 6.52 (d, J = 3.5 Hz, 1H), 6.42 (d, J = 2.4 Hz, 1H), 5.18 (dd, J = 13.3, 5.2 Hz, 1H), 4.54 (q, J = 17.6 Hz, 2H), 3.84–3.53 (m, 10H ), 3.50-3.38 (m, 4H), 3.24-3.05 (m, 8H), 2.94-2.73 (m, 4H), 2.67-2.54 (m, 3H), 2.42 (d, J = 13.2 Hz, 2H), 2.32-2.85(m,2H),2.25-2.15(m,2H),2.15-2.09(m,5H),2.02-1.97(m,2H),1.76-1.64(m,4H),1.57(t,J =6.3Hz, 2H), 1.01 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₉ H ₇₉ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1272.5466; measured value, 1272.5469.

Example 103: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(7- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)-(1,4'-linked (Piperidin)-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS346016) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS346016) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS292017), yellow powder, m=10mg, yield=30 %

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(d,J=2.0Hz,1H), 8.08(s,1H), 7.90(d,J=7.7Hz,1H), 7.78(s,1H) ,7.73(d,J＝7.6Hz,1H), 7.62(dd,J＝11.7,8.3Hz,2H), 7.56(d,J＝3.3Hz,1H),7.49(t,J＝7.6Hz,1H) ,7.36(d,J=8.2Hz,2H), 7.08(d,J=8.2Hz,2H), 7.05(d,J=9.3Hz,1H), 6.80(d,J=8.9Hz,1H), 6.54 (d, J = 3.4 Hz, 1H), 6.43 (s, 1H), 5.17 (dd, J = 13.4, 5.1 Hz, 1H), 4.53 (d, J = 17.5 Hz, 1H), 4.47 (d, J = 17.5Hz, 1H), 3.75 (d, J = 12.7Hz, 4H), 3.68 (s, 2H), 3.67–3.53 (m, 4H), 3.45–3.38 (m, 4H), 3.24–3.03 (m, 8H) ), 2.96-2.85 (m, 1H), 2.85-2.74 (m, 3H), 2.55 (t, J = 6.8 Hz, 2H), 2.41 (d, J = 13.3 Hz, 2H), 2.31 (s, 2H) ,2.27–2.15(m,2H),2.11(s,5H),1.85(d,J=8.6Hz,2H),1.71(q,J=7.5Hz,3H),1.62-1.55(m,4H), 1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₀ H ₈₁ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1286.5622; measured value, 1286.5635.

Example 104: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(8- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)-(1,4'-linked (Piperidin)-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS346017) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS292020) to prepare the target compound (SIAIS346017), yellow powder, m=8mg, yield=23 %

¹ H NMR(500MHz, methanol-d ₄ )δ8.69(d,J=2.3Hz,1H), 8.02(d,J=2.6Hz,1H), 7.90(dd,J=9.2,2.3Hz,1H) ,7.74(d,J=7.1Hz,1H), 7.66(d,J=8.9Hz,1H), 7.62(d,J=2.2Hz,1H), 7.60(d,J=7.0Hz,1H), 7.53 –7.47(m,2H),7.36(d,J=8.4Hz,2H), 7.07(d,J=8.4Hz,2H), 7.03(d,J=9.3Hz,1H), 6.79(dd,J= 8.9, 2.2 Hz, 1H), 6.46 (d, J = 3.5 Hz, 1H), 6.37 (d, J = 2.1 Hz, 1H), 5.18 (dd, J = 13.3, 5.2 Hz, 1H), 4.52 (d, J = 17.5Hz, 1H), 4.46 (d, J = 17.5Hz, 1H), 3.69 (q, J = 22.6, 18.2Hz, 7H), 3.55 (t, J = 11.1Hz, 1H), 3.47–3.37 ( m,4H), 3.19–3.03(m,8H), 2.93–2.85(m,1H), 2.84–2.74(m,3H), 2.53(q,J=6.1Hz,3H),2.41(d,J= 13.4Hz, 2H), 2.28 (s, 2H), 2.18 (d, J = 12.3 Hz, 2H), 2.12 (d, J = 12.2 Hz, 5H), 1.81 (d, J = 8.0 Hz, 2H), 1.67 (q,J=7.1Hz,4H),1.57(t,J=6.5Hz,4H),1.47(q,J=7.6Hz,2H),1.00(s,6H).HRMS(ESI)m/z: Calculated value C ₇₁ H ₈₃ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1300.5779; measured value, 1300.5785.

Example 105: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(9- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)-(1,4'-linked (Piperidin)-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS346018) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS346018) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS255127), yellow powder, m=14mg, yield=40 %

¹ H NMR(500MHz, methanol-d ₄ )δ8.65(d,J=2.2Hz,1H), 8.09(s,1H), 7.89(d,J=8.4Hz,1H), 7.79(s,1H) ,7.73(d,J=7.6Hz,1H),7.64-7.58(m,2H),7.56(d,J=3.0Hz,1H),7.50(t,J=7.6Hz,1H),7.35(d, J = 7.9 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 7.06 (s, 1H), 6.79 (d, J = 8.4 Hz, 1H), 6.57-6.52 (m, 1H), 6.43 ( s, 1H), 5.17 (dd, J = 13.3, 5.1 Hz, 1H), 4.52 (d, J = 17.5 Hz, 1H), 4.45 (d, J = 17.5 Hz, 1H), 375-3.55 (m, 8H ),3.41(t,J=12.0Hz,4H), 3.26–3.16(m,2H), 3.15–3.02(m,5H), 2.90(ddd,J＝18.3,13.5,5.3Hz,1H), 2.84– 2.74 (m, 3H), 2.51 (q, J = 8.8, 6.9 Hz, 3H), 2.40 (s, 2H), 2.32 (d, J = 6.5 Hz, 2H), 2.26-2.15 (m, 3H), 2.10 (s,5H),1.82–1.60(m,6H),1.55(dt,J=13.3,6.7Hz,4H),1.44(s,4H),1.00(s,6H).HRMS(ESI)m/z : Calculated value C ₇₂ H ₈₅ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1314.5935; measured value, 1314.5951.

Example 106: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3- (1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-1H-1,2,3-triazol-4-yl )Propyl)-[1,4'-Dipiperidin]-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS346019)

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS315194) to prepare the target compound SIAIS346019 (yellow powder, m = 12.6 mg, yield = 37%) ).

¹ H NMR(500MHz, methanol-d ₄ )δ8.64(d,J=2.3Hz,1H), 8.58(s,1H), 8.12(d,J=2.4Hz,1H), 8.02(d,J= 7.9Hz,1H),7.93-7.87(m,3H),7.75(t,J=7.8Hz,1H),7.64-7.59(m,2H),7.36(d,J=8.3Hz,2H),7.10- 7.08 (m, 2H), 7.07 (d, J = 9.5 Hz, 1H), 6.81 (dd, J = 9.0, 2.4 Hz, 1H), 6.59 (d, J = 3.3 Hz, 1H), 6.48 (d, J =2.3Hz, 1H), 5.19 (ddd, J = 13.3, 5.2, 3.0 Hz, 1H), 3.81 (d, J = 12.4 Hz, 2H), 3.75 (d, J = 13.6 Hz, 2H), 3.71-3.56 (m,6H), 3.46–3.38(m,4H), 3.23(dd,J=24.1,11.6Hz,3H), 3.17–3.07(m,3H),3.01–2.93(m,3H), 2.93–2.85 (m, 2H), 2.84–2.74 (m, 3H), 2.55 (qd, J = 13.2, 4.6 Hz, 1H), 2.46 (d, J = 13.5 Hz, 2H), 2.36–2.17 (m, 8H), 2.11(s,5H),1.72(d,J=15.0Hz,2H),1.57(t,J=6.4Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₈ H ₇₈ ClN ₁₄ O ₉ S ⁺ [M+H] ⁺ ,1301.5480; measured value,1301.5496.

Example 107: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( 1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-1H-1,2,3-triazol-4-yl) (Propyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS346020) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS315194) to prepare the target compound (SIAIS346020), yellow powder, m=11mg, yield=34 %

¹ H NMR(500MHz, methanol-d ₄ )δ8.64(d,J=2.3Hz,1H), 8.57(s,1H), 8.13-8.07(m,1H), 8.02-7.97(m,1H), 7.92–7.87 (m, 2H), 7.84 (d, J = 2.4 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H), 7.63–7.56 (m, 2H), 7.36 (d, J = 8.4 Hz) ,2H), 7.09(d,J=8.4Hz,2H), 7.05(d,J=9.3Hz,1H), 6.79(dd,J=8.9,2.3Hz,1H), 6.57(d,J=3.5Hz ,1H),6.46(s,1H),5.18(dd,J=13.3,5.1Hz,1H),3.80-3.60(m,5H),3.46-3.38(m,4H),3.25-3.17(m,3H) ), 23.02-2.95 (m, 4H), 2.95-2.90 (m, 2H), 2.86 (s, 3H), 2.83-2.74 (m, 3H), 2.70 (s, 2H), 2.53 (qd, J = 13.1 ,4.6Hz,1H),2.32(s,2H),2.28–2.17(m,3H),2.13–2.01(m,5H),1.70–1.52(m,4H),1.38-1.28(m,4H), 1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₆₉ ClN ₁₃ O ₉ S ⁺ [M+H] ⁺ , 1218.4745; measured value, 1218.4712.

Example 108: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( 1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-1H-1,2,3-triazol-4-yl) (Propyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS346021) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS346021) was prepared using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS315194), yellow powder, m=10mg, yield=31 %

¹ H NMR(500MHz, methanol-d ₄ )δ8.57–8.48(m,2H), 8.02(s,1H), 7.89(d,J=7.8Hz,1H), 7.84(d,J=8.7Hz, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.71 (s, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.49 (s, 1H), 7.33 (d, J = 7.9 Hz, 2H), 7.07 (d, J = 7.9 Hz, 2H), 7.00 (d, J = 9.3 Hz, 1H), 6.70 (d, J = 8.9 Hz, 1H) ,6.47(s,1H),6.35(s,1H), 5.14(dd,J=13.4,5.1Hz,1H), 4.78–4.66(m,2H), 3.76–3.59(m,6H), 3.47–3.36 (m,5H), 3.28(d,J=7.9Hz,2H), 3.23–3.12(m,2H), 3.01–2.70(m,8H), 2.48(q,J=12.7Hz,1H), 2.39– 2.15(m,6H),2.09(s,2H),2.02-1.90(m,3H),1.55(t,J=6.2Hz,2H),1.34(dd,J=34.4,21.0Hz,1H),0.99 (s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₆₉ ClN ₁₃ O ₉ S ⁺ [M+H] ⁺ , 1218.4745; measured value, 1218.4753.

Example 109: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1- (5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)-1H-1, 2,3-Triazol-4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS315186) preparation

first step

With reference to the method of Example 42, under appropriate conditions understandable in the art, the intermediate compound was prepared using intermediate BINDER (SIAIS230138) and propargyl bromide. HRMS (ESI) m/z: calculated value C ₄₈ H ₅₄ ClN ₈ O ₆ S ⁺ [M+H] ⁺ , 905.35; measured value 906.42.

Second step

Referring to the method of Example 56, the intermediate compound obtained in the previous step was reacted with the intermediate LM (SIAIS255121) to prepare the target compound SIAIS315186. ¹ H NMR (500MHz, DMSO-d ₆ )δ11.66(s, 1H), 11.00 (s, 1H), 8.93 (s, 1H), 8.57 (s, 0H), 8.51 (s, 1H), 8.24 (s, 0H), 8.00 (s, 1H), 7.75 (d, J = 11.8 Hz, 0H), 7.72 (d, J = 7.5 Hz, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.56-7.44 (m, 4H), 7.34 (d, J = 8.5 Hz, 2H), 7.04 ( d, J = 8.4Hz, 3H), 6.66 (dd, J = 9.0, 2.4 Hz, 1H), 6.37 (s, 1H), 6.20 (s, 1H), 5.15 (dd, J = 13.3, 5.1 Hz, 1H) ),4.54(d,J=6.1Hz,1H),4.53-4.46(m,1H), 4.34(d,J=17.7Hz,1H),3.61(td,J=6.8,4.1Hz,2H), 3.35 -3.28 (m, 6H), 3.13 (dd, J = 7.6, 4.1 Hz, 3H), 3.06 (s, 4H), 2.92 (ddd, J = 16.3, 13.2, 5.1 Hz, 2H), 2.73 (s, 2H) ), 2.64 (t, J = 1.9 Hz, 1H), 2.59 (d, J = 18.1 Hz, 1H), 2.37 (q, J = 1.9 Hz, 1H), 2.16 (dt, J = 13.8, 7.2 Hz, 8H ),2.06–1.99(m,1H),1.95(s,2H),1.81(s,3H),1.38(t,J=6.4Hz,3H),0.92(s,6H).HRMS(ESI)m/ z: Calculated value C ₆₆ H ₇₁ ClN ₁₃ O ₉ S ⁺ [M+H] ⁺ , 1256.4901; measured value, 1256.4903.

Example 110: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3- ((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)-[1,4'-dipiperidine] -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363034) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363034) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS213132), yellow powder, yield = 24%

¹ H NMR(500MHz, methanol-d ₄ )δ8.69(d,J=2.3Hz,1H),7.99(s,1H),7.89(dd,J=9.2,2.3Hz,1H),7.75(d, J=7.6Hz,1H), 7.70(d,J=7.5Hz,1H), 7.66(d,J=9.0Hz,1H), 7.61–7.54(m,2H),7.46(d,J=3.4Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 9.3 Hz, 1H), 6.78 (dd, J = 9.0, 2.4 Hz, 1H), 6.43 (d, J = 3.4 Hz, 1H), 6.34 (d, J = 2.3 Hz, 1H), 5.17 (dd, J = 13.4, 5.0 Hz, 1H), 4.52 (d, J = 17.3 Hz, 1H), 4.45(d,J=17.8Hz,1H), 3.76–3.60(m,8H), 3.56(dd,J=5.4,4.1Hz,2H), 3.47–3.37(m,6H), 3.26(d ,J=8.1Hz,2H), 3.24–3.03(m,8H), 2.90(ddd,J=18.4,13.6,5.4Hz,1H), 2.84–2.75(m,3H), 2.55(dd,J=14.4 ,9.8Hz,1H),2.41(d,J=13.2Hz,2H),2.28(s,2H),2.23-2.01(m,7H),1.67(d,J=11.2Hz,2H),1.56(t ,J=6.4Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₇ ClN ₁₁ O ₉ S ₂ ⁺ [M+H] ⁺ ,1266.5030; measured value, 1266.5036 .

Example 111: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4- ((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)-[1,4'-dipiperidine] -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363035) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS213134) to prepare the target compound (SIAIS363035), yellow powder, yield = 23%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.68 (d, J = 2.2 Hz, 1H), 8.07 (s, 1H), 7.90 (d, J = 9.4 Hz, 1H), 7.70 (d, J = 7.8Hz, 2H), 7.65 (dd, J = 11.2, 8.1 Hz, 2H), 7.57–7.52 (m, 2H), 7.36 (d, J = 7.8 Hz, 2H), 7.09 (d, J = 7.9 Hz, 2H), 7.04 (d, J = 9.3 Hz, 1H), 6.80 (d, J = 8.8 Hz, 1H), 6.51 (d, J = 3.4 Hz, 1H), 6.41 (s, 1H), 5.17 (dd, J = 13.3, 5.0 Hz, 1H), 4.50 (d, J = 17.4 Hz, 1H), 4.43 (d, J = 17.3 Hz, 1H), 3.77–3.56 (m, 10H), 3.48–3.37 (m, 5H) ), 3.19–3.07(m,9H), 2.94–2.86(m,1H), 2.78(d,J=16.2Hz,3H), 2.61–2.51(m,1H),2.42(d,J=12.8Hz, 2H), 2.30 (s, 2H), 2.18 (s, 2H), 2.11 (s, 5H), 1.94 (d, J = 7.8 Hz, 2H), 1.70 (d, J = 13.7 Hz, 4H), 1.57 ( t,J=6.3Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₉ ClN ₁₁ O ₉ S ₂ ⁺ [M+H] ⁺ ,1280.5187; measured value, 1280.5171.

Example 112: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5- ((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)-[1,4'-dipiperidine] -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363036) preparation

With reference to the method in Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363036) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS213135), yellow powder, yield = 24%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.03(s,1H), 7.89(dd,J=9.2,2.3Hz,1H), 7.68–7.63( m, 4H), 7.57–7.52 (m, 1H), 7.50 (d, J = 3.5 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.02(d,J=9.3Hz,1H), 6.79(dd,J=9.0,2.4Hz,1H), 6.47(d,J=3.5Hz,1H), 6.37(d,J=2.4Hz,1H), 5.16 (dd, J = 13.3, 5.2 Hz, 1H), 4.47 (d, J = 17.2 Hz, 1H), 4.41 (d, J = 17.3 Hz, 1H), 3.75–3.54 (m, 9H), 3.49–3.37 (m,5H),3.19–3.04(m,9H), 2.90(ddd,J=18.5,13.6,5.4Hz,1H), 2.83–2.75(m,3H),2.53(qd,J=13.2,4.6Hz ,1H),2.42(d,J=13.2Hz,2H),2.30(s,2H),2.25-2.15(m,3H),2.11(s,5H),1.81-1.65(m,6H),1.56( q,J＝8.1,7.1Hz,4H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₈ H ₈₁ ClN ₁₁ O ₉ S ₂ ⁺ [M+H] ⁺ ,1294.5343; actual measurement Value, 1294.5349.

Example 113: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4- ((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)-[1,4'-dipiperidine] -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363037) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363037) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS1222171), yellow powder, yield = 25%

¹ H NMR(500MHz, methanol-d ₄ )δ8.69(d,J=2.3Hz,1H), 8.06(s,1H), 7.90(dd,J=9.2,2.3Hz,1H), 7.65(d, J = 8.9Hz, 1H), 7.60 (s, 1H), 7.53-7.46 (m, 2H), 7.39 (d, J = 7.5 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.22 ( d, J = 7.8 Hz, 1H), 7.08 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 9.3 Hz, 1H), 6.78 (dd, J = 8.9, 2.3 Hz, 1H), 6.46 ( d, J = 3.4 Hz, 1H), 6.35 (d, J = 2.3 Hz, 1H), 5.15 (dd, J = 13.3, 5.1 Hz, 1H), 4.51 (d, J = 17.3 Hz, 1H), 4.42 ( d, J = 17.3 Hz, 1H), 4.21 (t, J = 5.6 Hz, 2H), 3.78 (d, J = 12.5 Hz, 2H), 3.74–3.61 (m, 6H), 3.60–3.55 (m, 1H) ), 3.44–3.37(m,3H),3.22(t,J=8.3Hz,2H),3.19–3.04(m,7H), 2.90(ddd,J=18.3,13.4,5.3Hz,1H), 2.79( t,J=13.7Hz,3H),2.60–2.50(m,1H),2.43(d,J=13.3Hz,2H),2.28(s,2H),2.24–2.15(m,3H),2.11(s , 3H), 2.03 (d, J = 8.2 Hz, 4H), 1.92 (dt, J = 14.0, 6.8 Hz, 2H), 1.69 (q, J = 12.4, 11.7 Hz, 2H), 1.56 (t, J = 6.3Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₉ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1264.5415; measured value, 1264.5435.

Example 114: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5- ((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)pentyl)-[1,4'-dipiperidine] -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363038) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363038) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS1222169), yellow powder, yield = 24%

¹ H NMR(500MHz, methanol-d ₄ )δ8.69(s,1H), 8.04(s,1H), 7.90(d,J=8.9Hz,1H), 7.65(d,J=9.6Hz,2H) ,7.51–7.46(m,2H),7.37(dd,J＝10.8,7.5Hz,3H), 7.22(d,J＝8.1Hz,1H), 7.08(d,J＝7.8Hz,2H), 7.03( d,J=9.2Hz,1H), 6.79(d,J=8.8Hz,1H), 6.47(d,J=3.3Hz,1H), 6.38(s,1H), 5.15(d,J=12.7Hz, 1H), 4.48 (d, J = 17.2 Hz, 1H), 4.40 (d, J = 17.3 Hz, 1H), 4.19 (t, J = 5.8 Hz, 2H), 3.77-3.61 (m, 8H), 3.58 ( t,J=4.8Hz,1H), 3.45–3.38(m,4H), 3.19–3.05(m,9H), 2.87(d,J=13.7Hz,1H), 2.77(d,J=15.8Hz,3H ),2.53(d,J=14.2Hz,1H),2.43(d,J=12.4Hz,2H),2.29(s,2H),2.20(d,J=22.3Hz,3H),2.11(s,4H ), 1.95–1.85 (m, 4H), 1.70 (dd, J = 20.7, 11.4 Hz, 2H), 1.62 (d, J = 6.9 Hz, 2H), 1.57 (t, J = 6.0 Hz, 2H), 1.00 (s,6H).HRMS(ESI)m/z: calculated value C ₆₈ H ₈₁ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1278.5572; measured value, 1278.5603.

Example 115: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3- ((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)-(1,4'-dipiper (Pyridin)-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363105) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363105) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS268007), yellow powder, m=10mg, yield=30 %

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(d,J=2.3Hz,1H), 8.08(d,J=2.5Hz,1H), 7.90(dd,J=9.2,2.3Hz,1H) , 7.78 (d, J = 2.5 Hz, 1H), 7.63 (d, J = 8.9 Hz, 1H), 7.61-7.54 (m, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.6Hz, 1H), 7.09 (d, J = 8.5 Hz, 3H), 7.05 (d, J = 9.3 Hz, 1H), 6.80 (dd, J = 8.9, 2.3 Hz, 1H), 6.54 (d, J = 3.5 Hz, 1H), 6.44 (d, J = 2.3 Hz, 1H), 5.05 (dd, J = 12.5, 5.4 Hz, 1H), 3.75 (dd, J = 24.2, 13.0 Hz, 4H), 3.68 ( s, 2H), 3.64 (d, J = 11.6 Hz, 2H), 3.50 (t, J = 6.6 Hz, 2H), 3.45–3.38 (m, 4H), 3.29–3.24 (m, 2H), 3.24–3.05 (m, 6H), 2.90–2.66 (m, 6H), 2.44 (d, J = 13.2 Hz, 2H), 2.31 (s, 2H), 2.11 (s, 10H), 1.70 (q, J = 14.2, 13.5 Hz, 2H), 1.57 (t, J = 6.3 Hz, 2H), 1.01 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₆ H ₇₆ ClN ₁₂ O ₁₀ S ⁺ [M+H] ⁺ , 1263.5211; measured value, 1263.5238.

Example 116: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5- ((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)-(1,4'-dipiper (Pyridin)-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363106) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363106) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS264016), yellow powder, yield = 47%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.05(d,J=2.5Hz,1H), 7.90(dd,J=9.2,2.3Hz,1H) ,7.68(d,J=2.5Hz,1H), 7.64(d,J=8.8Hz,1H), 7.56(dd,J=8.6,7.1Hz,1H), 7.52(d,J=3.5Hz,1H) ,7.36(d,J=8.4Hz,2H),7.11–7.02(m,5H), 6.79(dd,J=9.0,2.4Hz,1H), 6.50(d,J=3.5Hz,1H),6.40( d, J = 2.3Hz, 1H), 5.05 (dd, J = 12.7, 5.5Hz, 1H), 3.82–3.62 (m, 8H), 3.57 (t, J = 12.4Hz, 1H), 3.48–3.36 (m ,7H),3.22–3.05(m,8H),2.90–2.62(m,5H),2.44(d,J=13.5Hz,2H),2.30(s,2H),2..25-2.10(m, 7H), 1.85 (dd, J = 15.8, 7.8 Hz, 2H), 1.73 (dt, J = 19.7, 10.0 Hz, 4H), 1.55 (dt, J = 21.1, 6.8 Hz, 4H), 1.00 (s, 6H ).HRMS(ESI)m/z: Calculated value C ₆₈ H ₈₀ ClN ₁₂ O ₁₀ S ⁺ [M+H] ⁺ , 1291.5524; measured value, .1291.5539

Example 117: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)-[1,4'-dipiperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363107) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363107) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS255130), yellow powder, yield = 65%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.06(d,J=2.5Hz,1H), 7.90(dd,J=9.2,2.3Hz,1H) ,7.71(d,J=2.5Hz,1H), 7.67(dd,J=7.2,1.5Hz,1H), 7.64(d,J=8.9Hz,1H), 7.53(d,J=3.5Hz,1H) ,7.51(d,J=1.5Hz,1H),7.49(d,J=7.2Hz,1H),7.36(d,J=8.4Hz,2H),7.08(d,J=8.4Hz,2H),7.04 (d,J=9.3Hz,1H), 6.80(dd,J=9.0,2.4Hz,1H), 6.51(d,J=3.5Hz,1H), 6.41(d,J=2.4Hz,1H), 5.18 (dd,J=13.3,5.1Hz,1H),4.56(d,J=16.9Hz,1H), 4.48(d,J=17.0Hz,1H), 3.72(d,J=13.2Hz,4H), 3.68 (s, 2H), 3.64 (d, J = 11.9 Hz, 2H), 3.56 (d, J = 12.8 Hz, 1H), 3.45–3.38 (m, 4H), 3.20–3.05 (m, 8H), 2.95– 2.85(m,1H), 2.85–2.75(m,5H), 2.53(qd,J=13.2,4.6Hz,1H),2.42(d,J=13.3Hz,2H),2.30(s,2H),2.21 -2.17(m,3H),2.15-2.05(m,5H),1.85-1.75(m,4H),1.70(t,J=12.9Hz,2H), 1.57(t,J=6.3Hz,2H), 1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₉ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1248.5466; measured value, 1248.5498.

Example 118: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( (5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)(methyl)amino )Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363137) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363137) was prepared using intermediate BINDER (SIAIS363102) and intermediate LM (SIAIS255121), yellow powder, yield=34%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.04(d,J=2.5Hz,1H), 7.89(dd,J=9.2,2.3Hz,1H) ,7.74(dd,J=7.7,1.0Hz,1H),7.68–7.62(m,3H),7.53–7.46(m,2H),7.35(d,J=8.4Hz,2H),7.07(d,J ＝8.4Hz,2H), 7.01(d,J＝9.3Hz,1H), 6.78(dd,J＝8.9,2.3Hz,1H), 6.47(d,J＝3.5Hz,1H), 6.38(d,J =2.3Hz, 1H), 5.16 (dd, J = 13.3, 5.2 Hz, 1H), 4.59 (d, J = 17.7 Hz, 1H), 4.52 (d, J = 17.8 Hz, 1H), 3.85–3.57 (m ,10H),3.52–3.36(m,6H),3.18–3.10(m,2H),3.06(s,2H),3.00(s,3H),2.88(ddd,J=18.4,13.5,5.3Hz,1H ), 2.84–2.73 (m, 3H), 2.70 (t, J = 6.7 Hz, 2H), 2.59 (qd, J = 13.1, 4.5 Hz, 1H), 2.29 (s, 2H), 2.17 (p, J = 7.0Hz, 3H), 2.11 (s, 2H), 2.05 (d, J = 13.3 Hz, 3H), 1.78-1.68 (m, 2H), 1.56 (t, J = 6.3 Hz, 2H), 1.00 (s, 6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₅ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1232.5153; measured value, 1232.5124.

Example 119: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( (8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)(methyl)amino )Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363138) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363138) was prepared using intermediate BINDER (SIAIS363102) and intermediate LM (SIAIS292020), yellow powder, yield = 26%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.03(d,J=2.5Hz,1H), 7.89(dd,J=9.2,2.3Hz,1H) ,7.72(dd,J=7.7,1.0Hz,1H),7.67–7.63(m,2H),7.60(dd,J=7.6,1.1Hz,1H),7.51–7.47(m,2H),7.36(d ,J=8.4Hz,2H), 7.07(d,J=8.4Hz,2H), 7.02(d,J=9.2Hz,1H), 6.79(dd,J=9.0,2.4Hz,1H), 6.47(d ,J=3.5Hz,1H), 6.39(d,J=2.3Hz,1H), 5.17(dd,J=13.3,5.2Hz,1H),4.52(d,J=17.4Hz,1H), 4.46(d ,J=17.5Hz,1H),3.69(d,J=22.3Hz,7H),3.61(s,3H),3.50–3.36(m,5H),3.19–3.10(m,3H),3.06(s, 2H), 2.95 (s, 3H), 2.90 (ddd, J = 18.4, 13.6, 5.4 Hz, 1H), 2.83-2.75 (m, 3H), 2.59-2.50 (m, 3H), 2.28 (s, 2H) , 2.17 (ddq, J = 10.6, 5.3, 2.6 Hz, 1H), 2.08 (d, J = 24.3 Hz, 5H), 1.85 (p, J = 7.9 Hz, 2H), 1.79–1.71 (m, 2H), 1.70–1.65(m,2H),1.58(dt,J=12.9,7.1Hz,4H),1.49(q,J=7.6Hz,2H),1.00(s,6H).HRMS(ESI)m/z: Calculated value C ₆₉ H ₈₁ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1274.5622; measured value, 1274.5628.

Example 120: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( (4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)(methyl)amino)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363139) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363139) was prepared using intermediate BINDER (SIAIS363102) and intermediate LM (SIAIS255130), yellow powder, yield = 18%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.2Hz,1H), 8.05(d,J=2.5Hz,1H), 7.89(dd,J=9.2,2.3Hz,1H) ,7.69(d,J=2.5Hz,1H),7.67–7.61(m,2H),7.54–7.50(m,2H),7.48(t,J=7.5Hz,1H),7.36(d,J=8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 9.3 Hz, 1H), 6.79 (dd, J = 8.9, 2.3 Hz, 1H), 6.50 (d, J = 3.6 Hz, 1H), 6.41 (d, J = 2.3 Hz, 1H), 5.17 (dd, J = 13.3, 5.2 Hz, 1H), 4.58 (d, J = 17.0 Hz, 1H), 4.49 (d, J = 17.0 Hz, 1H), 3.78--3.65 (m, 7H), 3.60 (s, 3H), 3.47--3.36 (m, 5H), 3.20--3.12 (m, 2H), 3.06 (s, 2H), 2.94 (s, 3H), 2.91–2.85(m,1H), 2.84–2.75(m,5H), 2.55(qd,J=13.2,4.6Hz,1H), 2.29(s,2H), 2.20(ddd,J=9.9, 5.6,2.9Hz,1H),2.09(d,J=26.1Hz,5H),1.91-166(m,6H),1.57(t,J=6.4Hz,2H),1.01(s,6H).HRMS( ESI) m/z: calculated value C ₆₅ H ₇₇ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1222.5309; measured value, 1222.5304.

Example 121: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( (4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)(methyl)amino)ethyl )Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363140) preparation

With reference to the method in Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363140) was prepared using intermediate BINDER (SIAIS363102) and intermediate LM (SIAIS1222171), yellow powder, yield = 25%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.03(d,J=2.5Hz,1H), 7.89(dd,J=9.2,2.3Hz,1H) ,7.65(d,J=8.9Hz,1H),7.63(d,J=2.6Hz,1H),7.50(d,J=3.4Hz,1H),7.47(d,J=7.9Hz,1H),7.38 (d,J=7.4Hz,1H), 7.35(d,J=6.7Hz,2H), 7.22(d,J=8.0Hz,1H), 7.07(d,J=8.4Hz,2H), 7.01(d ,J=9.3Hz,1H), 6.78(dd,J=9.0,2.4Hz,1H), 6.46(d,J=3.4Hz,1H), 6.37(d,J=2.3Hz,1H), 5.13(dd ,J＝13.3,5.2Hz,1H),4.53(d,J＝17.5Hz,1H), 4.44(d,J＝17.4Hz,1H),4.22(s,2H), 3.69(d,J＝21.0Hz ,8H),3.63(s,2H),3.46–3.36(m,5H),3.18–3.11(m,2H),3.06(s,2H),2.98(s,3H),2.93-2.68(m,5H) ), 2.62–2.51(m,1H), 2.28(s,2H), 2.16(ddq,J=10.6,5.5,2.7Hz,1H), 2.12–2.00(m,7H),1.95(q,J=6.4 Hz, 2H), 1.74 (d, J = 14.0 Hz, 2H), 1.56 (t, J = 6.4 Hz, 2H), 1.00 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₅ H ₇₇ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1238.5259; measured value, 1238.5272.

Example 122: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-( (3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)(methyl)amino) (Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363141) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363141) was prepared using intermediate BINDER (SIAIS363102) and intermediate LM (SIAIS268007), yellow powder, yield=42%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.03(d,J=2.6Hz,1H), 7.89(dd,J=9.2,2.3Hz,1H) ,7.66–7.62(m,2H),7.58(dd,J=8.6,7.1Hz,1H), 7.50(d,J=3.4Hz,1H), 7.36(d,J=8.4Hz,2H), 7.14( d,J=8.5Hz,1H), 7.08(dd,J=8.0,1.9Hz,3H), 7.01(d,J=9.3Hz,1H), 6.78(dd,J=9.0,2.4Hz,1H), 6.47 (d, J = 3.4 Hz, 1H), 6.38 (d, J = 2.4 Hz, 1H), 5.04 (dd, J = 12.5, 5.5 Hz, 1H), 3.69 (d, J = 18.8 Hz, 8H), 3.62(s,2H),3.54(t,J=6.6Hz,2H),3.46–3.36(m,5H),3.19–3.10(m,2H),3.05(s,2H),2.98(s,3H) , 2.88–2.76(m, 3H), 2.75–2.63(m, 2H), 2.29(s, 2H), 2.17(p, J=7.1Hz, 2H), 2.11(s, 2H), 2.09–2.04(m , 3H), 1.74 (d, J = 13.7 Hz, 2H), 1.57 (t, J = 6.4 Hz, 2H), 1.00 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₄ H ₇₄ ClN ₁₂ O ₁₀ S ⁺ [M+H] ⁺ , 1237.5055; measured value, 1237.5077.

Example 123: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)(methyl)amino )Propyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363142) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363142) was prepared using intermediate BINDER (SIAIS363080) and intermediate LM (SIAIS255121), yellow powder, yield = 23%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.07(s,1H), 7.91(dd,J=9.3,2.3Hz,1H), 7.73(d, J = 7.5Hz, 1H), 7.68 (d, J = 2.3 Hz, 1H), 7.67–7.62 (m, 2H), 7.51 (d, J = 3.3 Hz, 1H), 7.49 (d, J = 7.7 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 9.3 Hz, 1H), 6.79 (dd, J = 8.9, 2.4 Hz, 1H), 6.49 (d, J = 3.4 Hz, 1H), 6.39 (d, J = 2.4 Hz, 1H), 5.17 (dd, J = 13.7, 5.0 Hz, 1H), 4.62-4.55 (m, 1H), 4.51 (dd, J = 17.7, 5.6 Hz, 1H), 3.68 (d, J = 8.6 Hz, 4H), 3.59 (d, J = 10.9 Hz, 2H), 3.51–3.35 (m, 7H), 3.25 (d ,J=7.8Hz,1H), 3.23–3.10(m,4H), 2.95(s,5H), 2.88(d,J=15.9Hz,1H), 2.77(d,J=17.2Hz,3H), 2.69 (d,J=6.5Hz,2H),2.64-2.52(m,1H),2.29(s,4H),2.20-2.09(m,5H),2.02(t,J=12.1Hz,3H),1.65( s,2H),1.57(t,J=6.4Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₇ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1246.5309; measured value, 1246.5321.

Example 124: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)(methyl)amino )Propyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363143) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363143) was prepared using intermediate BINDER (SIAIS363080) and intermediate LM (SIAIS292020), yellow powder, yield = 17%

¹ H NMR(500MHz, methanol-d ₄ )δ8.69(d,J=2.3Hz,1H), 8.02(d,J=2.6Hz,1H), 7.90(dd,J=9.2,2.3Hz,1H) ,7.73(dd,J=7.6,1.1Hz,1H), 7.65(d,J=8.9Hz,1H), 7.62(d,J=2.6Hz,1H), 7.60(dd,J=7.8,1.1Hz, 1H), 7.52–7.47 (m, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 9.3 Hz, 1H), 6.79 ( dd, J = 8.9, 2.5 Hz, 1H), 6.46 (d, J = 3.5 Hz, 1H), 6.37 (d, J = 2.4 Hz, 1H), 5.17 (dd, J = 13.3, 5.2 Hz, 1H), 4.52(d,J=17.5Hz,1H), 4.46(d,J=17.4Hz,1H), 3.74–3.61(m,6H), 3.47–3.36(m,5H), 3.27–3.08(m,7H) ,3.01(t,J=12.6Hz,2H), 2.96–2.85(m,4H), 2.84–2.72(m,3H), 2.59–2.47(m,3H), 2.26(d,J=25.8Hz,4H ),2.22-2.15(m,1H),2.13-2.05(m,5H),1.81(s,2H),1.72-1.65(m,4H),161-1.55(m,4H),1.48(q,J =7.5Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₀ H ₈₃ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1288.5779; measured value, 1288.5761.

Example 125: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)(methyl)amino)propyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363144) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363144) was prepared using intermediate BINDER (SIAIS363080) and intermediate LM (SIAIS255130), yellow powder, yield = 26%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 7.89(dd,J=9.2,2.3Hz,1H), 7.70(d,J=2.1Hz,1H) ,7.67–7.60(m,2H),7.53–7.45(m,3H),7.35(d,J=8.4Hz,2H),7.08(d,J=8.4Hz,2H),7.03(d,J=9.3 Hz, 1H), 6.78 (dd, J = 9.0, 2.3 Hz, 1H), 6.50 (d, J = 3.5 Hz, 1H), 6.40 (d, J = 2.3 Hz, 1H), 5.16 (dd, J = 13.3 ,5.1Hz,1H),4.58(d,J=17.0Hz,1H), 4.48(d,J=17.0Hz,1H), 3.66(q,J=11.9,8.9Hz,6H), 3.46–3.36(m ,4H),3.29–3.23(m,2H),3.22–3.09(m,6H),3.01(t,J=12.5Hz,2H), 2.94–2.84(m,4H), 2.84–2.72(m,5H) ), 2.55 (qd, J = 13.2, 4.6 Hz, 1H), 2.30 (t, J = 6.3 Hz, 2H), 2.25 (s, 2H), 2.19 (dp, J = 8.3, 3.1 Hz, 2H), 2.11 (s,2H),2.08(s,1H),2.06(s,1H),1.85-1.75(m,4H),1.70(q,J=14.0,13.5Hz,2H),1.56(t,J=6.3 Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₉ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1236.5466; measured value, 1236.5476.

Example 126: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)(methyl)amino)propyl )Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363145) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363145) was prepared using intermediate BINDER (SIAIS363080) and intermediate LM (SIAIS1222171), yellow powder, yield = 35%

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(d,J=2.3Hz,1H), 8.08(d,J=2.4Hz,1H), 7.90(dd,J=9.2,2.3Hz,1H) , 7.75 (d, J = 2.4 Hz, 1H), 7.63 (d, J = 8.9 Hz, 1H), 7.55 (d, J = 3.4 Hz, 1H), 7.47 (t, J = 7.8 Hz, 1H), 7.40 –7.33(m,3H),7.22(d,J=8.1Hz,1H), 7.08(d,J=8.4Hz,2H), 7.04(d,J=9.3Hz,1H), 6.79(dd,J= 9.0, 2.3 Hz, 1H), 6.53 (d, J = 3.5 Hz, 1H), 6.42 (d, J = 2.4 Hz, 1H), 5.13 (dd, J = 13.3, 5.2 Hz, 1H), 4.51 (d, J = 17.4Hz, 1H), 4.42 (d, J = 17.4 Hz, 1H), 4.22 (t, J = 5.6 Hz, 2H), 3.72 (d, J = 14.0 Hz, 2H), 3.68 (s, 2H) ,3.61(t,J=10.6Hz,2H),3.52–3.34(m,6H), 3.28–3.13(m,6H),3.05–2.96(m,2H), 2.92(s,3H), 2.86(d ,J＝13.1Hz,1H), 2.83–2.72(m,3H), 2.60–2.47(m,1H), 2.31(d,J＝6.5Hz,2H), 2.26(d,J＝6.9Hz,2H) ,2.21–2.14(m,1H),2.11(s,2H),2.03(d,J=9.1Hz,5H),1.94(q,J=6.9,6.2Hz,2H),1.69(t,J=13.9 Hz, 2H), 1.57 (t, J = 6.3 Hz, 2H), 1.00 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₆ H ₇₉ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ ,1252.5415; Measured value,1252.5447.

Example 127: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-( (3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)(methyl)amino) (Propyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS363146) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363146) was prepared using intermediate BINDER (SIAIS363080) and intermediate LM (SIAIS268007), yellow powder, yield = 25%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.04(s,1H), 7.90(dd,J=9.2,2.3Hz,1H), 7.69–7.62( m, 2H), 7.59 (dd, J = 8.6, 7.1 Hz, 1H), 7.51 (d, J = 3.4 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.5 Hz, 1H), 7.10–7.05 (m, 3H), 7.03 (d, J = 9.3 Hz, 1H), 6.78 (dd, J = 9.0, 2.4 Hz, 1H), 6.48 (d, J = 3.4 Hz, 1H ), 6.39(d,J=2.4Hz,1H),5.04(dd,J=12.5,5.5Hz,1H),3.75-3.65(m,4H),3.62(d,J=12.4Hz,2H),3.51 (t,J=6.7Hz,2H), 3.47–3.35(m,6H), 3.28–3.21(m,2H), 3.21–3.10(m,4H), 2.98(t,J=12.9Hz,2H), 2.93(s,3H), 2.90–2.62(m,5H), 2.30(d,J=5.9Hz,2H), 2.27–2.17(m,2H), 2.18–1.98(m,8H), 1.67(q, J = 13.0Hz, 2H), 1.57 (t, J = 6.4Hz, 2H), 1.00 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₅ H ₇₆ ClN ₁₂ O ₁₀ S ⁺ [M+ H] ⁺ ,1251.5211; measured value,1251.5226.

