WO2023075479A1 - Novel thieno[2,3-d]pyrimidine derivative, method for preparing same, and pharmaceutical composition for prevention or treatment of cancer or autoimmune disease comprising same as active ingredient - Google Patents

Novel thieno[2,3-d]pyrimidine derivative, method for preparing same, and pharmaceutical composition for prevention or treatment of cancer or autoimmune disease comprising same as active ingredient Download PDF

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WO2023075479A1
WO2023075479A1 PCT/KR2022/016628 KR2022016628W WO2023075479A1 WO 2023075479 A1 WO2023075479 A1 WO 2023075479A1 KR 2022016628 W KR2022016628 W KR 2022016628W WO 2023075479 A1 WO2023075479 A1 WO 2023075479A1
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Prior art keywords
amino
pyrimidin
methylthieno
phenyl
propan
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PCT/KR2022/016628
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French (fr)
Korean (ko)
Inventor
김소영
문희겸
임춘영
배기훈
오유진
이승연
추민기
하유나
김남희
한예리
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재단법인 대구경북첨단의료산업진흥재단
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Priority claimed from KR1020220138748A external-priority patent/KR20230061269A/en
Application filed by 재단법인 대구경북첨단의료산업진흥재단 filed Critical 재단법인 대구경북첨단의료산업진흥재단
Publication of WO2023075479A1 publication Critical patent/WO2023075479A1/en

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention relates to a thieno[2,3-d]pyrimidine derivative, a method for preparing the same, and a pharmaceutical composition for preventing or treating cancer or autoimmune disease containing the same as an active ingredient.
  • Interleukin-1 (IL-1) receptor-associated kinase-4 is a serine/threonine kinase enzyme that plays an essential role in signal transduction by the Toll/IL-1 receptor (TIR).
  • TIR Toll/IL-1 receptor
  • Various IRAK enzymes are key components in signal transduction pathways mediated by the interleukin-1 receptor (IL-1R) and Toll-like receptors (TLRs).
  • IL-1R interleukin-1 receptor
  • TLRs Toll-like receptors
  • IRAK proteins as well as MyD88, have been demonstrated to play a role in the transduction of signals other than those derived from the IL-1R receptor, including signals triggered by activation of the IL-18 receptor and the LPS receptor.
  • IRAK-4 is considered the "master IRAK". Under overexpression conditions, all IRAKs can mediate activation of nuclear factor- ⁇ and stress-induced mitogen-activated protein kinase (MAPK)-signaling cascades. However, only IRAK-1 and IRAK-4 were found to have active kinase activity.
  • MAPK stress-induced mitogen-activated protein kinase
  • IRAK-1 kinase activity may be dispensable for its function in IL-1 induced NF- ⁇ activation, whereas IRAK-4 requires its kinase activity for signal transduction.
  • IRAK4 inhibitors are implicated as beneficial therapeutics for inflammatory diseases, sepsis and autoimmune disorders.
  • Non-Patent Document 1 Wietek C, et al, Mol. Interv. 2: 2002, 212-215.
  • a tumorigenically active MyD88 mutation in diffuse large B-cell lymphoma has been shown to be sensitive to IRAK4 inhibition.
  • IRAK4 inhibitors can block signals transmitted by the TLR pathway, as well as signals transmitted by IL-1 and the IL-1 family. Modulation of IL-1 is associated with gout, gouty arthritis, type 2 diabetes, autologous inflammatory disease, tumor necrosis factor receptor-associated periodic syndrome, familial Mediterranean fever, adult-type Still's disease, systemic juvenile idiopathic arthritis, stroke, and host It has already been found to be effective for various diseases such as graft disease, asymptomatic multiple myeloma, recurrent pericarditis, osteoarthritis and emphysema (Non-Patent Document 3, Dinarello, C.A., 2011, Eur. J. Immunol. 41: 1203-1217).
  • IL-1 can trigger the differentiation of the effector T cell subset Th17 as an important link in the adaptive immune system. Therefore, IRAK4 inhibitors are predicted to be effective in Th17 cell-related diseases including multiple sclerosis, psoriasis, inflammatory bowel disease, autoimmune uveitis and rheumatoid arthritis.
  • An object of the present invention is to provide novel thieno[2,3-d]pyrimidine derivatives that inhibit IRAK4.
  • Another object of the present invention is to provide a novel pharmaceutical composition for preventing or treating cancer or autoimmune diseases.
  • Another object of the present invention is to provide a novel health functional food composition for preventing or improving cancer or autoimmune diseases.
  • the present invention provides a compound represented by Formula 1 below, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
  • R 1 is hydrogen or C 1-10 alkyl
  • R 2 is unsubstituted or substituted C 6-10 aryl, unsubstituted or substituted 5-10 membered heteroaryl, or
  • R 1 and R 2 together with the nitrogen atom to which they are bonded form an unsubstituted or substituted 5-10 membered heteroaryl;
  • R 2a and R 2b are independently hydrogen or C 1-10 alkyl
  • R 3 is substituted C 3-10 cycloalkyl, substituted C 6-10 aryl or substituted 5-10 membered heteroaryl ;
  • substituted 3-10 membered heterocycloalkyl is substituted with C 1-10 alkyl, C 3-10 cycloalkyl , 3-10 membered heterocycloalkyl or -NR 3a R 3b ;
  • R 3a and R 3b are each independently hydrogen, C 1-10 alkyl unsubstituted or substituted with -N(C 1-10 alkyl) 2 , or C 1-10 alkoxycarbonyl ;
  • R 4 is hydrogen or C 1-10 alkyl
  • Step 2 a method for preparing a compound represented by Chemical Formula 1 including the step (Step 2) of preparing a compound represented by Chemical Formula 1 by reacting a compound represented by Chemical Formula 2 with a compound represented by Chemical Formula 3.
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in Formula 1 above.
  • the present invention is for preventing or improving cancer or autoimmune diseases containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • a pharmaceutical composition is provided.
  • the compound represented by Formula 1 described herein is expected to be useful in autoimmune diseases by suppressing cancer or cytokine expression due to excellent cytotoxicity against cancer cells while exhibiting excellent inhibitory activity against IRAK4.
  • alkylene or “alkyl” includes straight or branched chain saturated hydrocarbon moieties, unless otherwise specified.
  • C 1-6 alkyl means an alkyl having a backbone of 1 to 6 carbons. Specifically, C 1-6 alkyl is methyl, ethyl, n-propyl, i-propyl, n - butyl, i-butyl, t-butyl, n-pentyl, i-pentyl, t-pentyl, sec-pentyl, neopentyl , hexyl, etc., and C 6 alkyl is a fully saturated hydrocarbon having 6 carbons, including regioisomers.
  • Alkyl means a monovalent substituent
  • alkylene means a divalent substituent.
  • cycloalkyl refers to a cyclic hydrocarbon moiety that forms a ring as a saturated hydrocarbon moiety
  • C 3-6 cycloalkyl refers to a cyclic hydrocarbon moiety containing 3 to 6 carbons as ring atoms. hydrocarbon residues.
  • heterocycloalkyl means, unless otherwise specified, one or more selected from N, O, or S (e.g., 1-5, 1-4, 1-3, 1-2, 1) means a monovalent saturated moiety consisting of 1 to 3 rings containing heteroatoms. The two or three rings may be bridged, fused or spiro heterocycloalkyl. When composed of a plurality of rings, heteroatoms may be present in all rings or only in some rings. “3-10 membered heterocycloalkyl” refers to a heterocycloalkyl having 3 to 10 ring atoms. On the other hand, when referring to a 3-10-membered heterocycloalkyl containing one or more N, it refers to one that always contains one or more nitrogen atoms (N) as a heteroatom constituting a ring.
  • N nitrogen atoms
  • aryl refers to an aromatic radical in which a single ring or two or three hydrocarbon aromatic rings are fused.
  • heteroaryl means one or more (e.g., 1-5, 1-4, 1-3, 1-2, 1) containing one or more aromatic rings (the remaining ring atoms are C), or a fused aromatic radical of 2 or 3 rings. When composed of a plurality of rings, heteroatoms may be present in all rings or only in some rings. “5-10 membered heteroaryl” refers to a heteroaryl having 5 to 10 atoms constituting a ring. On the other hand, when referring to a 5-10 membered heteroaryl containing one or more N, it refers to one containing one or more nitrogen atoms (N) as a heteroatom constituting a ring.
  • Alkoxy means a substituent in which an alkyl is linked to an oxygen atom
  • C 1-10 alkoxy refers to a substituent in which C 1-10 alkyl is linked to an oxygen atom and substituted through an oxygen atom.
  • Halogen means a halogen atom such as F, Cl, Br, I.
  • DiC 1-10 alkylamino means a substituent in which an amino group (—NH 2 ) is substituted with two C 1-10 alkyl groups through nitrogen .
  • isomers refers to compounds of the present invention that have the same chemical or molecular formula but differ structurally or sterically. Such isomers include constitutional isomers (or structural isomers) and stereoisomers.
  • structural isomer includes skeletal isomers and tautomers.
  • stereoisomer refers to R or S isomers (or DL isomers) that are produced by having asymmetric carbon or heteroatom (P, S, Si, N, etc.) centers, and those that can be produced by having two or more asymmetric atom centers. Includes enantiomers or diastereomers, geometric isomers (trans, cis), and the like.
  • hydrate refers to a compound of the present invention that contains a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces. or a salt thereof.
  • the hydrate of the compound represented by Formula 1 of the present invention may contain a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces.
  • the hydrate may contain 1 equivalent or more, preferably 1 to 5 equivalents of water.
  • Such a hydrate may be prepared by crystallizing the compound represented by Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof of the present invention from water or a water-containing solvent.
  • solvate refers to a compound of the present invention or a salt thereof that contains a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces.
  • Preferred solvents in this regard are those that are volatile, non-toxic, and/or suitable for administration to humans.
  • pharmaceutically acceptable salt refers to a pharmaceutically acceptable salt formed by ionic bonding with a compound containing a carboxylic acid or amine functional group.
  • the compound represented by Formula 1 of the present invention can be used in the form of a pharmaceutically acceptable salt, and an acid addition salt formed by a pharmaceutically acceptable free acid is useful as the salt.
  • Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, etc., aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanedios.
  • Such pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulphate, sulphite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, i.
  • the acid addition salt according to the present invention can be prepared by a conventional method.
  • a precipitate formed by dissolving a derivative of Formula 1 in an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile, etc. and adding an organic or inorganic acid thereto It may be prepared by filtering and drying, or by distilling the solvent and excess acid under reduced pressure, drying it, and crystallizing it in an organic solvent.
  • a compound represented by Formula 1 below, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof are provided.