Example 128: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-((5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)amino) (Cyclohexyl) methyl) amino)-3-nitrophenyl) sulfonyl) benzamide (SIAIS363148) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363148) was prepared using intermediate BINDER (SIAIS363101) and intermediate LM (SIAIS255121), yellow powder, yield = 22%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.05(s,1H), 7.89(dd,J=9.3,2.3Hz,1H), 7.75(d, J = 7.2Hz, 1H), 7.68–7.65 (m, 2H), 7.63 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 7.7 Hz, 1H), 7.49 (d, J = 3.4 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 9.3 Hz, 1H), 6.78 (dd, J = 8.9, 2.3 Hz, 1H), 5.17 (dd, J = 13.4, 5.1 Hz, 1H), 4.54 (d, J = 17.3 Hz, 1H), 4.46 (d, J = 17.4 Hz, 1H), 3.80-3.65 (m, 4H), 3.47–3.36(m,4H), 3.26–3.20(m,2H), 3.20–3.08(m,3H), 2.87(ddd,J=18.5,13.6,5.4Hz,1H), 2.83–2.71(m,3H) ), 2.68 (t, J = 6.8Hz, 2H), 2.48 (qd, J = 13.3, 4.6Hz, 1H), 2.29 (s, 2H), 2.26-2.15 (m, 3H), 2.11 (s, 2H) ,2.06–1.96(m,4H),1.75(s,1H),1.56(t,J=6.3Hz,2H),1.45(q,J=12.3Hz,2H),1.20(q,J=12.1,11.6 Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₀ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ ,1189.4731; measured value, 1189.4760.

Example 129: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-((8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)amino) (Cyclohexyl) methyl) amino)-3-nitrophenyl) sulfonyl) benzamide (SIAIS363149) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363149) was prepared using intermediate BINDER (SIAIS363101) and intermediate LM (SIAIS292020), yellow powder, yield=43%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.10(d,J=2.5Hz,1H), 7.90(dd,J=9.2,2.3Hz,1H) ,7.80(d,J=2.5Hz,1H),7.72(dd,J=7.6,1.0Hz,1H), 7.64(d,J=8.9Hz,1H), 7.59(dd,J=7.6,1.0Hz, 1H), 7.56 (d, J = 3.5 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H) ,6.99(d,J=9.4Hz,1H), 6.81(dd,J=9.0,2.4Hz,1H), 6.55(d,J=3.5Hz,1H), 6.45(d,J=2.3Hz,1H) ,5.16(dd,J=13.4,5.2Hz,1H),4.51(d,J=17.4Hz,1H), 4.45(d,J=17.4Hz,1H), 3.73(d,J=13.4Hz,2H) , 3.68 (s, 2H), 3.42 (d, J = 13.3 Hz, 2H), 3.29 (d, J = 7.0 Hz, 2H), 3.17 (d, J = 12.2 Hz, 2H), 3.10-2.98 (m, 3H), 2.90(ddd,J=17.7,13.7,5.5Hz,1H), 2.85–2.73(m,3H), 2.56–2.46(m,3H), 2.31(t,J=5.8Hz,2H), 2.22 –2.13(m,3H),2.11(s,2H),1.96(d,J＝13.8Hz,2H),1.69(ddd,J＝27.8,13.4,7.2Hz,5H),1.57(p,J＝8.5 Hz, 4H), 1.49 (q, J = 7.3 Hz, 2H), 1.44-1.35 (m, 2H), 1.17 (q, J = 15.4, 13.2 Hz, 2H), 1.01 (s, 6H).HRMS (ESI )m/z: Calculated value C ₆₇ H ₇₆ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1231.5200; measured value, 1231.5187.

Example 130: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-((4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide (SIAIS363150) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363150) was prepared using intermediate BINDER (SIAIS363101) and intermediate LM (SIAIS255130), yellow powder, yield = 31%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.05(d,J=2.5Hz,1H), 7.88(dd,J=9.2,2.3Hz,1H) ,7.71–7.61(m,3H),7.55–7.43(m,3H), 7.36(d,J=8.4Hz,2H), 7.08(d,J=8.4Hz,2H), 6.97(d,J=9.4 Hz, 1H), 6.79 (dd, J = 9.0, 2.4 Hz, 1H), 6.49 (d, J = 3.5 Hz, 1H), 6.39 (d, J = 2.4 Hz, 1H), 5.18 (dd, J = 13.3 ,5.2Hz,1H),4.55(d,J=16.9Hz,1H), 4.47(d,J=16.9Hz,1H), 3.70(d,J=20.1Hz,4H),3.41(d,J=12.1 Hz, 2H), 3.29 (d, J = 7.2 Hz, 2H), 3.16 (t, J = 11.7 Hz, 2H), 3.04 (dd, J = 10.5, 4.6 Hz, 3H), 2.91 (ddd, J = 17.6 ,13.6,5.4Hz,1H), 2.84–2.74(m,5H), 2.52(qd,J=13.2,4.6Hz,1H), 2.30(s,2H), 2.23–2.13(m,3H), 2.11( s, 2H), 1.98 (d, J = 13.0 Hz, 2H), 1.80 (dd, J = 11.1, 4.8 Hz, 2H), 1.73 (q, J = 11.5, 8.3 Hz, 3H), 1.57 (t, J =6.4Hz,2H),1.46-1.34(m,2H),1.19(q,J=12.3Hz,2H),1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₇₂ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1179.4887; measured value, 1179.4897.

Example 131: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-((4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)amino)cyclohexyl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364001) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364001) was prepared using intermediate BINDER (SIAIS363101) and intermediate LM (SIAIS1222171), yellow powder, yield = 24%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.07(s,1H), 7.89(dd,J=9.2,2.3Hz,1H), 7.70(d, J = 2.5Hz, 1H), 7.65 (d, J = 8.9 Hz, 1H), 7.51 (d, J = 3.5 Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.39 (d, J = 7.5Hz, 1H), 7.36 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 8.2 Hz, 1H), 7.08 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 9.3 Hz ,1H), 6.80 (dd, J = 9.0, 2.4 Hz, 1H), 6.50 (d, J = 3.5 Hz, 1H), 6.40 (d, J = 2.3 Hz, 1H), 5.15 (dd, J = 13.4, 5.1Hz, 1H), 4.46 (d, J = 17.0 Hz, 1H), 4.39 (d, J = 17.2 Hz, 1H), 4.21 (t, J = 5.4 Hz, 2H), 3.69 (d, J = 10.1 Hz ,4H),3.41(d,J=12.5Hz,2H),3.29(s,2H),3.21-3.05(m,5H),2.89(ddd,J=17.5,13.6,5.3Hz,1H),2.84-- 2.72 (m, 3H), 2.46 (qd, J = 13.3, 4.6 Hz, 1H), 2.29 (s, 2H), 2.23-2.14 (m, 3H), 2.11 (s, 2H), 1.99 (d, J = 13.6Hz, 2H), 1.94 (d, J = 8.1 Hz, 4H), 1.74 (s, 1H), 1.57 (t, J = 6.3 Hz, 2H), 1.43 (q, J = 12.1 Hz, 2H), 1.26 –1.16(m,2H),1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₇₂ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ ,1195.4837; measured value, 1195.4835.

Example 132: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-((3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)amino) ring (Hexyl) methyl) amino) -3-nitrophenyl) sulfonyl) benzamide (SIAIS364002) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364002) was prepared using intermediate BINDER (SIAIS363101) and intermediate LM (SIAIS268007), yellow powder, yield=34%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.05(d,J=2.5Hz,1H), 7.87(dd,J=9.3,2.3Hz,1H) ,7.67(d,J=2.5Hz,1H), 7.64(d,J=8.9Hz,1H), 7.58(dd,J=8.5,7.1Hz,1H), 7.50(d,J=3.5Hz,1H) ,7.36(d,J=8.4Hz,2H), 7.12(d,J=8.6Hz,1H), 7.10–7.06(m,3H), 6.97(d,J=9.4Hz,1H), 6.78(dd, J = 9.0, 2.4 Hz, 1H), 6.48 (d, J = 3.5 Hz, 1H), 6.39 (d, J = 2.3 Hz, 1H), 5.05 (dd, J = 12.5, 5.5 Hz, 1H), 3.69 ( d, J = 20.1 Hz, 4H), 3.50 (t, J = 6.6 Hz, 2H), 3.41 (d, J = 12.4 Hz, 2H), 3.29 (d, J = 6.9 Hz, 2H), 3.21-3.06 ( m, 5H), 2.90–2.65 (m, 5H), 2.30 (t, J = 6.5 Hz, 2H), 2.18 (d, J = 12.0 Hz, 2H), 2.11 (s, 2H), 2.09–1.95 (m ,5H),1.73(s,1H),1.57(t,J=6.4Hz,2H),1.42(q,J=12.3,11.9Hz,2H),1.19(q,J=14.4,12.6Hz,2H) ,1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₂ H ₆₉ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ ,1194.4633; measured value, 1194.4631.

Example 133: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-((5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)amino) (Cyclohexyl) methyl) amino) -3-nitrophenyl) sulfonyl) benzamide (SIAIS364006) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364006) was prepared using intermediate BINDER (SIAIS363103) and intermediate LM (SIAIS255121), yellow powder, yield = 31%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.08(d,J=2.4Hz,1H), 7.90(dd,J=9.2,2.3Hz,1H) ,7.77–7.73(m,2H),7.66–7.61(m,2H),7.54(d,J=3.4Hz,1H),7.50(t,J=7.7Hz,1H),7.36(d,J=8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 9.4 Hz, 1H), 6.80 (dd, J = 9.0, 2.3 Hz, 1H), 6.52 (d, J = 3.5 Hz, 1H), 6.43 (d, J = 2.3 Hz, 1H), 5.17 (dd, J = 13.3, 5.2 Hz, 1H), 4.56 (d, J = 17.5 Hz, 1H), 4.48 (d, J = 17.4 Hz,1H), 3.72(d,J=14.2Hz,2H), 3.68(s,2H), 3.45–3.39(m,4H), 3.27–3.22(m,2H), 3.20–3.12(m,2H) ,2.89(ddd,J=17.7,13.6,5.4Hz,1H),2.84-2.74(m,3H),2.69(t,J=6.8Hz,2H),2.52(qd,J=13.3,4.7Hz,1H ), 2.30 (s, 2H), 2.18 (ddq, J = 10.5, 5.3, 2.7 Hz, 1H), 2.11 (s, 2H), 2.05 (dt, J = 13.4, 7.2 Hz, 3H), 1.93 (d, J = 17.0Hz, 2H), 1.83 (dt, J = 13.6, 6.9Hz, 2H), 1.73 (t, J = 6.2Hz, 4H), 1.57 (t, J = 6.4Hz, 2H), 1.01 (s, 6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₀ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1189.4731; measured value, 1189.4752.

Example 134: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-((8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)amino) (Cyclohexyl) methyl) amino)-3-nitrophenyl) sulfonyl) benzamide (SIAIS364007) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364007) was prepared using intermediate BINDER (SIAIS363103) and intermediate LM (SIAIS292020), yellow powder, yield=38%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.10(d,J=2.4Hz,1H), 7.91(dd,J=9.2,2.3Hz,1H) ,7.79(d,J=2.5Hz,1H),7.73(dd,J=7.6,1.0Hz,1H), 7.64(d,J=8.9Hz,1H), 7.60(dd,J=7.7,1.0Hz, 1H), 7.57–7.54 (m, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 7.03 ( d, J = 9.4 Hz, 1H), 6.80 (dd, J = 9.0, 2.3 Hz, 1H), 6.54 (d, J = 3.5 Hz, 1H), 6.44 (d, J = 2.3 Hz, 1H), 5.16 ( dd, J = 13.3, 5.1 Hz, 1H), 4.51 (d, J = 17.4 Hz, 1H), 4.45 (d, J = 17.5 Hz, 1H), 3.73 (d, J = 13.0 Hz, 2H), 3.68 ( s, 2H), 3.45–3.39(m, 4H), 3.26–3.14(m, 3H), 3.06–3.00(m, 2H), 2.94–2.85(m, 1H), 2.84–2.73(m, 3H), 2.51(q,J=7.1Hz,3H), 2.31(d,J=5.5Hz,2H), 2.18(dtd,J=12.6,5.3,2.4Hz,1H), 2.11(s,2H), 2.06-1.96 (m,1H),1.87(q,J=5.2Hz,2H),1.83-1.73(m,4H),1.69(dq,J=11.2,7.8,5.7Hz,6H),1.61-1.54(m,4H ), 1.50(q,J=7.3Hz,2H),1.01(s,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₆ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ ,1231.5200; Measured value, 1231.5185.

Example 135: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-((4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide (SIAIS364008) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364008) was prepared using intermediate BINDER (SIAIS363103) and intermediate LM (SIAIS255130), yellow powder, yield = 31%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.66 (d, J = 2.3 Hz, 1H), 8.12-8.07 (m, 1H), 7.90 (dd, J = 9.3, 2.3 Hz, 1H), 7.78 ( d, J = 2.5Hz, 1H), 7.66 (dd, J = 7.2, 1.4 Hz, 1H), 7.64 (d, J = 8.9 Hz, 1H), 7.55 (d, J = 3.4 Hz, 1H), 7.53- 7.46 (m, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 9.3 Hz, 1H), 6.80 (dd, J = 8.9 ,2.3Hz,1H),6.54(d,J=3.5Hz,1H),6.44(d,J=2.4Hz,1H), 5.17(dd,J=13.3,5.2Hz,1H),4.56(d,J = 17.0Hz, 1H), 4.48 (d, J = 17.0 Hz, 1H), 3.73 (d, J = 14.3 Hz, 2H), 3.68 (s, 2H), 3.42 (dd, J = 13.9, 6.0 Hz, 5H ), 3.26–3.13 (m, 3H), 3.05 (t, J = 7.4 Hz, 2H), 2.91 (ddd, J = 18.5, 13.6, 5.4 Hz, 1H), 2.84–2.76 (m, 5H), 2.53 ( qd, J = 13.3, 4.6 Hz, 1H), 2.30 (s, 2H), 2.22-2.16 (m, 1H), 2.11 (s, 2H), 2.01 (s, 1H), 1.86 (d, J = 5.7 Hz) ,2H),1.84–1.74(m,6H),1.70(p,J=4.7Hz,3H),1.57(t,J=6.3Hz,2H),1.01(s,6H).HRMS(ESI)m/ z: Calculated value C ₆₃ H ₇₂ ClN ₁₀ O ₉ S ⁺ [M+H] ⁺ , 1179.4887; measured value, 1179.4866.

Example 136: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-((4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)amino)cyclohexyl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364009) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364009) was prepared using intermediate BINDER (SIAIS363103) and intermediate LM (SIAIS1222171), yellow powder, yield = 35%

¹ H NMR(500MHz, methanol-d ₄ )δ8.69(d,J=2.3Hz,1H), 8.01(d,J=2.6Hz,1H), 7.90 (dd,J=9.3,2.3Hz,1H) ,7.65(d,J=8.9Hz,1H),7.57(d,J=2.6Hz,1H),7.49(t,J=7.9Hz,1H),7.46(t,J=1.8Hz,1H),7.39 (d,J=7.5Hz,1H), 7.36(d,J=8.4Hz,2H), 7.23(d,J=8.1Hz,1H), 7.08(d,J=8.4Hz,2H), 6.99(d ,J=9.4Hz,1H), 6.77(dd,J=8.9,2.4Hz,1H), 6.43(d,J=3.5Hz,0H), 6.34(d,J=2.4Hz,1H), 5.15(dd ,J＝13.3,5.2Hz,1H), 4.48(d,J＝17.2Hz,1H), 4.40(d,J＝17.2Hz,1H),4.22(s,2H), 3.67(s,4H), 3.40 (d,J=7.5Hz,4H),3.29–3.24(m,1H),3.14(q,J=17.1,13.1Hz,4H), 2.90(ddd,J=17.6,13.6,5.3Hz,1H), 2.77 (ddd, J = 17.6, 4.6, 2.4 Hz, 3H), 2.48 (qd, J = 13.3, 4.6 Hz, 1H), 2.28 (s, 2H), 2.18 (ddd, J = 9.8, 5.2, 2.6 Hz, 1H), 2.11 (s, 2H), 2.05-1.99 (m, 1H), 1.95 (td, J = 5.4, 4.3, 2.3 Hz, 4H), 1.93-1.86 (m, 2H), 1.81 (d, J = 6.9Hz, 2H), 1.71 (dq, J = 12.1, 6.6, 5.5 Hz, 4H), 1.57 (t, J = 6.4 Hz, 2H), 1.01 (s, 6H). HRMS (ESI) m/z: calculation Value C ₆₃ H ₇₂ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ , 1195.4837; measured value, 1195.4857.

Example 137: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-((3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)amino) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364010) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364010) was prepared by using intermediate BINDER (SIAIS363103) and intermediate LM (SIAIS268007), yellow powder, yield = 46%

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(d,J=2.2Hz,1H), 8.11-8.06(m,1H), 7.90(dd,J=9.2,2.3Hz,1H), 7.76( d,J=2.4Hz,1H), 7.63(d,J=8.8Hz,1H), 7.60–7.56(m,1H), 7.54(d,J=3.4Hz,1H), 7.36(d,J=8.1 Hz, 2H), 7.13 (d, J = 8.6 Hz, 1H), 7.08 (dd, J = 7.8, 2.5 Hz, 3H), 7.02 (d, J = 9.3 Hz, 1H), 6.80 (dd, J = 8.9 ,2.2Hz,1H),6.53(d,J=3.4Hz,1H),6.43(d,J=2.4Hz,1H),5.05(dd,J=12.5,5.5Hz,1H),3.72(d,J =13.7Hz, 2H), 3.68 (s, 2H), 3.51 (t, J = 6.6 Hz, 2H), 3.46–3.38 (m, 4H), 3.27 (q, J = 3.9 Hz, 2H), 3.22–3.12 (m,4H),2.89–2.64(m,5H),2.30(s,2H),2.11(s,2H),2.09–2.04(m,2H),2.00(d,J=13.8Hz,1H), 1.88(s,2H),1.81(q,J=5.6Hz,2H),1.71(q,J=5.8,5.3Hz,4H), 1.57(t,J=6.3Hz,2H),1.01(s,6H ).HRMS(ESI)m/z: calculated value C ₆₂ H ₆₉ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1194.4633; measured value, 1194.4655.

Example 138: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)cyclohexyl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide (SIAIS364040) preparation

Dissolve 2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione (0.034mmol, 1.5equiv) in 1mL NMP, and add SIAIS363103 sequentially (0.023mmol, 1.0equiv) and N,N-diisopropylethylamine (3.0equiv), microwave reaction at 80°C for 3h, the reaction is complete. The reaction solution was cooled to room temperature, and SIAIS364040 was prepared by HPLC. Yellow powder, yield = 18%.

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.72 (s, 1H), 11.67 (s, 1H), 11.11 (s, 1H), 10.17 (s, 1H), 8.65 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 2.3 Hz, 1H), 8.05 (d, J = 2.6 Hz, 1H), 7.82 (dd, J = 9.2, 2.4 Hz, 1H), 7.60 (dd, J = 8.6, 7.1 Hz,1H),7.55(d,J=2.6Hz,1H),7.54–7.50(m,2H),7.39(d,J=8.4Hz,2H),7.17–7.11(m,2H),7.09(d ,J=8.4Hz,2H),7.05(d,J=7.0Hz,1H), 6.71(dd,J=9.0,2.3Hz,1H), 6.49(d,J=8.1Hz,1H), 6.40(dd ,J=3.4,1.8Hz,1H), 6.25(d,J=2.3Hz,1H), 5.06(dd,J=12.8,5.4Hz,1H), 3.85(s,1H), 3.64(d,J= 12.0Hz, 2H), 3.57-3.52 (m, 2H), 3.36 (t, J = 6.5 Hz, 2H), 3.26 (d, J = 10.5 Hz, 2H), 3.19 (t, J = 11.7 Hz, 2H) ,2.89(ddd,J=16.9,13.8,5.5Hz,1H),2.71(d,J=11.2Hz,2H),2.65-2.56(m,1H),2.29(s,2H),2.07-1.98(m ,3H),1.83(s,1H),1.76(s,2H),1.68(d,J=11.9Hz,4H),1.44(t,J=6.3Hz,2H),1.36(d,J=11.3Hz ,2H),0.94(s,6H).HRMS(ESI)m/z: calculated value C ₅₉ H ₆₂ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ ,1137.4054; measured value, 1137.4028.

Example 139: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)cyclohexyl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide (SIAIS364041) preparation

Dissolve 2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione (0.034mmol, 1.5equiv) in 1mL NMP, and add SIAIS363101 sequentially (0.023mmol, 1.0equiv) and N,N-diisopropylethylamine (3.0equiv), microwave reaction at 80°C for 3h, the reaction is complete. The reaction solution was cooled to room temperature, and SIAIS364041 was prepared by HPLC. Yellow powder, yield = 18%.

¹ H NMR (500MHz, DMSO-d ₆ ) δ 11.73 (s, 1H), 11.68 (s, 1H), 11.09 (s, 1H), 10.58 (s, 1H), 8.65 (t, J = 5.9 Hz, 1H), 8.57 (d, J = 2.4 Hz, 1H), 8.05 (d, J = 2.7 Hz, 1H), 7.82 (dd, J = 9.2, 2.3 Hz, 1H), 7.59 (d, J = 7.7 Hz, 1H), 7.57–7.55 (m, 1H), 7.54–7.50 (m, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.7 Hz, 1H), 7.12 (d, J ＝9.5Hz,1H), 7.09(d,J＝8.1Hz,2H), 7.03(d,J＝7.0Hz,1H), 6.72(dd,J＝9.0,2.3Hz,1H), 6.45–6.36(m ,1H), 6.25 (d, J = 2.2 Hz, 1H), 6.17 (d, J = 8.2 Hz, 1H), 5.04 (dd, J = 12.8, 5.4 Hz, 1H), 3.62 (d, J = 12.9 Hz ,2H),3.53(s,2H),3.34-3.25(m,5H),2.88(ddd,J=16.9,13.8,5.5Hz,1H),2.69(s,2H),2.65-2.57(m,2H ), 2.34 (q, J = 8.4, 6.5 Hz, 2H), 2.08-1.97 (m, 5H), 1.84 (d, J = 10.6 Hz, 2H), 1.69 (s, 1H), 1.44 (t, J = 6.0Hz, 2H), 1.26 (qd, J = 18.7, 15.1, 6.7 Hz, 6H), 0.94 (s, 6H). HRMS (ESI) m/z: calculated value C ₅₉ H ₆₂ ClN ₁₀ O ₁₀ S ⁺ [ M+H] ⁺ , 1137.4054; found value, 1137.4053.

Example 140: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)piperazine- 1-yl)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364048) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364048) was prepared using intermediate BINDER (SIAIS364025) and intermediate LM (SIAIS213132), yellow powder, yield = 60%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.2Hz,1H), 8.03(d,J=2.5Hz,1H), 7.87(dd,J=9.2,2.3Hz,1H) ,7.74(d,J=7.8Hz,1H),7.69(d,J=7.4Hz,1H),7.66-7.62(m,2H),7.59-7.53(m,1H),7.49(d,J=3.5 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 6.97 (d, J = 9.4 Hz, 1H), 6.78 (dd, J = 8.9, 2.3 Hz, 1H), 6.47 (d, J = 3.5 Hz, 1H), 6.37 (d, J = 2.3 Hz, 1H), 5.16 (dd, J = 13.4, 5.2 Hz, 1H), 4.52 (d, J = 17.4 Hz, 1H), 4.45 (d, J = 17.4 Hz, 1H), 3.69 (d, J = 13.7 Hz, 10H), 3.46–3.35 (m, 5H), 3.28 (d, J = 6.8 Hz, 4H), 3.21–3.10 (m, 4H), 2.90 (ddd, J = 18.5, 13.5, 5.6 Hz, 1H), 2.85–2.74 (m, 3H), 2.54 (qd, J = 13.2, 3.9 Hz, 1H), 2.30 ( d,J=6.1Hz,2H),2.27–2.16(m,3H),2.11(s,2H),2.04(d,J=12.8Hz,4H),1.74(s,1H),1.66–1.53(m ,4H),1.21(q,J=14.2,13.6Hz,2H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₇ ClN ₁₁ O ₉ S ₂ ⁺ [M+H ] ⁺ ,1266.5030; measured value,1266.5018.

Example 141: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)piperazine- 1-yl)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364049) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364049) was prepared using intermediate BINDER (SIAIS364025) and intermediate LM (SIAIS1222171), yellow powder, yield = 61%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.04(d,J=2.6Hz,1H), 7.88(dd,J=9.2,2.4Hz,1H) ,7.69–7.63(m,2H),7.52–7.46(m,2H),7.39(d,J=7.5Hz,1H),7.36(d,J=8.4Hz,2H),7.22(d,J=8.2 Hz, 1H), 7.08 (s, 2H), 6.98 (d, J = 9.2 Hz, 1H), 6.78 (dd, J = 8.9, 2.4 Hz, 1H), 6.47 (d, J = 3.5 Hz, 1H), 6.37 (d, J = 2.4 Hz, 1H), 5.14 (dd, J = 13.4, 5.2 Hz, 1H), 4.52 (d, J = 17.3 Hz, 1H), 4.43 (d, J = 17.4 Hz, 1H), 4.22(t,J=5.8Hz,2H), 3.85-3.50(m,9H), 3.45–3.38(m,2H), 3.35-3.25(m,8H), 3.18–3.09(m,2H), 2.89( ddd, J = 17.7, 13.6, 5.4 Hz, 1H), 2.84–2.73 (m, 3H), 2.55 (qd, J = 13.2, 4.6 Hz, 1H), 2.31–2.23 (m, 4H), 2.17 (dtd, J = 12.8, 5.3, 2.3 Hz, 1H), 2.11 (s, 2H), 2.08–2.00 (m, 4H), 1.94 (q, J = 6.5 Hz, 2H), 1.74 (s, 1H), 1.62 (d ,J=12.0Hz,2H),1.56(t,J=6.4Hz,2H),1.22(q,J=12.8,10.5Hz,2H),1.00(s,6H).HRMS(ESI)m/z: Calculated value C ₆₇ H ₇₉ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1264.5415; measured value, 1264.5420.

Example 142: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)piperazin-1-yl) (Cyclohexyl) methyl) amino)-3-nitrophenyl) sulfonyl) benzamide (SIAIS364050) preparation

With reference to the method in Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364050) was prepared using intermediate BINDER (SIAIS364025) and intermediate LM (SIAIS255130), yellow powder, yield = 61%

¹ H NMR(500MHz, methanol-d ₄ )δ8.67(d,J=2.3Hz,1H), 8.05(d,J=2.5Hz,1H), 7.87(dd,J=9.2,2.3Hz,1H) ,7.69–7.65(m,2H),7.64(d,J=8.9Hz,1H),7.54–7.46(m,3H),7.35(d,J=8.4Hz,2H),7.08(d,J=8.4 Hz, 2H), 6.98 (d, J = 9.4 Hz, 1H), 6.79 (dd, J = 8.9, 2.4 Hz, 1H), 6.49 (d, J = 3.5 Hz, 1H), 6.39 (d, J = 2.3 Hz, 1H), 5.17 (dd, J = 13.4, 5.2 Hz, 1H), 4.57 (d, J = 17.0 Hz, 1H), 4.49 (d, J = 17.1 Hz, 1H), 3.85-3.55 (m, 11H ), 3.45–3.36(m,4H), 3.36–3.31(m,4H), 3.21–3.11(m,2H), 2.95–2.85(m,1H), 2.85–2.75(m,5H), 2.54(qd ,J＝13.3,4.7Hz,1H),2.32–2.23(m,4H),2.20(ddq,J＝10.5,5.3,2.6Hz,1H),2.11(s,2H),2.04(d,J＝12.9 Hz,2H),1.88–1.70(m,5H),1.68–1.60(m,2H),1.56(t,J=6.4Hz,2H),1.27–1.19(m,2H),1.00(s,6H) .HRMS(ESI)m/z: calculated value C ₆₇ H ₇₉ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1248.5466; measured value, 1248.5454.

Example 143: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl) (Piperazin-1-yl)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364051) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364051) was prepared by using intermediate BINDER (SIAIS364025) and intermediate LM (SIAIS255121), yellow powder, yield = 60%

¹ H NMR(500MHz, methanol-d ₄ )δ8.58(d,J=2.3Hz,1H), 7.94(d,J=2.5Hz,1H), 7.78(dd,J=9.2,2.3Hz,1H) ,7.65(d,J=7.6Hz,1H),7.59–7.50(m,3H),7.43–7.37(m,2H),7.25(d,J=8.1Hz,2H),6.98(d,J=8.1 Hz, 2H), 6.87 (d, J = 9.3 Hz, 1H), 6.68 (dd, J = 8.9, 2.3 Hz, 1H), 6.37 (d, J = 3.5 Hz, 1H), 6.27 (d, J = 2.2 Hz, 1H), 5.09 (dd, J = 13.3, 5.2 Hz, 3H), 4.50 (d, J = 17.7 Hz, 1H), 4.43 (d, J = 17.6 Hz, 1H), 3.80-3.50 (m, 10H ), 3.40-3.20 (m, 9H), 3.08–3.01 (m, 2H), 2.80 (ddd, J = 18.3, 13.5, 5.4 Hz, 1H), 2.67 (ddd, J = 17.2, 4.5, 2.2 Hz, 3H ), 2.59 (td, J = 6.7, 2.4 Hz, 2H), 2.51 (tt, J = 13.2, 6.7 Hz, 1H), 2.18 (q, J = 13.0, 9.8 Hz, 4H), 2.10–2.00 (m, 5H), 1.95 (d, J = 13.4 Hz, 2H), 1.65 (s, 1H), 1.52 (d, J = 11.9 Hz, 2H), 1.47 (t, J = 6.4 Hz, 2H), 1.13 (q, J = 12.0Hz, 2H), 0.90 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₈ H ₇₇ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1258.5309; measured value, 1258.5335.

Example 144: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)piper (Azin-1-yl)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364052) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364052) was prepared using intermediate BINDER (SIAIS364025) and intermediate LM (SIAIS268007), yellow powder, yield=69%

¹ H NMR(500MHz, methanol-d ₄ )δ8.57(d,J=2.3Hz,1H), 7.95(d,J=2.6Hz,1H), 7.78(dd,J=9.2,2.3Hz,1H) ,7.58(d,J=2.6Hz,1H),7.54(d,J=8.9Hz,1H),7.47(dd,J=8.6,7.1Hz,1H),7.41(d,J=3.4Hz,1H) ,7.25(d,J=8.3Hz,2H),7.01(d,J=8.6Hz,1H), 6.97(dd,J=7.6,4.8Hz,3H), 6.89(d,J=9.4Hz,1H) ,6.68(dd,J=9.0,2.5Hz,1H), 6.39(d,J=3.5Hz,1H), 6.27(d,J=2.3Hz,1H), 4.94(dd,J=12.7,5.4Hz, 1H), 3.70-3.45 (m, 9H), 3.40 (t, J = 6.5 Hz, 2H), 3.31 (d, J = 12.4 Hz, 2H), 3.27-3.18 (m, 6H), 3.15-3.00 (m ,4H), 2.79–2.66(m,3H), 2.59(ddt,J=16.3,13.1,5.8Hz,2H), 2.17(dt,J=23.0,5.1Hz,4H),2.04–1.90(m,7H ),1.65(s,1H),1.57–1.49(m,2H),1.47(t,J=6.4Hz,2H),1.15(t,J=13.2Hz,2H),0.90(s,6H).HRMS (ESI) m/z: calculated value C ₆₆ H ₇₆ ClN ₁₂ O ₁₀ S ⁺ [M+H] ⁺ , 1263.5211; measured value, 1263.5230.

Example 145: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)piperazine- 1-yl)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364056) preparation

With reference to the method in Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364056) was prepared using intermediate BINDER (SIAIS364043) and intermediate LM (SIAIS213132), yellow powder, yield = 19%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.58 (d, J = 2.2 Hz, 1H), 7.97-7.92 (m, 1H), 7.79 (dd, J = 9.2, 2.2 Hz, 1H), 7.65 ( d, J = 7.7 Hz, 1H), 7.60 (d, J = 7.5 Hz, 1H), 7.55 (d, J = 8.3 Hz, 2H), 7.47 (t, J = 7.6 Hz, 1H), 7.40 (d, J = 3.2Hz, 1H), 7.26 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 9.3 Hz, 1H), 6.69 (dd, J = 8.9,2.3Hz,1H), 6.37(d,J=3.5Hz,1H), 6.28(d,J=2.2Hz,1H), 5.07(dd,J=13.3,5.2Hz,1H), 4.43(d, J＝17.4Hz,1H), 4.36(d,J＝17.4Hz,1H), 3.75-3.45(m,9H), 3.45-3.28(m,5H), 3.22-3.15(m,5H), 3.11–2.98 (m, 4H), 2.79 (ddd, J = 18.3, 13.5, 5.4 Hz, 1H), 2.68 (d, J = 15.8 Hz, 3H), 2.45 (qd, J = 13.2, 4.5 Hz, 1H), 2.19 ( s, 2H), 2.10 (dd, J = 9.7, 4.0 Hz, 1H), 2.05-1.98 (m, 5H), 1.87-1.75 (m, 6H), 1.60 (t, J = 13.1Hz, 2H), 1.47 (t,J=6.4Hz,2H),0.91(s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₇ ClN ₁₁ O ₉ S ₂ ⁺ [M+H] ⁺ ,1266.5030; measured value ,1266.5044.

Example 146: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)piperazine- 1-yl)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364057) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364057) was prepared using intermediate BINDER (SIAIS364043) and intermediate LM (SIAS1222171), yellow powder, yield = 24%

¹ H NMR(500MHz, methanol-d ₄ )δ8.59(d,J=2.3Hz,1H), 7.93(d,J=2.6Hz,1H), 7.79(dd,J=9.3,2.3Hz,1H) ,7.56(d,J=8.9Hz,1H),7.51(d,J=2.6Hz,1H),7.42-7.36(m,2H),7.30(d,J=7.5Hz,1H),7.26(d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.0 Hz, 1H), 6.98 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 9.3 Hz, 1H), 6.68 (dd, J = 9.0, 2.4Hz, 1H), 6.35 (d, J = 3.5 Hz, 1H), 6.26 (d, J = 2.3 Hz, 1H), 5.04 (dd, J = 13.4, 5.1 Hz, 3H), 4.42 (d, J=17.3Hz,1H), 4.33(d,J=17.4Hz,1H), 4.17–4.10(m,2H), 3.80-3.50(m,10H), 3.38–3.28(m,8H), 3.09–2.97 (m,2H),2.82–2.60(m,4H),2.51–2.40(m,1H),2.18(s,2H),2.07(ddd,J=9.8,5.3,2.6Hz,1H),2.02-1.93 (m,6H),1.89–1.75(m,8H),1.60(t,J=12.6Hz,2H),1.47(t,J=6.4Hz,2H),0.91(s,6H).HRMS(ESI) m/z: calculated value C ₆₇ H ₇₉ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1264.5415; measured value, 1264.5400.

Example 147: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)piperazin-1-yl) (Cyclohexyl) methyl) amino)-3-nitrophenyl) sulfonyl) benzamide (SIAIS364058) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364058) was prepared using intermediate BINDER (SIAIS364043) and intermediate LM (SIAIS255130), yellow powder, yield = 26%

¹ H NMR(500MHz, methanol-d ₄ )δ8.58(d,J=2.3Hz,1H), 7.93(d,J=2.5Hz,1H), 7.79(dd,J=9.2,2.3Hz,1H) ,7.59–7.54(m,2H),7.53(d,J=2.5Hz,1H),7.44-7.41(m,1H),7.41-7.37(m,2H),7.26(d,J=8.4Hz,2H ), 6.98 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 9.3 Hz, 1H), 6.69 (dd, J = 9.0, 2.4 Hz, 1H), 6.37 (d, J = 3.5 Hz, 1H ), 6.27 (d, J = 2.4 Hz, 1H), 5.08 (dd, J = 13.4, 5.2 Hz, 1H), 4.48 (d, J = 17.0 Hz, 1H), 4.40 (d, J = 16.9 Hz, 1H) ), 380-3.45 (m, 10H), 3.39-3.28 (m, 5H), 3.26-3.20 (m, 2H), 3.17 (s, 2H), 3.08-2.99 (m, 2H), 2.80 (ddd, J = 18.5, 13.5, 5.4 Hz, 1H), 2.76-2.65 (m, 5H), 2.45 (qd, J = 13.2, 4.6 Hz, 1H), 2.19 (s, 2H), 2.10 (ddd, J = 9.8, 5.3 ,2.6Hz,1H),2.03-1.97(m,3H),1.91–1.78(m,6H),1.78-1.70(m,4H),1.67–1.55(m,2H),1.47(t,J=6.4 Hz,2H),0.91(s,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₉ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ ,1248.5466; measured value, 1248.5462.

Example 148: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl) (Piperazin-1-yl)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364059) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364059) was prepared using intermediate BINDER (SIAIS364043) and intermediate LM (SIAIS255121), yellow powder, yield = 25%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.01(d,J=2.6Hz,1H), 7.89(d,J=9.2Hz,1H), 7.75 (dd,J=7.6,1.0Hz,1H), 7.67–7.65(m,1H), 7.64(dd,J=7.6,1.0Hz,1H), 7.56(d,J=2.5Hz,1H), 7.51( t,J=7.6Hz,1H),7.46(d,J=3.4Hz,1H),7.35(d,J=8.4Hz,2H),7.07(d,J=8.4Hz,2H),7.01(d, J = 9.4Hz, 1H), 6.77 (dd, J = 9.0, 2.4 Hz, 1H), 6.43 (d, J = 3.5 Hz, 1H), 6.33 (d, J = 2.4 Hz, 1H), 5.17 (dd, J = 13.3, 5.2 Hz, 1H), 4.57 (d, J = 17.5 Hz, 1H), 4.50 (d, J = 17.5 Hz, 1H), 3.67 (s, 4H), 3.61–3.35 (m, 12H), 3.23–3.15(m,3H),3.10(s,2H), 2.88(ddd,J=17.6,13.5,5.4Hz,1H), 2.76(ddd,J=17.6,4.7,2.4Hz,3H),2.66( t,J=6.8Hz,2H),2.61–2.50(m,1H),2.27(s,2H),2.18(ddd,J=9.8,5.3,2.6Hz,1H),2.11(s,2H),2.06 (q,J=7.8,7.3Hz,3H),1.88(s,6H),1.69(s,2H),1.56(t,J=6.4Hz,2H),1.00(s,6H).HRMS(ESI) m/z: calculated value C ₆₈ H ₇₇ ClN ₁₁ O ₉ S ⁺ [M+H] ⁺ , 1258.5309; measured value, 1258.5341.

Example 149: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)piper (Azin-1-yl)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364060) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364060) was prepared by using intermediate BINDER (SIAIS364043) and intermediate LM (SIAIS268007), yellow powder, yield = 25%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.58 (dd, J = 4.3, 2.3 Hz, 1H), 7.94 (s, 1H), 7.79 (dd, J = 9.2, 2.3 Hz, 1H), 7.57- 7.53 (m, 2H), 7.48 (dd, J = 8.6, 7.1 Hz, 1H), 7.40 (d, J = 3.4 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.02 (d, J =8.6Hz,1H),7.00–6.96(m,3H), 6.93(d,J=9.4Hz,1H), 6.68(dd,J=8.9,2.4Hz,1H), 6.38(d,J=3.5Hz ,1H), 6.28(d,J=2.4Hz,1H), 4.95(dd,J=12.5,5.5Hz,1H), 3.60(d,J=17.3Hz,10H), 3.45–3.27(m,8H) , 3.27-3.23 (m, 2H), 3.17-2.97 (m, 4H), 2.80-2.52 (m, 5H), 2.19 (s, 2H), 2.07-1.97 (m, 5H), 1.87 (s, 2H) ,1.80(d,J=11.4Hz,4H),1.61(s,2H),1.47(t,J=6.4Hz,2H),0.91(s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₆ ClN ₁₂ O ₁₀ S ⁺ [M+H] ⁺ , 1263.5211; found value, 1263.5216.

Example 150: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynyl)-[1,4'-bipiperidine] -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364070) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS364070) was prepared by using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS364068), yellow powder, yield=46%

¹ H NMR (500MHz, methanol-d ₄ ) δ8.59 (dd, J = 2.2, 1.0 Hz, 1H), 7.96 (d, J = 2.8 Hz, 1H), 7.84 (ddd, J = 15.1, 9.2, 2.4 Hz, 1H), 7.60 (dd, J = 6.2, 2.6 Hz, 1H), 7.57 (d, J = 7.6 Hz, 1H), 7.54-7.49 (m, 2H), 7.42 (d, J = 3.4 Hz, 1H ), 7.38 (t, J = 7.6 Hz, 1H), 7.26 (d, J = 8.1 Hz, 2H), 6.98 (d, J = 8.5 Hz, 2H), 6.91 (dd, J = 9.3, 2.9 Hz, 1H) ), 6.67(ddd,J=9.0,6.8,2.4Hz,1H), 6.40(dd,J=3.5,1.2Hz,1H), 6.29(d,J=2.3Hz,1H), 5.10–5.02(m, 1H), 4.40 (d, J = 17.8 Hz, 1H), 4.31 (d, J = 11.7 Hz, 0H), 4.16 (t, J = 13.1 Hz, 1H), 3.63-3.55 (m, 4H), 3.42– 3.23(m,9H), 3.16–3.00(m,4H), 2.82-2.78(m,2H), 2.74–2.63(m,5H), 2.61–2.48(m,2H), 2.41(dt,J=13.2 ,4.9Hz,1H),2.20(s,2H),2.05-1.95(m,5H),1.92-1.72(m,3H),1.52-1.34(m,6H),0.91(s,6H).HRMS( ESI) m/z: calculated value C ₆₈ H ₇₅ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1272.5102; measured value, 1272.5095.

Example 151: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynyl)piperazine- 1-yl)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364071) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS364071) was prepared using intermediate BINDER (SIAIS364025) and intermediate LM (SIAIS364068), yellow powder, yield=43%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.59 (d, J = 2.3 Hz, 1H), 7.95 (d, J = 2.4 Hz, 1H), 7.81 (s, 1H), 7.61 (d, J = 7.6Hz, 1H), 7.58–7.53(m, 2H), 7.52(dd, J=7.7, 1.0Hz, 1H), 7.42–7.37(m, 2H), 7.30–7.21(m, 2H), 6.98(d ,J=8.4Hz,2H), 6.87(d,J=9.3Hz,1H), 6.68(d,J=8.9Hz,1H), 6.38(d,J=3.5Hz,1H), 6.28(d,J =2.3Hz,1H),5.08(d,J=12.5Hz,1H), 4.68–4.60(m,1H), 4.41(d,J=17.8Hz,1H), 4.32(d,J=17.8Hz,1H ), 4.23 (s, 1H), 3.62-3.57 (m, 4H), 3.44 (d, J = 16.8Hz, 3H), 3.36–3.27 (m, 2H), 3.17 (d, J = 6.8Hz, 2H) ,3.12–2.86(m,6H), 2.82(ddd,J=18.3,13.5,5.3Hz,2H), 2.75–2.65(m,5H), 2.60(s,1H),2.41(qd,J=13.2, 4.5Hz, 1H), 2.19 (s, 2H), 2.10-2.03 (m, 1H), 2.01 (s, 2H), 2.00-1.92 (m, 1H), 1.86 (t, J = 10.8 Hz, 3H), 1.57(s,1H),1.50-1.20(m,4H),1.06(q,J=10.8,9.5Hz,2H),0.91(s,6H).HRMS(ESI)m/z: calculated value C ₆₈ H ₇₅ ClN ₁₁ O ₁₀ S ⁺ [M+H] ⁺ , 1272.5102; measured value, 1272.5108.

Example 152: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)- 4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynylamino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364072) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS364072) was prepared using intermediate BINDER (SIAIS363101) and intermediate LM (SIAIS364068), yellow powder, yield=42%

¹ H NMR(500MHz, methanol-d ₄ )δ8.56(d,J=2.3Hz,1H), 7.95(d,J=2.4Hz,1H), 7.75(dd,J=9.2,2.3Hz,1H) ,7.61(dd,J=7.6,1.0Hz,1H),7.58–7.52(m,2H),7.49(dd,J=7.6,1.0Hz,1H),7.41–7.34(m,2H),7.23(d ,J=8.4Hz,2H), 6.96(d,J=8.4Hz,2H), 6.84(d,J=9.3Hz,1H), 6.69(dd,J=9.0,2.3Hz,1H), 6.36(d ,J=3.5Hz,1H),6.28(d,J=2.3Hz,1H),5.02(dd,J=13.4,5.2Hz,1H), 4.38(d,J=17.5Hz,1H),4.31(d ,J＝17.6Hz,1H),3.70-3.50(m,5H),3.31(d,J＝12.6Hz,2H),3.14(d,J＝6.8Hz,2H),3.04(t,J＝12.4Hz ,2H),2.77–2.60(m,6H),2.41–2.33(m,3H),2.18(s,2H),2.08–2.02(m,1H),2.00(s,2H),1.84(d,J =9.6Hz,2H),1.75(d,J=12.4Hz,2H),1.54(s,1H),1.46(t,J=6.4Hz,2H),1.15-1.00(m,4H),0.90(s ,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₆₈ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ ,1203.4524; measured value, 1203.4539.

Example 153: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3 ,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)- 4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynylamino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide (SIAIS364073) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS364073) was prepared by using intermediate BINDER (SIAIS363103) and intermediate LM (SIAIS364068), yellow powder, yield=50%

¹ H NMR(500MHz, methanol-d ₄ )δ8.57(d,J=2.3Hz,1H), 7.96(d,J=2.5Hz,1H), 7.77(dd,J=9.2,2.3Hz,1H) ,7.59(d,J=2.5Hz,1H),7.55(d,J=8.9Hz,1H),7.47(ddd,J=11.0,7.7,1.1Hz,2H),7.39(d,J=3.5Hz, 1H), 7.28 (t, J = 7.7 Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.4 Hz, 2H), 6.73 (d, J = 9.4 Hz, 1H) ,6.66(dd,J＝9.0,2.4Hz,1H), 6.37(d,J＝3.4Hz,1H), 6.26(d,J＝2.4Hz,1H), 5.01(dd,J＝13.4,5.2Hz, 1H), 4.37 (d, J = 17.5 Hz, 1H), 4.31 (d, J = 17.5 Hz, 1H), 3.84 (t, J = 4.3 Hz, 1H), 3.64-3.55 (m, 4H), 3.30 ( d, J = 12.6Hz, 2H), 3.09–2.89 (m, 4H), 2.78 (ddd, J = 17.7, 13.6, 5.4 Hz, 1H), 2.74–2.63 (m, 5H), 2.42 (t, J = 6.7Hz, 2H), 2.36 (dd, J = 13.3, 4.7 Hz, 1H), 2.19 (s, 2H), 2.08-2.03 (m, 1H), 2.01 (s, 2H), 1.65 (s, 3H), 1.52–1.40(m,6H),1.31–1.21(m,2H),0.90(s,6H).HRMS(ESI) m/z: calculated value C ₆₄ H ₆₈ ClN ₁₀ O ₁₀ S ⁺ [M+H] ⁺ ,1203.4524; measured value,1203.4538.

Example 154: (2S,4R)-1-((S)-2-(5-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)valerylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361001) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361001) was prepared using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS360137), yellow powder, yield = 19%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.90 (s, 1H), 8.69 (d, J = 2.2 Hz, 1H), 7.99 (d, J = 2.5 Hz, 1H), 7.90 (dd, J = 9.2,2.3Hz,1H), 7.64(d,J=8.7Hz,1H),7.55(d,J=2.6Hz,1H),7.46-7.41(m,3H),7.39(d,J=8.3Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.5 Hz, 2H), 6.99 (d, J = 9.3 Hz, 1H), 6.75 (dd, J = 8.9, 2.3 Hz, 1H), 6.42 (d, J = 3.5 Hz, 1H), 6.32 (d, J = 2.4 Hz, 1H), 4.59 (s, 1H), 4.52 (dd, J = 16.4, 8.9 Hz, 3H), 4.35 ( d, J = 15.5 Hz, 1H), 3.91 (d, J = 11.0 Hz, 1H), 3.80 (dd, J = 10.9, 3.9 Hz, 1H), 3.66 (s, 3H), 3.60 (t, J = 11.8 Hz, 4H), 3.49–3.34 (m, 6H), 3.24–3.14 (m, 2H), 3.08 (q, J = 4.0 Hz, 2H), 2.93 (t, J = 11.9 Hz, 2H), 2.46 (s , 3H), 2.37 (t, J = 6.8 Hz, 2H), 2.23 (d, J = 31.4 Hz, 4H), 2.12-2.03 (m, 5H), 1.80-1.65 (m, 5H), 1.55 (t, J = 6.4Hz, 3H), 1.04 (s, 9H), 1.00 (s, 6H). HRMS (ESI) m/z: calculated value C ₇₂ H ₈₈ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1379.5871; measured value, 1379.5887.

Example 155: (2S,4R)-1-((S)-2-(6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)hexanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361004) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361004) was prepared using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS360131), yellow powder, yield = 28%

¹ H NMR(500MHz, methanol-d ₄ )δ9.12(s,1H), 8.66(d,J=2.2Hz,1H), 8.03(d,J=2.4Hz,1H), 7.88(dd,J= 9.3, 2.3 Hz, 1H), 7.65 (d, J = 2.5 Hz, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 3.3 Hz, 1H), 7.47 (t, J = 8.0Hz, 2H), 7.42 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 7.01 (d, J = 9.3 Hz ,1H),6.77(d,J=8.3Hz,1H),6.47(d,J=3.3Hz,1H),6.37(s,1H),4.63(s,1H),4.60–4.49(m,3H) , 4.37 (d, J = 15.6Hz, 1H), 3.90 (d, J = 10.8Hz, 1H), 3.80 (dd, J = 10.9, 3.8Hz, 1H), 3.67 (s, 4H), 3.61 (d, J = 12.8Hz, 2H), 3.47–3.36 (m, 4H), 3.26–3.13 (m, 2H), 3.07 (t, J = 8.2 Hz, 2H), 2.96 (t, J = 12.7 Hz, 2H), 2.79(s,2H),2.49(s,3H),2.32(s,5H),2.26-2.20(m,1H),2.11(s,2H),2.07(d,J=13.4Hz,3H),1.77 (s, 2H), 1.70-1.60 (m, 4H), 1.56 (t, J = 6.3 Hz, 3H), 1.40 (dt, J = 15.0, 7.2 Hz, 2H), 1.03 (s, 9H), 1.00 ( s,6H).HRMS(ESI)m/z: calculated value C ₇₃ H ₉₀ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ ,1393.6027; measured value, 1393.6020.

Example 156: (2S,4R)-1-((S)-2-(7-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)heptanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361005)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361005) was prepared using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS360135), yellow powder, yield = 22%

¹ H NMR(500MHz, methanol-d ₄ )δ8.95(s,1H), 8.58(d,J=2.2Hz,1H), 7.92(d,J=2.4Hz,1H), 7.79(dd,J= 9.2, 2.3 Hz, 1H), 7.53 (d, J = 8.9 Hz, 1H), 7.51 (d, J = 2.5 Hz, 1H), 7.37 (dt, J = 15.1, 5.1 Hz, 3H), 7.31 (d, J = 8.3 Hz, 2H), 7.26 (d, J = 8.3 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 9.3 Hz, 1H), 6.67 (dd, J = 9.0, 2.2 Hz, 1H), 6.35 (d, J = 3.5 Hz, 1H), 6.26 (d, J = 2.3 Hz, 1H), 4.53 (s, 1H), 4.49-4.37 (m, 3H), 4.27 ( d,J=15.6Hz,1H), 3.80(d,J=11.0Hz,1H), 3.70(dd,J=10.9,3.8Hz,1H),3.57(s,3H),3.51(d,J=12.4 Hz, 2H), 3.28 (d, J = 6.3 Hz, 4H), 3.07 (s, 2H), 3.01–2.93 (m, 2H), 2.85 (t, J = 13.0 Hz, 2H), 2.69 (s, 2H) ), 2.38 (s, 3H), 2.23-2.17 (m, 4H), 2.16-2.09 (m, 1H), 2.01 (s, 2H), 1.96 (d, J = 13.6 Hz, 3H), 1.65 (s, 2H), 1.60-1.45 (m, 6H), 1.29 (s, 5H), 0.93 (s, 9H), 0.90 (s, 6H). HRMS (ESI) m/z: calculated value C ₇₄ H ₉₂ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ ,1407.6184; measured value,1407.6222.

Example 157: (2S,4R)-1-((S)-2-(8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)octanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361006) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361006) was prepared using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS360138), yellow powder, yield = 18%

¹ H NMR(500MHz, methanol-d ₄ )δ8.93(s,1H), 8.68(d,J=2.3Hz,1H), 7.99(d,J=2.5Hz,1H), 7.89(dd,J= 9.2,2.3Hz,1H), 7.64(d,J=8.9Hz,1H),7.55(d,J=2.6Hz,1H),7.47–7.43(m,3H),7.41(d,J=8.3Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 9.4 Hz, 1H), 6.76 (dd, J = 8.9, 2.3 Hz, 1H), 6.42 (d, J = 3.5 Hz, 1H), 6.33 (d, J = 2.4 Hz, 1H), 4.64 (s, 1H), 4.60-4.48 (m, 3H), 4.37 (d, J = 15.5 Hz, 1H), 3.90 (d, J = 11.1 Hz, 1H), 3.80 (dd, J = 11.0, 3.9 Hz, 1H), 3.67 (s, 3H), 3.61 (d, J = 12.4 Hz, 2H), 3.50-3.32 (m, 5H), 3.17 (s, 2H), 3.11-3.04 (m, 2H), 2.96 (d, J = 11.9 Hz, 2H), 2.79 (s, 2H), 2.47 (s, 3H) ,2.32–2.19(m,5H),2.14–2.01(m,6H),1.73(d,J=8.1Hz,2H),1.59(dt,J=25.3,7.0Hz,6H),1.38(s,6H) ),1.03(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₅ H ₉₄ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ ,1421.6340; measured value, 1421.6396 .

Example 158: (2S,4R)-1-((S)-2-(9-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)nonanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361007) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361007) was prepared using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS360139), yellow powder, yield = 27%

¹ H NMR(500MHz, methanol-d ₄ )δ9.27(s,1H), 8.66(s,1H), 8.07(s,1H), 7.90(s,1H), 7.74(s,1H), 7.63( s, 1H), 7.54 (s, 1H), 7.50 (d, J = 7.8 Hz, 2H), 7.45 (d, J = 7.9 Hz, 2H), 7.36 (s, 2H), 7.10 (s, 2H), 7.07--7.00(m,1H), 6.80(s,1H), 6.52(s,1H), 6.42(s,1H), 4.64(s,1H), 4.61--4.47(m,3H), 4.38(d, J = 15.6Hz, 1H), 3.90 (d, J = 10.9Hz, 1H), 3.80 (dd, J = 11.0, 3.7Hz, 1H), 3.68 (s, 3H), 3.63 (s, 2H), 3.40 ( s, 4H), 3.21 (s, 2H), 3.08 (s, 2H), 2.96 (s, 2H), 2.80 (s, 2H), 2.52 (s, 3H), 2.37-2.19 (m, 6H), 2.17 -2.00(m,6H),1.75(s,2H),1.59(d,J=18.6Hz,6H),1.45-1.30(m,8H),1.03(s,9H),1.01(s,6H). HRMS (ESI) m/z: calculated value C ₇₆ H ₉₆ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1435.6497; measured value, 1435.6455.

Example 159: (2S,4R)-1-((S)-2-(10-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)decanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361008)

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS360140) to prepare the target compound (SIAIS361008), yellow powder, yield = 32%

¹ H NMR(500MHz, methanol-d ₄ )δ9.04(s,1H), 8.66(d,J=2.1Hz,1H), 8.01(s,1H), 7.87(dd,J=9.0,2.3Hz, 1H), 7.62 (d, J = 9.3 Hz, 2H), 7.47 (d, J = 8.2 Hz, 3H), 7.42 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H) ,7.08(d,J=7.9Hz,2H),7.00(d,J=9.3Hz,1H), 6.76(d,J=8.8Hz,1H), 6.44(d,J=3.4Hz,1H), 6.35 –6.31(m,1H),4.63(s,1H),4.62–4.48(m,3H), 4.37(d,J=15.6Hz,1H), 3.90(d,J=10.9Hz,1H), 3.80( dd,J=11.0,3.9Hz,1H),3.67(s,4H),3.61(d,J=12.2Hz,2H),3.50–3.35(m,4H),3.19(s,2H),3.10–3.03 (m, 2H), 2.95 (t, J = 12.6 Hz, 2H), 2.79 (s, 2H), 2.48 (s, 3H), 2.30 (dq, J = 10.6, 6.7, 5.0 Hz, 3H), 2.23 ( dt,J=14.9,8.1Hz,2H),2.12–2.01(m,6H),1.74(s,2H),1.67–1.53(m,6H),1.40–1.30(m,10H),1.03(s, 9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₇ H ₉₈ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1449.6653; measured value, 1449.6779.

Example 160: (2S,4R)-1-((S)-2-(11-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)undecylamido)- Preparation of 3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361009)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361009) was prepared using intermediate BINDER (SIAIS230138) and intermediate LM (SIAIS360141), yellow powder, yield = 34%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.98 (s, 1H), 8.67 (d, J = 2.3 Hz, 1H), 7.99 (d, J = 2.5 Hz, 1H), 7.87 (dd, J = 9.1, 2.3 Hz, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.57 (d, J = 2.5 Hz, 1H), 7.47 (d, J = 7.8 Hz, 3H), 7.41 (d, J = 8.3Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 9.3 Hz, 1H), 6.75 (dd, J = 9.0, 2.2Hz, 1H), 6.43 (d, J = 3.4 Hz, 1H), 6.32 (d, J = 2.3 Hz, 1H), 4.64 (s, 1H), 4.60-4.47 (m, 3H), 4.36 (d, J = 15.5 Hz, 1H), 3.90 (d, J = 11.1 Hz, 1H), 3.80 (dd, J = 11.0, 3.9 Hz, 1H), 3.67 (s, 3H), 3.61 (d, J = 12.1 Hz, 2H), 3.49–3.35(m, 4H), 3.27–3.13(m, 2H), 3.12–3.04(m, 2H), 2.96(t, J=12.5Hz, 2H), 2.79(s, 2H), 2.48 (s,3H),2.30(qd,J=6.8,6.2,3.1Hz,3H),2.28–2.19(m,2H),2.15-2.05(m,6H),1.74(s,2H),1.66–1.53 (m,6H),1.41-1.29(m,12H),1.03(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₈ H ₁₀₀ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1463.6810; measured value, 1463.6825.

Example 161: (2S,4R)-1-((2S)-2-(5-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)valerylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361010) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361010) was prepared using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS360137), yellow powder, yield = 21%

¹ H NMR(500MHz, methanol-d ₄ )δ9.01(s,1H), 8.68(d,J=2.3Hz,1H), 8.01(d,J=2.4Hz,1H), 7.93(dd,J= 9.3,2.3Hz,1H), 7.63(d,J=8.9Hz,1H), 7.60(d,J=2.5Hz,1H),7.50–7.44(m,3H),7.40(dd,J=8.3,1.8 Hz, 2H), 7.38–7.33 (m, 2H), 7.08 (d, J = 8.0 Hz, 2H), 7.04 (dd, J = 9.2, 3.7 Hz, 1H), 6.80–6.74 (m, 1H), 6.45 (d,J=3.4Hz,1H), 6.34(d,J=2.1Hz,1H), 4.64–4.47(m,4H), 4.36(dd,J=15.5,3.7Hz,1H), 3.90(t, J = 9.8Hz, 1H), 3.83–3.76 (m, 1H), 3.67 (s, 4H), 3.61–3.51 (m, 3H), 3.42 (d, J = 6.8 Hz, 4H), 3.25–3.05 (m ,4H), 2.88(t,J=13.0Hz,1H), 2.83–2.70(m,2H), 2.47(s,3H), 2.35(tt,J=7.0,5.5,2.4Hz,2H), 2.32– 2.26(m,3H),2.27–2.19(m,1H),2.10(s,3H),1.99(d,J=13.1Hz,2H),1.85–1.71(m,3H),1.66(q,J= 6.7Hz,2H),1.56(t,J=6.3Hz,2H),1.33(dt,J=21.9,8.1Hz,1H),1.03(s,9H),1.00(s,6H).HRMS(ESI) m/z: Calculated value C ₇₂ H ₈₈ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1379.5871; measured value, 1379.5877.

Example 161: (2S,4R)-1-((2S)-2-(6-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)hexanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361011) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361011) was prepared using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS360131), yellow powder, yield = 21%

¹ H NMR(500MHz, methanol-d ₄ )δ9.04(s,1H), 8.68(d,J=2.3Hz,1H), 8.02(d,J=2.5Hz,1H), 7.92(ddd,J= 9.2,2.3,0.9Hz,1H),7.67–7.60(m,2H),7.50–7.44(m,3H),7.41(d,J=8.1Hz,2H),7.35(d,J=8.4Hz,2H ), 7.08 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 9.3 Hz, 1H), 6.77 (dd, J = 9.0, 2.4 Hz, 1H), 6.46 (d, J = 3.5 Hz, 1H ), 6.35 (d, J = 2.3 Hz, 1H), 4.63 (d, J = 4.4 Hz, 1H), 4.60-4.47 (m, 3H), 4.36 (d, J = 15.5 Hz, 1H), 3.94-3.87 (m, 1H), 3.79 (dd, J = 11.0, 3.7 Hz, 1H), 3.67 (s, 3H), 3.53 (d, J = 6.6 Hz, 3H), 3.43 (td, J = 7.8, 3.3 Hz, 4H), 3.24–3.14 (m, 2H), 3.10 (dd, J = 9.9, 6.6 Hz, 2H), 2.95–2.84 (m, 1H), 2.77 (t, J = 12.2 Hz, 2H), 2.48 (s ,3H),2.33–2.19(m,6H),2.10(s,3H),2.00(d,J=10.9Hz,2H),1.81–1.70(m,2H),1.64(p,J=7.3Hz, 2H),1.56(t,J=6.4Hz,3H),1.40-1.25(m,3H),1.02(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₃ H ₉₀ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1393.6027; found value, 1393.6067.

Example 162: (2S,4R)-1-((2S)-2-(7-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)heptanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361012) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361012) was prepared using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS360135), yellow powder, yield = 22%

¹ H NMR(500MHz, methanol-d ₄ )δ9.05(s,1H), 8.71–8.66(m,1H), 8.02(d,J=2.5Hz,1H), 7.93(dd,J=9.2,2.3 Hz,1H), 7.67–7.60(m,2H), 7.50–7.43(m,3H), 7.43–7.40(m,2H), 7.39–7.33(m,2H), 7.08(d,J=8.4Hz, 2H), 7.04 (d, J = 9.3 Hz, 1H), 6.77 (dd, J = 9.0, 2.3 Hz, 1H), 6.46 (d, J = 3.5 Hz, 1H), 6.35 (d, J = 2.3 Hz, 1H), 4.63(d,J=3.0Hz,1H), 4.61–4.46(m,3H), 4.37(dd,J=15.6,2.4Hz,1H), 3.94–3.87(m,1H), 3.80(dt ,J＝10.9,3.4Hz,1H),3.67(s,3H),3.64-3.50(m,3H),3.42(h,J＝6.7,4.2Hz,3H),3.16(dt,J＝3.4,1.7 Hz, 1H), 3.09 (t, J = 8.3 Hz, 1H), 2.92–2.70 (m, 3H), 2.49 (d, J = 9.9 Hz, 3H), 2.32–2.19 (m, 5H), 2.14–1.97 (m,4H),1.86-1.68(m,2H),1.57(tt,J=18.1,6.5Hz,5H),1.45-1.29(m,5H),1.03(d,J=4.9Hz,9H), 1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₄ H ₉₂ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1407.6184; measured value, 1407.6202.

Example 163: (2S,4R)-1-((2S)-2-(8-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)octanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361013) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361013) was prepared using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS360138), yellow powder, yield = 18%

¹ H NMR(500MHz, methanol-d ₄ )δ9.12(s,1H), 8.68(d,J=2.3Hz,1H), 8.03(d,J=2.2Hz,1H), 7.93(dd,J= 9.2, 2.3 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 7.64 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 3.4 Hz, 1H), 7.48 (d, J = 8.1Hz, 2H), 7.43 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 9.3 Hz ,1H), 6.78(dd,J=8.9,2.1Hz,1H), 6.48(d,J=3.4Hz,1H), 6.37(s,1H), 4.63(s,1H), 4.61–4.47(m, 3H), 4.37 (d, J = 15.5 Hz, 1H), 3.90 (d, J = 10.9 Hz, 1H), 3.80 (dd, J = 11.0, 3.9 Hz, 1H), 3.67 (s, 4H), 3.63- 3.52(m,2H),3.51–3.37(m,4H),3.17(dt,J=3.4,1.7Hz,2H),3.10(t,J=8.3Hz,2H),2.88(t,J=12.6Hz ,1H),2.77(t,J=11.9Hz,3H),2.49(s,3H),2.33-2.20(m,6H),2.09(d,J=14.6Hz,3H),2.07-1.97(m, 2H), 1.83 (d, J = 13.4Hz, 1H), 1.74 (s, 2H), 1.58 (dt, J = 13.0, 7.0 Hz, 4H), 1.45-1.30 (m, 7H), 1.03 (s, 9H) ),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₅ H ₉₄ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ ,1421.6340; measured value, 1421.6408.

Example 164: (2S,4R)-1-((2S)-2-(9-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)nonanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361014) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361014) was prepared using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS360139), yellow powder, yield = 11%

¹ H NMR(500MHz, methanol-d ₄ )δ8.95(s,1H), 8.71–8.67(m,1H), 8.00(d,J=2.5Hz,1H), 7.93(dd,J=9.2,2.3 Hz, 1H), 7.65 (d, J = 8.9 Hz, 1H), 7.57 (d, J = 2.6 Hz, 1H), 7.49-7.43 (m, 3H), 7.41 (d, J = 8.2 Hz, 2H), 7.36(d,J=8.4Hz,2H), 7.08(d,J=8.3Hz,2H), 7.03(s,1H), 6.77(dd,J=9.0,2.4Hz,1H), 6.43(d,J =3.5Hz,1H),6.33(d,J=2.4Hz,1H),4.63(s,1H),4.61-4.48(m,3H),4.36(d,J=15.5Hz,1H),3.89(d ,J=10.9Hz,1H), 3.80(dd,J=10.9,3.9Hz,1H), 3.67(s,4H), 3.59(dd,J=16.7,10.6Hz,2H), 3.46–3.38(m, 4H), 3.19–3.06 (m, 4H), 2.88 (t, J = 12.4 Hz, 1H), 2.76 (t, J = 12.2 Hz, 2H), 2.47 (s, 3H), 2.34–2.20 (m, 6H ),2.09(d,J=13.5Hz,3H),2.03(d,J=14.3Hz,2H),1.82(t,J=13.6Hz,1H),1.73(s,2H),1.64-1.55(m ,4H),1.38–1.28(m,10H),1.02(s,9H),1.00(s,6H).HRMS(ESI) m/z: calculated value C ₇₆ H ₉₆ ClN ₁₂ O ₁₀ S ₂ ⁺ (M +H] ⁺ ,1435.6497; measured value,1435.6564.

Example 165: (2S,4R)-1-((2S)-2-(10-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)decanoylamino)-3,3 -Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361015)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361015) was prepared using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS360140), yellow powder, yield = 22%

¹ H NMR(500MHz, methanol-d ₄ )δ9.01(s,1H), 8.68(d,J=2.1Hz,1H), 8.01(d,J=2.4Hz,1H), 7.92(dd,J= 9.1,2.3Hz,1H), 7.63(d,J=8.8Hz,1H), 7.60(d,J=2.5Hz,1H), 7.47(dd,J=6.0,2.4Hz,3H),7.42(s, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 9.2 Hz, 1H), 6.79-6.73 (m, 1H), 6.44 ( d,J=3.4Hz,1H), 6.34(d,J=2.2Hz,1H), 4.63(s,1H), 4.60–4.48(m,3H), 4.36(d,J=15.5Hz,1H), 3.89 (d, J = 10.7 Hz, 1H), 3.80 (dd, J = 11.0, 3.9 Hz, 1H), 3.67 (s, 4H), 3.64-3.53 (m, 3H), 3.43 (dt, J = 7.6, 3.9Hz, 4H), 3.25–3.14(m, 2H), 3.13–3.06(m, 2H), 2.87(d, J = 11.4Hz, 1H), 2.77(t, J = 12.1Hz, 2H), 2.48( s,3H),2.33–2.19(m,6H),2.10(d,J=3.0Hz,3H),2.07–1.97(m,2H),1.83(t,J=13.4Hz,1H),1.73(s ,2H),1.56(q,J=7.1,6.4Hz,4H),1.45-1.30(m,11H),1.02(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculation Value C ₇₇ H ₉₈ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1449.6653; measured value, 1449.6628.

Example 166: (2S,4R)-1-((2S)-2-(11-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)undecylamido)- Preparation of 3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361016)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361016) was prepared using intermediate BINDER (SIAIS255123) and intermediate LM (SIAIS360141), yellow powder, yield = 19%

¹ H NMR(500MHz, methanol-d ₄ )δ8.97(s,1H), 8.68(d,J=2.2Hz,1H),8.00(d,J=2.5Hz,1H),7.92(dd,J= 9.2,2.3Hz,1H), 7.64(d,J=8.8Hz,1H), 7.58(d,J=2.6Hz,1H), 7.50–7.45(m,3H),7.41(d,J=8.3Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 7.03 (d, J = 9.3 Hz, 1H), 6.76 (dd, J = 9.0, 2.3 Hz, 1H), 6.43 (d, J = 3.5 Hz, 1H), 6.33 (d, J = 2.2 Hz, 1H), 4.63 (s, 1H), 4.60-4.46 (m, 3H), 4.36 (d, J = 15.5 Hz, 1H), 3.89 (dt, J = 11.0, 1.7 Hz, 1H), 3.80 (dd, J = 11.0, 3.9 Hz, 1H), 3.67 (s, 3H), 3.64–3.53 (m, 3H), 3.47 –3.37(m,4H),3.16(dt,J=3.3,1.9Hz,2H),3.12–3.05(m,2H),2.88(t,J=12.4Hz,1H),2.83–2.71(m,2H ),2.47(s,3H),2.33–2.18(m,6H),2.13–2.07(m,3H),2.07–1.98(m,2H),1.83(t,J=13.4Hz,1H),1.73( s, 2H), 1.57 (q, J = 8.8, 6.3 Hz, 5H), 1.45-1.28 (m, 13H), 1.03 (d, J = 3.0 Hz, 9H), 1.00 (d, J = 2.2 Hz, 6H ).HRMS(ESI)m/z: calculated value C ₇₈ H ₁₀₀ ClN ₁₂ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1463.6810; measured value, 1463.6781.

Example 167: (2S,4R)-1-((S)-2-(5-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'- Yl)pentanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361018 )preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361018) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS360137), yellow powder, yield = 26%

¹ H NMR(500MHz, methanol-d ₄ )δ9.24(s,1H), 8.65(d,J=2.3Hz,1H), 8.05(d,J=2.5Hz,1H), 7.88(dd,J= 9.3, 2.3 Hz, 1H), 7.72 (d, J = 2.5 Hz, 1H), 7.61 (d, J = 8.9 Hz, 1H), 7.53 (d, J = 3.5 Hz, 1H), 7.49 (d, J = 8.2Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 8.3 Hz, 2H), 7.03 (d, J = 9.3 Hz ,1H), 6.78 (d, J = 8.9 Hz, 1H), 6.51 (d, J = 3.4 Hz, 1H), 6.40 (d, J = 2.3 Hz, 1H), 4.61 (s, 1H), 4.60–4.48 (m, 3H), 4.39 (d, J = 15.6 Hz, 1H), 3.92 (d, J = 10.9 Hz, 1H), 3.80 (dd, J = 11.0, 3.8 Hz, 1H), 3.73 (d, J = 11.0Hz, 4H), 3.68(s, 2H), 3.66-3.51(m, 4H), 3.47-3.35(m, 4H), 3.20(s, 2H), 3.16-3.04(m, 6H), 2.79(s , 2H), 2.50 (s, 3H), 2.46 (d, J = 13.3 Hz, 2H), 2.38 (t, J = 6.7 Hz, 2H), 2.32 (s, 2H), 2.26 (dd, J = 13.1, 7.7Hz, 1H), 2.19 (d, J = 10.9 Hz, 1H), 2.13-2.02 (m, 6H), 1.83-1.65 (m, 6H), 1.56 (t, J = 6.3 Hz, 2H), 1.05 ( s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₇ H ₉₇ ClN ₁₃ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1462.6606; measured value, 1462.6608.

Example 168: (2S,4R)-1-((S)-2-(6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'- Yl)hexanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361019 )preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361019) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS360131), yellow powder, yield = 33%

¹ H NMR(500MHz, methanol-d ₄ )δ9.30(s,1H), 8.65(d,J=2.3Hz,1H), 8.07(d,J=2.5Hz,1H), 7.88(dd,J= 9.2, 2.3 Hz, 1H), 7.75 (d, J = 2.5 Hz, 1H), 7.61 (d, J = 8.9 Hz, 1H), 7.55 (d, J = 3.4 Hz, 1H), 7.50 (d, J = 8.0Hz, 2H), 7.44 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 9.3 Hz ,1H), 6.79(dd,J=9.0,2.3Hz,1H), 6.52(d,J=3.5Hz,1H), 6.42(d,J=2.3Hz,1H), 4.63(s,1H), 4.61 –4.48(m,3H), 4.39(d,J=15.7Hz,1H), 3.91(d,J=10.9Hz,1H), 3.86–3.52(m,11H), 3.49–3.36(m,4H), 3.21 (s, 2H), 3.11 (d, J = 7.3 Hz, 5H), 2.79 (s, 2H), 2.51 (s, 3H), 2.45 (d, J = 13.0 Hz, 2H), 2.32 (td, J =7.2,3.1Hz,4H),2.28– 2.17(m,3H), 2.16–2.01(m,6H),1.83–1.62(m,6H),1.56(t,J=6.3Hz,2H),1.46– 1.34(m,2H),1.04(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₈ H ₉₉ ClN ₁₃ O ₁₀ S ₂ ⁺ [M+H] ⁺ ,1476.6762 ; Measured value, 1476.6785.

Example 169: (2S,4R)-1-((S)-2-(7-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'- Yl)heptanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361020 )preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361020) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS360135), yellow powder, yield = 31%

¹ H NMR(500MHz, methanol-d ₄ )δ9.28(s,1H), 8.65(d,J=2.3Hz,1H), 8.06(d,J=2.5Hz,1H), 7.88(dd,J= 9.1, 2.3 Hz, 1H), 7.73 (d, J = 2.5 Hz, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 3.4 Hz, 1H), 7.50 (d, J = 8.2Hz, 2H), 7.44 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 9.3 Hz ,1H), 6.79 (dd, J = 8.9, 2.3 Hz, 1H), 6.52 (d, J = 3.4 Hz, 1H), 6.41 (d, J = 2.2 Hz, 1H), 4.63 (s, 1H), 4.61 –4.47(m,3H), 4.39(d,J=15.6Hz,1H), 3.91(d,J=10.6Hz,1H), 3.84–3.52(m,11H), 3.48–3.36(m,4H), 3.20(s, 2H), 3.16–3.05(m, 6H), 2.79(s, 2H), 2.51(s, 3H), 2.44(d, J = 12.1Hz, 2H), 2.35–2.27(m, 4H) ,2.23(tdd,J＝12.1,8.8,5.2Hz,3H),2.14-2.04(m,6H),1.74(dd,J＝23.3,10.3Hz,4H),1.63(t,J＝7.0Hz,2H ),1.56(t,J=6.3Hz,2H),1.40(s,4H),1.03(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₉ H ₁₀₁ ClN ₁₃ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1490.6919; measured value, 1490.6916.

Example 170: (2S,4R)-1-((S)-2-(8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'- (Yl)octanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361021 )preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361021) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS360138), yellow powder, yield = 25%

¹ H NMR (500MHz, methanol-d ₄ ) δ 9.15 (s, 1H), 8.66 (d, J = 2.3 Hz, 1H), 8.03 (d, J = 2.4 Hz, 1H), 7.88 (dd, J = 9.3, 2.3 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 3.4 Hz, 1H), 7.49 (d, J = 8.1Hz, 2H), 7.43 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.2 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 7.02 (d, J = 9.3 Hz ,1H), 6.78 (dd, J = 9.0, 2.2 Hz, 1H), 6.48 (d, J = 3.4 Hz, 1H), 6.38 (d, J = 2.2 Hz, 1H), 4.64 (s, 1H), 4.60 –4.48(m,3H), 4.38(d,J=15.6Hz,1H), 3.90(d,J=11.1Hz,1H), 3.85–3.56(m,10H), 3.48–3.36(m,4H), 3.18(d,J=11.2Hz,2H), 3.11(t,J=12.7Hz,6H), 2.79(s,2H), 2.50(s,3H), 2.45(d,J=13.4Hz,2H), 2.35–2.17(m,7H), 2.14–2.02(m,6H), 1.81–1.68(m,4H), 1.61(t,J=7.1Hz,2H), 1.56(t,J=6.4Hz,2H) ,1.38(s,6H),1.03(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₈₀ H ₁₀₃ ClN ₁₃ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1504.7075; measured value, 1504.7046.

Example 171: (2S,4R)-1-((S)-2-(9-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'- Yl)nonanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361022 )preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361022) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS360139), yellow powder, yield = 14%

¹ H NMR(500MHz, methanol-d ₄ )δ9.18(s,1H), 8.67(d,J=2.3Hz,1H), 8.04(d,J=2.5Hz,1H), 7.89(dd,J= 9.2, 2.3 Hz, 1H), 7.67 (d, J = 2.5 Hz, 1H), 7.63 (d, J = 8.9 Hz, 1H), 7.52 (d, J = 3.4 Hz, 1H), 7.49 (d, J = 8.3Hz, 2H), 7.44 (d, J = 8.3 Hz, 2H), 7.36 (d, J = 8.3 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 7.03 (d, J = 9.3 Hz ,1H), 6.79 (dd, J = 8.9, 2.3 Hz, 1H), 6.49 (d, J = 3.4 Hz, 1H), 6.39 (d, J = 2.3 Hz, 1H), 4.64 (s, 1H), 4.60 –4.45(m,3H), 4.38(d,J=15.6Hz,1H), 3.90(d,J=11.0Hz,1H), 3.84–3.57(m,10H), 3.46–3.37(m,4H), 3.21–3.05(m,8H), 2.79(s,2H), 2.50(s,3H), 2.44(d,J=12.9Hz,2H), 2.34–2.17(m,7H), 2.14–2.02(m, 6H),1.82–1.66(m,4H),1.58(dt,J=18.6,7.0Hz,4H),1.45-1.32(m,8H),1.03(s,9H),1.00(s,6H).HRMS (ESI) m/z: calculated value C ₈₁ H ₁₀₅ ClN ₁₃ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1518.7232 (1519.7265); measured value, 1519.7345.

Example 172: (2S,4R)-1-((S)-2-(10-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'- Yl)decanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361023 )preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361023) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS360140), yellow powder, yield = 28%

¹ H NMR(500MHz, methanol-d ₄ )δ9.10(s,1H), 8.66(d,J=2.2Hz,1H), 8.02(d,J=2.5Hz,1H), 7.87(dd,J= 9.3,2.3Hz,1H), 7.67–7.59(m,2H), 7.52–7.46(m,3H), 7.43(d,J=8.2Hz,2H), 7.35(d,J=8.2Hz,2H), 7.08 (d, J = 8.2 Hz, 2H), 7.01 (d, J = 9.3 Hz, 1H), 6.77 (dd, J = 9.0, 2.2 Hz, 1H), 6.46 (d, J = 3.5 Hz, 1H), 6.36(d,J=2.2Hz,1H), 4.63(s,1H), 4.61–4.48(m,3H), 4.37(d,J=15.6Hz,1H), 3.90(d,J=11.1Hz,1H ), 3.84–3.60(m,10H), 3.40(t,J=10.0Hz,4H), 3.25–3.06(m,8H), 2.79(s,2H), 2.49(s,3H), 2.45(d, J = 12.7Hz, 2H), 2.34-2.19 (m, 7H), 2.09 (dtt, J = 13.3, 9.1, 4.1 Hz, 6H), 1.74 (d, J = 16.3 Hz, 4H), 1.58 (dt, J =12.7,7.6Hz,4H),1.41–1.31(m,10H),1.03(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₈₂ H ₁₀₇ ClN ₁₃ O ₁₀ S ₂ ⁺ [M+H] ⁺ , 1532.7388; measured value, 1532.7359.

Example 173: (2S,4R)-1-((S)-2-(11-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'- Yl)undecylamido)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-methan Amide (SIAIS361024) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361024) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS360141), yellow powder, yield = 33%

¹ H NMR(500MHz, methanol-d ₄ )δ9.09(s,1H), 8.66(d,J=2.3Hz,1H), 8.01(d,J=2.6Hz,1H), 7.87(dd,J= 9.2, 2.3 Hz, 1H), 7.62 (s, 1H), 7.61 (d, J = 6.9 Hz, 1H), 7.51-7.46 (m, 3H), 7.43 (d, J = 8.2 Hz, 2H), 7.35 ( d, J = 8.5 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 9.3 Hz, 1H), 6.76 (dd, J = 9.0, 2.4 Hz, 1H), 6.46 ( d, J = 3.5Hz, 1H), 6.35 (d, J = 2.4 Hz, 1H), 4.63 (s, 1H), 4.57 (d, J = 8.8 Hz, 1H), 4.53 (d, J = 16.0 Hz, 1H), 4.50 (s, 1H), 4.37 (d, J = 15.5 Hz, 1H), 3.90 (d, J = 11.1 Hz, 1H), 3.80 (dd, J = 11.0, 3.9 Hz, 1H), 3.78- 3.54 (m, 9H), 3.47–3.34 (m, 4H), 3.13 (q, J = 20.0, 13.2 Hz, 8H), 2.49 (s, 3H), 2.35–2.27 (m, 3H), 2.22 (dddd, J = 11.8, 9.8, 8.0, 4.7 Hz, 4H), 2.15–2.03 (m, 6H), 1.74 (q, J = 13.3, 11.5 Hz, 4H), 1.57 (q, J = 9.5, 6.4 Hz, 4H) ,1.45-1.32(m,12H),1.03(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₈₃ H ₁₀₉ ClN ₁₃ O ₁₀ S ₂ ⁺ [M+H] ⁺ ,1546.7545; measured value, 1546.7593.

Example 174: (2S,4R)-1-((S)-2-((6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b] Pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl] -2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1' -Yl)hexyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide ( SIAIS363047) preparation

With reference to the method in Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363047) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS363013), yellow powder, yield = 24%

¹ H NMR(500MHz, methanol-d ₄ )δ9.42(s,1H), 8.69–8.63(m,1H), 8.12(s,1H), 7.90(d,J=8.6Hz,1H), 7.86( s, 1H), 7.61 (dd, J = 14.0, 5.5 Hz, 2H), 7.52 (d, J = 7.8 Hz, 2H), 7.46 (d, J = 7.8 Hz, 2H), 7.37 (d, J = 7.2 Hz,2H),7.15-7.04(m,3H),6.82(d,J=8.5Hz,1H),6.62-6.56(m,1H),6.49(s,1H),4.72(t,J=8.5Hz ,1H),4.59–4.51(m,2H), 4.38(d,J=15.6Hz,1H), 4.16(s,1H), 3.97(d,J=11.1Hz,1H), 3.76(s,4H) , 3.67(d,J=12.0Hz,6H),3.42(t,J=9.6Hz,4H), 3.23(s,2H),3.13(s,5H),3.08–2.94(m,2H),2.80( s, 2H), 2.53 (s, 3H), 2.44 (d, J = 11.9 Hz, 2H), 2.34 (dt, J = 13.2, 6.5 Hz, 3H), 2.27 (s, 2H), 2.11 (s, 6H) ),1.76(d,J=39.6Hz,6H),1.57(s,2H),1.44(s,4H),1.17(s,9H),1.01(s,6H).HRMS(ESI)m/z: Calculated value C ₇₈ H ₁₀₁ ClN ₁₃ O ₉ S ₂ ⁺ [M+H] ⁺ , 1462.6970 (1463.7003); measured value, 1463.7041.

Example 175: (2S,4R)-1-((S)-2-((7-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b] Pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl] -2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1' -Yl)heptyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363048) Preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363048) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS363039), yellow powder, yield = 22%

¹ H NMR(500MHz, methanol-d ₄ )δ9.11(s,1H), 8.68(d,J=2.3Hz,1H), 8.04(s,1H), 7.89(dd,J=9.2,2.3Hz, 1H), 7.66 (d, J = 2.5 Hz, 1H), 7.64 (d, J = 8.9 Hz, 1H), 7.51 (d, J = 3.4 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H) ,7.43(d,J=8.2Hz,2H), 7.36(d,J=8.3Hz,2H), 7.09(d,J=8.4Hz,2H), 7.03(d,J=9.3Hz,1H), 6.79 (dd,J=9.0,2.3Hz,1H),6.48(d,J=3.5Hz,1H),6.39(d,J=2.3Hz,1H),4.75-4.68(m,1H),4.56(d, J = 15.6Hz, 1H), 4.53 (s, 1H), 4.36 (d, J = 15.6Hz, 1H), 4.14 (s, 1H), 3.93 (d, J = 11.3Hz, 1H), 3.79-3.53 ( m,12H),3.47–3.37(m,4H),3.14(t,J=12.4Hz,7H),3.06–2.98(m,1H),2.94(td,J=11.9,5.4Hz,1H),2.79 (t,J＝11.5Hz,2H), 2.49(s,3H), 2.44(d,J＝12.6Hz,2H), 2.33(dt,J＝20.7,7.0Hz,3H), 2.23(d,J＝ 12.5Hz, 2H), 2.10 (d, J = 7.1Hz, 5H), 1.82-1.64 (m, 6H), 1.57 (t, J = 6.4Hz, 2H), 1.41 (s, 6H), 1.17 (s, 9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₉ H ₁₀₃ ClN ₁₃ O ₉ S ₂ ⁺ [M+H] ⁺ ,1476.7126(1477.7160); measured value, 1477.7202.