  • R 1 is hydrogen or C 1-10 alkyl
  • R 2 is unsubstituted or substituted C 6-10 aryl, unsubstituted or substituted 5-10 membered heteroaryl, or
  • R 1 and R 2 together with the nitrogen atom to which they are bonded form an unsubstituted or substituted 5-10 membered heteroaryl;
  • R 2a and R 2b are independently hydrogen or C 1-10 alkyl ;
  • R 3 is substituted C 3-10 cycloalkyl, substituted C 6-10 aryl or substituted 5-10 membered heteroaryl ;
  • substituted 3-10 membered heterocycloalkyl is substituted with C 1-10 alkyl, C 3-10 cycloalkyl , 3-10 membered heterocycloalkyl or -NR 3a R 3b ;
  • R 3a and R 3b are each independently hydrogen, C 1-10 alkyl unsubstituted or substituted with N(C 1-10 alkyl ) 2 , or C 1-10 alkoxycarbonyl ;
  • R 4 is hydrogen or C 1-10 alkyl
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is unsubstituted or substituted phenyl unsubstituted or substituted 5-10 membered heteroaryl containing at least one heteroatom selected from the group consisting of N and O, or
  • R 1 and R 2 together with the nitrogen atom to which they are bonded form a 5- to 10-membered heteroaryl containing one or more unsubstituted or substituted N atoms;
  • R 2a and R 2b are independently hydrogen or C 1-6 alkyl ;
  • R 3 is a 5-8 membered heteroaryl containing at least one heteroatom selected from the group consisting of substituted C 4-8 cycloalkyl, substituted phenyl or substituted N and O;
  • the 3-10 membered heterocycloalkyl is a 3-7 membered monocyclic heterocycloalkyl or a 7-10 membered spiro bicyclic heterocycloalkyl,
  • the substituted 3-10 membered heterocycloalkyl is C 1-6 alkyl , C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl containing at least one heteroatom selected from the group consisting of N and O, or -NR 3a R 3b is substituted;
  • R 3a and R 3b are each independently hydrogen, C 1-6 alkyl unsubstituted or substituted with N(C 1-6 alkyl) 2 , or C 1-6 alkoxycarbonyl ;
  • R 4 is hydrogen or C 1-6 alkyl
  • R 1 is hydrogen or C 1-4 alkyl
  • R 2 is an unsubstituted or substituted phenyl, an unsubstituted or substituted 5-6 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N and O, or one or more unsubstituted or substituted N atoms is a fused 9-10 membered heteroaryl comprising
  • R 1 and R 2 together with the nitrogen atom to which they are bonded form a 5-membered heteroaryl containing one or more unsubstituted or substituted N atoms;
  • R 2a and R 2b are independently hydrogen or C 1-4 alkyl ;
  • R 3 is substituted C 5-6 cycloalkyl, substituted phenyl or substituted 5-6 membered heteroaryl containing one or more N atoms;
  • substituted 4-10 membered heterocycloalkyl is substituted with C 1-4 alkyl , C 3-6 cycloalkyl, 3-7 membered heterocycloalkyl or -NR 3a R 3b ;
  • R 3a and R 3b are each independently hydrogen, C 1-4 alkyl unsubstituted or substituted with N(C 1-4 alkyl) 2 , or C 1-4 alkoxycarbonyl ;
  • R 4 is hydrogen or C 1-4 alkyl
  • R 1 is hydrogen
  • R 2 is unsubstituted or substituted phenyl, unsubstituted or substituted heteroaryl, wherein heteroaryl is pyridyl, pyrazolyl, oxazolyl, indazolyl or quinolinyl; or
  • R 1 and R 2 together with the nitrogen atom to which they are attached form a substituted imidazolyl
  • the substituted phenyl, substituted heteroaryl, and substituted imidazolyl are each independently selected from unsubstituted or substituted C 1-4 alkyl, halogen, C 1-4 alkoxy, hydroxy, C 1-4 alkylsulfonyl , di(C 1-4 alkyl)aminosulfonyl, C 1-4 alkoxycarbonyl, di(C 1-4 alkyl)phosphinyl , carboxyl, hydroxy substituted oxetanyl, hydroxy substituted cyclobutyl, and substituted with one or more selected from the group consisting of CONH 2 , wherein the substituted C 1-4 alkyl is substituted with hydroxy, C 1-4 alkoxy, halogen or CN;
  • R 3 is substituted cyclopentyl, cyclohexyl, phenyl or substituted pyrazolyl
  • the substituent of the substituted 3-10 membered heterocycloalkyl is C 1-2 alkyl , C 3-4 cycloalkyl, aziridinyl, azetidinyl, pyrrolidinyl, methylpiperazinyl, oxetanyl, NMe 2 , NEt 2 , NHMe, NHCO 2 t-Bu, methoxy, NH 2 or acetyl;
  • R 4 is hydrogen
  • R 3 is a compound selected from the following, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof:
  • substituted 3-10 membered heterocycloalkyl is substituted with C 1-10 alkyl, C 3-10 cycloalkyl , 3-10 membered heterocycloalkyl or -NR 3a R 3b ;
  • R 3a and R 3b are each independently hydrogen or C 1-10 alkyl unsubstituted or substituted with N(C 1-10 alkyl ) 2 ;
  • R 7a , R 8a and R 8b are each independently hydrogen, unsubstituted or hydroxy- or halogen-substituted C 1-10 alkyl, C 1-10 alkoxy , halogen , or C 1-10 alkoxycarbonyl;
  • R 9 is C 1-10 alkyl substituted with hydroxy or 3-10 membered heterocycloalkyl ;
  • R 9a and R 9b are hydrogen or hydroxy
  • n 1 or 2;
  • R 1 is hydrogen
  • R 2 is selected from;
  • R 1 and R 2 are bonded to each other form
  • R 3 is selected from
  • R 4 is hydrogen
  • R 5 is hydrogen or methyl
  • the compound represented by Formula 1 is selected from the following compound groups.
  • a method for preparing a compound represented by Chemical Formula 1 comprising the step of preparing a compound represented by Chemical Formula 1 by reacting a compound represented by Chemical Formula 2 with a compound represented by Chemical Formula 3.
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in Formula 1 above.
  • Step 1 is a step of subjecting a compound represented by Chemical Formula 2 to a compound represented by Chemical Formula 3 by a nucleophilic substitution reaction, wherein the compound represented by Chemical Formula 2 is reacted with a compound represented by Chemical Formula 3 to obtain Chemical Formula
  • This is a step for preparing a compound displayed in 1 package.
  • an organic solvent such as DMF or sec-butanol may be used as the solvent, and conditions commonly used for nucleophilic substitution reactions may be used.
  • the preparation method is not limited to one embodiment of the present invention presented as an example, and can be performed by modifying solvents, reactants, temperature conditions, etc. under conventional organic chemistry knowledge.
  • the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof is intended for use in the prevention or treatment of cancer or autoimmune diseases.
  • a pharmaceutical composition for preventing or treating cancer or autoimmune disease containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the compound represented by Formula 1 is characterized in that it inhibits IRAK4.
  • the compound represented by Formula 1 is characterized by suppressing the expression of TNF- ⁇ and IL-6, which are inflammatory cytokines related to autoimmune diseases, as inflammatory factors.
  • the cancer is any one of leukemia, lymphoma, multiple myeloma, bladder cancer, breast cancer, colon cancer, kidney cancer, liver cancer, lung cancer, small cell lung cancer, esophageal cancer, gallbladder cancer, ovarian cancer, pancreatic cancer, stomach cancer, cervical cancer, thyroid cancer, prostate cancer, or skin cancer. may be
  • the autoimmune disease is psoriasis, rheumatoid arthritis, vasculitis, inflammatory bowel disease, dermatitis, osteoarthritis, asthma, inflammatory muscle disease, allergic disease, vaginitis, interstitial cystitis, scleroderma, osteoporosis, eczema, allogeneic or xenogeneic transplant rejection , Graft-versus-host disease (GVHD), lupus erythematosus, inflammatory disease, type I diabetes, pulmonary fibrosis, dermatomyositis, Sjogren's syndrome, thyroiditis, myasthenia gravis, autoimmune hemolytic anemia, multiple sclerosis, cystic fibrosis, chronic recurrent hepatitis , primary biliary cirrhosis, allergic conjunctivitis, or atopic dermatitis.
  • GVHD Graft-versus-host disease
  • lupus erythematosus inflammatory disease
  • the term "contained as an active ingredient” means that it is contained in a dosage range that results in the prevention, improvement, or treatment of cancer or autoimmune disease, and the dosage range may vary depending on the severity and formulation. The number of times of application may also vary according to the age, weight and constitution of the target subject.
  • the compound represented by Formula 1 in the pharmaceutical composition of the present invention is, for example, 0.001 mg/kg or more, preferably 0.1 mg/kg or more, more preferably 10 mg/kg or more, more preferably 100 mg/kg or more, even more preferably 250 mg/kg or more, and most preferably 0.1 g/kg or more.
  • the upper limit of the amount of the compound represented by Formula 1 included in the pharmaceutical composition of the present invention can be selected and implemented within an appropriate range by those skilled in the art.
  • the pharmaceutical composition according to the present invention may include an effective amount of the compound represented by Formula 1 alone or may include one or more pharmaceutically acceptable carriers, excipients, or diluents.
  • the pharmaceutically acceptable carrier, excipient or diluent refers to a material that is physiologically acceptable and does not cause an allergic reaction such as gastrointestinal disorder or dizziness or similar reaction when administered to humans.
  • the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, but are not limited thereto.
  • fillers, anti-coagulants, lubricants, wetting agents, flavoring agents, emulsifiers and preservatives may be further included.
  • the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be administered in various oral and parenteral dosage forms during clinical administration.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in one or more compounds, such as starch, calcium carbonate, sucrose or lactose ( lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc.
  • Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, and emulsions.
  • Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
  • a pharmaceutical composition comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient may be administered parenterally, and parenteral administration is performed by subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection. depending on how
  • the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof is mixed in water together with a stabilizer or buffer to prepare a solution or suspension, which is prepared in an ampoule or vial unit dosage form can be manufactured with
  • the composition may be sterilized and/or contain preservatives, stabilizers, hydration agents or emulsification accelerators, salts and/or buffers for osmotic pressure control, and other therapeutically useful substances, and may contain conventional methods such as mixing and granulation. It can be formulated according to the coating or coating method.
  • prevention means suppressing the symptoms of cancer or autoimmune disease by administering, ingesting, or applying the pharmaceutical composition or health functional food composition of the present invention to a subject not suffering from cancer or autoimmune disease.
  • blocking it means preventing symptoms of cancer or autoimmune disease from occurring in advance.
  • the term "treatment” refers to the cure of symptoms of cancer or autoimmune disease as well as the treatment of symptoms of cancer or autoimmune disease as a result of administering the pharmaceutical composition of the present invention to an individual suffering from cancer or autoimmune disease. It includes partial cure, improvement and remission.
  • the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
  • the term "pharmaceutically effective amount” means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment or improvement, and the effective dose level is the type and severity of the subject, age, It may be determined according to factors including sex, activity of drug, sensitivity to drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used concurrently, and other factors well known in the medical field. Examples include 0.001 mg/kg or more, 0.1 mg/kg or more, 10 mg/kg or more, 100 mg/kg or more, 250 mg/kg or more, and 0.1 g/kg or more. The upper limit of the amount of the pharmaceutical composition of the present invention can be selected and implemented by those skilled in the art within an appropriate range.