Example 176: (2S,4R)-1-((S)-2-((8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b] Pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl] -2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1' -Yl)octyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363049) Preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS363040) to prepare the target compound (SIAIS363049), yellow powder, yield = 24%

¹ H NMR(500MHz, methanol-d ₄ )δ9.12(s,1H), 8.68(d,J=1.9Hz,1H), 8.05(s,1H), 7.89(d,J=8.7Hz,1H) ,7.70–7.62(m,2H),7.53–7.47(m,3H),7.43(d,J=8.2Hz,2H),7.37(d,J=7.4Hz,2H),7.09(d,J=7.7 Hz, 2H), 7.03 (d, J = 9.0 Hz, 1H), 6.80 (d, J = 8.6 Hz, 1H), 6.49 (d, J = 3.3 Hz, 1H), 6.40 (s, 1H), 4.70 ( t,J=8.5Hz,1H),4.56(d,J=15.5Hz,1H),4.53(s,1H), 4.36(d,J=15.6Hz,1H), 4.13(s,1H), 3.92( d,J=11.2Hz,1H),3.82–3.50(m,12H),3.42 (d,J=17.0Hz,4H), 3.15(d,J=23.5Hz,6H),3.06–2.98(m,1H ), 2.97–2.89 (m, 1H), 2.79 (s, 2H), 2.49 (s, 3H), 2.44 (d, J = 11.0 Hz, 2H), 2.32 (d, J = 15.8 Hz, 3H), 2.23 (s, 2H), 2.13 (d, J = 20.1 Hz, 6H), 1.84-1.65 (m, 6H), 1.57 (t, J = 6.2 Hz, 2H), 1.39 (s, 8H), 1.16 (d, J = 1.9Hz, 9H), 1.01 (s, 6H). HRMS (ESI) m/z: calculated value C ₈₀ H ₁₀₅ ClN ₁₃ O ₉ S ₂ ⁺ [M+H] ⁺ ,1490.7283 (1491.7316); measured value ,1491.7349.

Example 177: (2S,4R)-1-((S)-2-((9-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b] Pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl] -2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1' -Yl)nonyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363008) Preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363008) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS363033), yellow powder, yield = 25%

¹ H NMR(500MHz, methanol-d ₄ )δ9.30(s,1H), 8.67(d,J=2.3Hz,1H), 8.09(s,1H), 7.90(dd,J=9.2,2.4Hz, 1H), 7.78 (d, J = 2.5 Hz, 1H), 7.64 (d, J = 8.9 Hz, 1H), 7.56 (d, J = 3.4 Hz, 1H), 7.50 (d, J = 8.1 Hz, 2H) ,7.45(d,J=8.2Hz,2H), 7.37(d,J=8.3Hz,2H), 7.09(d,J=8.4Hz,2H), 7.05(d,J=9.3Hz,1H), 6.82 (dd,J=8.9,2.3Hz,1H), 6.55(d,J=3.5Hz,1H), 6.46(d,J=2.3Hz,1H), 4.69(dd,J=9.6,7.7Hz,1H) ,4.56(d,J=15.6Hz,1H),4.53(s,1H), 4.38(d,J=15.6Hz,1H), 4.12(s,1H), 3.90(d,J=11.4Hz,1H) ,3.75(d,J=9.8Hz,4H),3.72-3.56(m,7H),3.46-3.39(m,5H),3.17-3.09(m,6H),2.99(dt,J=11.8,6.0Hz ,1H),2.93(dt,J=12.1,6.1Hz,1H),2.81(d,J=14.5Hz,2H),2.52(s,3H),2.44(d,J=12.4Hz,2H),2.32 (d,J=7.3Hz,3H), 2.22(q,J=11.9Hz,2H), 2.16–2.06(m,6H),1.83–1.66(m,6H), 1.57(t,J=6.3Hz, 2H),1.45-1.32(m,10H),1.16(s,9H),1.01(s,6H).HRMS(ESI)m/z: calculated value C ₈₁ H ₁₀₇ ClN ₁₃ O ₉ S ₂ ⁺ (M+ H] ⁺ ,1504.7439 (1505.7473); measured value, 1505.7581.

Example 178: (2S,4R)-1-((S)-2-((10-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b] Pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl] -2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1' -Yl)decyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363001) Preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS363041) to prepare the target compound (SIAIS363001), yellow powder, yield = 56%

¹ H NMR(500MHz, methanol-d ₄ )δ9.21(s,1H), 8.66(d,J=2.3Hz,1H), 8.06(d,J=2.5Hz,1H), 7.88(dd,J= 9.2, 2.4 Hz, 1H), 7.72 (d, J = 2.6 Hz, 1H), 7.62 (d, J = 8.9 Hz, 1H), 7.54 (d, J = 3.4 Hz, 1H), 7.49 (d, J = 8.3Hz, 2H), 7.44 (d, J = 8.3 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 9.3 Hz ,1H), 6.79 (dd, J = 9.0, 2.4 Hz, 1H), 6.51 (d, J = 3.4 Hz, 1H), 6.41 (d, J = 2.3 Hz, 1H), 4.69 (dd, J = 9.6, 7.6Hz, 1H), 4.56 (d, J = 15.5 Hz, 1H), 4.53 (s, 1H), 4.37 (d, J = 15.6 Hz, 1H), 4.13 (s, 1H), 3.91 (d, J = 11.2Hz,1H), 3.78–3.60(m,10H), 3.48–3.36(m,4H), 3.26–3.18(m,2H), 3.18–3.08(m,6H), 3.00(dt,J=11.9, 6.1Hz, 1H), 2.93 (dt, J = 12.1, 6.1 Hz, 1H), 2.79 (t, J = 11.1 Hz, 2H), 2.50 (s, 3H), 2.45 (d, J = 13.0 Hz, 2H) ,2.32(t,J=6.6Hz,3H),2.22(q,J=12.5,12.0Hz,2H),2.15-2.05(m,6H),1.81-1.64(m,6H),1.56(t,J ＝6.3Hz,2H),1.45-1.32(m,12H),1.16(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₈₂ H ₁₀₉ ClN ₁₃ O ₉ S ₂ ⁺ [M+H] ⁺ ,1518.7596 (1519.7629); measured value, 1519.7707.

Example 179: (2S,4R)-1-((S)-2-((2-(2-(2-(4-(((4-(N-(2-((1H-pyrrolo[ 2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1, 1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-bis Piperidine)-1'-yl)ethoxy)ethoxy)ethyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazole- 5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363009) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363009) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS363110), yellow powder, yield = 51%

¹ H NMR(500MHz, methanol-d ₄ )δ9.19(s,1H), 8.66(d,J=2.3Hz,1H), 8.06(d,J=2.6Hz,1H), 7.89(dd,J= 9.3, 2.3 Hz, 1H), 7.71 (d, J = 2.5 Hz, 1H), 7.63 (d, J = 8.9 Hz, 1H), 7.54 (d, J = 3.4 Hz, 1H), 7.49 (dd, J = 8.3,6.5Hz,2H),7.47–7.42(m,2H),7.36(d,J=8.4Hz,2H), 7.09(d,J=8.4Hz,2H), 7.03(d,J=9.4Hz, 1H), 6.80 (dd, J = 9.0, 2.4 Hz, 1H), 6.51 (d, J = 3.5 Hz, 1H), 6.41 (d, J = 2.4 Hz, 1H), 4.72 (dd, J = 9.5, 7.7 Hz,1H),4.57–4.51(m,2H), 4.38(d,J=15.6Hz,1H), 4.30(s,1H), 3.98–3.88(m,3H), 3.83(td,J=8.7, 7.0,4.0Hz,4H), 3.79–3.61(m,14H),3.45-3.32(m,4H), 3.28–3.08(m,8H), 2.79(t,J=13.8Hz,2H), 2.50(s ,3H), 2.46(d,J=13.0Hz,2H), 2.31(dt,J=10.9,6.4Hz,5H), 2.15–2.03(m,6H),1.72(q,J=13.0Hz,2H) ,1.57(t,J=6.4Hz,2H),1.19(s,9H),1.00(s,6H).HRMS(ESI)m/z: calculated value C ₇₈ H ₁₀₁ ClN ₁₃ O ₁₁ S ₂ ⁺ (M +H] ⁺ , 1494.6868; measured value, 1494.6844.

Example 180: (2S,4R)-1-((S)-14-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)- 2-(tert-butyl)-6,9,12-trioxa-3-azatetradecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl ) Preparation of pyrrolidine-2-carboxamide (SIAIS364020)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364020) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS363111), yellow powder, yield=52%

¹ H NMR (500MHz, methanol-d ₄ ) δ 9.80 (s, 1H), 8.63 (t, J = 2.5 Hz, 1H), 8.21 (t, J = 2.7 Hz, 1H), 8.08 (dd, J = 5.5, 2.4 Hz, 1H), 7.91 (dt, J = 9.2, 2.5 Hz, 1H), 7.69 (dd, J = 3.6, 2.0 Hz, 1H), 7.61 (d, J = 8.9 Hz, 1H), 7.55 ( d,J=8.4Hz,2H),7.50(d,J=8.3Hz,2H),7.41-7.35(m,3H),7.11(d,J=8.4Hz,4H),6.86(dd,J=9.0 ,2.4Hz,1H),6.70(t,J=3.4Hz,1H),6.58(d,J=2.4Hz,1H),4.72(dd,J=9.7,7.7Hz,1H),4.55(d,J = 15.6Hz, 2H), 4.41 (d, J = 15.7Hz, 1H), 4.35 (s, 1H), 3.96 (d, J = 11.1Hz, 1H), 3.91–3.76 (m, 7H), 3.75–3.63 (m,14H),3.59(dd,J=13.4,3.2Hz,2H), 3.48–3.37(m,7H), 3.28–3.19(m,4H), 3.17–3.07(m,4H), 2.81(t ,J=11.7Hz,2H),2.58(s,3H),2.45(dd,J=26.1,13.2Hz,2H),2.36(d,J=7.1Hz,2H),2.31–2.22(m,1H) ,2.14-2.05(m,8H),1.75(t,J=12.2Hz,2H),1.57(t,J=6.4Hz,2H),1.19(s,9H),1.01(s,6H).HRMS( ESI) m/z: calculated value C ₈₀ H ₁₀₅ ClN ₁₃ O ₁₂ S ₂ ⁺ [M+H] ⁺ , 1538.7130; measured value, 1538.7103.

Example 181: (2S,4R)-1-((S)-17-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)- 2-(tert-butyl)-6,9,12,15-tetraoxa-3-azaheptadecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl) Benzyl)pyrrolidine-2-carboxamide (SIAIS364021) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364021) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS363112), yellow powder, yield = 70%

¹ H NMR (500MHz, methanol-d ₄ ) δ 9.86 (s, 1H), 8.62 (t, J = 2.3 Hz, 1H), 8.22 (t, J = 2.5 Hz, 1H), 8.11 (dd, J = 4.4, 2.4 Hz, 1H), 7.91 (dt, J = 9.2, 2.1 Hz, 1H), 7.71 (dd, J = 3.4, 1.6 Hz, 1H), 7.60 (d, J = 8.9 Hz, 1H), 7.58- 7.53(m,2H),7.53–7.49(m,2H),7.40–7.35(m,2H),7.11(dd,J=8.9,2.4Hz,3H), 6.86(dd,J=9.0,2.4Hz, 1H), 6.71 (dd, J = 3.5, 2.7 Hz, 1H), 6.59 (d, J = 2.4 Hz, 1H), 4.72 (dd, J = 9.5, 7.5 Hz, 1H), 4.61–4.53 (m, 2H ), 4.40 (dd, J = 15.7, 2.2 Hz, 1H), 4.35 (d, J = 5.5 Hz, 1H), 3.97 (d, J = 10.9 Hz, 1H), 3.91–3.76 (m, 7H), 3.77 –3.56(m,22H), 3.50–3.37(m,6H), 3.28–3.09(m,6H), 2.81(t,J=11.8Hz,2H), 2.59(d,J=2.5Hz,3H), 2.48(d,J=13.1Hz,2H), 2.38–2.30(m,3H), 2.30–2.21(m,1H), 2.14–2.04(m,6H), 1.77(d,J=11.5Hz,2H) ,1.57(t,J=6.4Hz,2H),1.19(s,9H),1.01(s,6H).HRMS(ESI) m/z: calculated value C ₈₂ H ₁₀₉ ClN ₁₃ O ₁₃ S ₂ ⁺ [M +H] ⁺ ,1582.7392(1583.7426); measured value,1583.7585.

Example 182: (2S,4R)-1-((S)-20-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)- 2-(tert-butyl)-6,9,12,15,18-pentaoxa-3-azaeicosanyl)-4-hydroxy-N-(4-(4-methylthiazole-5- Benzyl) pyrrolidine-2-carboxamide (SIAIS364022) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364022) was prepared using intermediate BINDER (SIAIS346012) and intermediate LM (SIAIS363119), yellow powder, yield = 66%

¹ H NMR (500MHz, methanol-d ₄ ) δ 9.84 (s, 1H), 8.62 (t, J = 2.1 Hz, 1H), 8.22 (t, J = 2.5 Hz, 1H), 8.11 (dd, J = 4.6, 2.4 Hz, 1H), 7.91 (dt, J = 9.2, 2.0 Hz, 1H), 7.70 (dd, J = 3.5, 1.5 Hz, 1H), 7.60 (d, J = 8.9 Hz, 1H), 7.58- 7.55(m,2H),7.54–7.49(m,2H),7.40–7.34(m,2H),7.11(dd,J=8.6,2.0Hz,3H), 6.86(dd,J=8.9,2.4Hz, 1H), 6.71 (t, J = 3.1 Hz, 1H), 6.59 (d, J = 2.5 Hz, 1H), 4.75-4.67 (m, 1H), 4.63-4.53 (m, 2H), 4.40 (d, J =15.7Hz,1H), 4.35(d,J=5.3Hz,1H), 3.95(dd,J=11.4,7.6Hz,1H), 3.90–3.77(m,7H), 3.75–3.57(m,26H) ,3.50–3.37(m,6H), 3.26–3.09(m,6H), 2.81(t,J=12.0Hz,2H), 2.59(s,3H), 2.47(t,J=13.0Hz,2H), 2.38–2.31(m,3H), 2.29–2.20(m,1H), 2.12(s,6H), 1.77(d,J=11.7Hz,2H), 1.57(t,J=6.3Hz,2H), 1.18 (s,9H),1.01(s,6H).HRMS(ESI)m/z: calculated value C ₈₄ H ₁₁₃ ClN ₁₃ O ₁₄ S ₂ ⁺ [M+H] ⁺ , 1626.7654; measured value, 1626.7646.

Example 183: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1 -Oxoisoindolin-4-yl)pent-4-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butane-2-yl)amino)-3-( (Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS361043) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS255121) to prepare the target compound (SIAIS361043), white powder, yield = 29%

¹ H NMR(500MHz, methanol-d ₄ )δ8.31(d,J=2.1Hz,1H), 8.09–8.06(m,1H), 7.79–7.73(m,3H), 7.64(d,J=7.5 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.39 (d, J = 7.5 Hz, 2H), 7.33 (d, J = 7.3 Hz, 2H), 7.20 (t, J = 7.5 Hz, 2H), 7.18–7.12 (m, 3H), 7.02 (d, J = 9.5 Hz, 1H), 6.98 (d, J = 7.6 Hz, 2H), 5.16 (ddd, J = 13.2, 5.2, 3.1 Hz, 1H ), 4.60(d,J=15.8Hz,1H),4.52(d,J=17.7Hz,1H), 4.18(s,1H), 3.88(d,J=13.7Hz,2H), 3.70(s,3H ), 3.64–3.43(m,6H),3.42–3.36(m,3H),3.31-3.20(m,7H),3.12(s,1H),3.08–3.01(m,1H),2.93-2.82(m ,3H), 2.81–2.73(m,1H), 2.68(t,J=7.0Hz,2H), 2.60(qd,J=13.0,4.4Hz,1H), 2.40(s,2H), 2.29(s, 1H), 2.18-2.10 (m, 5H), 1.57 (t, J = 6.4 Hz, 2H), 1.08 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₅ H ₇₃ ClF ₃ N ₈ O ₈ S ₃ ⁺ [M+H] ⁺ ,1281.4349; measured value,1281.4370.

Example 184: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1 -Oxoisoindolin-4-yl)hex-5-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-( (Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS361044) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361044) was prepared using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS255119), white powder, yield = 37%

¹ H NMR(500MHz, methanol-d ₄ )δ8.31(s,1H), 8.07(dd,J=9.3,2.5Hz,1H), 7.75(d,J=8.9Hz,2H), 7.73(dd, J=7.6,1.0Hz,1H),7.63(dd,J=7.7,1.0Hz,1H),7.49(t,J=7.6Hz,1H),7.41-7.35(m,2H),7.33(d,J =7.6Hz,2H),7.20(t,J=7.7Hz,2H),7.17–7.12(m,3H),7.01(d,J=9.6Hz,1H),6.98(d,J=8.8Hz,2H ), 5.15 (dt, J = 13.3, 5.7 Hz, 1H), 4.57 (d, J = 17.6 Hz, 1H), 4.51 (dd, J = 17.6, 3.4 Hz, 1H), 4.18 (t, J = 7.2 Hz ,1H), 3.89(d,J=14.0Hz,2H), 3.83–3.43(m,11H),3.42–3.35(m,2H), 3.29–3.19(m,7H), 3.16(p,J=1.6 Hz, 1H), 2.92–2.81 (m, 3H), 2.81–2.69 (m, 1H), 2.60 (t, J = 6.6 Hz, 2H), 2.40 (s, 2H), 2.30 (dd, J = 14.2, 9.5Hz, 1H), 2.16 (ddd, J = 11.2, 5.7, 3.1 Hz, 2H), 2.11 (s, 2H), 2.01 (ddd, J = 11.0, 5.8, 2.7 Hz, 2H), 1.72 (p, J ＝6.9Hz,2H),1.57(t,J＝6.4Hz,2H),1.07(s,6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₅ ClF ₃ N ₈ O ₈ S ₃ ⁺ [ M+H] ⁺ ,1295.4505; measured value,1295.4503.

Example 185: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1 -Oxoisoindolin-4-yl)hept-6-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-( (Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS361045) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361045) was prepared using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS292017), white powder, yield = 32%

¹ H NMR(500MHz, methanol-d ₄ )δ8.31(d,J=2.2Hz,1H), 8.07(dd,J=9.3,2.3Hz,1H), 7.76(d,J=8.6Hz,2H) ,7.73(d,J=7.4Hz,1H), 7.60(d,J=7.3Hz,1H), 7.39(d,J=8.3Hz,2H), 7.33(d,J=7.4Hz,2H), 7.20 (t,J=7.5Hz,2H),7.18–7.12(m,3H),7.03–6.96(m,3H), 5.17(dd,J＝13.2,5.0Hz,1H),4.53(d,J＝17.5 Hz, 1H), 4.47 (d, J = 17.5 Hz, 1H), 4.17 (s, 1H), 3.89 (d, J = 14.0 Hz, 2H), 3.80-3.65 (m, 4H), 3.65–3.43 (m ,6H),3.43–3.35(m,2H), 3.30–3.19(m,6H), 3.13(s,1H), 2.95–2.82(m,3H), 2.81–2.73(m,1H), 2.55(t ,J=6.7Hz,3H),2.46-2.36(m,2H),2.29(s,1H),2.17(d,J=15.4Hz,2H),2.11(s,3H),1.86(s,2H) ,1.71(p,J=7.1Hz,2H),1.59(dt,J=18.9,6.7Hz,4H),1.08(s,6H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₇ ClF ₃ N ₈ O ₈ S ₃ ⁺ [M+H] ⁺ ,1309.4662; measured value,1309.4681.

Example 186: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(8-(2-(2,6-dioxopiperidin-3-yl)-1 -Oxoisoindolin-4-yl)oct-7-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-( (Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS361046) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361046) was prepared by using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS292020), white powder, yield = 23%

¹ H NMR(500MHz, methanol-d ₄ )δ8.31(d,J=2.3Hz,1H), 8.07(dd,J=9.2,2.3Hz,1H), 7.76(d,J=9.0Hz,2H) ,7.73(d,J=7.4Hz,1H),7.60(d,J=7.5Hz,1H),7.49(t,J=7.6Hz,1H),7.39(d,J=8.3Hz,2H),7.33 (d,J=7.2Hz,2H), 7.20(t,J=7.5Hz,2H), 7.18–7.11(m,3H), 6.99(dd,J=8.6,4.9Hz,3H), 5.20–5.14( m, 1H), 4.52 (d, J = 17.5 Hz, 1H), 4.46 (d, J = 17.6 Hz, 1H), 4.17 (t, J = 6.6 Hz, 1H), 3.89 (d, J = 13.9 Hz, 2H), 3.71 (d, J = 7.4 Hz, 5H), 3.52 (d, J = 11.9 Hz, 4H), 3.37 (dd, J = 14.4, 5.0 Hz, 2H), 3.23 (dq, J = 16.5, 5.3 Hz,7H),3.07(s,1H),2.94–2.82(m,3H),2.80–2.72(m,1H),2.55–2.49(m,3H),2.41(d,J=6.3Hz,3H) ,2.27(s,1H),2.20–2.14(m,1H),2.10(s,3H),1.81(td,J=11.7,9.9,6.1Hz,2H),1.71-1.63(m,2H),1.58 (dp, J = 11.8, 5.7 Hz, 4H), 1.47 (p, J = 7.5 Hz, 2H), 1.08 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₈ H ₇₉ ClF ₃ N ₈ O ₈ S ₃ ⁺ [M+H] ⁺ , 1323.4818; measured value, 1323.4856.

Example 187: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(9-(2-(2,6-dioxopiperidin-3-yl)-1 -Oxoisoindolin-4-yl)non-8-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-( (Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS361047) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361047) was prepared using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS255127), white powder, yield = 14%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.30 (d, J = 2.3 Hz, 1H), 8.07 (ddd, J = 9.3, 2.3, 1.3 Hz, 1H), 7.76 (d, J = 9.1 Hz, 2H), 7.73 (dd, J = 7.6, 1.0 Hz, 1H), 7.60 (dd, J = 7.6, 1.1 Hz, 1H), 7.49 (t, J = 7.7 Hz, 1H), 7.39 (d, J = 8.4 Hz, 2H), 7.33 (dd, J = 8.3, 1.3 Hz, 2H), 7.20 (t, J = 7.5 Hz, 2H), 7.17-7.13 (m, 3H), 6.99 (dd, J = 9.4, 2.8 Hz ,3H), 5.17 (dd, J = 13.3, 5.2 Hz, 1H), 4.51 (d, J = 17.4 Hz, 1H), 4.45 (d, J = 17.4 Hz, 1H), 4.16 (dd, J = 8.5, 5.3Hz, 1H), 3.89 (d, J = 13.9 Hz, 2H), 3.70 (s, 4H), 3.52 (d, J = 12.5 Hz, 4H), 3.41-3.34 (m, 2H), 3.28-3.16 ( m, 6H), 3.12–2.99 (m, 2H), 2.88 (dt, J = 13.6, 4.8 Hz, 3H), 2.78 (ddd, J = 17.6, 4.8, 2.4 Hz, 1H), 2.54–2.45 (m, 3H), 2.41(d,J=6.8Hz,2H), 2.30–2.22(m,1H), 2.22–2.13(m,1H), 2.14–2.03(m,3H), 1.79(d,J=8.4Hz) ,2H),1.65(p,J＝6.9Hz,2H),1.56(dt,J＝16.2,7.1Hz,4H),1.44(t,J＝3.6Hz,4H),1.08(s,6H).HRMS (ESI) m/z: calculated value C ₆₉ H ₈₁ ClF ₃ N ₈ O ₈ S ₃ ⁺ [M+H] ⁺ , 1337.4975; measured value, 1337.4992.

Example 188: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1 -Oxoisoindolin-5-yl)pent-4-yn-1-yl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-(( (Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS361048) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361048) was prepared by using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS292111), white powder, yield = 27%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.30 (d, J = 2.3 Hz, 1H), 8.08 (dd, J = 9.1, 2.5 Hz, 1H), 7.77 (dd, J = 8.6, 3.6 Hz, 2H), 7.73 (d, J = 7.8 Hz, 1H), 7.64 (s, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.39 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.4Hz, 2H), 7.20 (t, J = 7.5Hz, 2H), 7.14 (dd, J = 15.1, 7.8Hz, 3H), 7.03-6.96 (m, 3H), 5.18-5.11 (m, 1H ), 4.51(d,J=17.2Hz,1H), 4.48–4.41(m,1H), 4.17(s,1H), 3.89(d,J=13.3Hz,2H), 3.70(s,3H), 3.68 –3.45(m,7H),3.42–3.34(m,4H),3.22(dq,J=10.7,7.3,6.4Hz,5H),3.13(s,1H),3.05(s,1H),2.89(dq ,J=13.7,6.8,5.5Hz,3H), 2.77(ddd,J=17.6,4.6,2.3Hz,1H), 2.66(t,J=6.7Hz,2H), 2.48(qd,J=12.0,10.7 ,3.0Hz,1H),2.40(s,2H),2.27(s,1H),2.20-2.05(m,5H),1.57(t,J=6.4Hz,2H),1.08(s,6H).HRMS (ESI) m/z: calculated value C ₆₅ H ₇₃ ClF ₃ N ₈ O ₈ S ₃ ⁺ [M+H] ⁺ , 1281.4349; measured value, 1281.4388.

Example 189: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1 -Oxoisoindolin-5-yl)hex-5-yn-1-yl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-(( Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS361049) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361049) was prepared by using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS292112), white powder, yield = 18%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.30 (d, J = 2.3 Hz, 1H), 8.08 (ddd, J = 9.2, 2.3, 1.1 Hz, 1H), 7.76 (d, J = 7.5 Hz, 2H), 7.72 (d, J = 7.9 Hz, 1H), 7.61 (s, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.35–7.31 ( m, 2H), 7.20 (t, J = 7.5 Hz, 2H), 7.17-7.11 (m, 3H), 7.01-6.94 (m, 3H), 5.13 (dd, J = 13.4, 5.1 Hz, 1H), 4.50 (d,J=17.2Hz,1H), 4.44(d,J=17.2Hz,1H), 4.19–4.12(m,1H), 3.89(d,J=13.9Hz,2H), 3.71(s,4H) ,3.66–3.59(m,1H),3.52(d,J=12.4Hz,4H), 3.39–3.33(m,2H), 3.28–3.15(m,7H), 2.99(s,1H), 2.93–2.83 (m, 4H), 2.77 (ddd, J = 17.6, 4.6, 2.4 Hz, 1H), 2.58 (t, J = 6.8 Hz, 2H), 2.54-2.45 (m, 1H), 2.41 (s, 2H), 2.26–2.12(m,2H),2.09(s,2H),2.05–1.92(m,3H),1.79–1.68(m,2H),1.58(t,J=6.4Hz,2H),1.08(s, 6H).HRMS(ESI)m/z: calculated value C ₆₆ H ₇₅ ClF ₃ N ₈ O ₈ S ₃ ⁺ [M+H] ⁺ ,1295.4505; measured value, 1295.4521.

Example 190: (2S,4R)-1-((S)-2-(5-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)valerylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( Preparation of 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361026)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361026) was prepared by using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS360137), white powder, yield = 18%

¹ H NMR(500MHz, methanol-d ₄ )δ9.29(s,1H), 8.40(d,J=2.3Hz,1H), 8.19(dd,J=9.2,2.3Hz,1H), 7.73(d, J=9.0Hz,2H),7.49(d,J=8.3Hz,2H),7.47–7.42(m,2H),7.40(d,J=8.4Hz,2H),7.20(d,J=9.4Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 9.2 Hz, 2H), 4.58 (d, J = 7.6 Hz, 1H), 4.58-4.55 (m, 1H), 4.52 ( d, J = 15.6 Hz, 1H), 4.48 (q, J = 2.1 Hz, 1H), 4.38 (d, J = 15.6 Hz, 1H), 3.93 (d, J = 11.1 Hz, 1H), 3.89 (d, J = 13.2Hz, 2H), 3.78 (dd, J = 10.9, 3.8 Hz, 2H), 3.71 (s, 4H), 3.54 (q, J = 7.0 Hz, 9H), 3.29-3.18 (m, 6H), 2.87 (t, J = 10.9 Hz, 2H), 2.52 (s, 3H), 2.45–2.35 (m, 4H), 2.23 (ddt, J = 13.2, 7.5, 1.9 Hz, 1H), 2.15–2.03 (m, 5H),1.83–1.76(m,2H),1.71(ddd,J=17.0,8.8,6.4Hz,2H),1.58(t,J=6.5Hz,2H),1.08(s,6H),1.05(s ,9H).HRMS(ESI)m/z: calculated value C ₆₇ H ₈₇ ClF ₃ N ₁₀ O ₉ S ₃ ⁺ [M+H] ⁺ , 1363.5455; measured value, 1363.5445.

Example 191: (2S,4R)-1-((S)-2-(6-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)hexanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( Preparation of 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361027)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361027) was prepared using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS360131), white powder, yield = 31%

¹ H NMR(500MHz, methanol-d ₄ )δ9.31(s,1H), 8.39(d,J=2.3Hz,1H), 8.19(dd,J=9.3,2.3Hz,1H), 7.72(d, J = 8.9 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H), 7.44 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.23-7.18 (m, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 9.0 Hz, 2H), 4.63 (s, 1H), 4.58 (dd, J = 9.2, 7.6 Hz, 1H), 4.52 ( d,J=15.7Hz,1H),4.50–4.48(m,1H), 4.39(d,J=15.7Hz,1H), 3.90(t,J=11.7Hz,3H), 3.85–3.38(m,14H ), 3.24 (dd, J = 14.8, 7.4 Hz, 6H), 2.92–2.80 (m, 2H), 2.52 (s, 3H), 2.40 (s, 2H), 2.33 (t, J = 7.2 Hz, 2H) ,2.29–2.21(m,1H),2.17–2.04(m,5H),1.80(h,J=6.5Hz,2H),1.68(h,J=7.0Hz,2H),1.57(t,J=6.4 Hz,2H),1.41(h,J=7.3Hz,2H),1.08(s,6H),1.04(s,9H).HRMS(ESI)m/z: calculated value C ₆₈ H ₈₉ ClF ₃ N ₁₀ O ₉ S ₃ ⁺ [M+H] ⁺ , 1377.5611; measured value, 1377.5655.

Example 192: (2S,4R)-1-((S)-2-(7-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)heptanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( Preparation of 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361028)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361028) was prepared by using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS360135), white powder, yield = 26%

¹ H NMR(500MHz, methanol-d ₄ )δ9.34(s,1H), 8.40(d,J=2.4Hz,1H), 8.19(dd,J=9.3,2.3Hz,1H), 7.73(d, J = 9.0Hz, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 9.4Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 9.1 Hz, 2H), 4.64 (s, 1H), 4.57 (dd, J = 9.2, 7.6 Hz, 1H) ,4.52(d,J=15.6Hz,1H), 4.49(s,1H), 4.40(d,J=15.6Hz,1H), 3.90(t,J=12.2Hz,4H), 3.80(dd,J= 10.9,3.8Hz,2H),3.71(s,6H),3.55(q,J=9.4,8.4Hz,6H),3.29–3.19(m,6H),2.92–2.82(m,2H),2.52(s ,3H), 2.40(t,J=6.5Hz,2H),2.31(d,J=7.2Hz,2H),2.25(ddt,J=13.2,7.6,1.9Hz,1H),2.17–2.02(m, 5H), 1.79 (dq, J = 14.8, 7.4, 6.9 Hz, 2H), 1.64 (qt, J = 11.0, 5.3 Hz, 2H), 1.57 (t, J = 6.4 Hz, 2H), 1.46–1.35 (m ,4H),1.08(s,6H),1.03(s,9H).HRMS(ESI)m/z: calculated value C ₆₉ H ₉₁ ClF ₃ N ₁₀ O ₉ S ₃ ⁺ [M+H] ⁺ ,1391.5768; Measured value, 1391.5736.

Example 193: (2S,4R)-1-((S)-2-(8-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)octanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( Preparation of 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361029)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361029) was prepared by using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS360138), white powder, yield = 24%

¹ H NMR(500MHz, methanol-d ₄ )δ9.25(s,1H), 8.40(d,J=2.3Hz,1H), 8.19(dd,J=9.2,2.4Hz,1H), 7.73(d, J = 9.1Hz, 2H), 7.50 (d, J = 8.2Hz, 2H), 7.45 (s, 2H), 7.40 (d, J = 8.4Hz, 2H), 7.21 (d, J = 9.4Hz, 1H) ,7.16(d,J=8.4Hz,2H),6.97(d,J=9.1Hz,2H),4.63(s,1H),4.59–4.55(m,1H),4.53(d,J=15.6Hz, 1H), 4.50 (s, 1H), 4.38 (d, J = 15.6 Hz, 1H), 3.89 (t, J = 10.2 Hz, 3H), 3.84-3.58 (m, 9H), 3.54 (q, J = 7.3 Hz, 6H), 3.29--3.18 (m, 6H), 2.87 (s, 2H), 2.51 (s, 3H), 2.40 (s, 2H), 2.34 - 2.19 (m, 3H), 2.17 - 2.02 (m, 5H),1.83–1.75(m,2H),1.62(t,J=7.1Hz,2H),1.57(t,J=6.5Hz,2H),1.38(dp,J=17.0,6.6,5.5Hz,6H ),1.08(s,6H),1.03(s,9H).HRMS(ESI)m/z: calculated value C ₇₀ H ₉₃ ClF ₃ N ₁₀ O ₉ S ₃ ⁺ [M+H] ⁺ ,1405.5924; measured value ,1405.5963.

Example 194: (2S,4R)-1-((S)-2-(9-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)nonanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( Preparation of 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361030)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361030) was prepared by using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS360139), white powder, yield = 11%

¹ H NMR(500MHz, methanol-d ₄ )δ9.05(s,1H), 8.39(d,J=2.3Hz,1H), 8.19(dd,J=9.3,2.3Hz,1H), 7.74(d, J = 9.0Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.20-7.14 (m, 3H), 6.98 (d, J = 9.1Hz, 2H), 4.64 (s, 1H), 4.59–4.55 (m, 1H), 4.53 (d, J = 15.4Hz, 1H), 4.50 (t, J = 2.0 Hz, 1H), 4.37 (d, J = 15.5 Hz, 1H), 3.90 (d, J = 11.5 Hz, 3H), 3.84–3.78 (m, 1H), 3.71 (s, 4H), 3.58–3.41 (m ,8H),3.29–3.11(m,6H),2.99(s,2H), 2.87(t,J=11.7Hz,2H),2.49(s,3H),2.41(t,J=5.6Hz,2H) ,2.34–2.18(m,3H),2.10(s,2H),2.08–1.99(m,3H),1.76(s,2H),1.59(dt,J=13.0,6.9Hz,4H),1.42–1.32 (m,8H),1.08(s,6H),1.03(s,9H).HRMS(ESI)m/z: calculated value C ₇₁ H ₉₅ ClF ₃ N ₁₀ O ₉ S ₃ ⁺ [M+H] ⁺ , 1419.6081; measured value, 1419.6114.

Example 195: (2S,4R)-1-((S)-2-(10-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)decanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-( Preparation of 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361031)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361031) was prepared using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS360140), white powder, yield = 28%

¹ H NMR(500MHz, methanol-d ₄ )δ9.27(s,1H), 8.40(d,J=2.3Hz,1H), 8.19(dd,J=9.2,2.3Hz,1H), 7.76–7.69( m, 2H), 7.50 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 9.3 Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 9.1 Hz, 2H), 4.63 (s, 1H), 4.57 (d, J = 8.9 Hz, 1H), 4.53 (d, J = 15.5 Hz, 1H), 4.51–4.48 (m, 1H), 4.38 (d, J = 15.6 Hz, 1H), 3.94–3.84 (m, 3H), 3.83–3.39 (m, 15H), 3.29–3.18 (m, 6H), 2.87 (t, J = 11.8 Hz, 2H), 2.52 (s, 3H), 2.41 (d, J = 6.6 Hz, 2H), 2.34-2.19 (m, 3H), 2.18-2.04 ( m,5H),1.83–1.75(m,2H),1.59(dt,J=12.9,6.7Hz,4H),1.36(dd,J=25.3,5.5Hz,10H),1.08(s,6H),1.03 (s, 9H). HRMS (ESI) m/z: calculated value C ₇₂ H ₉₇ ClF ₃ N ₁₀ O ₉ S ₃ ⁺ [M+H] ⁺ , 1433.6237; measured value, 1433.6285.

Example 196: (2S,4R)-1-((S)-2-(11-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)undecanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N -(4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361032) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361032) was prepared using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS360141), white powder, yield = 28%

¹ H NMR(500MHz, methanol-d ₄ )δ9.25(s,1H), 8.40(d,J=2.2Hz,1H), 8.19(dd,J=9.3,2.3Hz,1H), 7.72(d, J = 9.0Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 9.4Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 9.1 Hz, 2H), 4.63 (s, 1H), 4.58 (d, J = 8.4 Hz, 1H), 4.53 (d,J=15.7Hz,1H),4.50(dt,J=4.4,2.4Hz,1H), 4.38(d,J=15.6Hz,1H), 3.94–3.85(m,3H), 3.85–3.41( m, 15H), 3.30–3.18 (m, 6H), 2.87 (t, J = 11.5 Hz, 2H), 2.51 (s, 3H), 2.43–2.37 (m, 2H), 2.34–2.19 (m, 3H) ,2.18–2.05(m,5H),1.83–1.74(m,2H),1.58(q,J=7.1,6.4Hz,4H),1.40–1.30(m,12H),1.08(s,6H),1.03 (s,9H).HRMS(ESI)m/z: calculated value C ₇₃ H ₉₉ ClF ₃ N ₁₀ O ₉ S ₃ ⁺ [M+H] ⁺ , 1447.6394; measured value, 1477.6396.

Example 197: (2S,4R)-1-((S)-2-(5-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-5-oxopentanoylamino)-3,3-dimethylbutyryl)-4- Hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361056) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS074012) 5-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy The target compound (SIAIS361056) was prepared by the preparation of (but-2-yl)amino)-5-oxovaleric acid, white powder, yield=34%

¹ H NMR(500MHz, methanol-d ₄ )δ9.42(s,1H), 8.40(d,J=2.3Hz,1H), 8.20(dd,J=9.3,2.3Hz,1H), 7.73(d, J = 9.1Hz, 2H), 7.51 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 9.3Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 9.1 Hz, 2H), 4.67-4.54 (m, 3H), 4.52 (d, J = 15.7 Hz, 1H) ,4.48(s,1H), 4.40(d,J=15.6Hz,1H), 4.15(s,1H), 3.91(t,J=14.6Hz,3H), 3.83–3.74(m,1H), 3.71( s, 2H), 3.65–3.51(m, 7H), 3.30–3.20(m, 4H), 3.11(s, 2H), 3.01(s, 1H), 2.87(t, J=11.2Hz, 2H), 2.53 (s, 3H), 2.41 (q, J = 8.9, 6.5 Hz, 4H), 2.34 (t, J = 7.3 Hz, 2H), 2.23 (dd, J = 13.1, 7.5 Hz, 1H), 2.13 (dt, J = 11.6, 3.4 Hz, 4H), 2.05 (ddt, J = 15.9, 11.3, 5.8 Hz, 1H), 1.89 (p, J = 7.1 Hz, 2H), 1.57 (t, J = 6.4 Hz, 2H), 1.08(s,6H),1.04(s,9H).HRMS(ESI)m/z: calculated value C ₆₇ H ₈₅ ClF ₃ N ₁₀ O ₁₀ S ₃ ⁺ [M+H] ⁺ ,1377.5247; measured value, 1377.5289 .

Example 198: (2S,4R)-1-((S)-2-(6-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-6-oxohexanoylamino)-3,3-dimethylbutyryl)-4- Hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361057) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS074013) 6-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy (Oxybut-2-yl)amino)-6-oxohexanoic acid was prepared to obtain the target compound (SIAIS361057), white powder, yield=52%

¹ H NMR(500MHz, methanol-d ₄ )δ9.38(s,1H), 8.39(d,J=2.4Hz,1H), 8.19(dd,J=9.3,2.4Hz,1H), 7.72(d, J = 9.0Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 9.3Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.96 (d, J = 9.1 Hz, 2H), 4.62 (s, 2H), 4.61-4.55 (m, 1H), 4.52 (d, J = 15.6Hz, 1H), 4.50–4.47(m, 1H), 4.39(d, J = 15.6Hz, 1H), 4.16(s, 1H), 3.94–3.85(m, 3H), 3.79(dd, J = 10.9, 3.9Hz, 1H), 3.71(s, 2H), 3.66–3.50(m, 7H), 3.29–3.21(m, 4H), 3.12(s, 2H), 3.01(s, 1H), 2.93– 2.81 (m, 2H), 2.52 (s, 3H), 2.39 (s, 4H), 2.31 (q, J = 6.8 Hz, 2H), 2.23 (ddq, J = 11.5, 7.6, 2.4, 1.9 Hz, 1H) ,2.18–2.10(m,4H),2.07(ddd,J＝13.3,9.2,4.5Hz,1H),1.64(ddd,J＝17.3,7.9,3.3Hz,4H),1.57(t,J＝6.6Hz ,2H),1.08(s,6H),1.03(s,9H).HRMS(ESI)m/z: calculated value C ₆₈ H ₈₇ ClF ₃ N ₁₀ O ₁₀ S ₃ ⁺ [M+H] ⁺ ,1391.5404; Measured value, 1391.5403.