  • the compound represented by Formula 1 may be used in the form of not only pharmaceutically acceptable salts thereof, but also stereoisomers, solvates, and hydrates that may be prepared therefrom.
  • a pharmaceutical composition for preventing or treating cancer containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient is administered as an individual therapeutic agent, It can be used in combination with other anticancer drugs currently in use.
  • a pharmaceutical composition for preventing or treating cancer containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient is administered in combination with an anticancer agent. effect can be enhanced.
  • a health functional food composition for preventing or improving cancer or autoimmune diseases containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the term "improvement" means that the pharmaceutical composition or food composition of the present invention is administered, ingested, or applied to a subject suffering from cancer or autoimmune disease to reduce or alleviate the symptoms of cancer or autoimmune disease. am.
  • cancer or autoimmunity comprising the step of administering to a subject in need of a compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof described herein.
  • a method for preventing or treating a disease is provided.
  • a compound represented by Formula 1 described herein, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof is used to prepare a medicament for preventing or treating cancer or autoimmune diseases.
  • UV detector 254nm
  • UV detector 254nm
  • UV detector 254nm
  • Step 1 Preparation of 2-(6-((2-chlorothieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol
  • Step 2 2-(6-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridine -2-yl)propan-2-ol
  • Step 1 Methyl2-chloro-4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxylate manufacturing
  • a target compound was prepared by performing the same method as in step 1 of Example 1 above. MS m/z : 393 [M+H] +
  • Step 2 sec-butyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropane- Preparation of 2-yl) pyridin-2-yl) amino) thieno [2,3-d] pyrimidine-5-carboxylate
  • a target compound was prepared by performing the same method as in step 2 of Example 1 above. MS m/z : 634 [M+H] +
  • the compound of Example 20 was prepared in the same manner as in the preparation method of Example 19, except for the reactants.
  • Step 1 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl) Preparation of )pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxylic acid
  • Step 2 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl) Preparation of )pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxamide
  • Example 22 The compound of Example 22 was prepared in the same manner as in Example 21, except for the reactants.
  • Step 1 Preparation of 2-(6-((2-chloro-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol
  • a target compound was prepared in a manner similar to step 1 of Example 1 above.
  • Step 2 (1R,4R)-4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d Preparation of ]pyrimidin-2-yl)amino)cyclohexan-1-ol
  • Step 1 Methyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2- Preparation of yl) pyridin-2-yl) amino) thieno [2,3-d] pyrimidine-5-carboxylate
  • Step 1 Preparation of 5-(tert-butyl)-N-(2-chloro-5-methylthieno[2,3-d]pyrimidin-4-yl)isoxazol-3-amine
  • Step 2 N4-(5-(tert-butyl)isoxazol-3-yl)-5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3- d] Preparation of pyrimidine-2,4-diamine
  • a target compound was prepared by performing similarly to step 2 of Example 1 above. MS m/z : 478 [M+H] +
  • Examples 54 to 63 Compounds of Examples 54-63 were prepared in a similar manner to Example 1.
  • Step 1 Preparation of 2-(3-((2-chloro-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol
  • a target compound was prepared in the same manner as in Example 1, step 1. MS m/z : 334 [M+H] +
  • Step 2 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno Preparation of [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol
  • Example 65 The compounds of Examples 65-68, 70-73, 75-76, and 78-80 were prepared in a similar manner to Example 1.
  • Example 69, 74, 77 and 81 were prepared in a similar manner to Example 64.
  • the compound of Example 81 was obtained in the form of a 2,2,2-trifluoroacetic acid salt as it was after purification by Prep HPLC.
  • Step 1 2-(6-((2-((3-methoxy-4-(4-(methylamino)piperidin-1-yl)phenyl)amino)-5-methylthieno[2,3 -d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol, the preparation of 2,2,2-trifluoroacetic acid
  • Example 86 The compounds of Examples 86, 88-89, 101, 103, 108, 115, 117, 121, 124-125, and 128-130 were prepared in a similar manner to Example 64.
  • Step 1 Preparation of 5-(tert-butyl)-N-(2-chloro-5-methylthieno[2,3-d]pyrimidin-4-yl)isoxazol-3-amine
  • Example 135> The compound of Example 135 was prepared in a similar manner to Example 134.
  • Example 136-144, 147, 150-153, 155-161, 170, 172-178, 183-184, 186-191, 194-199, 201, 205, 207-209 in a similar manner to Example 1 compound was prepared.
  • Example 145-146 and 179-180 were prepared in a similar manner to Example 82.
  • Example 149 The compound of Example 149 was prepared in a similar manner to Example 134 above.
  • Tables 1-2 below show the structures of the compounds of Examples 1-209.
  • Tables 3 to 6 below show the names of compounds and analysis results.
  • a white 384-well plate 12 concentrations of compounds (including DMSO control) serially diluted in 5-fold were added, and MBP substrate at a concentration of 0.1 ⁇ g/ ⁇ l and ATP at a concentration of 10 ⁇ M were added per well, respectively, to obtain the final compound. After making the concentration 0.000005 ⁇ 50 ⁇ M, it was incubated for 1 hour in a 25°C incubator. After 1 hour, 5 ⁇ l of ADP-Glo (Promega) was treated and incubated in a 25°C incubator for 40 minutes, followed by 10 ⁇ l of Detection Reagent (Promega) and incubated in a 25°C incubator for 30 minutes. Then, the degree of kinase activity was measured through the luminescence value with a microplate reader. IC50 values were calculated using GraphPad Prism 7.0 (GraphPad Software Inc.).
  • the measured IC50 values of kinases were classified as A when less than 100 nM, B when 100 nM to 1 ⁇ M, and C when greater than 1 ⁇ M, and are summarized in Table 7 below.
  • the compounds of the present invention can effectively inhibit IRAK4 and thus be useful for the treatment of cancer or autoimmune diseases.
  • Example IRAK4 IC 50 Example IRAK4 IC 50 One B 106 A 2 A 107 A 3 A 108 A 4 B 109 B 5 B 110 A 6 B 111 B 7 B 112 B 8 C 113 A 9 B 114 A 10 A 115 A 11 C 116 B 12 B 117 A 13 C 118 C 14 A 119 C 15 B 120 A 16 B 121 A 17 A 122 A 18 A 123 B 19 C 124 A 20 C 125 B 21 B 126 B 22 B 127 B 23 C 128 A 24 B 129 A 25 C 130 A 26 B 131 C 27 B 132 C 28 B 133 B 29 C 134 B 30 A 135 B 31 A 136 A 32 B 137 B 33 A 138 B 34 B 139 B 35 B 140 B 36 B 141 A 37 C 142 C 38 B 143 C 39 B 144 C 40 A 145 B 41 A 146 B 42 A 147 C 43 A 148 A 44 A 149 B 45 A 150 C 46 A 151 C 47 B 152 C 48 C 153 A 49 C
  • hPBMC frozen human Peripheral Blood Mononuclear Cells
  • the measured percentage value is more than 50%, it is classified as A grade, 50% to 10% as B grade, and less than 10% as C grade, and summarized in Table 8 below.
  • the compounds of the present invention effectively inhibit the expression of TNF- ⁇ and IL-6, which are cytokines as inflammatory factors related to autoimmune diseases, and it was confirmed that they are effective in treating autoimmune diseases. .
  • Example TNF- ⁇ IL-6 Example TNF- ⁇ IL-6 2 C C 122 B A 3 B B 124 B B 30 B B 128 C B 31 B B 130 B B 33 B C 136 C C 41 C C 154 B B 42 C C 158 B B 43 C C 162 B B 44 C C 163 A B 45 B C 164 A A 46 B C 165 B B 60 B B 166 A A 64 B B 169 C B 69 B B 171 B B 87 B B 181 B B 88 B B 182 B B 89 A B 185 A B 100 B B 186 B B B 101 C B 192 B B 104 B B 193 A A 105 C C 201 C C C 107 B B 202 A A 108 B B 203 B B 110 C C C 204 B B B 113 C C 206 A A 114 B C 115 B B B 117 B C 120 A B 121 A B

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Abstract

The present invention relates to a novel thieno[2,3-D]pyrimidine derivative, a method for preparing same, and a pharmaceutical composition for the prevention or treatment of cancer or an autoimmune disease, the pharmaceutical composition comprising same as an active ingredient. A compound represented by chemical formula 1 described in the present specification exhibits excellent inhibitory activity against IRAK4, and is expected to be useful for cancer due to excellent cytotoxicity against cancer cells or an autoimmune disease through inhibition of the expression of cytokines.

Description

신규한 티에노[2,3-D]피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 암 또는 자가면역질환의 예방 또는 치료용 약학적 조성물Novel thieno[2,3-D]pyrimidine derivative, preparation method thereof, and pharmaceutical composition for preventing or treating cancer or autoimmune disease containing the same as an active ingredient
본 발명은 티에노[2,3-d]피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 암 또는 자가면역질환의 예방 또는 치료용 약학적 조성물에 관한 것이다.The present invention relates to a thieno[2,3-d]pyrimidine derivative, a method for preparing the same, and a pharmaceutical composition for preventing or treating cancer or autoimmune disease containing the same as an active ingredient.
인터루킨-1(IL-1) 수용체 관련 키나제-4(IRAK-4)는 Toll/IL-1 수용체(TIR)에 의한 신호 형질도입에서 필수 역할을 하는 세린/트레오닌 키나제 효소이다. 다양한 IRAK 효소는 인터루킨-1 수용체(IL-1R) 및 Toll 유사 수용체(TLR)에 의해 매개되는 신호 형질도입 경로에서 주요 성분이다. 포유동물 IRAK 패밀리에는 IRAK-1, IRAK-2, IRAK-M 및 IRAK-4의 4종이 있다. 이들 단백질은 MyD88패밀리 어댑터(adaptor) 단백질과의 상호작용을 매개하는 통상의 N-말단 사멸 도메인 및 중심에 위치한 키나제 도메인을 특징으로 한다. MyD88뿐만 아니라 IRAK 단백질은 IL-18 수용체 및 LPS 수용체의 활성화에 의해 촉발되는 신호를 포함하는, IL-1R 수용체로부터 유래되는 것들 이외의 신호의 형질도입에서 역할을 하는 것으로 입증됐다. 4종의 포유동물 IRAK 패밀리 중에서, IRAK-4는 "마스터 IRAK"인 것으로 간주된다. 과발현 조건하에서, 모든 IRAK는 핵인자(nuclear factor)-κκ의 활성화 및 스트레스 유도된 미토겐 활성화된 단백질 키나제(MAPK)-신호화 케스케이드를 매개할 수 있다. 그러나, IRAK-1 및 IRAK-4 만이 활발한 키나제 활성을 갖는 것으로 밝혀졌다. IRAK-1 키나제 활성은 IL-1 유도된 NF-κ활성화에서 그의 기능이 불필요할 수 있는 반면, IRAK-4는 신호 형질도입에 그의 키나제 활성이 필요하다. Toll 유사/IL-1R 신호화 및 면역적 보호에서 IRAK4의 중심 역할을 고려하면, IRAK4 억제제는 염증성 질환, 패혈증 및 자가면역 장애의 유익한 치료제로서 관련되어 있다. (비특허문헌 1, Wietek C, et al, Mol. Interv. 2: 2002, 212-215). 또한, 미만성 거대 B-세포 림프종(diffuse large B-cell lymphoma)에서 종양발생적으로 활성인 MyD88 돌연변이는 IRAK4 억제에 민감한 것으로 확인된 바 있다. 전체 게놈 시퀀싱(WGS,　whole-genome sequencing)에 의해서도 MyD88 돌연변이가 만성 림프구성 백혈병과 연관되어 있는 것이 확인되었으며, 이는 백혈병 치료에서의 IRAK4 억제제 응용의 가능성을 제시하고 있다(비특허문헌 2, Puente, X.S. et al, 2011, Nature 475: 101-105).Interleukin-1 (IL-1) receptor-associated kinase-4 (IRAK-4) is a serine/threonine kinase enzyme that plays an essential role in signal transduction by the Toll/IL-1 receptor (TIR). Various IRAK enzymes are key components in signal transduction pathways mediated by the interleukin-1 receptor (IL-1R) and Toll-like receptors (TLRs). There are four species in the mammalian IRAK family: IRAK-1, IRAK-2, IRAK-M and IRAK-4. These proteins are characterized by a common N-terminal death domain and a centrally located kinase domain that mediate interactions with MyD88 family adapter proteins. IRAK proteins, as well as MyD88, have been demonstrated to play a role in the transduction of signals other than those derived from the IL-1R receptor, including signals triggered by activation of the IL-18 receptor and the LPS receptor. Of the four mammalian IRAK families, IRAK-4 is considered the "master IRAK". Under overexpression conditions, all IRAKs can mediate activation of nuclear factor-κκ and stress-induced mitogen-activated protein kinase (MAPK)-signaling cascades. However, only IRAK-1 and IRAK-4 were found to have active kinase activity. IRAK-1 kinase activity may be dispensable for its function in IL-1 induced NF-κ activation, whereas IRAK-4 requires its kinase activity for signal transduction. Given the central role of IRAK4 in Toll-like/IL-1R signaling and immune protection, IRAK4 inhibitors are implicated as beneficial therapeutics for inflammatory diseases, sepsis and autoimmune disorders. (Non-Patent Document 1, Wietek C, et al, Mol. Interv. 2: 2002, 212-215). In addition, a tumorigenically active MyD88 mutation in diffuse large B-cell lymphoma has been shown to be sensitive to IRAK4 inhibition. Whole-genome sequencing (WGS) also confirmed that the MyD88 mutation was associated with chronic lymphocytic leukemia, suggesting the possibility of IRAK4 inhibitor application in leukemia treatment (Non-Patent Document 2, Puente, X.S. et al, 2011, Nature 475: 101-105).
IRAK4 억제제는 TLR 경로에 의해 전달되는 신호를 차단할 수 있을뿐만 아니라 IL-1 및 IL-1가족에 의해 전달되는 신호 전달도 차단할 수 있다. IL-1에 대한 조절은 통풍, 통풍성 관절염, 제2형 당뇨병, 자가 염증성 질환, 종양 괴사 인자 수용체 관련 주기성 증후군, 가족성 지중해 열, 성인형 스틸병, 전신형 소아기 특발성 관절염, 뇌졸중, 대숙주성이식편병, 무증상 다발성 골수종, 재발성 심낭염, 골관절염 및 폐기종 등 다양한 질병에 효과적이라는 것이 이미 밝혀졌다(비특허문헌 3, Dinarello, C.A., 2011, Eur. J. Immunol. 41: 1203-1217). 알츠하이머 병의 마우스 모형에서, IL-1 수용체를 차단할 경우, 인지결손이 개선되고, Tau 단백질 병변이 저하되었으며, β아밀로이드 단백질의 올리고머화가 감소되었다. IL-1은 후천성 면역계의 중요한 연결 고리로서 효과 T 세포 서브 세트(effector T　cell subset) Th17의 분화를 작동시킬 수 있는 것이 증명되었다. 따라서， IRAK4 억제제는 다발성 경화증, 건선, 염증성 장질환, 자가면역성 포도막염 및 류마티스성 관절염 등을 포함한 Th17 세포 관련 질환에서 효과를 나타낼 것으로 예측된다.IRAK4 inhibitors can block signals transmitted by the TLR pathway, as well as signals transmitted by IL-1 and the IL-1 family. Modulation of IL-1 is associated with gout, gouty arthritis, type 2 diabetes, autologous inflammatory disease, tumor necrosis factor receptor-associated periodic syndrome, familial Mediterranean fever, adult-type Still's disease, systemic juvenile idiopathic arthritis, stroke, and host It has already been found to be effective for various diseases such as graft disease, asymptomatic multiple myeloma, recurrent pericarditis, osteoarthritis and emphysema (Non-Patent Document 3, Dinarello, C.A., 2011, Eur. J. Immunol. 41: 1203-1217). In a mouse model of Alzheimer's disease, blocking the IL-1 receptor improved cognitive deficits, reduced Tau protein lesions, and reduced oligomerization of β-amyloid protein. It has been demonstrated that IL-1 can trigger the differentiation of the effector T cell subset Th17 as an important link in the adaptive immune system. Therefore, IRAK4 inhibitors are predicted to be effective in Th17 cell-related diseases including multiple sclerosis, psoriasis, inflammatory bowel disease, autoimmune uveitis and rheumatoid arthritis.
본 발명의 목적은 IRAK4를 저해하는 신규한 티에노[2,3-d]피리미딘 유도체를 제공하는 데 있다.An object of the present invention is to provide novel thieno[2,3-d]pyrimidine derivatives that inhibit IRAK4.
본 발명의 다른 목적은 신규한 암 또는 자가면역질환의 예방 또는 치료용 약학적 조성물을 제공하는 데 있다.Another object of the present invention is to provide a novel pharmaceutical composition for preventing or treating cancer or autoimmune diseases.
본 발명의 다른 목적은 신규한 암 또는 자가면역질환의 예방 또는 개선용 건강기능식품 조성물을 제공하는 데 있다.Another object of the present invention is to provide a novel health functional food composition for preventing or improving cancer or autoimmune diseases.
상기 목적을 달성하기 위하여,In order to achieve the above purpose,
본 발명은 하기 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 제공한다.The present invention provides a compound represented by Formula 1 below, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
[화학식 1][Formula 1]
Figure PCTKR2022016628-appb-img-000001
Figure PCTKR2022016628-appb-img-000001
상기 화학식 1에서,In Formula 1,
R1은 수소 또는 C1-10알킬이고, R 1 is hydrogen or C 1-10 alkyl;
R2는 비치환 또는 치환된 C6- 10아릴, 비치환 또는 치환된 5-10원자헤테로아릴이거나, 또는R 2 is unsubstituted or substituted C 6-10 aryl, unsubstituted or substituted 5-10 membered heteroaryl, or
R1와 R2는 이들이 결합된 질소원자와 함께 비치환 또는 치환된 5-10원자헤테로아릴을 형성하고,R 1 and R 2 together with the nitrogen atom to which they are bonded form an unsubstituted or substituted 5-10 membered heteroaryl;
여기서, 상기 치환된 C6- 10아릴 및 치환된 5-10원자헤테로아릴은 각각 독립적으로 비치환 또는 치환된 C1- 10알킬, 비치환 또는 치환된 C3- 10시클로알킬, 할로겐, 하이드록시, C1- 10알콕시, -SO2R2a, -C(=O)NR2aR2b, -SO2NR2aR2b, 비치환 또는 치환된 3-10원자헤테로시클로알킬, -C(=O)OR2a, -P(=O)R2aR2b 로 하나 이상 치환되고, 이때 치환된 C1- 10알킬, 치환된 C3- 10시클로알킬 및 치환된 3-10원자헤테로시클로알킬은 독립적으로 하이드록시, C1- 10알콕시, 할로겐 및 CN로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환되고,Here, the substituted C 6-10 aryl and the substituted 5-10-membered heteroaryl are each independently selected from unsubstituted or substituted C 1-10 alkyl , unsubstituted or substituted C 3-10 cycloalkyl, halogen, hydroxy , C 1-10 alkoxy, -SO 2 R 2a , -C(=O)NR 2a R 2b , -SO 2 NR 2a R 2b , unsubstituted or substituted 3-10 membered heterocycloalkyl, -C( = O )OR 2a , -P(=O)R 2a R 2b , wherein the substituted C 1-10 alkyl, substituted C 3-10 cycloalkyl and substituted 3-10 membered heterocycloalkyl are independently substituted with one or more substituents selected from the group consisting of hydroxy, C 1-10 alkoxy, halogen and CN;
여기서, R2a 및 R2b는 독립적으로 수소 또는 C1-10알킬이고;wherein R 2a and R 2b are independently hydrogen or C 1-10 alkyl;
R3는 치환된 C3- 10시클로알킬, 치환된 C6- 10아릴 또는 치환된 5-10원자헤테로아릴이고, R 3 is substituted C 3-10 cycloalkyl, substituted C 6-10 aryl or substituted 5-10 membered heteroaryl ;
여기서, 치환된 C3- 10시클로알킬, 치환된 C6- 10아릴 및 치환된 5-10원자 헤테로아릴은 각각 독립적으로 하이드록시, C1- 10알콕시, 할로겐, C1- 10알콕시카보닐, -NR3aR3b, 비치환 또는 치환된 C1- 10알킬, 또는 링커 L을 통해 연결되는 비치환 또는 치환된 3-10원자헤테로시클로알킬로 치환되고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, Here, substituted C 3-10 cycloalkyl, substituted C 6-10 aryl , and substituted 5-10 membered heteroaryl are each independently hydroxy , C 1-10 alkoxy, halogen, C 1-10 alkoxycarbonyl, -NR 3a R 3b , unsubstituted or substituted C 1-10 alkyl, or unsubstituted or substituted 3-10 membered heterocycloalkyl linked through a linker L, wherein the linker L is a single bond, -C( =O)- or -C(=O)NH-,
여기서, 치환된 C1- 10알킬은 할로겐, C1- 10알콕시, 디C1 - 10알킬아미노, 하이드록시 또는 -C(=O)NH2로 치환되고, wherein the substituted C 1-10 alkyl is substituted with halogen, C 1-10 alkoxy, diC 1-10 alkylamino, hydroxy or -C(=O)NH 2 ;
여기서, 치환된 3-10원자헤테로시클로알킬은 C1- 10알킬, C3- 10시클로알킬, 3-10원자헤테로시클로알킬 또는 -NR3aR3b로 치환되고,wherein the substituted 3-10 membered heterocycloalkyl is substituted with C 1-10 alkyl, C 3-10 cycloalkyl , 3-10 membered heterocycloalkyl or -NR 3a R 3b ;
여기서 R3a 및 R3b는 각각 독립적으로 수소, 비치환 또는 -N(C1- 10알킬)2로 치환된C1 -10알킬, 또는 C1-10알콕시카보닐이고; wherein R 3a and R 3b are each independently hydrogen, C 1-10 alkyl unsubstituted or substituted with -N(C 1-10 alkyl) 2 , or C 1-10 alkoxycarbonyl ;
R4는 수소 또는 C1-10알킬이고; R 4 is hydrogen or C 1-10 alkyl;
R5 및 R6는 각각 독립적으로 수소, 비치환 또는 하나 이상의 할로겐으로 치환된 C1- 10알킬, -C(=O)NR5aR5b 또는 -C(=O)OR5a이고, 이때 R5a 및 R5b는 수소 또는 C1- 10알킬이다.R 5 and R 6 are each independently hydrogen, C 1-10 alkyl unsubstituted or substituted with one or more halogens, -C(=O)NR 5a R 5b or -C( = O)OR 5a , wherein R 5a and R 5b is hydrogen or C 1-10 alkyl .