Example 199: (2S,4R)-1-((S)-2-(7-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-7-oxoheptanoylamino)-3,3-dimethylbutyryl)-4- Hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361058) preparation

Referring to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS074014) 7-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy The target compound (SIAIS361058) was prepared by preparing (but-2-yl)amino)-7-oxoheptanoic acid, white powder, yield=48%

¹ H NMR(500MHz, methanol-d ₄ )δ9.52(s,1H), 8.40(d,J=2.4Hz,1H), 8.19(dd,J=9.2,2.3Hz,1H), 7.72(d, J=9.0Hz,2H),7.54–7.50(m,2H),7.49–7.44(m,2H),7.39(d,J=8.4Hz,2H), 7.21(d,J=9.4Hz,1H), 7.16(d,J=8.4Hz,2H),6.97(d,J=9.1Hz,2H),4.62(s,1H),4.60–4.56(m,1H),4.53(d,J=15.2Hz,1H ), 4.49 (q, J = 3.5, 2.8 Hz, 1H), 4.41 (s, 1H), 4.18 (s, 1H), 3.94-3.84 (m, 3H), 3.80 (dd, J = 10.9, 3.9 Hz, 1H), 3.71 (s, 2H), 3.54 (dd, J = 9.3, 5.6 Hz, 8H), 3.25 (dd, J = 10.9, 5.0 Hz, 4H), 3.11 (s, 2H), 3.02 (s, 1H) ), 2.87(t,J=11.1Hz,2H),2.54(s,3H),2.41(dt,J=11.7,6.8Hz,4H),2.34–2.19(m,4H),2.18–2.11(m, 4H),2.07(ddd,J=13.3,9.2,4.5Hz,1H),1.66-1.56(m,6H),1.41-1.33(m,2H),1.08(s,6H),1.03(s,9H) .HRMS(ESI)m/z: calculated value C ₆₉ H ₈₉ ClF ₃ N ₁₀ O ₁₀ S ₃ ⁺ [M+H] ⁺ , 1405.5560; measured value, 1405.5555.

Example 200: (2S,4R)-1-((S)-2-(8-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-8-oxooctanoylamino)-3,3-dimethylbutyryl)-4- Hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361059) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS074015) 8-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy (Oxybut-2-yl)amino)-8-oxooctanoic acid to obtain the target compound (SIAIS361059), white powder, yield=44%

¹ H NMR(500MHz, methanol-d ₄ )δ9.47(s,0H), 8.40(d,J=2.2Hz,1H), 8.20(dd,J=9.3,2.4Hz,1H), 7.73(d, J=9.2Hz, 2H), 7.55–7.50(m, 2H), 7.50–7.45(m, 2H), 7.40(d, J=8.4Hz, 2H), 7.21(d, J=9.4Hz, 1H), 7.16(d,J=8.4Hz,2H), 6.97(d,J=9.1Hz,2H), 4.63(s,1H), 4.57(d,J=7.8Hz,1H), 4.54(d,J=15.4 Hz, 1H), 4.49 (p, J = 2.1 Hz, 1H), 4.39 (d, J = 15.6 Hz, 1H), 4.19 (s, 1H), 3.95-3.85 (m, 3H), 3.80 (dd, J = 10.9, 3.9Hz, 1H), 3.71(s, 2H), 3.67–3.50(m, 8H), 3.29–3.22(m, 4H), 3.11(s, 2H), 3.02(s, 1H), 2.94– 2.82(m,2H),2.54(s,2H),2.47–2.38(m,4H),2.34–2.19(m,4H), 2.13(dd,J=12.8,5.0Hz,4H), 2.10–2.03( m,1H),1.67–1.54(m,6H),1.36(dd,J=8.0,4.8Hz,4H),1.08(s,6H),1.03(s,9H).HRMS(ESI)m/z: Calculated value C ₇₀ H ₉₁ ClF ₃ N ₁₀ O ₁₀ S ₃ ⁺ [M+H] ⁺ , 1419.5717; measured value, 1419.5746.

Example 201: (2S,4R)-1-((S)-2-(9-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-9-oxononanoylamino)-3,3-dimethylbutyryl)-4- Hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361060) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS074016) 9-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy The target compound (SIAIS361060) was prepared by preparing but-2-yl)amino)-9-oxononanoic acid, white powder, yield=67%

¹ H NMR(500MHz, methanol-d ₄ )δ9.32(s,1H), 8.40(d,J=2.3Hz,1H), 8.21(dd,J=9.3,2.3Hz,1H), 7.74(d, J = 9.0Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 9.4Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 9.1 Hz, 2H), 4.63 (s, 1H), 4.57 (d, J = 8.1 Hz, 1H), 4.54 (d,J=15.3Hz,1H),4.50(p,J=2.4Hz,1H), 4.38(d,J=15.6Hz,1H), 4.19(s,1H),3.94-3.85(m,3H) , 3.80 (dd, J = 10.9, 3.8 Hz, 1H), 3.71 (s, 2H), 3.66–3.48 (m, 8H), 3.25 (dd, J = 9.8, 6.8 Hz, 4H), 3.10 (s, 2H) ), 3.00 (s, 1H), 2.93-2.83 (m, 2H), 2.52 (s, 3H), 2.41 (q, J = 7.4 Hz, 4H), 2.33-2.19 (m, 4H), 2.16-2.05 ( m,5H),1.59(dt,J=12.8,6.4Hz,6H),1.35(s,6H),1.08(s,6H),1.03(s,9H).HRMS(ESI)m/z: calculated value C ₇₁ H ₉₃ ClF ₃ N ₁₀ O ₁₀ S ₃ ⁺ [M+H] ⁺ , 1433.5873; measured value, 1433.5908.

Example 202: (2S,4R)-1-((S)-2-(10-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-10-oxodecanoylamino)-3,3-dimethylbutyryl)-4- Hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361061) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS360149) and the intermediate LM prepared according to Scheme 12 (SIAIS074019) 10-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy (Oxybut-2-yl)amino)-10-oxodecanoic acid to prepare the target compound (SIAIS361061), white powder, yield=32%

¹ H NMR(500MHz, methanol-d ₄ )δ9.36(s,1H), 8.40(d,J=2.3Hz,1H), 8.20(dd,J=9.3,2.3Hz,1H), 7.73(d, J = 9.1Hz, 2H), 7.51 (d, J = 8.3 Hz, 2H), 7.46 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 9.4Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 9.2 Hz, 2H), 4.63 (s, 2H), 4.59-4.55 (m, 1H), 4.54 (d, J = 13.3Hz, 1H), 4.50 (td, J = 4.4, 1.8Hz, 1H), 4.38 (d, J = 15.6Hz, 1H), 4.19 (s, 1H), 3.93–3.86 (m, 3H), 3.80(dd,J=10.9,3.9Hz,1H), 3.71(s,2H), 3.66–3.49(m,7H), 3.29–3.21(m,4H), 3.10(s,2H), 3.00(s, 1H), 2.87(t,J=11.0Hz,2H), 2.53(s,3H), 2.46–2.37(m,4H), 2.34–2.19(m,3H), 2.19–2.04(m,5H), 1.58 (q,J=6.8Hz,6H),1.33(s,8H),1.08(s,6H),1.03(s,9H).HRMS(ESI)m/z: calculated value C ₇₂ H ₉₅ ClF ₃ N ₁₀ O ₁₀ S ₃ ⁺ [M+H] ⁺ ,1447.6030; measured value,1447.6042.

Example 203: (2S,4R)-1-((S)-2-(11-(4-(3-((4-(N-(4-(4-((4'-chloro-4, 4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)- 2-((Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-11-oxoundecanoylamino)-3,3-dimethylbutyryl)- Preparation of 4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS361062)

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS074020) 11-(((S)-1-((2S, 4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxy (Oxybut-2-yl)amino)-11-oxoundecanoic acid was prepared to obtain the target compound (SIAIS361062), white powder, yield=43%

¹ H NMR(500MHz, methanol-d ₄ )δ9.42(s,1H), 8.40(d,J=2.2Hz,1H), 8.20(dd,J=9.2,2.4Hz,1H), 7.73(d, J = 9.0Hz, 2H), 7.51 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 9.3Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 9.1 Hz, 2H), 4.63 (s, 2H), 4.59-4.55 (m, 1H), 4.54 (d, J = 13.7Hz, 1H), 4.50 (dq, J = 4.2, 2.0Hz, 1H), 4.38 (d, J = 15.6Hz, 1H), 4.19 (s, 1H), 3.93–3.85 (m, 3H), 3.80(dd,J=11.0,3.9Hz,1H), 3.71(s,2H), 3.66–3.48(m,7H), 3.28–3.21(m,4H), 3.09(s,2H), 3.01(s, 1H), 2.87 (t, J = 12.0 Hz, 2H), 2.53 (s, 3H), 2.40 (d, J = 7.9 Hz, 4H), 2.36-2.19 (m, 4H), 2.11 (td, J = 13.4 ,11.3,7.8Hz,5H),1.58(q,J=6.7Hz,6H),1.31(s,10H),1.08(s,6H),1.03(s,9H).HRMS(ESI)m/z: Calculated value C ₇₃ H ₉₇ ClF ₃ N ₁₀ O ₁₀ S ₃ ⁺ [M+H] ⁺ , 1461.6186; measured value, 1461.6215.

Example 204: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-((3-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)pent-4-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzene Formamide (SIAIS361034) preparation

With reference to the method in Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361034) was prepared using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS255121), white powder, yield = 24%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.38 (d, J = 2.3 Hz, 1H), 8.18 (dd, J = 9.3, 2.3 Hz, 1H), 7.74 (t, J = 8.4 Hz, 3H) ,7.63(dd,J=7.7,1.0Hz,1H), 7.50(t,J=7.6Hz,1H), 7.39(d,J=8.4Hz,2H), 7.21–7.13(m,3H), 6.96( d, J = 9.1Hz, 2H), 5.16 (dd, J = 13.3, 5.2 Hz, 1H), 4.57 (d, J = 17.6 Hz, 1H), 4.50 (d, J = 17.5 Hz, 1H), 3.88 ( d, J=13.9Hz, 2H), 3.71(s, 2H), 3.68–3.36(m,10H), 3.29–3.14(m,6H), 3.01(s,2H), 2.95–2.81(m,3H) ,2.76(ddd,J＝17.6,4.6,2.4Hz,1H), 2.66(t,J＝6.8Hz,2H), 2.56(qd,J＝13.2,4.6Hz,1H), 2.40(s,2H), 2.17 (dtd, J = 12.8, 5.3, 2.3 Hz, 1H), 2.11 (d, J = 2.4 Hz, 4H), 2.06-1.97 (m, 2H), 1.57 (t, J = 6.4 Hz, 2H), 1.08 (s,6H).HRMS(ESI)m/z: calculated value C ₅₈ H ₆₇ ClF ₃ N ₈ O ₈ S ₂ ⁺ [M+H] ⁺ , 1159.4158; measured value, 1159.4188.

Example 205: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-((3-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)hex-5-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzene Formamide (SIAIS361035) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361035) was prepared using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS255119), white powder, yield = 25%

¹ H NMR(500MHz, methanol-d ₄ )δ8.39(d,J=2.3Hz,1H), 8.18(dd,J=9.3,2.3Hz,1H), 7.73(d,J=9.0Hz,3H) , 7.61 (d, J = 1.0 Hz, 1H), 7.49 (t, J = 7.7 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 9.4 Hz, 1H), 7.15 (d,J=8.4Hz,2H), 6.96(d,J=9.1Hz,2H), 5.16(dd,J=13.3,5.2Hz,1H), 4.56(d,J=17.6Hz,1H), 4.49 (d,J=17.5Hz,1H), 3.89(d,J=13.8Hz,2H), 3.71(s,2H), 3.67–3.38(m,11H), 3.24(dd,J=10.0,6.5Hz, 5H),3.05(s,2H),2.93-2.81(m,3H),2.74(ddd,J=17.6,4.7,2.4Hz,1H), 2.60(t,J=6.7Hz,2H),2.55(td ,J＝13.2,4.6Hz,1H), 2.40(t,J＝6.5Hz,2H), 2.17(ddq,J＝10.5,5.2,2.7Hz,1H),2.10(s,2H),2.08–2.02( m,2H),1.99(ddt,J=11.9,8.3,3.7Hz,2H),1.77–1.69(m,2H),1.57(t,J=6.4Hz,2H),1.08(s,6H).HRMS (ESI) m/z: calculated value C ₅₉ H ₆₉ ClF ₃ N ₈ O ₈ S ₂ ⁺ [M+H] ⁺ , 1173.4315; measured value, 1173.4317.

Example 206: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-((3-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)hepta-6-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzene Formamide (SIAIS361036) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361036) was prepared by using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS292017), white powder, yield = 27%

¹ H NMR(500MHz, methanol-d ₄ )δ8.40(d,J=2.2Hz,1H), 8.19(dd,J=9.2,2.3Hz,1H), 7.73(d,J=8.2Hz,3H) ,7.60(dd,J=7.6,1.0Hz,1H),7.49(t,J=7.6Hz,1H), 7.39(d,J=8.0Hz,2H), 7.21(d,J=9.3Hz,1H) ,7.15(d,J=8.0Hz,2H),6.97(d,J=8.7Hz,2H), 5.17(dd,J=13.2,5.0Hz,1H),4.54(d,J=17.6Hz,1H) ,4.48(d,J=17.6Hz,1H),3.92–3.86(m,2H), 3.81(s,3H), 3.70(s,2H), 3.68–3.43(m,8H), 3.30-3.20(m ,7H),2.93-2.83(m,3H),2.77(d,J=15.8Hz,1H),2.55(t,J=6.7Hz,3H),2.40(s,2H),2.20-2.10(m, 5H), 1.88 (s, 2H), 1.71 (t, J = 7.4 Hz, 2H), 1.61 (t, J = 7.5 Hz, 2H), 1.57 (t, J = 6.3 Hz, 2H), 1.07 (s, 6H).HRMS(ESI)m/z: calculated value C ₆₀ H ₇₁ ClF ₃ N ₈ O ₈ S ₂ ⁺ [M+H] ⁺ , 1187.4471; measured value, 1187.4494.

Example 207: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-((3-(4-(8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)oct-7-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzene Formamide (SIAIS361037) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361037) was prepared by using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS292020), white powder, yield = 32%

¹ H NMR(500MHz, methanol-d ₄ )δ8.40(d,J=2.3Hz,1H), 8.19(dd,J=9.2,2.3Hz,1H), 7.73(d,J=9.1Hz,3H) ,7.60(dd,J=7.7,1.0Hz,1H),7.49(t,J=7.6Hz,1H), 7.38(d,J=8.1Hz,2H), 7.21(d,J=9.3Hz,1H) ,7.15(d,J=8.1Hz,2H),6.97(d,J=8.7Hz,2H), 5.16(dd,J=13.2,5.1Hz,1H),4.52(d,J=17.5Hz,1H) ,4.46(d,J=17.5Hz,1H), 3.89(d,J=13.9Hz,2H), 3.79(s,3H), 3.70(s,2H), 3.70–3.38(m,9H), 3.25( q,J=7.2,5.5Hz,6H), 2.87(td,J=12.9,4.4Hz,3H), 2.84–2.74(m,1H), 2.60–2.49(m,3H), 2.40(s,2H) ,2.21–2.08(m,5H),1.83(ddt,J=12.1,7.8,4.3Hz,2H),1.67(p,J=6.8Hz,2H),1.62–1.55(m,4H),1.48(q ,J=7.5Hz,2H),1.08(s,6H).HRMS(ESI)m/z: calculated value C ₆₁ H ₇₃ ClF ₃ N ₈ O ₈ S ₂ ⁺ [M+H] ⁺ ,1201.4628; measured value ,1201.4648.

Example 208: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-((3-(4-(9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)non-8-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzene Formamide (SIAIS361038) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361038) was prepared using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS255127), white powder, yield = 19%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.39 (d, J = 2.3 Hz, 1H), 8.19 (dd, J = 9.3, 2.3 Hz, 1H), 7.73 (ddd, J = 7.7, 4.0, 1.5 Hz, 3H), 7.60 (dd, J = 7.7, 1.1 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.39 (d, J = 8.5 Hz, 2H), 7.16 (t, J = 8.6 Hz, 3H), 6.97 (d, J = 9.1 Hz, 2H), 5.17 (dd, J = 13.4, 5.2 Hz, 1H), 4.51 (d, J = 17.4 Hz, 1H), 4.45 (d, J = 17.4 Hz, 1H), 3.89 (d, J = 13.8 Hz, 2H), 3.70 (s, 2H), 3.65-3.35 (m, 11H), 3.24 (t, J = 12.7 Hz, 3H), 3.18–3.09 (m , 2H), 2.89 (dq, J = 13.6, 5.3, 4.8 Hz, 5H), 2.78 (ddd, J = 17.6, 4.6, 2.4 Hz, 1H), 2.56-2.46 (m, 3H), 2.40 (t, J ＝6.5Hz,2H), 2.18(ddd,J＝9.9,5.3,2.7Hz,1H), 2.10(s,2H),1.99(d,J＝9.4Hz,2H),1.77(q,J＝7.5Hz ,2H),1.65(p,J=6.9Hz,2H),1.56(q,J=8.9,7.7Hz,4H),1.50–1.40(m,4H),1.08(s,6H).HRMS(ESI) m/z: calculated value C ₆₂ H ₇₅ ClF ₃ N ₈ O ₈ S ₂ ⁺ [M+H] ⁺ , 1215.4784; measured value, 1215.4763.

Example 209: Preparation of 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) Methyl)piperazin-1-yl)-N-((4-((3-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-5-yl)pent-4-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl) Benzamide (SIAIS361039)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361039) was prepared by using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS292111), white powder, yield = 18%

¹ H NMR(500MHz, methanol-d ₄ )δ8.40(d,J=2.3Hz,1H), 8.19(dd,J=9.3,2.3Hz,1H), 7.73(d,J=9.1Hz,3H) ,7.63(s,1H),7.56–7.51(m,1H),7.40(d,J=8.4Hz,2H),7.19(d,J=9.4Hz,1H),7.16(d,J=8.4Hz, 2H), 6.97 (d, J = 9.1Hz, 2H), 5.14 (dd, J = 13.3, 5.2Hz, 1H), 4.51 (d, J = 17.3Hz, 1H), 4.45 (d, J = 17.2Hz, 1H), 3.88(d, J=13.9Hz, 2H), 3.71(s, 2H), 3.70–3.33(m, 13H), 3.28–3.18(m, 3H), 3.09(s, 2H), 2.94–2.82 (m, 3H), 2.77 (ddd, J = 17.6, 4.7, 2.5 Hz, 1H), 2.65 (t, J = 6.8 Hz, 2H), 2.50 (td, J = 13.1, 4.6 Hz, 1H), 2.41 ( d, J = 6.5Hz, 2H), 2.17 (dtd, J = 12.9, 5.4, 2.4 Hz, 1H), 2.15-2.01 (m, 6H), 1.57 (t, J = 6.4 Hz, 2H), 1.08 (s ,6H).HRMS(ESI)m/z: calculated value C ₅₈ H ₆₇ ClF ₃ N ₈ O ₈ S ₂ ⁺ [M+H] ⁺ ,1159.4158; measured value, 1159.4147.

Example 210: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-((3-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-5-yl)hex-5-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzene Formamide (SIAIS361040) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS361040) was prepared by using intermediate BINDER (SIAIS360149) and intermediate LM (SIAIS292112), white powder, yield = 20%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.39 (d, J = 2.3 Hz, 1H), 8.18 (dd, J = 9.3, 2.3 Hz, 1H), 7.72 (dd, J = 8.6, 6.7 Hz, 3H), 7.61 (s, 1H), 7.52 (dd, J = 7.9, 1.3 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.20-7.13 (m, 3H), 6.97 (d, J =9.1Hz, 2H), 5.13 (dd, J = 13.3, 5.2 Hz, 1H), 4.50 (d, J = 17.2 Hz, 1H), 4.44 (d, J = 17.2 Hz, 1H), 3.88 (d, J =13.8Hz, 2H), 3.71(s, 2H), 3.68–3.35(m, 11H), 3.25(d, J = 10.2Hz, 5H), 2.97(s, 2H), 2.94–2.83(m, 3H) ,2.77(ddd,J=17.6,4.6,2.4Hz,1H),2.58(t,J=6.8Hz,2H), 2.49(td,J=13.2,4.7Hz,1H),2.41(q,J=7.4 ,6.5Hz,2H),2.16(dtd,J=12.9,5.4,2.4Hz,1H),2.11(d,J=2.2Hz,2H),1.99(ddd,J=16.1,13.2,7.8Hz, 4H) ,1.73(p,J=7.0Hz,2H),1.57(t,J=6.4Hz,2H),1.08(s,6H).HRMS(ESI)m/z: calculated value C ₅₉ H ₆₉ ClF ₃ N ₈ O ₈ S ₂ ⁺ [M+H] ⁺ , 1173.4315; measured value, 1173.4328.

Example 211: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(3-(2-(2,6-dioxopiperidin-3-yl)-1 -Oxoisoindolin-4-yl)prop-2-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butane-2-yl)amino)-3-( (Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS363018) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS360129) and intermediate 3-(4-(3-chloroprop-1-yn-1-yl)-1-oxygen were used. Substitute isoindolin-2-yl) piperidine-2,6-dione (Eur.J.Med.Chem.176(2019)476-491) to prepare the target compound (SIAIS363018), white powder, yield= 59%

¹ H NMR(500MHz, methanol-d ₄ )δ8.31(d,J=2.2Hz,1H), 8.08(dd,J=9.3,2.3Hz,1H), 7.90(d,J=9.0Hz,1H) ,7.85–7.80(m,1H),7.79–7.72(m,3H),7.55(t,J=7.7Hz,1H),7.43-7.38(m,2H),7.33(d,J=7.0Hz,2H ), 7.23-7.10 (m, 5H), 6.98 (ddt, J = 9.1, 6.1, 4.3 Hz, 3H), 5.16 (dt, J = 13.3, 4.8 Hz, 1H), 4.67 (d, J = 17.8 Hz, 1H), 4.57(d,J=17.7Hz,1H), 4.16(d,J=6.6Hz,1H), 4.11(s,2H), 3.88(d,J=13.4Hz,2H), 3.71(d, J = 4.9 Hz, 3H), 3.69–3.66 (m, 1H), 3.58–3.55 (m, 1H), 3.53 (d, J = 12.5 Hz, 3H), 3.44-3.31 (m, 4H), 3.28–3.10 (m, 6H), 2.94–2.84(m, 3H), 2.80–2.73(m, 1H), 2.59(qd, J = 13.2, 4.5Hz, 1H), 2.40(s, 2H), 2.35–2.26(m ,1H), 2.17(td,J=7.7,3.8Hz,2H),2.10(s,2H),1.62-1.56(m,2H),1.08(s,6H).HRMS(ESI)m/z: calculation Value C ₆₃ H ₆₉ ClF ₃ N ₈ O ₈ S ₃ ⁺ [M+H] ⁺ , 1253.4036; measured value, 1253.4010.

Example 212: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(3-((2-(2,6-dioxopiperidin-3-yl)- 1-oxoisoindolin-4-yl)thio)propyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) (Phenyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS363021) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS213132) to prepare the target compound (SIAIS363021), white powder, yield = 42%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.30 (d, J = 2.3 Hz, 1H), 8.10-8.03 (m, 1H), 7.76 (dd, J = 9.0, 1.7 Hz, 2H), 7.73 ( dd,J=7.8,0.9Hz,1H),7.70–7.66(m,1H),7.55(t,J=7.7Hz,1H),7.39(dd,J=8.4,1.9Hz,2H),7.35-7.31 (m, 2H), 7.20 (t, J = 7.5 Hz, 2H), 7.15 (t, J = 8.0 Hz, 3H), 7.01-6.96 (m, 3H), 5.16 (ddd, J = 13.4, 5.2, 2.6 Hz, 1H), 4.51 (d, J = 15.9 Hz, 1H), 4.46 (s, 1H), 4.15 (dq, J = 10.3, 5.4 Hz, 1H), 3.89 (d, J = 13.9 Hz, 2H), 3.71(s,2H), 3.60–3.48(m,4H), 3.39–3.32(m,4H), 3.28–3.19(m,6H), 3.15(dtd, J=14.5,7.4,6.8,5.2Hz,3H ),3.04(s,1H),2.98(s,1H),2.88(ddt,J=13.7,11.0,6.8Hz,4H),2.81-2.74(m,1H),2.53(qd,J=13.3,4.7 Hz, 1H), 2.40 (d, J = 5.8 Hz, 2H), 2.27-2.14 (m, 2H), 2.10 (s, 2H), 2.06 (q, J = 6.8 Hz, 3H), 1.58 (t, J ＝6.4Hz,2H),1.08(s,6H).HRMS(ESI)m/z: calculated value C ₆₃ H ₇₃ ClF ₃ N ₈ O ₈ S ₄ ⁺ [M+H] ⁺ ,1289.4069; measured value, 1289.4094 .

Example 213: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)- 1-oxoisoindolin-4-yl)thio)butyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) (Phenyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS363022) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363022) was prepared by using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS213134), white powder, yield = 40%

¹ H NMR(500MHz, methanol-d ₄ )δ8.30(d,J=2.3Hz,1H), 8.08(dd,J=9.3,2.4Hz,1H), 7.76(d,J=8.8Hz,2H) ,7.69(d,J=7.7Hz,1H),7.66(d,J=7.4Hz,1H),7.53(t,J=7.7Hz,1H),7.39(d,J=8.3Hz,2H),7.33 (d,J=7.0Hz,2H), 7.21(d,J=7.4Hz,2H), 7.15(dd,J=7.8,6.0Hz,3H), 6.99(dd,J=9.0,1.7Hz,3H) , 5.16(dd,J=13.2,5.1Hz,1H), 4.49(d,J=17.4Hz,1H), 4.44(s,1H), 4.16(s,1H), 3.89(d,J=15.0Hz, 2H), 3.71 (s, 2H), 3.61-3.49 (m, 4H), 3.36 (dd, J = 14.4, 5.1 Hz, 4H), 3.28-3.20 (m, 4H), 3.19-2.97 (m, 6H) , 2.88 (qd, J = 9.5, 8.9, 5.8 Hz, 4H), 2.77 (ddd, J = 17.7, 4.9, 2.4 Hz, 1H), 2.61-2.50 (m, 1H), 2.40 (s, 2H), 2.29 –2.13(m,3H),2.10(s,2H),2.04(d,J＝6.9Hz,1H),1.92(dd,J＝15.2,7.3Hz,2H),1.70(dp,J＝20.9,7.1 Hz,2H),1.58(t,J=6.4Hz,2H),1.08(s,6H).HRMS(ESI)m/z: calculated value C ₆₄ H ₇₅ ClF ₃ N ₈ O ₈ S ₄ ⁺ [M+ H] ⁺ ,1303.4226; measured value,1303.4186.

Example 214: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(5-((2-(2,6-dioxopiperidin-3-yl)- 1-oxoisoindolin-4-yl)thio)pentyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) (Phenyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS363023) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363023) was prepared using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS213135), white powder, yield = 55%

¹ H NMR(500MHz, methanol-d ₄ )δ8.30(d,J=2.3Hz,1H), 8.07(dd,J=9.2,2.3Hz,1H), 7.76(d,J=8.7Hz,2H) ,7.66–7.63(m,2H),7.52(t,J=7.6Hz,1H),7.42–7.36(m,2H),7.36–7.31(m,2H),7.20(t,J=7.6Hz,2H ), 7.15 (d, J = 8.4 Hz, 3H), 6.99 (dd, J = 9.0, 4.7 Hz, 3H), 5.16 (ddd, J = 13.4, 5.2, 2.1 Hz, 1H), 4.44 (d, J = 5.3Hz, 1H), 4.42 (d, J = 4.2 Hz, 1H), 4.16 (d, J = 8.1 Hz, 1H), 3.95-3.86 (m, 2H), 3.76-3.63 (m, 4H), 3.61- 3.49(m,5H),3.41–3.34(m,2H), 3.23(dd,J＝14.2,5.3Hz,3H),3.19–3.13(m,2H),3.08(dt,J＝14.1,7.1Hz, 4H), 2.95–2.82 (m, 4H), 2.78 (ddt, J = 15.3, 4.1, 2.1 Hz, 2H), 2.53 (qd, J = 13.3, 4.7 Hz, 2H), 2.40 (t, J = 6.5 Hz , 2H), 2.24 (dd, J = 9.4, 4.6 Hz, 1H), 2.18 (dtd, J = 12.9, 5.3, 2.4 Hz, 2H), 2.10 (s, 3H), 1.82–1.74 (m, 3H), 1.74–1.65(m,3H),1.65–1.51(m,5H),1.08(s,6H).HRMS(ESI)m/z: calculated value C ₆₅ H ₇₇ ClF ₃ N ₈ O ₈ S ₄ ⁺ (M +H] ⁺ ,1317.4382; measured value,1317.4438.

Example 215: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)- 1-oxoisoindolin-4-yl)oxy)butyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) (Phenyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS363025) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363025) was prepared using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS1222171), white powder, yield = 45%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.30 (d, J = 2.3 Hz, 1H), 8.12-8.05 (m, 1H), 7.76 (dd, J = 9.0, 1.9 Hz, 2H), 7.48 ( t,J=7.9Hz,1H),7.41–7.37(m,3H),7.33(d,J=7.4Hz,2H),7.20(t,J=7.9Hz,3H),7.18–7.12(m,3H ), 7.01–6.94 (m, 3H), 5.13 (ddd, J = 13.3, 5.2, 2.8 Hz, 1H), 4.50 (dd, J = 17.4, 3.4 Hz, 1H), 4.42 (d, J = 17.3 Hz, 1H), 4.21 (t, J = 5.8 Hz, 2H), 4.20-4.14 (m, 1H), 3.88 (d, J = 13.9 Hz, 2H), 3.79-3.61 (m, 4H), 3.55-3.49 (m ,4H),3.45–3.34(m,4H), 3.29–3.17(m,5H),3.05(s,2H), 2.88(dtd,J=13.5,9.0,7.6,5.2Hz,3H),2.77(dddt ,J=12.8,9.8,4.8,2.4Hz,1H), 2.53(qd,J=13.1,5.3Hz,1H), 2.40(t,J=6.5Hz,2H), 2.23(s,1H), 2.20– 2.12(m,1H),2.10(s,2H),2.08–1.96(m,3H),1.96–1.88(m,2H),1.58(t,J=6.4Hz,2H),1.08(s,6H) .HRMS(ESI)m/z: Calculated value C ₆₄ H ₇₅ ClF ₃ N ₈ O ₉ S ₃ ⁺ [M+H] ⁺ , 1287.4454; measured value, 1287.4524.

Example 216: 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methane Yl)piperazin-1-yl)-N-((4-(((2R)-4-(4-(5-((2-(2,6-dioxopiperidin-3-yl)- 1-oxoisoindolin-4-yl)oxy)pentyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) (Phenyl)sulfonyl)phenyl)sulfonyl)benzamide (SIAIS363026) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363026) was prepared using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS1222169), white powder, yield = 39%

¹ H NMR (500MHz, methanol-d ₄ ) δ 8.30 (d, J = 2.3 Hz, 1H), 8.08 (dd, J = 9.3, 2.4 Hz, 1H), 7.76 (dd, J = 9.0, 1.3 Hz, 2H), 7.47 (t, J = 7.8 Hz, 1H), 7.38 (t, J = 8.9 Hz, 3H), 7.33 (d, J = 7.1 Hz, 2H), 7.24-7.18 (m, 3H), 7.18- 7.12 (m, 3H), 6.99 (d, J = 8.8 Hz, 3H), 5.14 (ddd, J = 13.4, 5.2, 1.5 Hz, 1H), 4.52–4.43 (m, 1H), 4.42–4.35 (m, 1H), 4.26–4.12(m,3H), 3.89(d,J=13.8Hz,2H), 3.82–3.49(m,8H), 3.42–3.34(m,4H), 3.22(td,J=10.1, 5.4Hz,5H),3.02(s,1H),2.94-2.82(m,4H),2.76(ddt,J=15.0,4.7,2.6Hz,1H),2.51(qd,J=13.3,4.7Hz,1H ),2.40(s,2H),2.28–2.13(m,3H),2.09(s,2H),2.01(dd,J=14.7,8.4Hz,1H),1.91(p,J=6.6Hz,2H) , 1.85 (q, J = 7.8, 6.8 Hz, 2H), 1.60 (dt, J = 25.4, 7.0 Hz, 4H), 1.08 (s, 6H). HRMS (ESI) m/z: calculated value C ₆₅ H ₇₇ ClF ₃ N ₈ O ₉ S ₃ ⁺ [M+H] ⁺ , 1301.4611; measured value, 1301.4652.

Example 217: (2S,4R)-1-((S)-2-((6-(4-((R)-3-((4-(N-(4-(4-((4' -Chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl) Sulfamoyl)-2-((trifluoromethyl)sulfonyl)phenyl)amino)-4-(thiophenyl)butyl)piperazin-1-yl)hexyl)amino)-3,3-di (Methylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS363046) preparation

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS363046) was prepared using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS363013), white powder, yield = 24%

¹ H NMR(500MHz, methanol-d ₄ )δ9.11(s,1H), 8.30(s,1H), 8.07(s,1H), 7.77(s,2H), 7.48(d,J=7.6Hz, 2H),7.46–7.37(m,4H),7.33(d,J=7.1Hz,2H),7.25-7.09(m,5H),7.00(s,3H),4.73(s,1H),4.56(d ,J=15.8Hz,2H),4.36(d,J=15.4Hz,1H),4.16(s,2H),4.03-3.82(m,3H),3.71(s,4H),3.54(s,4H) ,3.45-3.32(m,7H), 3.28–3.11(m,5H), 3.09–2.93(m,3H), 2.87(s,2H), 2.49(s,3H),2.41(s,2H), 2.34 (s, 1H), 2.27 (s, 1H), 2.12 (s, 4H), 1.80 (s, 4H), 1.58 (s, 2H), 1.45 (s, 4H), 1.17 (s, 9H), 1.08 ( s,6H).HRMS(ESI)m/z: calculated value C ₇₅ H ₉₇ ClF ₃ N ₁₀ O ₈ S ₄ ⁺ [M+H] ⁺ , 1485.6009; measured value, 1485.6031.

Example 218: (2S,4R)-1-((S)-2-((7-(4-((R)-3-((4-(N-(4-(4-((4' -Chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl) Sulfamoyl)-2-((trifluoromethyl)sulfonyl)phenyl)amino)-4-(thiophenyl)butyl)piperazin-1-yl)heptyl)amino)-3,3- Preparation of dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS364019)

With reference to the method of Example 42, under appropriate conditions understandable in the art, the target compound (SIAIS364019) was prepared by using intermediate BINDER (SIAIS360129) and intermediate LM (SIAIS363039), white powder, yield = 30%

¹ H NMR(500MHz, methanol-d ₄ )δ9.46(s,1H), 8.31(d,J=2.3Hz,1H), 8.07(dd,J=9.2,2.3Hz,1H), 7.77(d, J = 9.2Hz, 2H), 7.52 (d, J = 8.2 Hz, 2H), 7.47 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.3Hz, 2H), 7.21–7.13 (m, 5H), 7.00 (dd, J = 9.1, 5.6 Hz, 3H), 4.71 (dd, J = 9.6, 7.7 Hz, 1H), 4.61–4.51 (m, 2H) ), 4.39 (d, J = 15.6 Hz, 1H), 4.17 (d, J = 7.4 Hz, 1H), 4.14 (s, 1H), 3.92 (dd, J = 21.4, 12.7 Hz, 4H), 3.69 (d ,J=18.7Hz,7H), 3.39(dd,J=14.5,4.9Hz,3H), 3.29–3.15(m,7H),3.02(td,J=12.0,5.3Hz,1H), 2.94(td, J = 12.0, 5.5 Hz, 1H), 2.87 (t, J = 12.0 Hz, 2H), 2.53 (s, 3H), 2.41 (d, J = 6.5 Hz, 2H), 2.18 (s, 1H), 2.14- 2.05(m,3H),1.85-1.65(m,4H),1.57(t,J=6.4Hz,2H),1.17(s,9H),1.08(s,6H).HRMS(ESI)m/z: Calculated value C ₇₆ H ₉₉ ClF ₃ N ₁₀ O ₈ S ₄ ⁺ [M+H] ⁺ , 1499.6165; measured value, 1499.6176.

Example 219: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2- (3-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)propionyl Amino)ethyl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3 -Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS346183) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS346181) and the intermediate LM (SIAIS151001) prepared according to Scheme 1 were used as 3-(2-((2-(2,6- Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)propionic acid was prepared to obtain the target compound (SIAIS346183), yellow powder, yield = 55%

¹ H NMR(500MHz, methanol-d ₄ )δ8.69–8.66(m,1H), 8.00(d,J=2.5Hz,1H), 7.89–7.82(m,1H), 7.61–7.44(m,7H ), 7.36–7.27(m,2H), 7.21–7.04(m,1H), 7.02–6.90(m,4H), 6.69(t,J=9.2Hz,1H), 6.42(dt,J=8.6,3.4 Hz, 1H), 6.31 (d, J = 2.2 Hz, 1H), 5.04 (dd, J = 12.6, 5.5 Hz, 1H), 4.41 (d, J = 42.1 Hz, 5H), 4.23 (d, J = 10.0 Hz,1H),4.15(s,1H),3.97–3.91(m,2H),3.79–3.59(m,5H),3.55–3.37(m,10H), 3.27(d,J=7.0Hz,3H) , 3.24–3.14(m,3H), 2.95–2.79(m,3H), 2.68(dd,J=31.1,15.9Hz,2H),2.52–2.43(m,2H),2.11–2.00(m,2H) ,1.94(tt,J=7.5,4.0Hz,1H),1.69(d,J=12.9Hz,2H),1.43-1.33(m,3H).HRMS(ESI)m/z: calculated value C ₆₇ H ₇₂ ClN ₁₂ O ₁₄ S ⁺ [M+H] ⁺ , 1335.4695; found value, 1335.4678.

Example 220: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2- (3-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy )Ethoxy)propionylamino)ethyl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl )-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS346184) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS346181) and the intermediate LM (SIAIS151004) prepared according to Scheme 1 were used as 3-(2-(2-((2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxo-isoindolin-4-yl)amino)ethoxy)ethoxy)propionic acid was prepared to obtain the target compound (SIAIS346184 ), yellow powder, yield=53%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(s,1H), 8.01(d,J=2.6Hz,1H), 7.86(dd,J=9.3,2.4Hz,1H), 7.62(d, J=8.9Hz,1H), 7.59–7.43(m,6H), 7.30(d,J=8.2Hz,2H), 7.16(dd,J=39.4,8.4Hz,1H), 7.07–6.92(m,4H ), 6.70(d,J=9.0Hz,1H),6.41(d,J=3.3Hz,1H),6.31(s,1H),5.06–4.98(m,1H),4.48–4.30(m,5H) ,4.23(t,J=10.2Hz,1H),4.16(t,J=9.8Hz,1H),3.98–3.92(m,2H),3.77–3.49(m,11H),3.51–3.34(m,10H ), 3.27(d,J=7.0Hz,3H), 3.23–3.13(m,2H), 2.98–2.76(m,3H), 2.68(dd,J=23.3,16.0Hz,2H), 2.44(dd, J = 13.1, 6.7 Hz, 2H), 2.03 (q, J = 6.5 Hz, 2H), 1.94 (tt, J = 7.4, 3.9 Hz, 1H), 1.75-1.65 (m, 2H), 1.38 (td, J = 12.5, 4.4 Hz, 3H). HRMS (ESI) m/z: calculated value C ₆₉ H ₇₆ ClN ₁₂ O ₁₅ S ⁺ [M+H] ⁺ , 1379.4957; measured value, 1379.4932.

Example 221: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(1- ((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-12-oxo-3,6,9- Trioxa-13-azapentadecane-15-yl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (SIAIS346185) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS346181) and the intermediate LM (SIAIS151005) prepared according to Scheme 1 were used as 3-(2-(2-((2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxo isoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)propionic acid Target compound (SIAIS346185), yellow powder, yield = 51%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.3Hz,1H), 8.02(d,J=2.4Hz,1H), 7.86(dd,J=9.1,2.3Hz,1H) ,7.64-7.58(m,2H),7.55-7.45(m,5H),7.31(d,J=8.1Hz,2H),7.16(dd,J=39.2,8.5Hz,1H),7.04-6.94(m , 4H), 6.71 (d, J = 8.9 Hz, 1H), 6.43 (d, J = 3.6 Hz, 1H), 6.32 (s, 1H), 5.03 (d, J = 6.4 Hz, 1H), 4.48–4.32 (m,5H), 4.24(t,J=10.2Hz,1H), 4.16(t,J=9.9Hz,1H), 3.97–3.92(m,2H), 3.73–3.52(m,14H), 3.46– 3.36(m,10H), 3.27(d,J=7.0Hz,3H), 3.25–3.15(m,2H), 2.95–2.78(m,3H), 2.68(dd,J=25.4,15.2Hz,2H) ,2.47–2.40(m,2H),2.12–2.00(m,2H),1.94(ddt,J=11.1,7.7,4.0Hz,1H),1.70(d,J=11.4Hz,2H),1.38(td ,J=12.5,4.4Hz,3H).HRMS(ESI)m/z: calculated value C ₇₁ H ₈₀ ClN ₁₂ O ₁₆ S ⁺ [M+H] ⁺ ,1423.5219; measured value, 1423.5183.

Example 222: N-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-( ((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methane Yl)-4'-chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)-1-((2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxapentadecane-15- Amide (SIAIS346186) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS346181) and the intermediate LM (SIAIS151006) prepared according to Scheme 1 were used to prepare 1-((2-(2,6-dioxo) Piperidin-3-yl)-1,3-dioxo-isoindolin-4-yl)amino)-3,6,9,12-tetraoxapentadecane-15-acid to prepare the target Compound (SIAIS346186), yellow powder, yield = 50%

¹ H NMR(500MHz, methanol-d ₄ )δ8.68(d,J=2.1Hz,1H), 8.01(d,J=2.6Hz,1H), 7.89-7.82(m,1H), 7.62(d, J = 8.9 Hz, 1H), 7.57–7.45 (m, 6H), 7.31 (d, J = 7.8 Hz, 2H), 7.16 (dd, J = 41.8, 8.4 Hz, 1H), 7.04–6.94 (m, 4H ), 6.71 (d, J = 8.7 Hz, 1H), 6.42 (d, J = 3.5 Hz, 1H), 6.30 (s, 1H), 5.02 (dd, J = 12.7, 5.5 Hz, 1H), 4.49–4.33 (m, 5H), 4.26 (d, J = 10.0 Hz, 1H), 4.16 (t, J = 9.8 Hz, 1H), 3.95 (dd, J = 11.1, 3.7 Hz, 2H), 3.70–3.50 (m, 18H), 3.46–3.36(m,10H), 3.27(d,J=7.0Hz,3H), 3.23–3.13(m,2H), 2.96–2.79(m,3H), 2.77–2.62(m,2H) ,2.43(dd,J=10.9,5.6Hz,2H),2.13-2.01(m,2H),1.96(ddq,J=15.1,7.4,3.9,3.3Hz,1H),1.70(d,J=13.5Hz , 2H), 1.38 (td, J = 12.5, 4.4 Hz, 3H). HRMS (ESI) m/z: calculated value C ₇₃ H ₈₄ ClN ₁₂ O ₁₇ S ⁺ [M+H] ⁺ ,1467.5481; measured value, 1467.5463.