다른 측면에서, 본 발명은 하기 반응식 1에 나타낸 바와 같이,In another aspect, the present invention, as shown in Scheme 1 below,
화학식 2로 표시되는 화합물과 화학식 3으로 표시되는 화합물을 반응시켜 화학식 1로 표시되는 화합물을 제조하는 단계(단계 2)를 포함하는 화학식 1로 표시되는 화합물의 제조방법을 제공한다.Provided is a method for preparing a compound represented by Chemical Formula 1 including the step (Step 2) of preparing a compound represented by Chemical Formula 1 by reacting a compound represented by Chemical Formula 2 with a compound represented by Chemical Formula 3.
[반응식 1][Scheme 1]
Figure PCTKR2022016628-appb-img-000002
Figure PCTKR2022016628-appb-img-000002
상기 반응식 1에서,In Scheme 1 above,
R1, R2, R3, R4, R5 및 R6는 상기 화학식 1에서 정의한 바와 같다.R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in Formula 1 above.
또 다른 측면에서, 본 발명은 상기 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 암 또는 자가면역질환의 예방 또는 개선용 약학적 조성물을 제공한다.In another aspect, the present invention is for preventing or improving cancer or autoimmune diseases containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. A pharmaceutical composition is provided.
본 명세서에 기재된 화학식 1로 표시되는 화합물은 IRAK4에 대한 우수한 억제 활성을 나타내면서, 암세포에 대한 세포 독성이 우수하여 암 또는 사이토카인 발현을 억제하여 자가면역질환에 유용할 것으로 기대된다.The compound represented by Formula 1 described herein is expected to be useful in autoimmune diseases by suppressing cancer or cytokine expression due to excellent cytotoxicity against cancer cells while exhibiting excellent inhibitory activity against IRAK4.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
한편, 본 발명의 실시 형태는 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 이하 설명하는 실시 형태로 한정되는 것은 아니다. 또한, 본 발명의 실시 형태는 당해 기술분야에서 평균적인 지식을 가진 자에게 본 발명을 더욱 완전하게 설명하기 위해서 제공되는 것이다.Meanwhile, the embodiments of the present invention may be modified in various forms, and the scope of the present invention is not limited to the embodiments described below. In addition, the embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.
나아가, 명세서 전체에서 어떤 구성요소를 "포함"한다는 것은 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성요소를 더 포함할 수 있다는 것을 의미한다.Furthermore, "include" a certain component throughout the specification means that other components may be further included without excluding other components unless otherwise stated.
용어 "알킬렌" 또는 "알킬"은, 달리 명시되지 않는 한, 직쇄 또는 분지쇄의 포화된 탄화수소 잔기를 포함한다. 예를 들어, "C1- 6알킬"은 1 내지 6개 탄소로 골격이 이루어진 알킬을 의미한다. 구체적으로 C1- 6알킬은 메틸, 에틸, n-프로필, i-프로필, n-부틸, i-부틸, t-부틸, n-펜틸, i-펜틸, t-펜틸, sec-펜틸, 네오펜틸, 헥실 등을 포함하며, C6알킬은 6개의 탄소를 가지는 완전 포화된 탄화수소로서, 구조이성질체를 포함한다. 알킬은 1가, 알킬렌은 2가의 치환기를 의미한다.The term "alkylene" or "alkyl" includes straight or branched chain saturated hydrocarbon moieties, unless otherwise specified. For example, "C 1-6 alkyl" means an alkyl having a backbone of 1 to 6 carbons. Specifically, C 1-6 alkyl is methyl, ethyl, n-propyl, i-propyl, n - butyl, i-butyl, t-butyl, n-pentyl, i-pentyl, t-pentyl, sec-pentyl, neopentyl , hexyl, etc., and C 6 alkyl is a fully saturated hydrocarbon having 6 carbons, including regioisomers. Alkyl means a monovalent substituent, and alkylene means a divalent substituent.
용어 “시클로알킬”은, 달리 명시되지 않는 한, 포화된 탄화수소 잔기로서 고리를 이루는 고리형 탄화수소 잔기를 의미하며, “C3- 6시클로알킬”은 3 내지 6개 탄소를 고리원자로 포함하는 고리형 탄화수소 잔기를 의미한다.The term “cycloalkyl”, unless otherwise specified, refers to a cyclic hydrocarbon moiety that forms a ring as a saturated hydrocarbon moiety, and “C 3-6 cycloalkyl” refers to a cyclic hydrocarbon moiety containing 3 to 6 carbons as ring atoms. hydrocarbon residues.
용어 “헤테로시클로알킬”은, 달리 명시되지 않는 한, N, O 또는 S로부터 선택되는 1개 이상 (예를 들면, 1-5개, 1-4개, 1-3개, 1-2개, 1개) 헤테로원자를 포함하는 1내지 3개의 고리로 이루어진 1가 포화 잔기를 의미한다. 2 또는 3개의 고리는 다리형(bridged), 융합형(fused) 또는 나선형(spiro)의 헤테로시클로알킬 일 수 있다. 복수개의 고리로 이루어지는 경우, 헤테로원자는 모든 고리 또는 일부 고리에만 존재할 수 있다. “3-10원자헤테로시클로알킬”은 헤테로시클로알킬로서, 고리를 이루는 원자가 3-10개인 헤테로시클로알킬을 의미한다. 한편, N을 1개 이상 포함하는 3-10원자헤테로시클로알킬이라고 할 때는, 고리를 이루는 헤테로원자로서 반드시 질소 원자(N)을 1개 이상 포함하는 것을 가리킨다.The term "heterocycloalkyl" means, unless otherwise specified, one or more selected from N, O, or S (e.g., 1-5, 1-4, 1-3, 1-2, 1) means a monovalent saturated moiety consisting of 1 to 3 rings containing heteroatoms. The two or three rings may be bridged, fused or spiro heterocycloalkyl. When composed of a plurality of rings, heteroatoms may be present in all rings or only in some rings. “3-10 membered heterocycloalkyl” refers to a heterocycloalkyl having 3 to 10 ring atoms. On the other hand, when referring to a 3-10-membered heterocycloalkyl containing one or more N, it refers to one that always contains one or more nitrogen atoms (N) as a heteroatom constituting a ring.
용어 “아릴”은 단일 고리 또는 2 또는 3개의 탄화수소 방향족 고리가 융합된 방향족 라디칼을 의미하며, C6- 10아릴은 탄소가 6-10개 포함된 방향족 고리 화합물을 의미하며, 페닐 또는 나프틸을 포함한다.The term “aryl” refers to an aromatic radical in which a single ring or two or three hydrocarbon aromatic rings are fused. include
용어 “헤테로아릴”은, 달리 명시되지 않는 한, N, O 또는 S로부터 선택되는 헤테로원자를 고리 원자로서 1개 이상 (예를 들면, 1-5개, 1-4개, 1-3개, 1-2개, 1개) 함유하는 하나 이상의 방향족고리(나머지 고리 원자는 C임)를 갖는 단일 고리 또는 2 또는 3개의 고리가 융합된 방향족 라디칼을 의미한다. 복수개의 고리로 이루어지는 경우, 헤테로원자는 모든 고리 또는 일부 고리에만 존재할 수 있다. “5-10원자헤테로아릴”은 헤테로아릴로서, 고리를 이루는 원자가 5-10개인 헤테로아릴을 의미한다. 한편, N을 1개 이상 포함하는 5-10원자헤테로아릴이라고 할 때는, 고리를 이루는 헤테로원자로서 반드시 질소 원자(N)을 1개 이상 포함하는 것을 가리킨다.The term “heteroaryl”, unless otherwise specified, means one or more (e.g., 1-5, 1-4, 1-3, 1-2, 1) containing one or more aromatic rings (the remaining ring atoms are C), or a fused aromatic radical of 2 or 3 rings. When composed of a plurality of rings, heteroatoms may be present in all rings or only in some rings. “5-10 membered heteroaryl” refers to a heteroaryl having 5 to 10 atoms constituting a ring. On the other hand, when referring to a 5-10 membered heteroaryl containing one or more N, it refers to one containing one or more nitrogen atoms (N) as a heteroatom constituting a ring.
“알콕시”는 알킬이 산소원자를 통해 연결되는 치환기를 의미하며, C1- 10알콕시는 C1- 10알킬이 산소원자에 연결되어 산소를 통해 치환되는 치환기를 가리킨다.“Alkoxy” means a substituent in which an alkyl is linked to an oxygen atom, and C 1-10 alkoxy refers to a substituent in which C 1-10 alkyl is linked to an oxygen atom and substituted through an oxygen atom.
“할로겐”은 F, Cl, Br, I와 같은 할로겐 원자를 의미한다. "Halogen" means a halogen atom such as F, Cl, Br, I.
“C1- 10알콕시카보닐”은 C1- 10알킬-O-C(=O)-와 같이 C1- 10알콕시의 산소원자가 카보닐(CO)에 연결되고, 카보닐의 탄소를 통해 치환되는 치환기를 의미한다.“C 1-10 alkoxycarbonyl” is a substituent in which the oxygen atom of C 1-10 alkoxy is connected to carbonyl (CO) and substituted through the carbon of carbonyl, such as C 1-10 alkyl - OC(=O)- means
“디C1 - 10알킬아미노”는 아미노기(-NH2)에 C1- 10알킬기가 2개 치환되어 질소를 통해 치환되는 치환기를 의미한다.“DiC 1-10 alkylamino” means a substituent in which an amino group (—NH 2 ) is substituted with two C 1-10 alkyl groups through nitrogen .
용어 "이성질체(isomer)"는 동일한 화학식 또는 분자식을 가지지만 구조적 또는 입체적으로 다른 본 발명의 화합물을 의미한다. 이러한 이성질체에는 구조 이성질체(constitutional isomer or structural isomer)와 입체이성질체를 포함한다.The term "isomer" refers to compounds of the present invention that have the same chemical or molecular formula but differ structurally or sterically. Such isomers include constitutional isomers (or structural isomers) and stereoisomers.
용어 “구조이성질체”는 골격이성질체(skeletal isomer) 및 호변이성질체(tautomer)를 포함한다.The term “structural isomer” includes skeletal isomers and tautomers.
용어 “입체이성질체”는 비대칭 탄소 또는 헤테로원자 (P, S, Si, N 등) 중심을 가짐으로써 생성되는 R 또는 S 이성질체(또는 DL 이성질체), 비대칭 원자 중심을 2개 이상 가짐으로써 생성될 수 있는 거울상이성질체 또는 부분입체이성질체(diastereomer), 기하이성질체(트랜스, 시스) 등을 포함한다.The term “stereoisomer” refers to R or S isomers (or DL isomers) that are produced by having asymmetric carbon or heteroatom (P, S, Si, N, etc.) centers, and those that can be produced by having two or more asymmetric atom centers. Includes enantiomers or diastereomers, geometric isomers (trans, cis), and the like.
용어 "수화물(hydrate)"은 비공유적 분자간력(non-covalent intermolecμLar force)에 의해 결합된 화학양론적(stoichiometric) 또는 비화학양론적(non-stoichiometric) 량의 물을 포함하고 있는 본 발명의 화합물 또는 그것의 염을 의미한다. 본 발명의 상기 화학식 1로 표시되는 화합물의 수화물은 비공유적 분자간 힘으로 결합되는 화학양론적 또는 비화학양론적 양의 물을 포함할 수 있다. 상기 수화물은 1당량 이상, 바람직하게는, 1당량 내지 5당량의 물을 함유할 수 있다. 이러한 수화물은 물 또는 물을 함유하는 용매로부터 본 발명의 상기 화학식 1로 표시되는 화합물, 이의 이성질체 또는 이들의 약제학적으로 허용 가능한 염을 결정화시켜 제조될 수 있다.The term "hydrate" refers to a compound of the present invention that contains a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces. or a salt thereof. The hydrate of the compound represented by Formula 1 of the present invention may contain a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces. The hydrate may contain 1 equivalent or more, preferably 1 to 5 equivalents of water. Such a hydrate may be prepared by crystallizing the compound represented by Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof of the present invention from water or a water-containing solvent.
용어 "용매화물(solvate)"은 비공유적 분자간력에 의해 결합된 화학양론적 또는 비화학양론적 양의 용매를 포함하고 있는 본 발명의 화합물 또는 그것의 염을 의미한다. 그에 관한 바람직한 용매들로는 휘발성, 비독성, 및/또는 인간에게 투여되기에 적합한 용매들이 있다.The term “solvate” refers to a compound of the present invention or a salt thereof that contains a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. Preferred solvents in this regard are those that are volatile, non-toxic, and/or suitable for administration to humans.
용어 “약학적으로 허용 가능한 염”은 화합물이 카르복실산 또는 아민 작용기를 포함할 때, 이와 이온결합하여 형성되는 염으로서 약제학적으로 허용되는 염을 의미한다.The term “pharmaceutically acceptable salt” refers to a pharmaceutically acceptable salt formed by ionic bonding with a compound containing a carboxylic acid or amine functional group.
본 발명의 상기 화학식 1로 표시되는 화합물은 약학적으로 허용가능한 염의 형태로 사용할 수 있으며, 염으로는 약학적으로 허용가능한 유리산(free acid)에 의해 형성된 산 부가염이 유용하다. 산 부가염은 염산, 질산, 인산, 황산, 브롬화수소산, 요드화수소산, 아질산, 아인산 등과 같은 무기산류, 지방족 모노 및 디카복실레이트, 페닐-치환된 알카노에이트, 하이드록시 알카노에이트 및 알칸디오에이트, 방향족 산류, 지방족 및 방향족 설폰산류 등과 같은 무독성 유기산, 트리플루오로아세트산, 아세테이트, 안식향산, 구연산, 젖산, 말레인산, 글루콘산, 메탄설폰산, 4-톨루엔설폰산, 주석산, 푸마르산 등과 같은 유기산으로부터 얻는다. 이러한 약학적으로 무독한 염의 종류로는 설페이트, 피로설페이트, 바이설페이트, 설파이트, 바이설파이트, 니트레이트, 포스페이트, 모노하이드로겐 포스페이트, 디하이드로겐 포스페이트, 메타포스페이트, 피로포스페이트 클로라이드, 브로마이드, 아이오다이드, 플루오라이드, 아세테이트, 프로피오네이트, 데카노에이트, 카프릴레이트, 아크릴레이트, 포메이트, 이소부티레이트, 카프레이트, 헵타노에이트, 프로피올레이트, 옥살레이트, 말로네이트, 석시네이트, 수베레이트, 세바케이트, 푸마레이트, 말리에이트, 부틴-1,4-디오에이트, 헥산-1,6-디오에이트, 벤조에이트, 클로로벤조에이트, 메틸벤조에이트, 디니트로 벤조에이트, 하이드록시벤조에이트, 메톡시벤조에이트, 프탈레이트, 테레프탈레이트, 벤젠설포네이트, 톨루엔설포네이트, 클로로벤젠설포네이트, 크실렌설포네이트, 페닐아세테이트, 페닐프로피오네이트, 페닐부티레이트, 시트레이트, 락테이트, β하이드록시부티레이트, 글리콜레이트, 말레이트, 타트레이트, 메탄설포네이트, 프로판설포네이트, 나프탈렌-1-설포네이트, 나프탈렌-2-설포네이트, 만델레이트 등을 포함한다.The compound represented by Formula 1 of the present invention can be used in the form of a pharmaceutically acceptable salt, and an acid addition salt formed by a pharmaceutically acceptable free acid is useful as the salt. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, etc., aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanedios. from organic acids such as trifluoroacetic acid, acetate, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid, etc. get Such pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulphate, sulphite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, i. Odide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, sube rate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycol lattice, maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate and the like.
본 발명에 따른 산 부가염은 통상의 방법으로 제조할 수 있으며, 예를 들면 화학식 1의 유도체를 메탄올, 에탄올, 아세톤, 메틸렌클로라이드, 아세토니트릴 등과 같은 유기용매에 녹이고 유기산 또는 무기산을 가하여 생성된 침전물을 여과, 건조시켜 제조하거나, 용매와 과량의 산을 감압 증류한 후 건조시켜 유기용매 하에서 결정화시켜서 제조할 수 있다.The acid addition salt according to the present invention can be prepared by a conventional method. For example, a precipitate formed by dissolving a derivative of Formula 1 in an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile, etc. and adding an organic or inorganic acid thereto It may be prepared by filtering and drying, or by distilling the solvent and excess acid under reduced pressure, drying it, and crystallizing it in an organic solvent.
본 발명의 일 측면은,One aspect of the present invention,
하기 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 제공한다.A compound represented by Formula 1 below, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof are provided.
[화학식 1][Formula 1]
Figure PCTKR2022016628-appb-img-000003
Figure PCTKR2022016628-appb-img-000003
상기 화학식 1에서,In Formula 1,
R1은 수소 또는 C1- 10알킬이고, R 1 is hydrogen or C 1-10 alkyl ;
R2는 비치환 또는 치환된 C6- 10아릴, 비치환 또는 치환된 5-10원자헤테로아릴이거나, 또는R 2 is unsubstituted or substituted C 6-10 aryl, unsubstituted or substituted 5-10 membered heteroaryl, or
R1와 R2는 이들이 결합된 질소원자와 함께 비치환 또는 치환된 5-10원자헤테로아릴을 형성하고,R 1 and R 2 together with the nitrogen atom to which they are bonded form an unsubstituted or substituted 5-10 membered heteroaryl;
여기서, 상기 치환된 C6- 10아릴 및 치환된 5-10원자헤테로아릴은 각각 독립적으로 비치환 또는 치환된 C1- 10알킬, 비치환 또는 치환된 C3- 10시클로알킬, 할로겐, 하이드록시, C1- 10알콕시, -SO2R2a, -C(=O)NR2aR2b, -SO2NR2aR2b, 비치환 또는 치환된 3-10원자헤테로시클로알킬, -C(=O)OR2a, -P(=O)R2aR2b 로 하나 이상 치환되고, 이때 치환된 C1- 10알킬, 치환된 C3- 10시클로알킬 및 치환된 3-10원자헤테로시클로알킬은 독립적으로 하이드록시, C1- 10알콕시, 할로겐 및 CN로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환되고,Here, the substituted C 6-10 aryl and the substituted 5-10-membered heteroaryl are each independently selected from unsubstituted or substituted C 1-10 alkyl , unsubstituted or substituted C 3-10 cycloalkyl, halogen, hydroxy , C 1-10 alkoxy, -SO 2 R 2a , -C(=O)NR 2a R 2b , -SO 2 NR 2a R 2b , unsubstituted or substituted 3-10 membered heterocycloalkyl, -C( = O )OR 2a , -P(=O)R 2a R 2b , wherein the substituted C 1-10 alkyl, substituted C 3-10 cycloalkyl and substituted 3-10 membered heterocycloalkyl are independently substituted with one or more substituents selected from the group consisting of hydroxy, C 1-10 alkoxy, halogen and CN;
여기서, R2a 및 R2b는 독립적으로 수소 또는 C1- 10알킬이고;wherein R 2a and R 2b are independently hydrogen or C 1-10 alkyl ;
R3는 치환된 C3- 10시클로알킬, 치환된 C6- 10아릴 또는 치환된 5-10원자헤테로아릴이고, R 3 is substituted C 3-10 cycloalkyl, substituted C 6-10 aryl or substituted 5-10 membered heteroaryl ;
여기서, 치환된 C3- 10시클로알킬, 치환된 C6- 10아릴 및 치환된 5-10원자 헤테로아릴은 각각 독립적으로 하이드록시, C1- 10알콕시, 할로겐, C1- 10알콕시카보닐, -NR3aR3b, 비치환 또는 치환된 C1- 10알킬, 또는 링커 L을 통해 연결되는 비치환 또는 치환된 3-10원자헤테로시클로알킬로 치환되고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, Here, substituted C 3-10 cycloalkyl, substituted C 6-10 aryl , and substituted 5-10 membered heteroaryl are each independently hydroxy, C 1-10 alkoxy, halogen, C 1-10 alkoxycarbonyl, -NR 3a R 3b , unsubstituted or substituted C 1-10 alkyl, or unsubstituted or substituted 3-10 membered heterocycloalkyl linked through a linker L, wherein the linker L is a single bond, -C( =O)- or -C(=O)NH-,
여기서, 치환된 C1- 10알킬은 할로겐, C1- 10알콕시, 디C1 - 10알킬아미노, 하이드록시 또는 -C(=O)NH2 로 치환되고, wherein the substituted C 1-10 alkyl is substituted with halogen, C 1-10 alkoxy, diC 1-10 alkylamino, hydroxy or -C(=O)NH 2 ;
여기서, 치환된 3-10원자헤테로시클로알킬은 C1- 10알킬, C3- 10시클로알킬, 3-10원자헤테로시클로알킬 또는 -NR3aR3b로 치환되고,wherein the substituted 3-10 membered heterocycloalkyl is substituted with C 1-10 alkyl, C 3-10 cycloalkyl , 3-10 membered heterocycloalkyl or -NR 3a R 3b ;
여기서 R3a 및 R3b는 각각 독립적으로 수소, 비치환 또는 N(C1- 10알킬)2로 치환된C1 -10알킬, 또는 C1- 10알콕시카보닐이고; wherein R 3a and R 3b are each independently hydrogen, C 1-10 alkyl unsubstituted or substituted with N(C 1-10 alkyl ) 2 , or C 1-10 alkoxycarbonyl ;
R4는 수소 또는 C1- 10알킬이고; R 4 is hydrogen or C 1-10 alkyl ;
R5 및 R6는 각각 독립적으로 수소, 비치환 또는 하나 이상의 할로겐으로 치환된 C1- 10알킬, -C(=O)NR5aR5b 또는 -C(=O)OR5a이고, 이때 R5a 및 R5b는 수소 또는 C1- 10알킬이다.R 5 and R 6 are each independently hydrogen, C 1-10 alkyl unsubstituted or substituted with one or more halogens, -C(=O)NR 5a R 5b or -C( = O)OR 5a , wherein R 5a and R 5b is hydrogen or C 1-10 alkyl .