Example 223: N-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-( ((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methane Yl)-4'-chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)-1-((2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12,15-pentaoxaoctadecane- 18-amide (SIAIS346187) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS346181) and the intermediate LM (SIAIS151007) prepared according to Scheme 1 were used as 1-((2-(2,6-dioxo) Piperidin-3-yl)-1,3-dioxo-isoindolin-4-yl)amino)-3,6,9,12,15-pentaoxaoctadecane-18-acid preparation Obtain the target compound (SIAIS346187), yellow powder, yield=46%

¹ H NMR(500MHz, methanol-d ₄ )δ8.69(d,J=2.2Hz,1H),8.00(d,J=2.6Hz,1H),7.86(dd,J=9.2,2.2Hz,1H) ,7.63(d,J=8.9Hz,1H),7.54(d,J=2.5Hz,2H),7.50–7.45(m,3H),7.44(d,J=3.5Hz,1H),7.31(d, J = 7.8Hz, 2H), 7.17 (dd, J = 37.8, 8.1 Hz, 1H), 7.04-6.94 (m, 4H), 6.70 (d, J = 8.5 Hz, 1H), 6.41 (d, J = 3.4 Hz, 1H), 6.29 (d, J = 2.3 Hz, 1H), 5.02 (dd, J = 12.7, 5.6 Hz, 1H), 4.50–4.32 (m, 6H), 4.21 (d, J = 45.7 Hz, 1H ), 3.98–3.92(m,2H), 3.73–3.49(m,22H), 3.47–3.37(m,10H), 3.27(d,J=7.0Hz,3H), 3.16(p,J=1.6Hz, 2H), 2.88(d,J=15.7Hz,2H), 2.85–2.79(m,1H), 2.75–2.62(m,2H), 2.42(d,J=5.8Hz,2H), 2.13–2.00(m ,2H),1.94(ddp,J=11.1,7.2,3.6Hz,1H),1.70(d,J=12.7Hz,2H),1.38(td,J=12.5,4.4Hz,3H).HRMS(ESI) m/z: calculated value C ₇₅ H ₈₈ ClN ₁₂ O ₁₈ S ⁺ [M+H] ⁺ , 1511.5743; measured value, 1511.5782. [001298] Example 224: (2S, 4R)-1-((S)- 16-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(((3-nitro- 4-(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methyl)-4'-chloro -[1,1'-Biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)-2-(tert-butyl)-4,13-dioxo-7, 10-Dioxa-3,14-diazahexadecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS346191 )preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS346181) and the intermediate LM (SIAIS151002) prepared according to Scheme 12 were used as 3-(2-(3-(((S)- 1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-di Methyl-1-oxobut-2-yl)amino)-3-oxopropoxy)ethoxy)propionic acid was prepared to obtain the target compound (SIAIS346191), yellow powder, yield=21%

¹ H NMR(500MHz, methanol-d ₄ )δ9.04(s,1H), 8.67(d,J=2.3Hz,1H), 8.02(s,1H), 7.85(dd,J=9.3,2.3Hz, 1H), 7.64 (d, J = 8.9 Hz, 1H), 7.58 (d, J = 2.5 Hz, 1H), 7.54 (t, J = 7.1 Hz, 1H), 7.50-7.43 (m, 6H), 7.40 ( d, J = 8.1 Hz, 2H), 7.31 (s, 2H), 7.21 (dd, J = 29.8, 8.2 Hz, 1H), 7.01 (d, J = 7.2 Hz, 1H), 6.95 (d, J = 9.3 Hz, 1H), 6.75 (d, J = 8.3 Hz, 1H), 6.44 (d, J = 3.4 Hz, 1H), 6.34 (s, 1H), 4.63 (s, 1H), 4.60–4.34 (m, 10H ), 4.27 (s, 1H), 4.20 (s, 1H), 3.95 (dd, J = 11.4, 4.3 Hz, 2H), 3.88 (d, J = 11.0 Hz, 1H), 3.79 (dd, J = 11.0, 3.8Hz,1H), 3.69(t,J=11.0Hz,4H),3.56(d,J=14.9Hz,8H), 3.50–3.36(m,5H), 3.28(d,J＝7.0Hz,2H) , 3.25–3.16 (m, 2H), 2.92 (s, 2H), 2.52-2.44 (m, 8H), 2.23 (dd, J = 13.0, 7.7 Hz, 1H), 2.07 (ddd, J = 13.3, 9.2, 4.4Hz, 1H), 1.95 (ddd, J = 11.3, 9.4, 6.0 Hz, 1H), 1.70 (d, J = 13.1 Hz, 2H), 1.38 (qd, J = 12.2, 4.5 Hz, 3H), 1.03 ( s,9H).HRMS(ESI)m/z: calculated value C ₇₉ H ₉₅ ClN ₁₃ O ₁₅ S ₂ ⁺ [M+H] ⁺ , 1564.6195; measured value, 1564.6237.

Example 225: (2S,4R)-1-((S)-19-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridine-5 -Yl)oxy)-4-(((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)benzene (Yl)piperazin-1-yl)methyl)-4'-chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)-2 -(Tert-butyl)-4,16-dioxo-7,10,13-trioxa-3,17-diazahexadecanoyl)-4-hydroxy-N-(4-(4- (Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (SIAIS346192) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, intermediate BINDER (SIAIS346181) and intermediate LM (SIAIS151003) prepared according to Scheme 12 (S)-15-((2S,4R)-4 -Hydroxy-2-((4-(4-Methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-16,16-dimethyl-13-oxo-4 ,7,10-Trioxa-14-azaheptadecanoic acid was prepared to obtain the target compound (SIAIS346192), yellow powder, yield=54%

¹ H NMR(500MHz, methanol-d ₄ )δ9.20(s,1H), 8.65(d,J=2.3Hz,1H), 8.05(d,J=2.4Hz,1H), 7.86(dd,J= 9.2, 2.3 Hz, 1H), 7.68 (d, J = 2.4 Hz, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 3.3 Hz, 2H), 7.47 (dd, J = 8.0, 4.8 Hz, 4H), 7.42 (d, J = 8.2 Hz, 2H), 7.31 (q, J = 7.2, 5.9 Hz, 2H), 7.25-7.15 (m, 1H), 7.00 (d, J = 7.4 Hz, 1H), 6.97 (d, J = 9.3 Hz, 1H), 6.75 (d, J = 8.7 Hz, 1H), 6.49 (d, J = 3.4 Hz, 1H), 6.37 (s, 1H), 4.63 ( s, 1H), 4.62–4.35 (m, 10H), 4.26 (dd, J = 34.2, 9.4 Hz, 2H), 4.00–3.93 (m, 2H), 3.88 (d, J = 10.9 Hz, 1H), 3.79 (dd,J=11.0,3.9Hz,1H), 3.69(dt,J=12.9,6.8Hz,4H), 3.66–3.51(m,12H), 3.49–3.38(m,5H), 3.29–3.21(m ,4H),2.92(s,2H),2.62–2.42(m,8H),2.27–2.18(m,1H),2.06(ddd,J=19.0,9.6,5.1Hz,1H),1.94(ddp,J = 11.1, 7.1, 3.6 Hz, 1H), 1.75–1.66 (m, 2H), 1.42–1.33 (m, 3H), 1.03 (s, 9H). HRMS (ESI) m/z: calculated value C ₈₁ H ₉₉ ClN ₁₃ O ₁₆ S ₂ ⁺ [M+H] ⁺ , 1608.6457; measured value, 1608.6442.

Example 226: N1-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-( ((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methane (Yl)-4'-chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)-N16-((S)-1 -((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl -1-oxobut-2-yl)-4,7,10,13-tetraoxahexadecane diamide (SIAIS346193) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS346181) and the intermediate LM (SIAIS151008) prepared according to Scheme 12 (S)-18-((2S,4R)-4 -Hydroxy-2-((4-(4-Methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-19,19-dimethyl-16-oxo-4 ,7,10,13-Tetraoxa-17-azaeicosanic acid was prepared to obtain the target compound (SIAIS346193), yellow powder, yield=38%

¹ H NMR (500MHz, methanol-d ₄ ) δ 9.15 (s, 1H), 8.66 (d, J = 2.3 Hz, 1H), 8.05 (s, 1H), 7.86 (dd, J = 9.3, 2.3 Hz, 1H), 7.66 (d, J = 2.2 Hz, 1H), 7.62 (d, J = 8.7 Hz, 1H), 7.54 (d, J = 7.4 Hz, 1H), 7.52-7.44 (m, 5H), 7.42 ( d,J=8.3Hz,2H), 7.32(d,J=7.5Hz,2H), 7.21(dd,J=29.6,8.4Hz,1H), 7.00(d,J=7.3Hz,1H), 6.97( d,J=9.3Hz,1H), 6.75(d,J=8.7Hz,1H), 6.48(d,J=3.4Hz,1H), 6.36(s,1H), 4.64(d,J=7.9Hz, 1H), 4.61–4.34(m,10H), 4.25(d,J=35.5Hz,1H), 3.97–3.92(m,2H), 3.88(d,J=10.8Hz,1H), 3.79(dd,J = 10.9, 3.8 Hz, 1H), 3.71 (qd, J = 13.1, 11.3, 7.0 Hz, 5H), 3.65-3.50 (m, 16H), 3.50-3.37 (m, 6H), 3.27 (t, J = 8.8 Hz, 4H), 2.93 (s, 2H), 2.58-2.44 (m, 8H), 2.22 (dd, J = 13.1, 7.7 Hz, 1H), 2.07 (ddd, J = 13.2, 9.1, 4.3 Hz, 1H) ,1.95(tt,J＝7.3,3.9Hz,1H),1.70(d,J＝11.9Hz,2H),1.38(tt,J＝12.1,6.2Hz,2H),1.03(s,9H).HRMS( ESI) m/z: calculated value C ₈₃ H ₁₀₃ ClN ₁₃ O ₁₇ S ₂ ⁺ [M+H] ⁺ , 1652.6719; measured value, 1652.6704.

Example 227: N1-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-( ((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methane Yl)-4'-chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)-N19-((S)-1 -((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl -1-oxobut-2-yl)-4,7,10,13,16-pentaoxaoctadecane diamide (SIAIS346194)

With reference to the method of Example 1, under appropriate conditions understandable in the art, the intermediate BINDER (SIAIS346181) and the intermediate LM (SIAIS151009) prepared according to Scheme 12 (S)-21-((2S,4R)-4 -Hydroxy-2-((4-(4-Methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-22,22-dimethyl-19-oxo-4 ,7,10,13,16-Pentoxa-20-azatricosanoic acid was prepared to obtain the target compound (SIAIS346194), yellow powder, yield=47%

¹ H NMR(500MHz, methanol-d ₄ )δ9.10(s,1H), 8.66(d,J=2.3Hz,1H), 8.03(s,1H), 7.85(dd,J=9.2,2.3Hz, 1H), 7.63–7.60(m,2H), 7.57–7.51(m,1H), 7.50–7.45(m,5H), 7.41(d,J=8.3Hz,2H),7.32(d,J=5.9Hz ,2H),7.27–7.15(m,1H),7.00(d,J=7.2Hz,1H), 6.96(d,J=9.3Hz,1H), 6.74(d,J=8.1Hz,1H), 6.46 (d,J=3.4Hz,1H),6.34(s,1H),4.64(s,1H),4.59–4.53(m,2H),4.50(dd,J=9.0,4.1Hz,3H),4.47– 4.40 (m, 3H), 4.36 (d, J = 15.5 Hz, 2H), 4.25 (dt, J = 35.8, 9.9 Hz, 2H), 3.98–3.93 (m, 2H), 3.88 (d, J = 11.0 Hz ,1H), 3.79(dd,J=11.0,3.9Hz,1H), 3.76–3.66(m,4H), 3.65–3.51(m,20H), 3.49–3.37(m,5H), 3.28(d,J =7.0Hz,4H), 2.91(s,2H), 2.59–2.53(m,1H), 2.51–2.43(m,7H), 2.26–2.16(m,1H), 2.12–2.00(m,1H), 1.95(dqd,J=11.2,7.3,3.4Hz,1H),1.70(d,J=12.9Hz,2H),1.42-1.32(m,3H),1.03(s,9H).HRMS(ESI)m/ z: Calculated value C ₈₅ H ₁₀₇ ClN ₁₃ O ₁₈ S ₂ ⁺ [M+H] ⁺ , 1696.6981; measured value, 1696.7010.

Example 228: (1S,3R,5S)-N-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl )Oxy)-4-(((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl) Piperazin-1-yl)methyl)-4'-chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)adamantine Alkyl-1-carboxamide (SIAIS360001) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS360001) was prepared using intermediate BINDER (SIAIS346181) and 1-adamantanecarboxylic acid, yellow powder, yield=62%

¹ H NMR(500MHz, methanol-d ₄ )δ8.65(d,J=2.1Hz,1H), 7.98(s,1H), 7.83(d,J=9.1Hz,1H), 7.59(d,J= 8.7Hz, 1H), 7.53 (d, J = 8.6 Hz, 2H), 7.45 (dd, J = 5.4, 3.6 Hz, 3H), 7.31 (d, J = 7.6 Hz, 2H), 7.27–7.16 (m, 1H), 6.99 (d, J = 6.9 Hz, 1H), 6.93 (d, J = 9.2 Hz, 1H), 6.71 (d, J = 8.6 Hz, 1H), 6.41 (d, J = 3.0 Hz, 1H) ,6.30(s,1H),4.57–4.34(m,6H),4.22(d,J=36.5Hz,2H),3.99–3.92(m,2H),3.53(s,3H),3.40(td,J = 11.5, 3.5 Hz, 7H), 3.27 (d, J = 6.8 Hz, 3H), 3.24 (s, 2H), 2.93 (s, 2H), 2.02-1.90 (m, 4H), 1.85 (s, 5H) ,1.78(d,J=2.9Hz,1H),1.75-1.63(m,8H),1.44-1.31(m,2H).HRMS(ESI)m/z: calculated value C ₆₀ H ₆₉ ClN ₉ O ₉ S ⁺ [M+H] ⁺ ,1126.4622; measured value,1126.4649.

Example 229: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((3-((1-(2-(2-(( 1S,3R,5S)-adamantan-1-yl)acetamido)ethyl)azetidin-3-yl)methoxy)-4'-chloro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfon Acyl) benzamide (SIAIS360002) preparation

With reference to the method of Example 1, under appropriate conditions understandable in the art, the target compound (SIAIS360002) was prepared by using intermediate BINDER (SIAIS346181) and 1-adamantane acetic acid, yellow powder, yield=64%

¹ H NMR(500MHz, methanol-d ₄ )δ8.66(d,J=2.3Hz,1H), 7.96(d,J=2.7Hz,1H), 7.82(dd,J=9.2,2.3Hz,1H) ,7.60(d,J=8.9Hz,1H),7.53(t,J=8.1Hz,1H),7.50–7.42(m,4H),7.30(d,J=8.4Hz,2H),7.21(d, J=8.0Hz,1H), 6.99(d,J=7.7Hz,1H), 6.92(d,J=9.3Hz,1H), 6.73–6.67(m,1H), 6.38(d,J=3.4Hz, 1H), 6.27(d,J=2.4Hz,1H),4.55–4.20(m,8H),3.97–3.93(m,2H), 3.60–3.35(m,11H), 3.27(d,J=7.0Hz ,3H),3.22(s,1H),2.94(s,2H),1.96(s,2H),1.88(s,3H),1.69(t,J=12.4Hz,6H),1.57(t,J= 12.7Hz,9H),1.43–1.33(m,2H).HRMS(ESI)m/z: calculated value C ₆₁ H ₇₁ ClN ₉ O ₉ S ⁺ [M+H] ⁺ ,1140.4778; measured value, 1140.4789.

Biological activity detection experiment

material:

RIPA Lysis Solution (Dingguo Company)

PMSF (Dingguo Company)

4×LDS (Thermo Fisher)

Cell TITER GLO Cell Proliferation Detection Kit (Promega)

RPMI1640 (hyclone company)

Fetal Bovine Serum (GIBCO Company)

Penicillin-Streptomycin (penicillin and streptomycin) (GIBCO)

Halt protease and phosphatase inhibitor (Thermo Fisher)

Cell TITER BLUE Detection Kit (Promega)

Cell TITER GLO Detection Kit (Promega)

CCK8 (WST) reagent (Tongjin Institute of Chemistry, Japan)

RPMI1640 (GIBICO company)

Calf serum (GIBICO company)

SuperSignal West Pico Chemiluminescent Substrate (Thermo Fisher)

SuperSignal West Femto Maximum Sensitivity Substrate (Thermo Fisher)

Cycloheximide (Sigma)

Fluorescent peptide FAM-Bim (Shanghai Anchi Biotechnology Co., Ltd.)

Fluorescent peptide FAM-Bax (Shanghai Anchi Biotechnology Co., Ltd.)

Fluorescent peptide FAM-Bad (Shanghai Anchi Biotechnology Co., Ltd.)

BCL-2 Recombinant Protein (Shanghai Anchi Biotechnology Co., Ltd.)

BCL-XL Recombinant Protein (Shanghai Anchi Biotechnology Co., Ltd.)

MCL-1 Recombinant Protein (Shanghai Anchi Biotechnology Co., Ltd.)

Antibody:

Most of the antibodies used in the experiment were purchased from Cell Signaling Technology, including MCL-1 (#94296), BCL-2 (#15071), BCL-w (#2724), BCL-XL (ab178844) and GAPDH antibodies from abcam The company, Tubulin antibody comes from Proteintech.

Cell culture

The cell line used RS4; 11, Molt-4 cells (human acute lymphoblastic leukemia cells), MV4; 11 (human myeloid monocytic leukemia cells), MM1S cells (human myeloma cells), NIH-3T3 cells ( Fibroblasts) and Light II cells can be obtained through commercial channels or purchased from ATCC, and are cultured routinely according to ATCC instructions. The cells used were identified as correct cells by STR cells, and were negative for mycoplasma through routine inspections.

Evaluation of anti-tumor cell proliferation activity in vitro

The compounds of the present disclosure are used for preliminary evaluation of tumor cell growth inhibition rate at single concentration or dual concentration, and IC ₅₀ determination is performed.

Determination of compound half inhibitory concentration (IC ₅₀ )---MTS experiment cell proliferation experiment

1) Research on the compound of the present invention based on ABT199/263 for MCL-1 or BCL-XL-dependent cell proliferation

_{The IC 50 of the} compound of the present invention is determined using Promega's Cell Titer GLO reagent. The specific steps are as follows: cells ^{are seeded in 90 microliters of serum-containing RPMI medium at a number of 1 to 2×10 4} cells/well, and at the same time, the original drug ABT-199/263 and the compound of the present invention are subjected to a concentration gradient After serial dilution to different concentrations, add to the cell suspension. The positive control is set as the original drug ABT199/263, the negative control is set as DMSO, and the positive control and the negative control are treated with the same treatment method as the compound of the present invention. This experiment should be repeated at least three times with 3 replicate holes in each group. After 48 hours of treatment with the compound of the present invention, according to CellTiter

The instructions of AQueous One Solution Cell Proliferation Assay (Promega) use chemiluminescence analyzer T20 (Promega) for detection. Compounds of the invention on cell growth experiments inhibition curves drawn by GraphPad Prism 5.01 software and statistics derived from the compounds of the invention IC _50. The results are shown in Table 3 below.

_{The IC 50 of the} compound of the present invention in the MMIS tumor cell line is determined using Promega's Cell Titer Blue, Cell Titer GLO or WST reagents. The specific steps are as follows: the cells are seeded in 100 microliters of serum-containing RPMI1640 medium at a rate of 15,000 cells/well. On the second day, the original drug and the compound of the present invention were serially diluted and added to the cells. After 72 hours of treatment with the compound of the present invention, the above-mentioned cell viability detection reagent was added to the culture medium for cell viability determination according to the instructions. The negative control is DMSO, and the positive control is the original drug, and the cells are treated in the same manner as the compound of the present invention. The growth inhibition of the compounds of the present invention on cells was plotted by Prism Graphpad software and the IC _{50 of the} compounds of the present invention was calculated from it. The results are shown in Table 4 below.

The compound's inhibition of hedgehog activity IC ₅₀ determination---Dual-luciferase experiment:

Light II cells (American Type Culture Collection) use DMEM (GIBCO) containing 10% (v/v) calf serum (GIBCO), 0.4mg/ml G418 (Sigma), 0.15mg/ml Zeocin (Invitrogen), penicillin/ Streptomycin (Hyclone), 37°C, 5% CO ₂ constant temperature culture. Inoculate 2.5×10 ⁴ cells in a 96-well plate, and then add different concentrations of drugs for 36 hours to terminate the reaction. Follow the instructions of Dual-luciferase reporter assay system (Promega). This experiment should be repeated at least three times with 3 replicate holes in each group.

_{The IC 50} determination of the compound's affinity inhibitory activity on BCL-2, BCL-XL, and MCL-1 proteins---Fluorescence polarization experiment:

Fluorescence polarization method:

Working solution preparation: experimental buffer: 20mM Na ₂ HPO ₄ .12H ₂ O; 20mM NaH ₂ PO ₄ .2H ₂ O; 1mM EDTA; 50mM NaCl; 0.05% PF-68 (Poloxamer 188)

Take a 96-well black reaction plate, add protein and different concentrations of test drugs, and make up with experimental buffer to a final volume of 135μL. After incubating for 10 minutes at room temperature, add 15 μL of the corresponding fluorescent peptide and incubate for 30 minutes at room temperature in the dark, and detect the polarization value at the excitation light/emission light at 480/535nm. This experiment was repeated three times for each group, with three duplicate holes each time.

Western Blot

Tumor cells were seeded into a six-well plate containing 2 mL of culture medium at 3×10 ⁵ -3×10 ^{6 cells/well.} At the same time, the cells are treated with the corresponding concentration of the drug. After 5-12 hours of drug action, the cells were collected and washed with PBS. Place the cells on ice and add RIPA protein lysate containing PMSF protease inhibitor to treat the cells. The lysate was centrifuged at 4°C, 10k rpm for 5 minutes, and the supernatant was collected. Add the same amount of protein to 4×LDS protein loading buffer, β-mercaptoethanol, vortex and mix, heat it in a dry-wet thermostat at 95℃ for 5 minutes after denaturation treatment, store at -80℃ or directly cool for protein electrophoresis . The electrophoresis gel uses 10% self-made polyacrylamide gel. The electrophoresis tank and other related components were purchased from Bio-rad. The electrophoresis conditions were low voltage 80V for 45 minutes, and then converted to high voltage 120V to continue electrophoresis for 1 hour. The transfer membrane uses PVDF membrane, and the transfer membrane system is placed on ice with an isocurrent of 399 mA for one hour. After transferring the membrane, it was sealed with TBST+5% skimmed milk powder at room temperature for 1 hour. The western blot was performed according to the relevant instructions of Cell Signaling Technology, and the specific steps refer to the antibody instructions.

DC ₅₀ (the drug concentration corresponding to protein degradation to 50%) calculation: ImageJ software can be used to read the gray value of the Western blotting band after drug treatment, and fit the relationship curve between drug concentration and gray value to calculate the corresponding The drug concentration range of half the gray value.

Experimental results

The specific experimental data are shown below.

1 The compound of the present invention based on ABT199/263 studies on MCL-1 or /BCL-XL dependent cell proliferation

We conducted dose-dependent experiments on the designed and synthesized compounds of the present invention in RS4;11 cells. The cells are highly sensitive to inhibitors of MCL-1 or BCL-XL. Compounds were treated with different concentrations (100 nM starting, 10-fold dilution gradient, 5 concentrations) for 48 hours, and the cells were detected using MTT reagent (available through a commercially available route). The experiment was repeated more than 3 times, and the specific results are shown in Table 3-1, 3-2, and 3-3.

The compound of the present invention developed based on ABT-199/263 that we designed and developed can well inhibit the proliferation of RS4;11 tumor cells (Table 3-1). _{The IC 50} of ABT-199 on RS4;11 cells is 7.79±2.25 nM, and the compound of the present invention developed by us maintains an inhibitory effect equivalent to that of the original drug ABT-199.

_{Table 3-1 The IC 50} (half inhibitory concentration) of the compounds of the present invention based on the ABT-199/263 series in lymphoma cell lines

Cell line	Test compound	Reagent	IC 50 (nΜ)
RS4; 11	ABT199	MTT	7.79±2.25
RS4; 11	SIAIS230148	MTT	1.931±0.415

RS4; 11	SIAIS230149	MTT	2.031±0.831
RS4; 11	SIAIS230150	MTT	3.414±0.083
RS4; 11	SIAIS230151	MTT	3.887±0.995
RS4; 11	SIAIS230152	MTT	23.122±22.239
RS4; 11	SIAIS230153	MTT	17.148±13.103
RS4; 11	SIAIS230159	MTT	17.342±8.039
RS4; 11	SIAIS230160	MTT	26.956±3.709
RS4; 11	SIAIS230161	MTT	44.997±12.708
RS4; 11	SIAIS230162	MTT	30.792±38.722
RS4; 11	SIAIS230163	MTT	8.248±3.986
RS4; 11	SIAIS230164	MTT	3.09±2.07
RS4; 11	SIAIS230165	MTT	20.555±10.688
RS4; 11	SIAIS230168	MTT	26.197±18.803
RS4; 11	SIAIS230169	MTT	33.262±28.904
RS4; 11	SIAIS230172	MTT	24.246±13.408
RS4; 11	SIAIS230173	MTT	23.885±1.395
RS4; 11	SIAIS255124	MTT	2.388±1.227
RS4; 11	SIAIS255126	MTT	1.535±0.286
RS4; 11	SIAIS255132	MTT	1.569±0.516
RS4; 11	SIAIS255134	MTT	1.464±0.327
RS4; 11	SIAIS255135	MTT	1.214±0.639
RS4; 11	SIAIS255136	MTT	1.671±0.396
RS4; 11	SIAIS255139	MTT	14.958±2.751
RS4; 11	SIAIS255145	MTT	7.211±2.557
RS4; 11	SIAIS255146	MTT	9.818±1.007
RS4; 11	SIAIS255148	MTT	10.451±2.177
RS4; 11	SIAIS255152	MTT	12.546±0.374
RS4; 11	SIAIS255153	MTT	4.983±0.354
RS4; 11	SIAIS255154	MTT	5.53
RS4; 11	SIAIS255155	MTT	11.199±2.046
RS4; 11	SIAIS255156	MTT	8.657±3.175
RS4; 11	SIAIS268024	MTT	0.421±0.102

RS4; 11	SIAIS268027	MTT	0.364±0.199
RS4; 11	SIAIS268178	MTT	1.486±0.179
RS4; 11	SIAIS268179	MTT	1.184±0.403
RS4; 11	SIAIS268180	MTT	1.235±0.337
RS4; 11	SIAIS268181	MTT	2.024±0.413
RS4; 11	SIAIS292026	MTT	0.898±0.267
RS4; 11	SIAIS292027	MTT	1.265±0.569
RS4; 11	SIAIS292113	MTT	1.13±0.19
RS4; 11	SIAIS292114	MTT	3.54±1.71
RS4; 11	SIAIS292115	MTT	31.21
RS4; 11	SIAIS292116	MTT	33.29
RS4; 11	SIAIS268194	MTT	14.71±1.84
RS4; 11	SIAIS346014	MTT	0.59±0.49
RS4; 11	SIAIS346015	MTT	0.40±0.33
RS4; 11	SIAIS346016	MTT	0.70±0.47
RS4; 11	SIAIS346017	MTT	0.53±0.41
RS4; 11	SIAIS346018	MTT	0.93±0.39
RS4; 11	SIAIS346019	MTT	2.92±0.98
RS4; 11	SIAIS346020	MTT	10.30±8.22
RS4; 11	SIAIS346021	MTT	4.68±4.26
RS4; 11	SIAIS315186	MTT	63.88±41.40
RS4; 11	SIAIS361001	MTT	6.02±2.63
RS4; 11	SIAIS361004	MTT	9.02±4.72
RS4; 11	SIAIS361005	MTT	4.94±1.34
RS4; 11	SIAIS361006	MTT	2.76±1.47
RS4; 11	SIAIS361007	MTT	1.36±0.66
RS4; 11	SIAIS361008	MTT	1.14±0.33
RS4; 11	SIAIS361009	MTT	1.3±0.25
RS4; 11	SIAIS361010	MTT	5.35±1.05
RS4; 11	SIAIS361011	MTT	4.05±0.91
RS4; 11	SIAIS361012	MTT	4.22±1.38
RS4; 11	SIAIS361013	MTT	2.03±0.26

RS4; 11	SIAIS361014	MTT	1.29±0.51
RS4; 11	SIAIS361015	MTT	0.72±0.46
RS4; 11	SIAIS361016	MTT	0.96±0.25
RS4; 11	SIAIS361018	MTT	10.05±6.39
RS4; 11	SIAIS361019	MTT	3.97±1.24
RS4; 11	SIAIS361020	MTT	2.83±1.54
RS4; 11	SIAIS361021	MTT	1.26±0.61
RS4; 11	SIAIS361022	MTT	0.55±0.21
RS4; 11	SIAIS361023	MTT	0.44±0.22
RS4; 11	SIAIS361024	MTT	0.34±0.14
RS4; 11	ABT-263	MTT	3.99±0.73
RS4; 11	SIAIS361043	MTT	2.17±0.62
RS4; 11	SIAIS361044	MTT	1.07±0.15
RS4; 11	SIAIS361045	MTT	1.2±0.46
RS4; 11	SIAIS361046	MTT	2.15±0.97
RS4; 11	SIAIS361047	MTT	3.94±2.79
RS4; 11	SIAIS361048	MTT	1.44±0.83
RS4; 11	SIAIS361049	MTT	1.75±0.96
RS4; 11	SIAIS361026	MTT	+
RS4; 11	SIAIS361027	MTT	+
RS4; 11	SIAIS361028	MTT	+
RS4; 11	SIAIS361029	MTT	+
RS4; 11	SIAIS361030	MTT	+
RS4; 11	SIAIS361031	MTT	+
RS4; 11	SIAIS361032	MTT	+
RS4; 11	SIAIS361056	MTT	+
RS4; 11	SIAIS361057	MTT	+
RS4; 11	SIAIS361058	MTT	+
RS4; 11	SIAIS361059	MTT	+
RS4; 11	SIAIS361060	MTT	+
RS4; 11	SIAIS361061	MTT	+
RS4; 11	SIAIS361062	MTT	+

RS4; 11	SIAIS361034	MTT	+
RS4; 11	SIAIS361035	MTT	+
RS4; 11	SIAIS361036	MTT	+
RS4; 11	SIAIS361037	MTT	+
RS4; 11	SIAIS361038	MTT	+
RS4; 11	SIAIS361039	MTT	+
RS4; 11	SIAIS361040	MTT	+
RS4; 11	SIAIS346183	MTT	+
RS4; 11	SIAIS346184	MTT	+
RS4; 11	SIAIS346185	MTT	+
RS4; 11	SIAIS346186	MTT	+
RS4; 11	SIAIS346187	MTT	+
RS4; 11	SIAIS346191	MTT	+
RS4; 11	SIAIS346192	MTT	+
RS4; 11	SIAIS346193	MTT	+
RS4; 11	SIAIS346194	MTT	+
RS4; 11	SIAIS360001	MTT	++
RS4; 11	SIAIS360002	MTT	++
RS4; 11	SIAIS292030	MTT	4.14±3.61
RS4; 11	SIAIS292031	MTT	1.37±0.70
RS4; 11	SIAIS292032	MTT	1.22±0.73
RS4; 11	SIAIS292033	MTT	4.61±1.81
RS4; 11	SIAIS292034	MTT	7.01±8.25
RS4; 11	SIAIS292035	MTT	3.97±2.09
RS4; 11	SIAIS292036	MTT	3.45±4.43
RS4; 11	SIAIS292037	MTT	3.34±1.70
RS4; 11	SIAIS292038	MTT	8.41±5.28
RS4; 11	SIAIS292039	MTT	13.68±8.43
RS4; 11	SIAIS268174	MTT	+
RS4; 11	SIAIS268163	MTT	+
RS4; 11	SIAIS268164	MTT	+
RS4; 11	SIAIS268165	MTT	+

RS4; 11	SIAIS268166	MTT	+
RS4; 11	SIAIS268167	MTT	+
RS4; 11	SIAIS268168	MTT	+
RS4; 11	SIAIS268169	MTT	+
RS4; 11	SIAIS292028	MTT	+
RS4; 11	SIAIS268170	MTT	+
RS4; 11	SIAIS268171	MTT	+
RS4; 11	SIAIS292021	MTT	++
RS4; 11	SIAIS292024	MTT	++
RS4; 11	SIAIS292025	MTT	++
RS4; 11	SIAIS292040	MTT	++
RS4; 11	SIAIS292041	MTT	++
RS4; 11	SIAIS292042	MTT	++
RS4; 11	SIAIS292043	MTT	++
RS4; 11	SIAIS292044	MTT	++
RS4; 11	SIAIS292045	MTT	++

Attachment: "+" means IC ₅₀ >100nM, "++" means 10nM<IC ₅₀ <100nM

Table 3-2 Preliminary screening of the activity of the compounds of the present invention based on the ABT-199/263 series in RS4; 11 (human acute lymphoblastic leukemia)

Table 3-3 Preliminary screening of the activity of the compounds of the present invention based on the ABT-199/263 series in RS4; 11 (human acute lymphoblastic leukemia)

Compound	Inhibition rate at 100nM	Inhibition rate at 10nM
SIAIS255138	87.41%	35.09%
SIAIS255139	94.90%	55.01%
SIAIS255144	96.96%	28.79%
SIAIS255141	91.08%	15.39%
SIAIS255142	71.73%	20.99%
SIAIS255143	62.67%	19.21%
SIAIS255145	95.98%	59.10%
SIAIS255146	96.62%	69.97%
SIAIS255147	93.58%	31.59%
SIAIS255148	93.43%	70.18%
SIAIS255149	88.24%	28.69%

SIAIS255150	90.89%	19.91%
SIAIS255151	96.08%	34.93%
SIAIS255152	97.50%	64.96%
SIAIS255153	97.01%	76.64%
SIAIS255154	96.28%	63.02%
SIAIS255155	92.41%	86.22%
SIAIS255156	88.54%	81.65%
SIAIS255157	91.18%	43.81%
SIAIS255158	91.23%	16.47%
SIAIS255159	93.48%	51.45%
SIAIS255160	90.34%	14.52%
SIAIS255161	89.92%	-0.40%
SIAIS255162	88.27%	58.29%

The compound of the present invention developed based on ABT-199 that we designed and developed can well inhibit the proliferation of multiple myeloma cell line MM1S (Table 4). The half-killing dose of ABT-199 on MM1S cells is 6670±1982.58nM. The compound of the present invention developed by us is superior to the original drug ABT-199 in inhibiting effect.

_{Table 4 IC 50} (nM, half inhibitory concentration) of the compounds of the present invention based on the ABT-199 series in myeloma cells

Cell line	Test compound	Reagent	IC 50 (nM)
MM1S	ABT-199	MTT	6670±1982.58
MM1S	AZD5991	MTT	445.547±523.509
MM1S	SIAIS255124	MTT	66.06±20.395
MM1S	SIAIS255126	MTT	67.733±17.92
MM1S	SIAIS292026	MTT	35.18±30.367
MM1S	SIAIS268178	MTT	4.279±1.742
MM1S	SIAIS268179	MTT	10.141±4.564
MM1S	SIAIS255135	MTT	53.64±25.459
MM1S	SIAIS255136	MTT	41.627±27.923
MM1S	SIAIS292027	MTT	26.767±26.521
MM1S	SIAIS268180	MTT	38.547±11.505
MM1S	SIAIS268181	MTT	88.393±27.009
MM1S	SIAIS268194	MTT	29.697±14.417

The compound of the present invention developed based on ABT-199/263 that we designed and developed can well inhibit the proliferation of myeloid monocytic leukemia cells MV4;11 (Table 5). _{The IC 50} of ABT-199 on MV4; 11 cells is 20.57±2.25nM, and the half-killing dose of ABT-263 on MV4; 11 cells is 34.1±10.95. The inhibitory effect of the compound of the present invention developed by us based on ABT199 is better than that of the original drug ABT -199, the inhibitory effect of the compound of the present invention developed based on ABT263 is equivalent to that of the original drug ABT-199.

_{Table 5 IC 50} (nM, half inhibitory concentration) of the compounds of the present invention based on the ABT-199/263 series in myeloid monocytic leukemia cells

Cell line	Test compound	Reagent	IC 50 (nM)
MV4; 11	MIK 665	MTT	3.9±2.28
MV4; 11	AMG 176	MTT	417.51±175.22
MV4; 11	AZD5991	MTT	68.13±44.38
MV4; 11	ABT-199	MTT	20.57±2.25
MV4; 11	SIAIS255124	MTT	4.72±4.56
MV4; 11	SIAIS255126	MTT	4.55±3.21
MV4; 11	SIAIS255135	MTT	8.98±13.54
MV4; 11	SIAIS255136	MTT	8.39±11.32
MV4; 11	SIAIS268178	MTT	4.75±1.64
MV4; 11	SIAIS268179	MTT	8.83±2.27
MV4; 11	SIAIS268180	MTT	5.16±1.73
MV4; 11	SIAIS268181	MTT	6.33±1.19
MV4; 11	SIAIS292026	MTT	3.15±1.12
MV4; 11	SIAIS292027	MTT	2.82±2.54
MV4; 11	SIAIS292113	MTT	4.48±2.48
MV4; 11	SIAIS292114	MTT	4.3±1.29
MV4; 11	SIAIS268024	MTT	8±4.34
MV4; 11	SIAIS268027	MTT	2.18±1.03
MV4; 11	SIAIS346014	MTT	1.39±0.4
MV4; 11	SIAIS346015	MTT	1.64±0.55
MV4; 11	SIAIS346016	MTT	1.91±1.05
MV4; 11	SIAIS346017	MTT	1.9±0.4
MV4; 11	SIAIS346018	MTT	2.1±0.28
MV4; 11	SIAIS346019	MTT	8.47±4.89
MV4; 11	SIAIS346020	MTT	34.25±29.97
MV4; 11	SIAIS346021	MTT	31.11±22.36
MV4; 11	SIAIS315186	MTT	382.72±636.94

MV4; 11	SIAIS361005	MTT	25.25±2.7
MV4; 11	SIAIS361006	MTT	19.93±0.66
MV4; 11	SIAIS361007	MTT	26.73±16.53
MV4; 11	SIAIS361008	MTT	97.11±80.38
MV4; 11	SIAIS361009	MTT	59.29±36.24
MV4; 11	SIAIS361010	MTT	43.45±16.54
MV4; 11	SIAIS361011	MTT	59.96±34.78
MV4; 11	SIAIS361012	MTT	44.03±5.48
MV4; 11	SIAIS361013	MTT	70.37±50.51
MV4; 11	SIAIS361014	MTT	145.6±107.61
MV4; 11	SIAIS361015	MTT	41.58±3.8
MV4; 11	SIAIS361016	MTT	78.93±52.54
MV4; 11	SIAIS361019	MTT	17.94±6.25
MV4; 11	SIAIS361020	MTT	21.12±13.65
MV4; 11	SIAIS361021	MTT	12.8±6.28
MV4; 11	SIAIS361022	MTT	23.39±3.86
MV4; 11	SIAIS361023	MTT	19.59±8.41
MV4; 11	SIAIS361024	MTT	44.23±28.25
MV4; 11	ABT263	MTT	34.1±10.95
MV4; 11	SIAIS361043	MTT	49.8±21.5
MV4; 11	SIAIS361044	MTT	40.75±1.08
MV4; 11	SIAIS361045	MTT	126.02±31.05
MV4; 11	SIAIS361046	MTT	490.37±246.77
MV4; 11	SIAIS361047	MTT	388.54±87.75
MV4; 11	SIAIS361048	MTT	69.1±34.36
MV4; 11	SIAIS361049	MTT	53.82±10.95

The compound of the present invention developed based on ABT-199/263 that we designed and developed can well inhibit the proliferation of human acute lymphoblastic leukemia cells Molt-4 (Table 7-1, 7-2, 7-3, 8). The inhibitory effect of the compound of the present invention developed by us based on ABT199/263 is significantly better than that of the original drug.

Table 7-1 Preliminary screening of anti-proliferation experimental activity of the compounds of the present invention based on the ABT-199/263 series in acute lymphoblastic leukemia cells Molt-4

Table 7-2 Preliminary screening of the anti-proliferation experimental activity of the compounds of the present invention based on the ABT-199/263 series in the acute lymphoblastic leukemia cell Molt-4

Table 7-3 Preliminary screening of anti-proliferation experimental activity of the compounds of the present invention based on the ABT-199/263 series in Molt-4 of acute lymphoblastic leukemia cells

_{Table 8 IC 50} (nM, half inhibitory concentration) of the compounds of the present invention based on the ABT-199/263 series in Molt-4 of acute lymphoblastic leukemia cells

Cell line	Test compound	Reagent	IC 50 (nM)
Molt-4	SIAIS363021	MTT	1.33±0.82
Molt-4	SIAIS363022	MTT	1.02±0.49
Molt-4	SIAIS363025	MTT	0.67±0
Molt-4	SIAIS363026	MTT	1.08±0.44
Molt-4	SIAIS363034	MTT	0.2±0.14
Molt-4	SIAIS363035	MTT	0.13±0.07
Molt-4	SIAIS363036	MTT	0.15±0.08
Molt-4	SIAIS363037	MTT	2.4±1.06
Molt-4	SIAIS363038	MTT	1.58±0.74
Molt-4	SIAIS268027	MTT	9.61±1.45
Molt-4	SIAIS364048	MTT	0.53±0.31
Molt-4	SIAIS364049	MTT	0.33±0.13
Molt-4	SIAIS364051	MTT	2.73±0.16
Molt-4	SIAIS364056	MTT	2.33±1.76

Molt-4	SIAIS364057	MTT	4.54±2.04
Molt-4	DT2216	MTT	74.49±20.34

_{The IC 50 of the} compound of the present invention based on ABT199 to inhibit Hedgehog (Hh) signaling pathway activity inhibition:

We designed and developed the compounds of the present invention based on ABT-199 to inhibit Hedgehog (Hh) signaling pathway screening (Table 9-1, 9-2, 10). We can achieve the inhibitory concentration IC ₅₀ 10nM or less based on the compound of the present invention ABT199 developed (e.g. SIAIS255126, SIAIS255134, SIAIS268027, SIAIS292113 etc.) half.