다른 측면에서,On the other side,
상기 화학식 1에서,In Formula 1,
R1은 수소 또는 C1- 6알킬이고, R 1 is hydrogen or C 1-6 alkyl ;
R2는 비치환 또는 치환된 페닐 비치환 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 5-10원자헤테로아릴이거나, 또는R 2 is unsubstituted or substituted phenyl unsubstituted or substituted 5-10 membered heteroaryl containing at least one heteroatom selected from the group consisting of N and O, or
R1와 R2는 이들이 결합된 질소원자와 함께 비치환 또는 치환된 N원자를 1 이상 포함하는 5-10원자헤테로아릴을 형성하고,R 1 and R 2 together with the nitrogen atom to which they are bonded form a 5- to 10-membered heteroaryl containing one or more unsubstituted or substituted N atoms;
여기서, 상기 치환된 페닐 및 치환된 5-10원자헤테로아릴은 각각 독립적으로 비치환 또는 치환된 C1- 6알킬, 비치환 또는 치환된 C3- 7시클로알킬, 할로겐, 하이드록시, C1- 6알콕시, -SO2R2a, -C(=O)NR2aR2b, -SO2NR2aR2b, 비치환 또는 치환된 3-7원자헤테로시클로알킬, -C(=O)OR2a, -P(=O)R2aR2b 로 하나 이상 치환되고, 이때 치환된 C1- 6알킬, 치환된 C3- 7시클로알킬 및 치환된 3-7원자헤테로시클로알킬은 독립적으로 하이드록시, C1- 6알콕시, 할로겐 또는 CN로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환되고,Here, the substituted phenyl and substituted 5-10-membered heteroaryl are each independently selected from unsubstituted or substituted C 1-6 alkyl , unsubstituted or substituted C 3-7 cycloalkyl , halogen, hydroxy, C 1- 6 alkoxy, -SO 2 R 2a , -C(=O)NR 2a R 2b , -SO 2 NR 2a R 2b , unsubstituted or substituted 3-7 membered heterocycloalkyl, -C(=O)OR 2a , -P(=O) R 2a is substituted with one or more R 2b , wherein the substituted C 1-6 alkyl, substituted C 3-7 cycloalkyl and substituted 3-7 membered heterocycloalkyl are independently hydroxy, C 1-6 is substituted with one or more substituents selected from the group consisting of alkoxy, halogen or CN;
여기서, R2a 및 R2b는 독립적으로 수소 또는 C1- 6알킬이고;wherein R 2a and R 2b are independently hydrogen or C 1-6 alkyl ;
R3는 치환된 C4- 8시클로알킬, 치환된 페닐 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 5-8원자헤테로아릴이고,R 3 is a 5-8 membered heteroaryl containing at least one heteroatom selected from the group consisting of substituted C 4-8 cycloalkyl, substituted phenyl or substituted N and O;
여기서, 치환된 C4- 8시클로알킬, 치환된 페닐 및 치환된 5-8원자 헤테로아릴은 각각 독립적으로 하이드록시, C1- 6알콕시, 할로겐, C1- 6알콕시카보닐, -NR3aR3b, 비치환 또는 치환된 C1- 6알킬, 또는 링커 L을 통해 연결되는 비치환 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 3-10원자헤테로시클로알킬로 치환되고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, Wherein, substituted C 4-8 cycloalkyl, substituted phenyl and substituted 5-8 membered heteroaryl are each independently hydroxy, C 1-6 alkoxy, halogen, C 1-6 alkoxycarbonyl , -NR 3a R 3b , unsubstituted or substituted C 1-6 alkyl, or 3-10 membered heterocycloalkyl containing at least one heteroatom selected from the group consisting of unsubstituted or substituted N and O linked through a linker L. substituted, wherein the linker L is a single bond, -C(=O)- or -C(=O)NH-,
여기서, 상기 3-10원자헤테로시클로알킬은 3-7원자 단일고리 헤테로시클로알킬 또는 7-10원자 스피로이중고리 헤테로시클로알킬이고,Here, the 3-10 membered heterocycloalkyl is a 3-7 membered monocyclic heterocycloalkyl or a 7-10 membered spiro bicyclic heterocycloalkyl,
여기서, 치환된 C1- 6알킬은 할로겐, C1- 6알콕시, 디C1 - 6알킬아미노, 하이드록시 또는 -C(=O)NH2로 치환되고,wherein the substituted C 1-6 alkyl is substituted with halogen, C 1-6 alkoxy, diC 1-6 alkylamino, hydroxy or -C(=O)NH 2 ;
여기서, 치환된 3-10원자헤테로시클로알킬은 C1- 6알킬, C3- 8시클로알킬, N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 3-8원자헤테로시클로알킬 또는 -NR3aR3b로 치환되고,Here, the substituted 3-10 membered heterocycloalkyl is C 1-6 alkyl , C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl containing at least one heteroatom selected from the group consisting of N and O, or -NR 3a R 3b is substituted;
여기서 R3a 및 R3b는 각각 독립적으로 수소, 비치환 또는 N(C1- 6알킬)2로 치환된C1 -6알킬, 또는 C1- 6알콕시카보닐이고; wherein R 3a and R 3b are each independently hydrogen, C 1-6 alkyl unsubstituted or substituted with N(C 1-6 alkyl) 2 , or C 1-6 alkoxycarbonyl ;
R4는 수소 또는 C1- 6알킬이고; R 4 is hydrogen or C 1-6 alkyl ;
R5 및 R6는 각각 독립적으로 수소, 비치환 또는 하나 이상의 할로겐으로 치환된 C1- 6알킬, -C(=O)NR5aR5b 또는 -C(=O)OR5a이고, 이때 R5a 및 R5b는 수소 또는 C1- 6알킬이다.R 5 and R 6 are each independently hydrogen, C 1-6 alkyl unsubstituted or substituted with one or more halogens, -C(=O)NR 5a R 5b or -C(=O) OR 5a , wherein R 5a and R 5b is hydrogen or C 1-6 alkyl .
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1에서,In Formula 1,
R1은 수소 또는 C1- 4알킬이고, R 1 is hydrogen or C 1-4 alkyl;
R2는 비치환 또는 치환된 페닐, 비치환 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 5-6원자 헤테로아릴, 또는 비치환 또는 치환된 N 원자를 1 이상 포함하는 융합된 9-10원자헤테로아릴이거나, 또는R 2 is an unsubstituted or substituted phenyl, an unsubstituted or substituted 5-6 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N and O, or one or more unsubstituted or substituted N atoms is a fused 9-10 membered heteroaryl comprising
R1와 R2는 이들이 결합된 질소원자와 함께 비치환 또는 치환된 N원자를 1 이상 포함하는 5-원자헤테로아릴을 형성하고,R 1 and R 2 together with the nitrogen atom to which they are bonded form a 5-membered heteroaryl containing one or more unsubstituted or substituted N atoms;
여기서, 상기 치환된 페닐, 치환된 5-6원자 헤테로아릴, 치환된 9-10원자 헤테로아릴 및 치환된 5원자헤테로아릴은 각각 독립적으로 비치환 또는 치환된 C1- 4알킬, 비치환 또는 치환된 C3- 6시클로알킬, 할로겐, 하이드록시, C1- 4알콕시, -SO2R2a, -C(=O)NR2aR2b, -SO2NR2aR2b, 비치환 또는 치환된 3-6원자헤테로시클로알킬, -C(=O)OR2a, -P(=O)R2aR2b 로 하나 이상 치환되고, 이때 치환된 C1- 4알킬, 치환된 C3- 6시클로알킬 및 치환된 3-6원자헤테로시클로알킬은 독립적으로 하이드록시, C1- 4알콕시, 할로겐 및 CN로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환되고,Here, the substituted phenyl, substituted 5-6 membered heteroaryl , substituted 9-10 membered heteroaryl and substituted 5-membered heteroaryl are each independently unsubstituted or substituted C 1-4 alkyl , unsubstituted or substituted C 3-6 cycloalkyl, halogen, hydroxy, C 1-4 alkoxy, -SO 2 R 2a , -C(=O ) NR 2a R 2b , -SO 2 NR 2a R 2b , unsubstituted or substituted 3 one or more substituted with -6-membered heterocycloalkyl, -C(=O)OR 2a , -P(=O)R 2a R 2b , wherein substituted C 1-4 alkyl, substituted C 3-6 cycloalkyl and Substituted 3-6 membered heterocycloalkyls are independently substituted with one or more substituents selected from the group consisting of hydroxy, C 1-4 alkoxy, halogen and CN ;
여기서, R2a 및 R2b는 독립적으로 수소 또는 C1- 4알킬이고;wherein R 2a and R 2b are independently hydrogen or C 1-4 alkyl ;
R3는 치환된 C5- 6시클로알킬, 치환된 페닐 또는 하나 이상의 N원자를 포함하는 치환된 5-6원자헤테로아릴이고,R 3 is substituted C 5-6 cycloalkyl, substituted phenyl or substituted 5-6 membered heteroaryl containing one or more N atoms;
여기서, 치환된 C5- 6시클로알킬, 치환된 페닐 및 치환된 5-6원자 헤테로아릴은 각각 독립적으로 하이드록시, C1- 4알콕시, 할로겐, C1- 4알콕시카보닐, -NR3aR3b, 비치환 또는 치환된 C1- 4알킬, 또는 링커 L을 통해 연결되는 비치환 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 4-10원자헤테로시클로알킬로 치환되고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, Wherein, substituted C 5-6 cycloalkyl, substituted phenyl and substituted 5-6 membered heteroaryl are each independently hydroxy, C 1-4 alkoxy, halogen , C 1-4 alkoxycarbonyl, -NR 3a R 3b , unsubstituted or substituted C 1-4 alkyl, or 4-10 membered heterocycloalkyl containing at least one heteroatom selected from the group consisting of unsubstituted or substituted N and O linked through a linker L. substituted, wherein the linker L is a single bond, -C(=O)- or -C(=O)NH-,
여기서, 치환된 C1- 4알킬은 할로겐, C1- 4알콕시, 디C1 - 4알킬아미노, 하이드록시 또는 -C(=O)NH2로 치환되고, wherein the substituted C 1-4 alkyl is substituted with halogen, C 1-4 alkoxy, diC 1-4 alkylamino, hydroxy or -C(=O) NH 2 ;
여기서, 치환된 4-10원자헤테로시클로알킬은 C1- 4알킬, C3- 6시클로알킬, 3-7원자헤테로시클로알킬 또는 -NR3aR3b로 치환되고,wherein the substituted 4-10 membered heterocycloalkyl is substituted with C 1-4 alkyl , C 3-6 cycloalkyl, 3-7 membered heterocycloalkyl or -NR 3a R 3b ;
여기서 R3a 및 R3b는 각각 독립적으로 수소, 비치환 또는 N(C1- 4알킬)2로 치환된 C1- 4알킬, 또는 C1- 4알콕시카보닐이고; wherein R 3a and R 3b are each independently hydrogen, C 1-4 alkyl unsubstituted or substituted with N(C 1-4 alkyl) 2 , or C 1-4 alkoxycarbonyl ;
R4는 수소 또는 C1- 4알킬이고; R 4 is hydrogen or C 1-4 alkyl ;
R5 및 R6는 각각 독립적으로 수소, 비치환 또는 하나 이상의 할로겐으로 치환된 C1-4알킬, -C(=O)NR5aR5b 또는 -C(=O)OR5a이고, 이때 R5a 및 R5b는 수소 또는 C1- 4알킬이다.R 5 and R 6 are each independently hydrogen, C 1-4 alkyl unsubstituted or substituted with one or more halogens, -C(=O)NR 5a R 5b or -C(=O)OR 5a , wherein R 5a and R 5b is hydrogen or C 1-4 alkyl .