Table 9-1. Preliminary Screening of Hedgehog Activity Inhibition Experiment of Compounds of the Invention Based on ABT-199 Series in Light II Cells

Table 9-2. Preliminary Screening of Hedgehog Activity Inhibition Experiments of the Compounds of the Invention Based on ABT-199 Series in Light II Cells

Compound name	Inhibition rate of 1000nM	Inhibition rate at 300nM
SIAIS361005	94.41%	104.65%
SIAIS361006	95.76%	101.95%
SIAIS361007	91.96%	97.77%
SIAIS361008	86.63%	106.00%
SIAIS361009	90.77%	78.18%
SIAIS361010	80.68%	92.55%
SIAIS361011	70.44%	90.81%
SIAIS361012	79.99%	77.63%
SIAIS361013	86.25%	92.18%
SIAIS361014	88.65%	93.65%
SIAIS361015	78.42%	88.29%
SIAIS361016	78.31%	88.39%
SIAIS361019	58.41%	72.88%
SIAIS361020	67.71%	76.87%
SIAIS361021	71.63%	87.80%
SIAIS361022	64.23%	71.64%
SIAIS361023	71.61%	75.57%
SIAIS361024	69.61%	63.02%
SIAIS361043	92.60%	90.56%

SIAIS361044	96.94%	98.21%
SIAIS361045	93.02%	100.72%
SIAIS361046	63.89%	94.13%
SIAIS361047	95.51%	105.16%
SIAIS361048	107.28%	113.06%
SIAIS361049	106.03%	95.48%
ABT263	108.39%	108.67%
ABT199	102.39%	110.97%

_{Table 10. IC 50} (nM, half inhibitory concentration) of the compounds of the present invention based on the ABT-199 series in Light II cells

cell	Compound number	experimental method	IC 50 /nM
LightII	ABT-199	Dual-luciferase assay	140.17±68.5
LightII	SIAIS230164	Dual-luciferase assay	50.51±32.02
LightII	SIAIS255124	Dual-luciferase assay	55.86±33.38
LightII	SIAIS255126	Dual-luciferase assay	3.89±3
LightII	SIAIS255134	Dual-luciferase assay	2.98±2.64
LightII	SIAIS255136	Dual-luciferase assay	65.49±45.24
LightII	SIAIS268024	Dual-luciferase assay	91.04±52.41
LightII	SIAIS268027	Dual-luciferase assay	6.14±1.62
LightII	SIAIS292113	Dual-luciferase assay	8.91±1.73
LightII	SIAIS346014	Dual-luciferase assay	12.7±5.35
LightII	SIAIS361005	Dual-luciferase assay	106.21
LightII	SIAIS361006	Dual-luciferase assay	76.66
LightII	ABT263	Dual-luciferase assay	22.76
LightII	SIAIS361043	Dual-luciferase assay	12.96
LightII	SIAIS361044	Dual-luciferase assay	149.84
LightII	SIAIS361048	Dual-luciferase assay	187.06
LightII	SIAIS361049	Dual-luciferase assay	29.96

Study on the inhibitory activity of the compounds of the present invention based on ABT199 on BCL-2, BCL-XL, and MCL-1:

The compound of the present invention we designed and developed based on ABT-199 maintains the inhibitory activity on BCL-2 protein, the inhibitory activity on BCL-XL protein is significantly weaker than BCL-2, and the inhibitory activity on MCL-1 protein is weaker ( Table 11).

Table 11. Study on the affinity of the compounds of the present invention based on the ABT-199 series to BCL-2/BCL-XL/MCL-1 in the fluorescence polarization experiment

3 The compound of the present invention based on ABT199 can effectively reduce the protein level of MCL-1 in the cell

RS4;11 cells were seeded at ^{3×10 6 cells per well.} The cells were treated with a drug concentration of 10 nM on the second day, and DMSO was selected for the control group. Collect protein samples after 5 hours to detect the total amount of BCL-2, MCL-1, and BCL-xL proteins by western blot. The results show that ABT-199 cannot degrade Mcl-1 protein. ABT-199 has no obvious effect on the degradation of MCL-1 protein, and the concentration of 5nM has no obvious effect on MCL-1 protein, and the level of MCL-1 protein does not significantly decrease (Figure 1). However, after using the compound of the present invention, the total amount of MCL-1 protein was significantly reduced. For example, the compounds developed in the present invention, such as SIAIS255124, SIAIS255126, SIAIS255135, SIAIS255136, SIAIS268178, SIAIS268179, SIAIS268180, SIAIS268181, SIAIS292026, SIAIS292027, etc., can reduce the level of MCL-1 protein at a concentration of about 10 nM and can significantly degrade MCL. -1 protein expression.

4 The compounds of the present invention based on ABT199/263 can effectively degrade RS4; 11 protein levels of MCL-1 and BCL-XL in cells

RS4;11 cells were seeded into a 6-well plate at a rate of 3×10 ^{6 cells per well.} On the second day, the cells were treated with a drug concentration of 50 nM, and DMSO was selected for the control group. Collect protein samples after 8 hours, and detect the total amount of BCL-2, MCL-1, and BCL-XL protein. The results show that after using the compound of the present invention, the total amount of MCL-1 protein has been significantly reduced, such as the compounds SIAIS361022 and SIAIS361023 developed by the present invention (as shown in Figure 3); the total amount of BCL-XL protein has been significantly reduced, such as the present invention. The compounds SIAIS361022, SIAIS361023, SIAIS361043, SIAIS361044, SIAIS361048, SIAIS361049, etc. developed by the invention can reduce BCL-XL protein levels at a concentration of about 50 nM (as shown in Figure 3).

5 The compounds of the present invention based on ABT199/263 can effectively reduce the protein levels of MCL-1 and BCL-XL in Molt-4 cells

Molt-4 cells were seeded in 6-well plates at ^{3×10 6 cells per well.} On the second day, the cells were treated with the test drug concentration of 10 nM, and DMSO was selected for the control group. The drug was terminated for 12 hours, and there was no cell death at the end. The protein samples were collected and the total amount of BCL-2, MCL-1, and BCL-XL protein was detected. The results showed that after using the compound of the present invention, the total amount of BCL-XL protein was significantly reduced. As shown in Figure 4, the compounds developed in the present invention, such as compounds SAIS363021, SIAIS363022, SIAIS363025, SIAIS363026, SIAIS363037, SIAIS363038, SIAIS364048, SIAIS364049, SIAIS364051, SIAIS364056, and SIAIS364057 can significantly degrade BCL-XL protein, of which DT2216 (CAS No. 2361172) 42-3) is a BCL-XL degradation agent reported in the literature, and SIAIS364041 is a low-activity compound. Compared with DT2216, the compound of the present invention has obvious advantages in protein degradation.

In vitro studies have also proved that the compound of the present invention can significantly degrade MCL-1 and BCL-XL proteins in Molt-4 cells, MV4; 11 cells, and NIH-3T3 cells. As shown in Figure 5, the compounds SIAIS346014 (DC ₅₀ : <1 nM), SIAIS268027 (DC ₅₀ : 9.73 nM), SIAIS292113 (DC ₅₀ : <10 nM), and SIAIS255134 (DC ₅₀ : 5.24 nM) were shown in Molt-4 cells Obviously degrade BCL-XL protein. In Molt-4 cells, the compounds SIAIS346014 (DC ₅₀ : 5.02 nM) and SIAIS292113 (DC ₅₀ : <10 nM) also showed a significant effect of degrading MCL-1 protein. The compound SIAIS268027 (DC ₅₀ : 12.47 nM) also showed a significant effect of degrading BCL-XL protein in MV4;11 cells. Compounds SIAIS346014 (DC ₅₀ : 12.47 nM) and SIAIS292113 (DC ₅₀ : 16.82 nM) also showed significant effect of degrading BCL-XL protein in NIH-3T3 cells.

It should be understood that although the present disclosure has been described in detail in conjunction with the above-mentioned embodiments for the purpose of clear understanding, it is obvious that certain changes and modifications can be made within the scope of the claims. Therefore, the embodiments of the present disclosure should be regarded as illustrative rather than limiting the scope of the present disclosure, and the present disclosure is not limited to the embodiments shown and described herein.

Claims (84)

1. The compound of formula (I) or its salt, enantiomer, stereoisomer, solvate, polymorph,

   R ¹ -A ¹ -LIN-A ² -R ² (I)

   Where R ¹ means:

   

   A ¹ does not exist or represents a carbonyl group;

   A ² does not exist or represents a carbonyl group;

   R ² represents the structural formula of formula (I-1) or formula (I-2):

   

   Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl; and

   LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The group consisting of interrupted groups, where when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1), wherein the R ³ group represents Ethynylene or vinylene;

   But the following compounds are excluded, among them:

   R ¹ means:

   

   A ¹ does not exist or represents a carbonyl group;

   LIN represents a substituted or unsubstituted linear or branched alkylene group interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof;

   A ² does not exist or represents a carbonyl group; and

   R ² represents the structural formula of formula (I-1) or formula (I-2):

   

   Where X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), and R ⁴ represents H.
2. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 1, which does not include the following compounds:

   In formula (I), R ¹ represents:

   

   A ¹ does not exist or represents a carbonyl group;

   LIN represents a substituted or unsubstituted linear or branched alkylene group; and

   A ² does not exist or represents a carbonyl group, and R ² represents the structural formula of formula (I-1):

   

   Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), wherein R ⁴ represents H or C _1-3 alkyl;

   or

   A ² represents a carbonyl group, and R ² represents the structural formula of formula (I-2):

   
3. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 1, wherein

   R ¹ means:

   

   A ¹ does not exist or represents a carbonyl group;

   A ² does not exist or represents a carbonyl group;

   R ² represents the structural formula of formula (I-1):

   

   Wherein X represents CH ₂ or CO, and R ³ represents S, ethynylene or vinylene; and

   LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The group consisting of interrupted groups, where when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1), wherein the R ³ group represents Ethynylene or vinylene.
4. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 1, wherein

   R ¹ means:

   

   A ¹ does not exist or represents a carbonyl group;

   LIN represents a substituted or unsubstituted linear or branched alkylene group; and

   A ² does not exist or represents a carbonyl group, and R ² represents the structural formula of formula (I-1):

   

   Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), wherein R ⁴ represents H or C _1-3 alkyl, and;

   or

   A ² does not exist, and R ² represents the structural formula of formula (I-2):

   
5. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 1, wherein

   R ¹ means:

   

   A ¹ does not exist or represents a carbonyl group;

   A ² does not exist or represents a carbonyl group; and

   R ² represents the structural formula of formula (I-1) or formula (I-2):

   

   Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl; and

   LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The group consisting of interrupted groups, where when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1), wherein the R ³ group represents Ethynylene or vinylene.
6. The compound of formula (I) according to claim 1 or 2, or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof, wherein

   R ¹ means:

   

   A ¹ does not exist or represents a carbonyl group;

   A ² does not exist or represents a carbonyl group, and R ² represents the structural formula of formula (I-1):

   

   Wherein X represents CH ₂ or CO, and R ³ represents S, ethynylene or vinylene; and

   LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The groups of the composition group are interrupted, where when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and the R ³ group represents an ethynylene group or a vinylene group.
7. The compound of formula (I) according to claim 1 or 2, or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof, wherein

   R ¹ means:

   

   A ¹ does not exist or represents a carbonyl group;

   A ² does not exist, and R ² represents the structural formula of formula (I-2)

   

   as well as

   LIN represents a substituted or unsubstituted linear or branched alkylene group.
8. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 1, wherein

   R ¹ means:

   

   A ¹ does not exist or represents a carbonyl group;

   A ² does not exist or represents a carbonyl group;

   R ² represents the structural formula of formula (I-1) or formula (I-2):

   

   Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl; and

   LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The group consisting of interrupted groups, where when LIN is not present, one of A ¹ and A ² is not present and the other represents a carbonyl group, and R ² represents the structural formula of formula (I-1), wherein the R ³ group represents Ethynylene or vinylene.
9. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 1, wherein

   R ¹ means:

   

   A ¹ does not exist or represents a carbonyl group;

   A ² does not exist or represents a carbonyl group;

   R ² represents the structural formula of formula (I-1) or formula (I-2):

   

   Wherein X represents CH ₂ or CO, R ³ is absent or represents N(R ⁴ ), S, ethynylene or vinylene, and R ⁴ represents H or C _1-3 alkyl; and

   LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof. The group is interrupted.
10. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 1, 2, 5, 8 or 9, wherein

    R ² means:

    

    
11. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 4, wherein

    R ² means:

    
12. The compound of formula (I) according to claim 3 or 6, or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof, wherein

    R ² means:

    
13. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to any one of claims 1-9-, wherein LIN represents substituted or unsubstituted Straight or branched C _1-30 alkylene, the substituent is selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, alkoxy, alkylamino, haloalkyl, cyano Or any combination thereof.
14. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 13, wherein LIN represents a substituted or unsubstituted group of the following:

    -CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) ₇ -; -(CH ₂ ) ₈ -; -(CH ₂ ) ₉ -; -(CH ₂ ) ₁₀ -; -(CH ₂ ) ₁₁ -; -(CH ₂ ) ₁₂ -; -(CH ₂ ) _13- ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl, alkoxy, alkylamino, haloalkyl, cyano or any combination thereof.
15. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to any one of claims 1-3, 5, 6 or 8-9, wherein LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group is optionally interrupted by one or more oxygens, and wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halo, aryl, alkoxy, alkylamino, haloalkyl, cyano, or any combination thereof.
16. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 15, wherein LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -,-(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _{a3 , R a4, R a5, R} a6, R a7, R a8, R a9, R a10 each independently represent H, C ₁ - ₃ alkyl, hydroxy, amino, mercapto, halo, aryl, alkoxy, _{R a1} , R _a2 , R _a3 , and R _{a4 are} not H at the same time, or R _a5 , R _a6 , R _a7 , R when in the same LIN. _a8 , R _a9 , and R _{a10 are} not H at the same time; and

    n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.
17. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 15, wherein LIN represents a substituted or unsubstituted group of the following:

    -CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₄ -( O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -( O(CH ₂ ) ₃ ) _2- , -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH ₂ -, -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH _2- O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -( O(CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH _2- O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl , Amino, mercapto, halogen, aryl, alkoxy, alkylamino, haloalkyl, cyano or any combination thereof.
18. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to any one of claims 1-3, 5-6 and 8-9, wherein LIN represents a substituted or unsubstituted linear or branched C _2-30 alkylene group, wherein the C _2-30 alkylene group is optionally substituted by one or more heteroatoms selected from O, N and S The optionally substituted heterocyclylene is interrupted, wherein the substituents of the C _2-30 alkylene and heterocyclylene are each independently selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl Group, alkoxy group, alkylamino group, haloalkyl group, cyano group, or any combination thereof.
19. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 18, wherein LIN represents -(CH ₂ ) _{n7 -heterocyclylene-} (CH ₂ ) _n8 -, where n7 and n8 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkyl Substituents of amino, haloalkyl, cyano or any combination thereof are substituted.
20. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 18, wherein the heterocyclylene is azetidinyl, Oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinylene, imidazolylidene, pyrazolidinylene, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, Furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, tetrahydrothiopyranyl, oxazolidinyl, oxazolylidene, isoxazolylidene, oxadiazolylidene , Thiazolylidene, thiazolylidene, isothiazolylidene, thiadiazolylidene, piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, sub Morpholinyl, thiomorpholinyl or dioxanyl, wherein the heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aromatic Substituents are substituted by the group, C _1-3 alkoxy, alkylamino, haloalkyl, cyano, or any combination thereof.
21. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 18, wherein LIN represents -(CH ₂ ) _n7 -piperidinylene- (CH ₂ ) _n8 -, where n7 and n8 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; wherein the piperidinylene group is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkyl Substituents of amino, haloalkyl, cyano or any combination thereof are substituted.
22. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 21, wherein LIN represents -CH ₂ -piperidinylene -CH _2- , - (CH _{2) 2} - piperidyl alkylene -CH ₂ -, - CH ₂ - alkylene-piperidyl _{- (CH 2) 2 -,} - (CH 2) 2 - alkylene-piperidyl - (CH _{2) 2} -, -(CH ₂ ) ₂ -piperidinylene -(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperidinylene -(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperidinylene Group -(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperidinylene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -piperidinylene-(CH ₂ ) ₃ -.
23. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 18, wherein LIN represents -(CH ₂ ) _n7 -piperazinylidene- (CH ₂ ) _n8 -, where n7 and n8 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; wherein the piperazinylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkyl Substituents of amino, haloalkyl, cyano or any combination thereof are substituted.
24. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 23, wherein LIN represents -(CH ₂ ) ₂ -piperazinylidene- CH ₂ -, - CH ₂ - piperazinyl alkylene -CH ₂ -, - CH ₂ - piperazinyl alkylene _{- (CH 2) 2 -,} - (CH 2) 2 - piperazinyl alkylene - (CH _{2) 2} -, -(CH ₂ ) ₂ -piperazinylidene -(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperazinylidene -(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -piperazinide -(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -piperazinylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -piperazinylidene-(CH ₂ ) ₃ -, or- (CH ₂ ) ₄ -piperazinylidene-(CH ₂ ) ₄ -.
25. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 18, wherein LIN represents -(CH ₂ ) _n7 -triazolylidene- (CH ₂ ) _n8 -, where n7 and n8 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; wherein the triazole group is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkyl Substituents of amino, haloalkyl, cyano or any combination thereof are substituted.
26. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 25, wherein LIN represents -CH ₂ -triazolylidene -CH _2- , -CH ₂ -triazolylidene-(CH ₂ ) ₂ -, -CH ₂ -triazolylidene-(CH ₂ ) ₃ -, -CH ₂ -triazolylidene-(CH ₂ ) ₄ -,- (CH ₂ ) ₂ -triazolylidene-CH ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -triazolylidene-(CH ₂ ) ₄ -, -(CH ₂ ) ₃ -triazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) _{3 -triazolylidene} Azolyl -(CH ₂ ) ₄ -or -(CH ₂ ) ₄ -triazolylidene-(CH ₂ ) ₂ -.
27. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 18, wherein LIN represents -(CH ₂ ) _n7 -imidazolylidene-( CH 2) _n8 -, where n7 and n8 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, _{16, 17, 18} , 19 or 20; wherein the imidazole group is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkylamino, Substituents of haloalkyl, cyano or any combination thereof are substituted.
28. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 27, wherein LIN represents -CH ₂ -imidazolylidene -CH ₂ -, -CH ₂ -imidazolylidene-(CH ₂ ) ₂ -, -CH ₂ -imidazolylidene-(CH ₂ ) ₃ -, -CH ₂ -imidazolylidene-(CH ₂ ) ₄ -, -(CH ₂ ) ₂ -imidazolylidene-CH ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -imidazolylidene-(CH ₂ ) ₄ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -imidazolylidene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -imidazolylidene-(CH ₂ ) ₂ -.
29. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 18, wherein LIN represents -(CH ₂ ) _n7 -pyrazolylidene- (CH ₂ ) _n8 -, where n7 and n8 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; wherein the pyrazolylene group is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkyl Substituents of amino, haloalkyl, cyano or any combination thereof are substituted.
30. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 29, wherein LIN represents -CH ₂ -pyrazolylidene -CH _2- , -CH ₂ -Pyrazolylene-(CH ₂ ) ₂ -, -CH ₂ -Pyrazolylene-(CH ₂ ) ₃ -, -CH ₂ -Pyrazolylene-(CH ₂ ) ₄ -,- (CH ₂ ) ₂ -Pyrazolylene-CH ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -Pyrazolylene-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -Pyrazolylene -(CH ₂ ) ₄ -, -(CH ₂ ) ₃ -Pyrazolylene -(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -Pyrazolylene Oxazolyl -(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -pyrazolylene-(CH ₂ ) ₄ -, or -(CH ₂ ) ₄ -pyrazolylene-(CH ₂ ) ₂ -.
31. The compound of formula (I) according to claim 1 or 2, or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof, which is selected from the group consisting of:

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2-(2,6 -Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)aminoacetyl)piperidin-4-yl)methyl)amino)-3-nitrobenzene (B) sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propionyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyryl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentanoyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)piperidin-4-yl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)acetyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)propionyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)butyryl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)pentanoyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)hexanoyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)heptanoyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)acetyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propionyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyryl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentanoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexanoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptanoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethoxy)acetyl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethoxy)ethoxy)acetyl)piperidine -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethoxy)ethoxy)ethoxy ((R)acetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(17-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)-3,6,9,12,15-pentaoxahexadecanoyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(14-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-3,6,9,12-tetraoxatetradecanoyl)piperidine -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethoxy)acetyl)piperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethoxy)ethoxy)acetyl )Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethoxy)ethoxy )Ethoxy)acetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(17-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)-3,6,9,12,15-pentaoxa 17 Alkanoyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(14-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)-3,6,9,12-tetraoxatetradecanoyl )Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)propyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)butyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)pentyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)hexyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)heptyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethoxy)ethyl)piperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)propoxy)ethyl)piperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethoxy)ethoxy)ethyl )Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)ethoxy)ethyl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propoxy)ethyl)piperidin-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethoxy)ethoxy)ethyl)piperidine -4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2-(2,6 -Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)aminoacetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfon Acyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)propionyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)butyryl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentanoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)hexanoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)heptanoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)dec-9-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)undec-10-yn-1-yl)piperidin-4-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hept-6-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)dec-9-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)undec-10-yn-1-yl)piperidin-4-yl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)oxy) Ethoxy)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy) Ethoxy)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl) (Oxy)ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hexyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfon Acyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)heptyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)octyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)nonyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)ethyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)propyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)butyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pentyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hexyl)piperidin-4-yl)methyl)amino)-3-nitrobenzene (B) sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)heptyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)octyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)nonyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hexyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfon Acyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)heptyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)octyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)nonyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)ethyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)propyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)butyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pentyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hexyl)piperidin-3-yl)methyl)amino)-3-nitrobenzene (B) sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)heptyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)octyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)nonyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)dec-9-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)undec-10-yn-1-yl)piperidin-3-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)ethyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hept-6-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)dec-9-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)undec-10-yn-1-yl)piperidin-3-yl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)ethyl) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy) Ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)oxy) Ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl) (Oxy)ethoxy)ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propionyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl) Sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2-(2,6 -Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)aminoacetyl)piperidin-3-yl)methyl)amino)-3-nitrobenzene (B) sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propionyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyryl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentanoyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)octanoyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)piperidin-3-yl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)acetyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)propionyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)butyryl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)pentanoyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)hexanoyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)heptanoyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)ethyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)propyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)butyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)pentyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)hexyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)heptyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethoxy)ethyl)piperidin-3-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)propoxy)ethyl)piperidin-3-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)sulfanyl)propoxy)propyl)piperidin-3-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)thio)ethoxy)ethoxy)ethyl ) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)acetyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propionyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)butyryl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentanoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexanoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptanoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)ethoxy)ethyl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propoxy)ethyl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)propoxy)propyl)piperidin-3-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethoxy)ethoxy)ethyl)piperidine -3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2-(2,6 -Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)aminoacetyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfon Acyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)butyryl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentanoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)hexanoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)heptanoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)prop-2-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)but-3-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)pent-4-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)hex-5-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)hept-6-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oct-7-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)non-8-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)dec-9-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)undec-10-yn-1-yl)piperidin-4-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)prop-2-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)but-3-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)pent-4-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)hex-5-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)hept-6-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)oct-7-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)non-8-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)dec-9-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)undec-10-yn-1-yl)piperidin-4-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)but-3-yn-1-yl)oxy)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)but-3-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)prop-2-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)but-3-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)hept-6-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)dec-9-yn-1-yl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)undec-10-yn-1-yl)piperidin-4-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)prop-2-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)but-3-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)pent-4-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)hex-5-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)hept-6-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)oct-7-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)non-8-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)dec-9-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)undec-10-yn-1-yl)piperidin-3-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)but-3-yn-1-yl)oxy)ethyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)pent-4-yn-1-yl)oxy)ethyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)but-3-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)prop-2-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)but-3-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)hepta-6-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)oct-7-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)non-8-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)dec-9-yn-1-yl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-Dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)undec-10-yn-1-yl)piperidin-3-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethoxy )Ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)but-3-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)pent-4-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)hex-5-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)hept-6-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oct-7-yn-1-yl)piperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)but-3-yn-1-yl)oxy)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)pent-4-yn-1-yl)oxy)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl) (Oxy)ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)but-3-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)pent-4-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)hex-5-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)hept-6-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oct-7-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)non-8-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)dec-9-yn-1-yl)piperidin-3-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)undec-10-yn-1-yl)piperidin-3-yl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)oxy)ethyl) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)but-3-yn-1-yl)oxy)ethyl) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)but-3-yn-1-yl)oxy)propyl) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)but-3-yn-1-yl)oxy) Ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)prop-2-yn-1-yl) (Oxy)ethoxy)ethoxy)ethyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)-1H-1,2,3-triazole-4 -Base)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)-1H-1,2,3-triazole-4 -Base)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)-1H-1,2,3-triazole-4 -Base)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)-1H-1,2,3-triazole-4 -Base)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)-1H-1,2,3-triazole-4 -Base)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl)-1H- 1,2,3-Triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl)-1H- 1,2,3-Triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)propyl)-1H- 1,2,3-Triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethoxy )Ethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)-1H-1,2,3-tri (Azol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)-1H-1,2,3-tri (Azol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hept-6-yn-1-yl)-1H-1,2,3-tri (Azol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-yn-1-yl)-1H-1,2,3-tri (Azol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)non-8-yn-1-yl)-1H-1,2,3-tri (Azol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl) -1H-1,2,3-triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl) -1H-1,2,3-triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy)propyl) -1H-1,2,3-triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl) (Oxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)propyl)-1H-1,2,3-triazol-4-yl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)butyl)-1H-1,2,3-triazol-4-yl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentyl)-1H-1,2,3-triazol-4-yl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)hexyl)-1H-1,2,3-triazol-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)-1H-1,2,3-triazole-4- (Yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)-1H-1,2,3-triazole-4- (Yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)-1H-1,2,3-triazole-4- (Yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)-1H-1,2,3-triazole-4- (L)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)-1H-1,2,3-triazol-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4- (3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)prop-2-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl) (B) sulfonyl) phenyl) sulfonyl) benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)but-3-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl) (B) sulfonyl) phenyl) sulfonyl) benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)pent-4-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl) (B) sulfonyl) phenyl) sulfonyl) benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)hex-5-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl) (B) sulfonyl) phenyl) sulfonyl) benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)hept-6-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl) (B) sulfonyl) phenyl) sulfonyl) benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)oct-7-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl) (B) sulfonyl) phenyl) sulfonyl) benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)non-8-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl) (B) sulfonyl) phenyl) sulfonyl) benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(10-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)dec-9-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl) (B) sulfonyl) phenyl) sulfonyl) benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(11-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-4-yl)undec-10-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((three Fluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(3-(2-(2,6-dioxopiperidin-3-yl)-1,3-di Oxoisoindolin-4-yl)prop-2-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-(( Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-di Oxoisoindolin-4-yl)but-3-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-(( Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1,3-di Oxoisoindolin-4-yl)pent-4-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butane-2-yl)amino)-3-(( Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1,3-di Oxoisoindolin-4-yl)hex-5-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butane-2-yl)amino)-3-(( Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1,3-di (Oxoisoindolin-4-yl)hept-6-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-(( Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(8-(2-(2,6-dioxopiperidin-3-yl)-1,3-di Oxoisoindolin-4-yl)oct-7-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butane-2-yl)amino)-3-(( Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(9-(2-(2,6-dioxopiperidin-3-yl)-1,3-di Oxoisoindolin-4-yl)non-8-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-(( Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(10-(2-(2,6-dioxopiperidin-3-yl)-1,3-di Oxoisoindolin-4-yl)dec-9-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butane-2-yl)amino)-3-(( Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(11-(2-(2,6-dioxopiperidin-3-yl)-1,3-di Oxoisoindolin-4-yl)undec-10-yn-1-yl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3- ((Trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-((2-(2, 6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)aminoacetyl)piperidin-4-yl)methoxy)-(1,1' -Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino )Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propionyl)piperidin-4-yl)methoxy)-[ 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyryl)piperidin-4-yl)methoxy)-[ 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentanoyl)piperidin-4-yl)methoxy)-( 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)piperidin-4-yl)methoxy)-( 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(7-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoyl)piperidin-4-yl)methoxy)-( 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-(2-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)propionyl)piperidin-4-yl )Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H- Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-(2-( 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)propionyl )Piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-( ((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-(2-( 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy )Ethoxy)propionyl)piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3 -Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(1-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxapentadecano- 15-Acyl)piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro- 4-(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(1-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12,15-pentaoxa-18 Carbon-18-acyl)piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro Base-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)piperidin-4-yl)methoxy)-( 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)piperidin-4-yl)methoxy)-( 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)piperidin-4-yl)methoxy)-( 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)piperidin-4-yl)methoxy)-(1 ,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl (Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethyl)piperidin-4-yl )Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H- Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethyl )Piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-( ((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy )Ethoxy)ethyl)piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3 -Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(14-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxatetradecyl )Piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-( ((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(17-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12,15-pentaoxa-15 Alkyl)piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4 -(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-((2-(2, 6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)aminoacetyl)piperidin-4-yl)methoxy)-[1,1'-biphenyl ]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl )Sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)propionyl)piperidin-4-yl)methoxy)-(1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl) Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)butyryl)piperidin-4-yl)methoxy)-(1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl) Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentanoyl)piperidin-4-yl)methoxy)-(1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl) Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-((2- (2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)hexanoyl)piperidin-4-yl)methoxy)-(1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl) Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(7-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)heptanoyl)piperidin-4-yl)methoxy)-(1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl) Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-(2-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)propionyl)piperidin-4-yl)methoxy Yl)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran- 4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-(2-( 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)ethoxy)propionyl)piperidine -4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((四Hydrogen-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-(2-( 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy (Yl)propionyl)piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro -4-(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(1-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxapentadec-15-acyl )Piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-( ((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(1-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)-3,6,9,12,15-pentaoxaocta-18 -Acyl)piperidin-4-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4 -(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)propyl)piperidin-4-yl)methoxy)-(1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl) Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)butyl)piperidin-4-yl)methoxy)-(1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl) Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-(2-( 2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pentyl)piperidin-4-yl)methoxy)-(1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl) Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hexyl)piperidin-4-yl)methoxy)-(1,1' -Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino )Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)piperidin-4-yl)methoxy)-(1,1'-linked Benzene)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzene (B)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)piperidin-4-yl)methoxy)-(1,1'-linked Benzene)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzene (B) sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)piperidin-4-yl)methoxy)-[1,1'-linked Benzene)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzene (B)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hexyl)piperidin-4-yl)methoxy)-[1,1'-biphenyl ]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl )Sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-4-yl)methoxy)- [1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl )Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-4-yl)methoxy Yl)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran- 4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-4-yl)methoxy)- [1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl )Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)piperidin-4-yl)methoxy Yl)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran- 4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-(4-((2-(2,6 -Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butoxy)-[1,1'-biphenyl]-2-yl)methan Yl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide ；

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((5-((2-(2, 6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)oxy)-[1,1'-biphenyl]-2- Yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl) Benzamide

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((6-((2-(2, 6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)oxy)-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzene Formamide

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-(2-(2-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)-[1,1'-biphenyl ]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl )Sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-(2-(2-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)-[ 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-(2-(2-(2-(2 -((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy )Ethoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H- Pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((14-((2-(2, 6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxatetradecyl)oxy )-[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4 -Base)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-(4-((2-(2,6 -Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)butoxy)-[1,1'-biphenyl]-2-yl)methyl)piper (Azin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((5-((2-(2, 6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentyl)oxy)-[1,1'-biphenyl]-2-yl)methyl Yl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide ；

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((6-((2-(2, 6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)hexyl)oxy)-[1,1'-biphenyl]-2-yl)methyl )Piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-(2-(2-((2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)ethoxy)-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl ) Benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-(2-(2-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)-(1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl) Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-(2-(2-(2-(2 -((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)ethoxy Yl)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran- 4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((14-((2-(2, 6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxatetradecyl)oxy)-[ 1,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl) (Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((6-(2-(2,6 -Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)oxy)-[1,1'-biphenyl ]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl )Sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((6-(2-(2,6 -Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)oxy)-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl ) Benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((5-(2-(2,6 -Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)-[1,1'-biphenyl ]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl )Sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((5-(2-(2,6 -Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl ) Benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-((2-(2, 6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)aminoacetyl)azetidin-3-yl)methoxy)-(1, 1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl )Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propionyl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyryl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentanoyl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(7-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptanoyl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)azetidin-3-yl)methoxy)- [1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl )Methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(7-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptyl)azetidin-3-yl)methoxy) -[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4- (L)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethyl)azetidine-3 -Yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro- 2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(3-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propoxy)ethyl)azetidin-3 -Yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro- 2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethyl )Azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4 -(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy )Ethoxy)ethyl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-( (3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(14-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxatetradecyl )Azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4 -(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethyl)azetidin-3-yl)methoxy)-(1 ,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl (Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(3-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)propyl)azetidin-3-yl)methoxy)-(1 ,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl (Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)butyl)azetidin-3-yl)methoxy)-(1 ,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl (Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)pentyl)azetidin-3-yl)methoxy)-(1 ,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl (Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)hexyl)azetidin-3-yl)methoxy)-(1, 1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl )Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(7-((2- (2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)heptyl)azetidin-3-yl)methoxy)-(1 ,1'-Biphenyl)-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl (Amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)ethyl)azetidin-3-yl) Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyridine) (Pan-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(3-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)propoxy)ethyl)azetidin-3-yl) Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyridine) (Pan-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethyl)aza Cyclobut-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(( (Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy Yl)ethyl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3- Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(14-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxatetradecyl)aza Cyclobut-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(( (Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)azetidin-3-yl) Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyridine) (Pan-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)azetidin-3-yl) Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyridine) (Pan-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)azetidin-3-yl) Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyridine) (Pan-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(7-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hept-6-yn-1-yl)azetidin-3-yl) Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyridine) (Pan-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(8-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-yn-1-yl)azetidin-3-yl) Methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyridine) (Pan-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(4-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)azetidin-3-yl)methoxy )-[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4 -Base)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(5-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)azetidin-3-yl)methoxy )-[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4 -Base)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(6-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)azetidin-3-yl)methoxy )-[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4 -Base)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(7-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)azetidin-3-yl)methoxy )-[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4 -Base)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(8-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)azetidin-3-yl)methoxy )-[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4 -Base)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(9-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)azetidin-3-yl)methoxy )-[1,1'-Biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4 -Base)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-((3- (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl )Azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4 -(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-((4- (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl )Azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4 -(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( (3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy )Ethoxy)ethyl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-( (3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( 2-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl )Oxy)ethoxy)ethoxy)ethyl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazine-1 -Yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-((3- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethyl)azepine Cyclobut-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(( (Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-((4- (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethyl)azepine Cyclobut-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(( (Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( (3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethoxy Yl)ethyl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3- Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(2-( 2-((3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy )Ethoxy)ethoxy)ethyl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl) -N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    (2S,4R)-1-((S)-2-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-4-oxobutyrylamino)-3, 3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-6-oxohexanamido)-3, 3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-8-oxooctanoylamino)-3, 3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(10-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-10-oxodecanoylamino)-3, 3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(5-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-5-oxopentanoylamino)-3, 3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(7-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-7-oxoheptanoylamino)-3, 3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(9-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)-9-oxononanoylamino)-3, 3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propioyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl )Sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-ynyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-ynyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-alkynoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-alkynoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-alkynoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)dec-9-alkynoyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)undec-10-ynyl)piperidin-4-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)acetyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)acetyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)propionyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)ethoxy )Acetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethoxy )Acetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)acetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)propioyl)piperidin-4-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-ynyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-ynyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-ynyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hepta-6-alkynoyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-alkynoyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)non-8-alkynoyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)dec-9-ynyl)piperidin-4-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)undec-10-ynyl)piperidin-4-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)acetyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy)acetyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)propionyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)oxy) Ethoxy)acetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy) Ethoxy)acetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl) (Oxy)ethoxy)ethoxy)acetyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propioyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl )Sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-ynyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-ynyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-alkynoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-alkynoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-alkynoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)dec-9-alkynoyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)undec-10-ynyl)piperidin-3-yl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)acetyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)acetyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)acetyl)piperidine- 3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)ethoxy )Acetyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)oxy)ethoxy )Acetyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)ethoxy )Acetyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)ethoxy)acetyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)propioyl)piperidin-3-yl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(4-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-ynyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(2 ,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-ynyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(6-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-ynyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(7-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hepta-6-alkynoyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(8-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-alkynoyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(9-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)non-8-alkynoyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(10-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)dec-9-ynyl)piperidin-3-yl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(11-(2-(2 ,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)undec-10-ynyl)piperidin-3-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy)acetyl) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy)acetyl) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)oxy)acetyl) Piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)oxy) Ethoxy)acetyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)oxy) Ethoxy)acetyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)oxy) Ethoxy)acetyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(2-(2 -((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl) (Oxy)ethoxy)ethoxy)acetyl)piperidin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)-[1,4'-bipiperidine]- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)-[1,4'-bipiperidine]- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)-[1,4'-bipiperidine]- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(6-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)-[1,4'-bipiperidine]- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(7-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)-[1,4'-bipiperidine]- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(8-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)-[1,4'-bipiperidine]- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(9-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)-[1,4'-bipiperidine]- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)piperidin-4-yl)methyl )Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(1-(3 -(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)piperidin-4-yl) (Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(4-(3 -(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)piperazin-1-yl) (Ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)-1H-1,2,3- Triazol-4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)-1H-1,2,3- Triazol-4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)-1H-1,2,3- Triazol-4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)-1H-1,2,3- Triazol-4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)-1H-pyrazol-4-yl )Methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)-1H-pyrazol-4-yl )Methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)-1H-pyrazol-4-yl )Methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)-1H-pyrazol-4-yl )Methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)-[1,4'-bipiper (Pyridin]-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)-[1,4'-bipiper (Pyridin]-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5-(2-( 2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)-[1,4'-bipiper (Pyridin]-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(6-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)-[1,4'-bipiper (Pyridin]-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(7-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hept-6-yn-1-yl)-[1,4'-bipiper (Pyridin]-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(8-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oct-7-yn-1-yl)-[1,4'-bipiper (Pyridin]-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(9-(2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)non-8-yn-1-yl)-[1,4'-bipiper (Pyridin]-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)piperidin-4-yl )Methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(1-(3 -(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)piperidine-4 -Yl)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-(4-(3 -(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)piperazine-1 -Yl)ethyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)-1H-1,2 ,3-Triazol-4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)-1H-1,2 ,3-Triazol-4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)-1H-1,2 ,3-Triazol-4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)-1H-1,2 ,3-Triazol-4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(3-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)prop-2-yn-1-yl)-1H-pyrazole- 4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(4-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)but-3-yn-1-yl)-1H-pyrazole- 4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(5-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)pent-4-yn-1-yl)-1H-pyrazole- 4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((1-(6-( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hex-5-yn-1-yl)-1H-pyrazole- 4-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propioyl)-[1,4'-bipiperidine]-4-yl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-ynyl)-[1,4'-bipiperidin]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynyl)-[1,4'-bipiperidine]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(6-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-ynyl)-[1,4'-bipiperidine]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(7-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-alkynoyl)-[1,4'-bipiperidin]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(8-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-alkynoyl)-[1,4'-bipiperidin]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide; or

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(9-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-alkynoyl)-[1,4'-bipiperidin]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide.
32. The compound of formula (I) according to claim 1 or 2, or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof, which is selected from the group consisting of:

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-5-yl)prop-2-yn-1-yl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-5-yl)but-3-yn-1-yl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-5-yl)pent-4-yn-1-yl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-5-yl)hex-5-yn-1-yl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoiso Indolin-5-yl)hept-6-yn-1-yl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    (2S,4R)-1-((S)-2-((5-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)pentyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((6-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)hexyl)amino)-3,3-dimethylbutyryl )-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((7-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)heptyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((8-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)octyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((9-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)nonyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((10-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)decyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)butyrylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)hexanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)octanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(10-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)decanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(12-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)dodecylamido)-3,3- Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(5-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)valeramido)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(7-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)heptanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(9-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)nonanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(11-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)undecylamido)-3,3- Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((2S)-2-(4-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)butyrylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((2S)-2-(5-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)valeramido)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((2S)-2-(6-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)hexanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((2S)-2-(7-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)heptanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((2S)-2-(8-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)octanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((2S)-2-(9-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)nonanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((2S)-2-(10-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)decanoylamino)-3,3-dimethyl Butyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((2S)-2-(11-(3-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)piperidin-1-yl)undecylamido)-3,3- Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)butyryl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(5-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)valeryl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)hexanoyl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(7-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)heptanoyl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)octanoyl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(9-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)nonanoyl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(10-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)decanoyl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(11-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)undecane (Alkylamido)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)butyl (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((5-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)pentan (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)hexyl )Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((7-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)heptan (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)octane (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((9-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)nonane (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((11-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)10 Monoalkyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((2-(2-(2-(4-(((4-(N-(2-((1H-pyrrolo[2,3- b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-linked (Phenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]- 1'-yl)ethoxy)ethoxy)ethyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl) Benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-14-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl)oxy )-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl) (Piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)-2-(tert Butyl)-6,9,12-trioxa-3-azatetradecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine- 2-formamide;

    (2S,4R)-1-((S)-17-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl)oxy )-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl) (Piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)-2-(tert Butyl)-6,9,12,15-tetraoxa-3-azaheptadecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrole Alkyl-2-carboxamide;

    (2S,4R)-1-((S)-20-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl)oxy )-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl) (Piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)-2-(tert Butyl)-6,9,12,15,18-pentaoxa-3-azaeicosanyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl ) Pyrrolidine-2-carboxamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3- Dioxoisoindolin-4-yl)thio)ethyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3- Dioxoisoindolin-4-yl)thio)propyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3- Dioxoisoindolin-4-yl)thio)butyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(5-((2-(2,6-dioxopiperidin-3-yl)-1,3- Dioxoisoindolin-4-yl)thio)pentyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3- Dioxoisoindolin-4-yl)thio)hexyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(7-((2-(2,6-dioxopiperidin-3-yl)-1,3- Dioxoisoindolin-4-yl)thio)heptyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl) )Sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)thio)ethyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl )Phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)thio)propyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl )Phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)thio)butyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl )Phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)thio)pentyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl )Phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)thio)hexyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl) (Phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)thio)heptyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl )Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-((2-(2, 6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-[1,4'-dipiperidin-4-yl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(2-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)-[1,4'-dipiperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)-[1,4'-dipiperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)-[1,4'-dipiperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)-[1,4'-dipiperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(6-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hexyl)-[1,4'-dipiperidin-4-yl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(7-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)heptyl)-[1,4'-dipiperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(8-(2-( 2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)octyl)-[1,4'-dipiperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(9-(2-( 2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)nonyl)-[1,4'-dipiperidin-4-yl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(2-((2- (2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)ethyl)-[1,4'-dipiperidin]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)propyl)-[1,4'-dipiperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)-[1,4'-dipiperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5-((2- (2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)-[1,4'-dipiperidin]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(6-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)hexyl)-[1,4'-dipiperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(7-((2- (2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)heptyl)-[1,4'-dipiperidine]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(8-((2- (2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)octyl)-[1,4'-dipiperidin]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(2-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)-[1,4'-dipiperidine]-4 -Base)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)-[1,4'-dipiperidine]-4 -Base)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)-[1,4'-dipiperidine]-4 -Base)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)-[1,4'-dipiperidine]-4 -Base)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(6-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)-[1,4'-dipiperidine]-4- (Yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(7-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptyl)-[1,4'-dipiperidine]-4 -Yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide; or

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(8-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)octyl)-[1,4'-dipiperidine]-4 -Yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide.
33. A pharmaceutical composition comprising the compound of formula (I) according to any one of claims 1 to 32 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
34. The pharmaceutical composition of claim 33, further comprising at least one additional therapeutic agent.
35. The use of the compound of formula (I) according to any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 32 or 33, for preparation for prevention And/or agents for treating diseases related to BCL-2 family proteins or Hedgehog signaling pathway.
36. The use according to claim 35, wherein the diseases include myelofibrosis, renal fibrosis, liver fibrosis, liver cirrhosis and tumors.
37. The use according to claim 36, wherein the tumor is a tumor that depends on BCL-2 family proteins, or a tumor that depends on the Hedgehog signaling pathway.
38. The use according to claim 37, wherein the tumor is a tumor dependent on BCL-2 and/or MCL-1 and/or BCL-XL protein.
39. The use of claim 35, wherein the disease is selected from the group consisting of: myeloma, including multiple myeloma (MM); leukemia, including chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML); lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B cell lymphoma; myelodysplastic syndrome; bone marrow fibrosis, renal fibrosis , Liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer; prostate cancer; medulloblastoma; basal cell carcinoma; Goering syndrome; esophageal cancer; colorectal cancer; medulloblastoma; rhabdomyosarcoma; hepatoblastic carcinoma; glioma; astrocytoma; liver cancer; liver cirrhosis; soft tissue sarcoma; and pancreatic cancer.
40. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 32, which is used for the prevention and/or treatment of diseases related to BCL-2 family proteins or Hedgehog signaling pathway.
41. The compound of formula (I) according to claim 40, or a pharmaceutically acceptable salt thereof, wherein the diseases include myelofibrosis, renal fibrosis, liver fibrosis, liver cirrhosis and tumors.
42. The compound of formula (I) according to claim 41, or a pharmaceutically acceptable salt thereof, wherein the tumor is a tumor that depends on BCL-2 family proteins, or a tumor that depends on the Hedgehog signaling pathway.
43. The compound of formula (I) according to claim 41, or a pharmaceutically acceptable salt thereof, wherein the tumor is a tumor dependent on BCL-2 and/or MCL-1 and/or BCL-XL protein.
44. The compound of formula (I) according to claim 40, or a pharmaceutically acceptable salt thereof, wherein the disease is selected from the group consisting of: myeloma, including multiple myeloma (MM); leukemia, including Chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML); lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B cell lymphoma ; Myelodysplastic syndrome; Myelofibrosis, renal fibrosis, liver fibrosis; Breast cancer; Lung cancer, including non-small cell lung cancer and small cell lung cancer; Melanoma; Mesothelioma; Neuroblastoma; Osteosarcoma; Ovarian Carcinoma; Prostate cancer; Medulloblastoma; Basal cell carcinoma; Goering syndrome; Esophageal cancer; Colorectal cancer; Medulloblastoma; Rhabdomyosarcoma; Hepatoblastic carcinoma; Glioma; Astrocytoma; Liver cancer; liver cirrhosis; soft tissue sarcoma; and pancreatic cancer.
45. A method for treating or preventing diseases related to BCL-2 family proteins or Hedgehog signaling pathway, which comprises administering to a subject in need thereof a therapeutically effective amount of the formula (I) according to any one of claims 1-32 A compound, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claims 33 to 34.
46. The method of claim 45, wherein the diseases include myelofibrosis, renal fibrosis, liver fibrosis, liver cirrhosis, and tumors.
47. The method of claim 45, wherein the tumor is a tumor that depends on BCL-2 family proteins, or a tumor that depends on the Hedgehog signaling pathway.
48. The method of claim 47, wherein the tumor is a tumor that depends on BCL-2 and/or MCL-1 and/or BCL-XL protein, or a tumor that depends on the Hedgehog signaling pathway.
49. The method of claim 45, wherein the disease is selected from the group consisting of: myeloma, including multiple myeloma (MM); leukemia, including chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML); lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B cell lymphoma; myelodysplastic syndrome; bone marrow fibrosis, renal fibrosis , Liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer; prostate cancer; medulloblastoma; basal cell carcinoma; Goering syndrome; esophageal cancer; colorectal cancer; medulloblastoma; rhabdomyosarcoma; hepatoblastic carcinoma; glioma; astrocytoma; liver cancer; liver cirrhosis; soft tissue sarcoma; and pancreatic cancer.
50. The method according to any one of claims 45-49, wherein at least one selected from the group consisting of nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural cavity administration Drugs, peritoneal administration, vaginal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural administration, intrathecal administration and intravenous administration are administered to the subject .
51. The compound of formula (II) or its salt, enantiomer, stereoisomer, solvate, polymorph,

    R ₁₂ -A ₁₂ -LIN-A ₂₂ -R ₂₂ (II)

    Where R ₁₂ means:

    

    Where R _x means

    

    The symbol * represents the connection point with NH, and the symbol ** represents _{the connection point with A 12} , n represents an integer of 1-3, R _b1 , R _b2 , R _b3 and R _{b4 are the} same or different and are independently H Or oxo group, and R _b5 represents H or C _1-3 alkyl;

    Where R _y means

    

    The symbol * represents the connection point with O, and the symbol ** represents _{the connection point with A 12} , m represents an integer of 1-3, and

    A ₁₂ does not exist or represents a carbonyl group;

    A ₂₂ does not exist or represents a carbonyl group;

    R ₂₂ represents an optionally substituted adamantyl group, formula (II-1) structural formula, or formula (II-2) structural formula:

    

    Where X represents CH ₂ or CO, R _c does not exist or represents N(R _c1 ), O, S, ethynylene, vinylene, or five- or six-membered heterocyclylene, where R _c1 and R _c2 are independent of each other地 represents H or C _1-3 alkyl, and R _d represents H or methyl; and

    LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The group of the composition is interrupted, wherein when LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are not present, and R ₂₂ represents an optional substitution Or R ₂₂ represents the structural formula of formula (II-1), wherein R _c does not exist or represents an ethynylene group, a vinylene group, or a five- or six-membered heterocyclylene;

    requirement is:

    When R ₁₂ represents any of the following structural formulae:

    

    Where R _x means

    

    The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12,}

    R ₂₂ represents an optionally substituted adamantyl group or the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents a five-membered or six-membered heterocyclylene, and LIN does not exist or represents A substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof The group is interrupted, where in the absence of LIN, one of A ₁₂ and A ₂₂ does not exist and the other represents a carbonyl group or both A ₁₂ and A ₂₂ do not exist, or

    R ₂₂ represents the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents O, and LIN represents a substituted or unsubstituted linear or branched alkylene group, or

    R ₂₂ represents the structural formula of formula (II-2), wherein R _d represents a methyl group, and A _{22 is} not present, and LIN represents a substituted or unsubstituted linear or branched alkylene group;

    as well as

    requirement is:

    When R ₁₂ represents the following structural formula:

    

    Where R _x means

    

    The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12;}

    R ₂₂ represents an optionally substituted adamantyl group or the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents a five-membered or six-membered heterocyclylene or O, and LIN is not present Or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof Where in the absence of LIN, one of A ₁₂ and A ₂₂ is absent and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are absent, and R ₂₂ represents an optionally substituted Adamantyl, or R ₂₂ represents the structural formula of formula (II-1), wherein R _c represents a five-membered or six-membered heterocyclylene, or

    R ₂₂ represents the structural formula of formula (II-1), where X represents CH ₂ or CO, and R _c represents vinylene or ethynylene, and R _c2 represents C _1-3 alkyl, and LIN does not exist or represents substitution Or an unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof Interrupt, or

    R ₂₂ represents the structural formula of formula (II-2), wherein R _d represents a methyl group, and LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted.
52. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 51, wherein R ₁₂ represents:

    

    Where R _x means

    

    The symbol * represents the connection point with NH, and the symbol ** represents _{the connection point with A 12} , n represents an integer of 1-3, R _b1 , R _b2 , R _b3 and R _{b4 are the} same or different and are independently H Or oxo group, and R _b5 represents H or C _1-3 alkyl;

    Where R _y means

    

    The symbol * represents the connection point with O, and the symbol ** represents _{the connection point with A 12} , m represents an integer of 1-3, and

    A ₁₂ does not exist or represents a carbonyl group;

    A ₂₂ does not exist or represents a carbonyl group;

    R ₂₂ represents an optionally substituted adamantyl group, formula (II-1) structural formula, or formula (II-2) structural formula:

    

    Where X represents CH ₂ or CO, R _c does not exist or represents N(R _c1 ), O, S, ethynylene, vinylene, or five- or six-membered heterocyclylene, where R _c1 and R _c2 are independent of each other地 represents H or C _1-3 alkyl, and R _d represents H or methyl; and

    LIN does not exist or represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more selected from oxygen, optionally substituted heterocyclylene, or any combination thereof The group of the composition is interrupted, wherein when LIN is not present, one of A ₁₂ and A ₂₂ is not present and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are not present, and R ₂₂ represents an optional substitution Or R ₂₂ represents the structural formula of formula (II-1), wherein R _c does not exist or represents an ethynylene group, a vinylene group, or a five- or six-membered heterocyclylene.
53. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 51, wherein R ₁₂ represents:

    

    Where R _x means

    

    The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12,}

    A ₁₂ does not exist or represents a carbonyl group;

    A ₂₂ does not exist or represents a carbonyl group;

    R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1):

    

    Where X represents CH ₂ or CO, and R _c represents a five-membered or six-membered heterocyclylene, R _c2 represents H or a C _1-3 alkyl group, and LIN is absent or represents a substituted or unsubstituted linear or branched chain An alkylene group, wherein the alkylene group is optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof, wherein in the absence of LIN Below, one of A ₁₂ and A ₂₂ does not exist and the other represents a carbonyl group or both A ₁₂ and A ₂₂ do not exist, or

    R ₂₂ represents the structural formula of formula (II-1), wherein X represents CH ₂ or CO, and R _c represents O, and LIN represents a substituted or unsubstituted linear or branched alkylene group, or

    R ₂₂ represents the structural formula of formula (II-2):

    

    Where R _d represents a methyl group, and LIN represents a substituted or unsubstituted linear or branched alkylene group, provided that A _{22 is} not present.
54. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 51, wherein R ₁₂ represents:

    

    Where R _x means

    

    The symbol * indicates the connection point with NH, and the symbol ** indicates the connection point _{with A 12;}

    A ₁₂ does not exist or represents a carbonyl group;

    A ₂₂ does not exist or represents a carbonyl group; and

    R ₂₂ represents an optionally substituted adamantyl group, or the structural formula of formula (II-1):

    

    Where X represents CH ₂ or CO, R _c represents a five-membered or six-membered heterocyclylene or O, R _c2 represents H or C _1-3 alkyl, and LIN is absent or represents a substituted or unsubstituted linear or branched Chain alkylene, wherein the alkylene is optionally interrupted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene, or any combination thereof, wherein the non-existent LIN In this case, one of A ₁₂ and A ₂₂ is absent and the other represents a carbonyl group or both A ₁₂ and A ₂₂ are absent, and R ₂₂ represents an optionally substituted adamantyl group, or

    R ₂₂ represents the structural formula of formula (II-1), wherein R _c represents a five-membered or six-membered heterocyclylene,

    or

    R ₂₂ represents the structural formula of formula (II-1), where X represents CH ₂ or CO, and R _c represents vinylene or ethynylene, and R _c2 represents C _1-3 alkyl, and LIN does not exist or represents substitution Or an unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more groups selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof Interrupt,

    or

    R ₂₂ represents the structural formula of formula (II-2), wherein R _d represents a methyl group, and LIN represents a substituted or unsubstituted linear or branched alkylene group, wherein the alkylene group is optionally substituted by one or more A group selected from the group consisting of oxygen, optionally substituted heterocyclylene or any combination thereof is interrupted.
55. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to any one of claims 51-54, wherein when said R _c represents a five-membered Or in the case of a six-membered heterocyclylene, the five-membered or six-membered heterocyclylene is triazolylidene, azetidinyl, pyrrolidinylene, pyrrolylene, imidazolidinylene, imidazolylidene , Pyrazolidine, pyrazolylidene, tetrahydrofuranylene, furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, tetrahydrothiophenylene, oxazolidinylene, Oxazolyl, isoxazolyl, oxadiazolyl, thiazolidine, thiazolyl, isothiazolyl, thiadiazole, piperidinylene, piperazinylene, pyridinylene , Pyrimidinylene, pyridazinylene, pyrazinylene, morpholinylene, thiomorpholinylene, or dioxanylene, wherein the five-membered or six-membered heterocyclylene is unsubstituted Or a substituent selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, C _1-3 alkoxy, alkylamino, halogenated C _1-3 alkyl, cyano or any combination thereof replace.
56. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to any one of claims 51-54, wherein R ₂₂ represents an adamantyl group, so The adamantyl group is adamantane-1-yl, adamantane-2-yl, adamantane-3-yl, adamantane-4-yl, adamantane-5-yl, adamantane-6-yl, adamantane- 7-yl, adamantane-8-yl, adamantane-9-yl or adamantane-10-yl, which are optionally selected from halogen, hydroxyl, mercapto, oxo, cyano, C _1-3 alkane Group, halogenated C _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkylamino, C _1-3 alkyl -NHC(O)- or any combination thereof Multiple substituents are substituted.
57. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to any one of claims 51-54, wherein LIN represents a substituted or unsubstituted straight Chain or branched C _1-30 alkylene, the substituent is selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, alkoxy, alkylamino, haloalkyl, cyano or Any combination of them.
58. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to any one of claims 51-54, wherein LIN represents substituted or unsubstituted The following groups:

    -CH ₂ -; -(CH ₂ ) ₂ -; -(CH ₂ ) ₃ -; -(CH ₂ ) ₄ -; -(CH ₂ ) ₅ -; -(CH ₂ ) ₆ -; -(CH ₂ ) _{7 - ;-( CH 2) 8 -} ;-( CH 2) 9 -; - (CH 2) 10 - ;-( CH 2) 11 - ;-( CH 2) 12 - ;-( CH 2) 13 - ; -(CH ₂ ) ₁₄ -; -(CH ₂ ) ₁₅ -; -(CH ₂ ) ₁₆ -; -(CH ₂ ) ₁₇ -; -(CH ₂ ) ₁₈ -; -(CH ₂ ) ₁₉ -;- (CH ₂ ) ₂₀ -; -(CH ₂ ) ₂₁ -; -(CH ₂ ) ₂₂ -; -(CH ₂ ) ₂₃ -; -(CH ₂ ) ₂₄ -; -(CH ₂ ) ₂₅ -; -(CH ₂ ) ₂₆ -; -(CH ₂ ) ₂₇ -; -(CH ₂ ) ₂₈ -; -(CH ₂ ) ₂₉ -; or -(CH ₂ ) ₃₀ -; wherein the substituent is selected from C ₁ -C ₃ alkyl , Hydroxy, amino, mercapto, halogen, aryl, alkoxy, alkylamino, haloalkyl, cyano or any combination thereof.
59. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to any one of claims 51-54, wherein LIN represents a substituted or unsubstituted straight Chain or branched C _2-30 alkylene, wherein the C _2-30 alkylene is optionally interrupted by one or more oxygens, and wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl, amino , Mercapto, halogen, aryl, alkoxy, alkylamino, haloalkyl, cyano or any combination thereof.
60. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 59, wherein LIN represents -(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -,-(CH ₂ ) _n1 -(O(CH ₂ ) _n2 ) _m1 -(O(CH ₂ ) _n3 ) _m2 -,-(CR _a1 R _a2 ) _n1 -(O(CR _a3 R _a4 ) _n2 ) _m1 -, or -(CR _a5 R _a6 ) _n1 -(O(CR _a7 R _a8 ) _n2 ) _m1 -(O(CR _a9 R _a10 ) _n3 ) _m2 -, where R _a1 , R _a2 , R _{a3 , R a4, R a5, R} a6, R a7, R a8, R a9, R a10 each independently represent H, C ₁ - ₃ alkyl, hydroxy, amino, mercapto, halo, aryl, alkoxy, Amino group, haloalkyl group, cyano group or any combination thereof, wherein when in the same LIN, _Ra1 , _Ra2 , _Ra3 , and _{Ra4 are} not H at the same time, or _Ra5 , _Ra6 , _Ra7 , R _a8 , R _a9 , and R _{a10 are} not H at the same time; and

    n1, n2, n3, m1, m2 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.
61. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 59, wherein LIN represents a substituted or unsubstituted group of the following:

    -CH ₂ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O( CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -( CH ₂ ) ₂ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₁₀ -, -(CH ₂ ) ₄ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₄ -( O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₇ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₈ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₉ -, -(CH ₂ ) ₄ -(O(CH ₂ ) ₂ ) ₁₀ -, -CH ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -( O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₇ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₈ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₉ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₇ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₁₀ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₇ -,- (CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₈ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₉ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₁₀ -, -CH ₂ -OCH ₂ -, -(CH ₂ ) ₂ -OCH ₂ -, -(CH ₂ ) ₃ -OCH ₂ -, -(CH ₂ ) ₄ -OCH ₂ -, -(CH ₂ ) ₅ -OCH ₂ -, -(CH ₂ ) ₆ -OCH ₂ -, -(CH ₂ ) ₇ -OCH ₂ -, -(CH ₂ ) ₈ -OCH ₂ -, -(CH ₂ ) ₉ -OCH ₂ -, -(CH ₂ ) ₁₀ -OCH ₂ -, -CH _2- O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -( O(CH ₂ ) ₂ ) ₃ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -CH ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -O-(CH ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₃ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₄ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₅ -O-CH ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₂ ) ₆ -O-CH ₂ -, -CH _2- O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -CH ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₂ -O -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, -(CH ₂ ) ₂ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -O-(CH ₂ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₂ -(O( CH ₂ ) ₃ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₄ -(O(CH ₂ ) ₃ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₂ ) ₅ -(O(CH ₂ ) ₃ ) ₅ -, -(CH ₂ ) ₃ -( O(CH ₂ ) ₂ ) ₆ -(O(CH ₂ ) ₃ ) ₆ -, -(CH ₂ ) ₃ -O-(CH ₂ ) ₃ -O-(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₂ -(O(CH ₂ ) ₂ ) ₂ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₃ -(O(CH ₂ ) ₂ ) _3- , -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₄ -(O(CH ₂ ) ₂ ) ₄ -, -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₅ -(O(CH ₂ ) ₂ ) ₅ -, or -(CH ₂ ) ₃ -(O(CH ₂ ) ₃ ) ₆ -(O(CH ₂ ) ₂ ) ₆ -; wherein the substituent is selected from C ₁ -C ₃ alkyl, hydroxyl , Amino, mercapto, halogen, aryl, alkoxy, alkylamino, haloalkyl, cyano or any combination thereof.
62. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to any one of claims 51-54, wherein LIN represents substituted or unsubstituted C _2-30 alkylene, wherein said C _2-30 alkylene is optionally interrupted by one or more optionally substituted heterocyclylene having heteroatoms selected from O, N and S, wherein said The substituents of C _2-30 alkylene and heterocyclylene are independently selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, alkoxy, alkylamino, haloalkyl, Cyano or any combination thereof.
63. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 62, wherein LIN represents -(CH ₂ ) _{n7 -heterocyclylene-} (CH ₂ ) _n8 -, where n7 and n8 independently represent integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, and the heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxy, amino, mercapto, halogen, aryl, C _1-3 alkoxy, alkyl Substituents of amino, haloalkyl, cyano or any combination thereof are substituted.
64. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 62, wherein the heterocyclylene is azetidinyl, Oxetanylene, pyrrolidinylene, pyrrolylene, imidazolidinylene, imidazolylidene, pyrazolidinylene, pyrazolylidene, pyridinylene, triazolylidene, tetrahydrofuranylene, Furanylene, tetrahydropyranylene, tetrahydrothienylene, thienylene, tetrahydrothiopyranyl, oxazolidinyl, oxazolylidene, isoxazolylidene, oxadiazolylidene , Thiazolylidene, thiazolylidene, isothiazolylidene, thiadiazolylidene, piperidinylene, piperazinylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, sub Morpholinyl, thiomorpholinyl or dioxanyl, wherein the heterocyclylene is unsubstituted or selected from C ₁ -C ₃ alkyl, hydroxyl, amino, mercapto, halogen, aromatic Substituents are substituted by the group, C _1-3 alkoxy, alkylamino, haloalkyl, cyano, or any combination thereof.
65. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 51, wherein LIN is not present, _{and one of A 12} and A ₂₂ is not present And the other represents a carbonyl group or _{neither A 12} nor A ₂₂ is present, and R ₂₂ represents an optionally substituted adamantyl group.
66. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof according to claim 51, which is selected from the group consisting of:

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)oxy)ethyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl )Phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)oxy)propyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl )Phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)oxy)butyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl )Phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)oxy)pentyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl )Phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-(((2R)-4-(4-(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxo Isoindolin-4-yl)oxy)hexyl)piperazin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl) (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(2-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)ethyl)-[1,4'-dipiperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)propyl)-[1,4'-dipiperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(4-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)-[1,4'-dipiperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(5-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)pentyl)-[1,4'-dipiperidin]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(6-((2- (2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)hexyl)-[1,4'-dipiperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(7-((2- (2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)heptyl)-[1,4'-dipiperidin]-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(8-((2- (2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)octyl)-[1,4'-dipiperidin-4-yl )Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)(methyl)amino)ethyl)piperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)(methyl)amino)ethyl)piperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)(methyl)amino)ethyl)piperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)(methyl)amino)ethyl)piperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((6-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hexyl)(methyl)amino)ethyl)piperidin-4-yl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)(methyl)amino)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)(methyl)amino)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)(methyl)amino)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((6-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)(methyl)amino)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((7-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)(methyl)amino)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((8-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)(methyl)amino)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((9-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)(methyl)amino)ethyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)ethyl)(methyl)amino)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)propyl)(methyl)amino)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)(methyl)amino)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)pentyl)(methyl)amino)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)(methyl)amino)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)propyl)(methyl)amino)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)butyl)(methyl)amino)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)pentyl)(methyl)amino)ethyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((2-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)(methyl)amino)ethyl)piper (Pyridin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((3-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)(methyl)amino)ethyl)piper (Pyridin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((4-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)(methyl)amino)ethyl)piper (Pyridin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(2-((5-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)(methyl)amino)ethyl)piper (Pyridin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)(methyl)amino)propyl)piperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)(methyl)amino)propyl)piperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)(methyl)amino)propyl)piperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)(methyl)amino)propyl)piperidin-4-yl) (Methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((3-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)(methyl)amino)propyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((4-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)(methyl)amino)propyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((5-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)(methyl)amino)propyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((6-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)(methyl)amino)propyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((7-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)(methyl)amino)propyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((8-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)(methyl)amino)propyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((9-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)(methyl)amino)propyl) Piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)ethyl)(methyl)amino)propyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((3-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)propyl)(methyl)amino)propyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((4-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)(methyl)amino)propyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)(methyl)amino)propyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((3-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)(methyl)amino)propyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((4-( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)butyl)(methyl)amino)propyl)piperidine- 4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((2-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)(methyl)amino)propyl)piper (Pyridin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((3-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)(methyl)amino)propyl)piper (Pyridin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-((4-( (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)(methyl)amino)propyl)piper (Pyridin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)piperazine-1 -Base)cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)piperazin-1-yl)cyclohexyl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)piperazin-1-yl)cyclohexyl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)piperazin-1-yl)cyclohexyl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)piperazin-1-yl)cyclohexyl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)piperazin-1-yl)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hexyl)piperazin-1-yl)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)heptyl)piperazin-1-yl)cyclohexyl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)octyl)piperazin-1-yl)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)nonyl)piperazin-1-yl)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)piperazin-1-yl)cyclohexyl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)piperazin-1-yl)cyclohexyl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)piperazin-1-yl)cyclohexyl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)piperazin-1-yl)cyclohexyl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)piperazin-1-yl)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hexyl)piperazin-1-yl)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)heptyl)piperazin-1-yl)cyclohexyl)methyl (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)octyl)piperazin-1-yl)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)nonyl)piperazin-1-yl)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexyl)piperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)heptyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)octyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexyl)piperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)heptyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)octyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)ethyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)propyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)pentyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)hexyl)piperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)heptyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)octyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)ethyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)propyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)pentyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)hexyl)piperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)heptyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)piperazin-1-yl )Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)heptyl)piperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(4 -(8-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)octyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)piperazin-1-yl )Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(8-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)octyl)piperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(5-(2 -(2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)-3-oxopiperazine-1- ((Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(3-(2 -(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)-3-oxopiperazin-1-yl)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(4-(2 -(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)-3-oxopiperazin-1-yl)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(5-(2 -(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)-3-oxopiperazin-1-yl)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)ethyl)-3-oxopiperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)propyl)-3-oxopiperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(4-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)-3-oxopiperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)-3-oxopiperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)-3-oxopiperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(4-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)-3-oxopiperazin-1-yl) ring (Hexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)-3-oxopiperazin-1-yl )Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)-3-oxopiperazin-1-yl )Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(4-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)-3-oxopiperazin-1-yl )Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(4 -(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynyl)piperazin-1-yl) Cyclohexyl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(3-(2 -(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propionyl)piperazin-1-yl)cyclohexyl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(4-(2 -(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyryl)piperazin-1-yl)cyclohexyl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(5-(2 -(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)valeryl)piperazin-1-yl)cyclohexyl)methyl)amino)-3 -Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)cyclohexyl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)propionyl)piperazin-1-yl)cyclohexyl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(4-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyryl)piperazin-1-yl)cyclohexyl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-((2-( 2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)aminoacetyl)piperazin-1-yl)cyclohexyl)methyl)amino) -3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propionyl)piperazin-1-yl)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(4-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyryl)piperazin-1-yl)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(2-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)acetyl)piperazin-1-yl)cyclohexyl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(3-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)propionyl)piperazin-1-yl)cyclohexyl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((4-(4-(4-(( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)sulfanyl)butyryl)piperazin-1-yl)cyclohexyl)methyl) Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)cyclohexyl)methyl)amino)-3-nitrobenzene (B) sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)amino)cyclohexyl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)amino)cyclohexyl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)amino)cyclohexyl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)amino)cyclohexyl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)amino)cyclohexyl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)ethyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)propyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)amino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)amino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)amino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(( 5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)amino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)cyclohexyl)methyl)amino)-3-nitrobenzene (B) sulfonyl) benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)amino)cyclohexyl)methyl)amino)-3-nitro (Phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)amino)cyclohexyl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)propyl)amino)cyclohexyl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)butyl)amino)cyclohexyl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)amino)cyclohexyl)methyl)amino)-3- Nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 3-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)prop-2-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hept-6-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)non-8-yn-1-yl)amino)cyclohexyl)methan (Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)ethyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)propyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)butyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)amino)cyclohexyl)methyl)amino )-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)amino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)amino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)amino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(( 5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)amino)cyclohexyl)methyl )Amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1r,4r)-4-(5 -(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynylamino)cyclohexyl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((((1s,4s)-4-(5 -(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-ynylamino)cyclohexyl)methyl)amino)- 3-nitrophenyl)sulfonyl)benzamide;

    (2S,4R)-1-((S)-2-(4-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)butyrylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(5-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)valerylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(6-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)hexanoylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(7-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)heptanoylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(8-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)octanoylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(9-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)nonanoylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(11-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)undecanoylamino) -3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((4-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)butyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((5-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)pentyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((6-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)hexyl)amino)- 3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((7-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)heptyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((8-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)octyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((9-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)nonyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((11-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)undecyl) Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(4-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)butyrylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide ；

    (2S,4R)-1-((S)-2-(5-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)valerylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide ；

    (2S,4R)-1-((S)-2-(6-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)hexanoylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide ；

    (2S,4R)-1-((S)-2-(7-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)heptanoylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide ；

    (2S,4R)-1-((S)-2-(8-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)octanoylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide ；

    (2S,4R)-1-((S)-2-(9-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)nonanoylamino)-3 ,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide ；

    (2S,4R)-1-((S)-2-(11-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine- 5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2 -Yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)undecanoylamino) -3,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- Formamide

    (2S,4R)-1-((S)-2-((4-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)butyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- Formamide

    (2S,4R)-1-((S)-2-((5-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)pentyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- Formamide

    (2S,4R)-1-((S)-2-((6-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)hexyl)amino)- 3,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-methyl Amide

    (2S,4R)-1-((S)-2-((7-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)heptyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- Formamide

    (2S,4R)-1-((S)-2-((8-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)octyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- Formamide

    (2S,4R)-1-((S)-2-((9-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)nonyl)amino) -3,3-Dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- Formamide

    (2S,4R)-1-((S)-2-((11-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b]pyridine -5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]- 2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)undecyl) Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine- 2-formamide;

    (2S,4R)-1-((S)-2-((2-(2-(2-(4-(4-(((4-(N-(2-((1H-pyrrolo[2 ,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl )Ethoxy)ethoxy)ethyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrole Alkyl-2-carboxamide;

    (2S,4R)-1-((S)-14-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)-2-(tert-butyl)- 6,9,12-Trioxa-3-aza (azatetradecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-methan Amide

    (2S,4R)-1-((S)-17-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)-2-(tert-butyl)- 6,9,12,15-Tetraoxa-3-azaheptadecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2- Formamide

    (2S,4R)-1-((S)-20-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)-2-(tert-butyl)- 6,9,12,15,18-Pentoxa-3-azaeicosanyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine- 2-formamide;

    (2S,4R)-1-((S)-2-((2-(2-(2-(4-(4-(((4-(N-(2-((1H-pyrrolo[2 ,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1 '-Biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl )Ethoxy)ethoxy)ethyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazole-5) -Base) phenyl) ethyl) pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-14-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)-2-(tert-butyl)- 6,9,12-Trioxa-3-aza (azatetradecanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl )Ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-17-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)-2-(tert-butyl)- 6,9,12,15-Tetraoxa-3-azaheptadecanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)benzene Yl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-20-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)cyclohexyl)piperazin-1-yl)-2-(tert-butyl)- 6,9,12,15,18-Pentoxa-3-azaeicosanyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl) )Phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(5-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)valeramido)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4 -Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(6-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)hexanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4 -Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(7-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)heptanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4 -Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(8-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)octanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4 -Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(9-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)nonanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4 -Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(10-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)decanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4-(4 -Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(11-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)undecanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N-(4- (4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(6-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-6-oxohexanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N- (4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(7-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-7-oxoheptanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N- (4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(8-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-8-oxooctanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N- (4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(9-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-9-oxononanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N- (4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(10-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-10-oxodecanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N- (4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(11-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-11-oxoundecanoylamino)-3,3-dimethylbutyryl)-4-hydroxy- N-(4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-((3-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline- 4-yl)pent-4-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-((3-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline- 4-yl)hex-5-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-((3-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline- 4-yl)hept-6-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-((3-(4-(8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline- 4-yl)oct-7-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-((3-(4-(9-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline- 4-yl)non-8-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-((3-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline- 5-yl)pent-4-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine -1-yl)-N-((4-((3-(4-(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline- 5-yl)hex-5-yn-1-yl)piperazin-1-yl)propyl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(3-( 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)propionylamino)ethyl )Azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro- 4-(((Tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(2-(3-( 2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy )Propionylamino)ethyl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N- ((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-3-((1-(1-((2- (2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-12-oxo-3,6,9-trioxa- 13-azapentadecane-15-yl)azetidin-3-yl)methoxy)-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl )-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide;

    N-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(((3- Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methyl)-4 '-Chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)-1-((2-(2,6-di (Oxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxapentadecane-15-amide;

    N-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(((3- Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methyl)-4 '-Chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)-1-((2-(2,6-di (Oxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12,15-pentaoxaoctadecane-18-amide;

    (2S,4R)-1-((S)-16-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b)pyridin-5-yl)oxy Yl)-4-(((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazine -1-yl)methyl)-4'-chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)-2-(tert-butyl Yl)-4,13-dioxo-7,10-dioxa-3,14-diazahexadecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl) )Benzyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-19-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b)pyridin-5-yl)oxy Yl)-4-(((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazine -1-yl)methyl)-4'-chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)-2-(tert-butyl Yl)-4,16-dioxo-7,10,13-trioxa-3,17-diazahexadecanoyl)-4-hydroxy-N-(4-(4-methylthiazole- 5-yl)benzyl)pyrrolidine-2-carboxamide;

    N1-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(((3- Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methyl)-4 '-Chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)-N16-((S)-1-((2S ,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1- (Oxobut-2-yl)-4,7,10,13-tetraoxahexadecane diamide;

    N1-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(((3- Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methyl)-4 '-Chloro-[1,1'-Biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)-N19-((S)-1-((2S ,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1- (Oxobut-2-yl)-4,7,10,13,16-pentaoxaoctadecane diamide;

    (1S,3R,5S)-N-(2-(3-(((2-((4-(3-((1H-pyrrolo[2,3-b)pyridin-5-yl)oxy) -4-(((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazine-1 -Yl)methyl)-4'-chloro-[1,1'-biphenyl]-3-yl)oxy)methyl)azetidin-1-yl)ethyl)adamantane-1- Formamide

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((3-((1-(2-(2-((1S,3R, 5S)-adamantan-1-yl)acetamido)ethyl)azetidin-3-yl)methoxy)-4'-chloro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzyl Amide

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1'-(3-(1-( 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-1H-1,2,3-triazol-4-yl)propyl) -[1,4'-Dipiperidin]-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(1-(2 -(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-1H-1,2,3-triazol-4-yl)propyl)piper (Pyridin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(3-(1-(2 -(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-1H-1,2,3-triazol-4-yl)propyl)piper (Pyridin-3-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

    (2S,4R)-1-((S)-2-((5-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)pentyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((6-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)hexyl)amino)-3,3-dimethylbutyryl )-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((7-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)heptyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((8-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)octyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((9-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)nonyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((10-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4 ,4-Dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl) -2-((Trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)decyl)amino)-3,3-dimethylbutyl Acyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)butyryl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine- 2-formamide;

    (2S,4R)-1-((S)-2-(5-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)valeryl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine- 2-formamide;

    (2S,4R)-1-((S)-2-(6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)hexanoyl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine- 2-formamide;

    (2S,4R)-1-((S)-2-(7-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)heptanoyl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine- 2-formamide;

    (2S,4R)-1-((S)-2-(8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)octanoyl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine- 2-formamide;

    (2S,4R)-1-((S)-2-(9-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)nonanoyl Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine- 2-formamide;

    (2S,4R)-1-((S)-2-(11-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl )Oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl) (Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)undecane Alkylamido)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl) Pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((4-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)butyl (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrole Alkyl-2-carboxamide;

    (2S,4R)-1-((S)-2-((5-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)pentan (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrole Alkyl-2-carboxamide;

    (2S,4R)-1-((S)-2-((6-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)hexyl )Amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine -2-carboxamide;

    (2S,4R)-1-((S)-2-((7-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)heptan (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrole Alkyl-2-carboxamide;

    (2S,4R)-1-((S)-2-((8-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)octane (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrole Alkyl-2-carboxamide;

    (2S,4R)-1-((S)-2-((9-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)nonane (Yl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrole Alkyl-2-carboxamide;

    (2S,4R)-1-((S)-2-((11-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridine-5- Yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl )Methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)10 Monoalkyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl ) Pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-((2-(2-(2-(4-(((4-(N-(2-((1H-pyrrolo[2,3- b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-linked (Phenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]- 1'-yl)ethoxy)ethoxy)ethyl)amino)-3,3-dimethylbutyryl)-4-hydroxy-N-((S)-1-(4-(4-methyl) Thiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-14-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl)oxy )-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl) (Piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)-2-(tert Butyl)-6,9,12-trioxa-3-azatetradecanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl )Phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-17-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl)oxy )-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl) (Piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)-2-(tert Butyl)-6,9,12,15-tetraoxa-3-azaheptadecanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazole-5 -Base) phenyl) ethyl) pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-20-(4-(((4-(N-(2-((1H-pyrrolo[2,3-b)pyridin-5-yl)oxy )-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl) (Piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)methyl)-[1,4'-dipiperidine]-1'-yl)-2-(tert Butyl)-6,9,12,15,18-pentaoxa-3-azaeicosanyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazole) -5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide;

    (2S,4R)-1-((S)-2-(5-(4-(3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl -3,4,5,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-(( (Trifluoromethyl)sulfonyl)phenyl)amino)propyl)piperazin-1-yl)-5-oxopentanoylamino)-3,3-dimethylbutyryl)-4-hydroxy-N- (4-(4-Methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide; or

    2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5 ,6-Tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-(5-(2-(1 -Methyl-2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pent-4-yn-1-yl)piperidin-3-yl)methyl (Yl)amino)-3-nitrophenyl)sulfonyl)benzamide.
67. A pharmaceutical composition comprising the compound of formula (II) according to any one of claims 51 to 66 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
68. The pharmaceutical composition of claim 67, further comprising at least one additional therapeutic agent.
69. The use of the compound of formula (II) according to any one of claims 51 to 66, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 67 or 68, for preparation for prevention And/or agents for treating diseases related to BCL-2 family proteins or Hedgehog signaling pathway.
70. The use according to claim 69, wherein the diseases include myelofibrosis, renal fibrosis, liver fibrosis, liver cirrhosis and tumors.
71. The compound of formula (II) according to claim 70, or a pharmaceutically acceptable salt thereof, wherein the tumor is a tumor dependent on BCL-2 family proteins, or a tumor dependent on the Hedgehog signaling pathway.
72. The compound of formula (II) according to claim 71, or a pharmaceutically acceptable salt thereof, wherein the tumor is a tumor dependent on BCL-2 and/or MCL-1 and/or BCL-XL protein.
73. The use of claim 69, wherein the disease is selected from the group consisting of: myeloma, including multiple myeloma (MM); leukemia, including chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia ( ALL), acute myeloid leukemia (AML); lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B-cell lymphoma; myelodysplastic syndrome; bone marrow fibrosis, renal fibrosis, Liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer; prostate cancer; medulloblastoma; basal cell carcinoma; Ge Lin syndrome; esophageal cancer; colorectal cancer; medulloblastoma; rhabdomyosarcoma; hepatoblastoma; glioma; astrocytoma; liver cancer; liver cirrhosis; soft tissue sarcoma; and pancreatic cancer.
74. The compound of formula (II) or a pharmaceutically acceptable salt thereof according to any one of claims 51 to 66, which is used for the prevention and/or treatment of diseases related to BCL-2 family proteins or Hedgehog signaling pathway.
75. The compound of formula (II) according to claim 74, or a pharmaceutically acceptable salt thereof, wherein the diseases include myelofibrosis, renal fibrosis, liver fibrosis, liver cirrhosis, and tumors.
76. The compound of formula (II) according to claim 75, or a pharmaceutically acceptable salt thereof, wherein the tumor is a tumor dependent on BCL-2 family proteins, or a tumor dependent on the Hedgehog signaling pathway.
77. The compound of formula (II) according to claim 76, or a pharmaceutically acceptable salt thereof, wherein the tumor is a tumor dependent on BCL-2 and/or MCL-1 and/or BCL-XL protein.
78. The compound of formula (II) according to claim 74, or a pharmaceutically acceptable salt thereof, wherein the disease is selected from the group consisting of: myeloma, including multiple myeloma (MM); leukemia, including chronic Lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML); lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B cell lymphoma; Myelodysplastic syndrome; myelofibrosis, renal fibrosis, liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer Prostate cancer; Medulloblastoma; Basal cell carcinoma; Goring syndrome; Esophageal cancer; Colorectal cancer; Medulloblastoma; Rhabdomyosarcoma; Hepatoblastic carcinoma; Glioma; Astrocytoma; Liver cancer ; Liver cirrhosis; soft tissue sarcoma; and pancreatic cancer.
79. A method for treating or preventing diseases related to BCL-2 family proteins or Hedgehog signaling pathway, which comprises administering to a subject in need thereof a therapeutically effective amount of the formula (II) according to any one of claims 51 to 66 The compound, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 67 or 68.
80. The method of claim 79, wherein the diseases include myelofibrosis, renal fibrosis, liver fibrosis, liver cirrhosis, and tumors.
81. The method of claim 79, wherein the tumor is a tumor that depends on BCL-2 family proteins, or a tumor that depends on the Hedgehog signaling pathway.
82. The method of claim 81, wherein the tumor is a tumor dependent on BCL-2 and/or MCL-1 and/or BCL-XL protein.
83. The method of claim 79, wherein the disease is selected from the group consisting of: myeloma, including multiple myeloma (MM); leukemia, including chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML); lymphoma, including non-Hodgkin’s lymphoma, anaplastic large cell lymphoma, diffuse large B cell lymphoma; myelodysplastic syndrome; bone marrow fibrosis, renal fibrosis , Liver fibrosis; breast cancer; lung cancer, including non-small cell lung cancer and small cell lung cancer; melanoma; mesothelioma; neuroblastoma; osteosarcoma; ovarian cancer; prostate cancer; medulloblastoma; basal cell carcinoma; Goering syndrome; esophageal cancer; colorectal cancer; medulloblastoma; rhabdomyosarcoma; hepatoblastic carcinoma; glioma; astrocytoma; liver cancer; liver cirrhosis; soft tissue sarcoma; and pancreatic cancer.
84. The method according to any one of claims 79-83, wherein at least one selected from the group consisting of nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural cavity administration Drug, peritoneal, vaginal, intramuscular, subcutaneous, transdermal, epidural, intrathecal, and intravenous administration methods are administered to the subject .

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