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1에서,In Formula 1,
R1은 수소이고, R 1 is hydrogen;
R2는 비치환 또는 치환된 페닐, 비치환 또는 치환된 헤테로아릴이되, 이 때 헤테로아릴은 피리딜, 피라졸릴, 옥사졸릴, 인다졸릴 또는 퀴놀리닐이거나, 또는R 2 is unsubstituted or substituted phenyl, unsubstituted or substituted heteroaryl, wherein heteroaryl is pyridyl, pyrazolyl, oxazolyl, indazolyl or quinolinyl; or
R1와 R2는 이들이 결합된 질소원자와 함께 치환된 이미다졸릴을 형성하고,R 1 and R 2 together with the nitrogen atom to which they are attached form a substituted imidazolyl,
여기서, 상기 치환된 페닐, 치환된 헤테로아릴 및 치환된 이미다졸릴은 각각 독립적으로 비치환 또는 치환된 C1- 4알킬, 할로겐, C1- 4알콕시, 하이드록시, C1- 4알킬설포닐, 디(C1-4알킬)아미노설포닐, C1- 4알콕시카보닐, 디(C1-4알킬)포스피닐, 카르복실, 하이드록시 치환된 옥세타닐, 하이드록시 치환된 시클로부틸 및 CONH2 로 이루어지는 군에서 선택되는 1 이상으로 치환되고, 이때 치환된 C1- 4알킬은 하이드록시, C1-4알콕시, 할로겐 또는 CN로 치환되고;Here, the substituted phenyl, substituted heteroaryl, and substituted imidazolyl are each independently selected from unsubstituted or substituted C 1-4 alkyl, halogen, C 1-4 alkoxy, hydroxy, C 1-4 alkylsulfonyl , di(C 1-4 alkyl)aminosulfonyl, C 1-4 alkoxycarbonyl, di(C 1-4 alkyl)phosphinyl , carboxyl, hydroxy substituted oxetanyl, hydroxy substituted cyclobutyl, and substituted with one or more selected from the group consisting of CONH 2 , wherein the substituted C 1-4 alkyl is substituted with hydroxy, C 1-4 alkoxy, halogen or CN;
R3는 치환된 시클로펜틸, 시클로헥실, 페닐 또는 치환된 피라졸릴이고,R 3 is substituted cyclopentyl, cyclohexyl, phenyl or substituted pyrazolyl;
여기서, 치환된 시클로펜틸, 시클로헥실, 페닐 또는 피라졸릴은 각각 독립적으로 하이드록시, C1- 3알콕시, 할로겐, 메톡시카보닐, 디메틸아미노에틸(메틸)아미노, 비치환되거나 하나 이상의 할로겐, 메톡시, 디메틸아미노, -C(=O)NH2 또는 하이드록시로 치환된 C1- 4알킬, 또는 링커 L을 통해 연결되는 비치환 또는 치환된 비치환 또는 치환된 3-10원자헤테로시클로알킬로 치환되고, 여기서 3-10원자헤테로시클로알킬은 옥세타닐, 테트라하이드로퓨라닐, 테트라하이드로피라닐, 피롤리디닐, 피페리디닐, 피페라지닐, 아제파닐, 몰포리닐, 1,4-디옥사-8-아자스피로[4.5]데카닐, 2,6-디아자스피로[3.3]헵타닐, 2-옥사-6-아자스피로[3.3]헵타닐, 및 2-옥사스피로[3.3]헵타닐로부터 선택되고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, wherein each substituted cyclopentyl, cyclohexyl, phenyl or pyrazolyl is independently hydroxy, C 1-3 alkoxy, halogen, methoxycarbonyl, dimethylaminoethyl ( methyl)amino, unsubstituted or one or more halogen, methyl C 1-4 alkyl substituted with oxy, dimethylamino, -C(=0)NH 2 or hydroxy, or unsubstituted or substituted 3-10 membered heterocycloalkyl connected through a linker L; substituted, wherein the 3-10 membered heterocycloalkyl is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, morpholinyl, 1,4-di from oxa-8-azaspiro[4.5]decanyl, 2,6-diazaspiro[3.3]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 2-oxaspiro[3.3]heptanyl selected, wherein the linker L is a single bond, -C(=O)- or -C(=O)NH-,
여기서, 치환된 3-10원자헤테로시클로알킬의 치환기는 C1- 2알킬, C3- 4시클로알킬, 아지리디닐, 아제티디닐, 피롤리디닐, 메틸피페라지닐, 옥세타닐, NMe2, NEt2, NHMe, NHCO2t-Bu, 메톡시, NH2 또는 아세틸이고; Here, the substituent of the substituted 3-10 membered heterocycloalkyl is C 1-2 alkyl , C 3-4 cycloalkyl, aziridinyl, azetidinyl, pyrrolidinyl, methylpiperazinyl, oxetanyl, NMe 2 , NEt 2 , NHMe, NHCO 2 t-Bu, methoxy, NH 2 or acetyl;
R4는 수소이고; R 4 is hydrogen;
R5 및 R6는 각각 독립적으로 수소, 비치환 또는 1 내지 3의 할로겐으로 치환된 C1- 4알킬, -C(=O)NR5aR5b 또는 -C(=O)OR5a이고, 이때 R5a 및 R5b는 수소 또는 C1- 4알킬이다.R 5 and R 6 are each independently hydrogen, unsubstituted or 1 to 3 halogen-substituted C 1-4 alkyl, -C(=O)NR 5a R 5b or -C(=O)OR 5a , wherein R 5a and R 5b are hydrogen or C 1-4 alkyl.
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1에서,In Formula 1,
상기 R3는 하기에서 선택되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염:R 3 is a compound selected from the following, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof:
Figure PCTKR2022016628-appb-img-000004
Figure PCTKR2022016628-appb-img-000004
여기서,here,
R7 및 R8은 독립적으로 비치환 또는 치환된 C1- 10알킬, -NR3aR3b 또는 링커 L을 통해 연결되는 비치환 또는 치환된 3-10원자헤테로시클로알킬이고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, R 7 and R 8 are independently unsubstituted or substituted C 1-10 alkyl, -NR 3a R 3b or unsubstituted or substituted 3-10 membered heterocycloalkyl linked through a linker L, wherein the linker L is a single a bond, -C(=O)- or -C(=O)NH-;
여기서, 치환된 C1- 10알킬은 C1- 10알콕시, 디C1 - 10알킬아미노, 하이드록시 또는 --C(=O)NH2로 치환되고,wherein the substituted C 1-10 alkyl is substituted with C 1-10 alkoxy, diC 1-10 alkylamino, hydroxy or --C( = O)NH 2 ;
여기서, 치환된 3-10원자헤테로시클로알킬은 C1- 10알킬, C3- 10시클로알킬, 3-10원자헤테로시클로알킬 또는 -NR3aR3b로 치환되고,wherein the substituted 3-10 membered heterocycloalkyl is substituted with C 1-10 alkyl, C 3-10 cycloalkyl , 3-10 membered heterocycloalkyl or -NR 3a R 3b ;
여기서 R3a 및 R3b는 각각 독립적으로 수소, 또는 비치환 또는 N(C1- 10알킬)2로 치환된C1-10알킬이고,Wherein R 3a and R 3b are each independently hydrogen or C 1-10 alkyl unsubstituted or substituted with N(C 1-10 alkyl ) 2 ;
R7a, R8a 및 R8b는 각각 독립적으로, 수소, 비치환 또는 하이드록시 또는 할로겐으로 치환된 C1- 10알킬, C1- 10알콕시, 할로겐, 또는 C1- 10알콕시카보닐이고,R 7a , R 8a and R 8b are each independently hydrogen, unsubstituted or hydroxy- or halogen-substituted C 1-10 alkyl, C 1-10 alkoxy , halogen , or C 1-10 alkoxycarbonyl;
R9는 하이드록시로 치환된 C1- 10알킬 또는 3-10원자헤테로시클로알킬이고,R 9 is C 1-10 alkyl substituted with hydroxy or 3-10 membered heterocycloalkyl ;
R9a 및 R9b는 수소 또는 하이드록시이고,R 9a and R 9b are hydrogen or hydroxy;
n은 1 또는 2이다.n is 1 or 2;
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1에서,In Formula 1,
R1은 수소이고;R 1 is hydrogen;
R2는 다음 중에서 선택되거나,R 2 is selected from;
Figure PCTKR2022016628-appb-img-000005
Figure PCTKR2022016628-appb-img-000005
Figure PCTKR2022016628-appb-img-000006
Figure PCTKR2022016628-appb-img-000006
또는 R1와 R2는 서로 결합하여
Figure PCTKR2022016628-appb-img-000007
를 형성한다.Or R 1 and R 2 are bonded to each other
Figure PCTKR2022016628-appb-img-000007
form
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1에서,In Formula 1,
R3는 다음 중에서 선택되고,R 3 is selected from
Figure PCTKR2022016628-appb-img-000008
Figure PCTKR2022016628-appb-img-000008
Figure PCTKR2022016628-appb-img-000009
Figure PCTKR2022016628-appb-img-000009
Figure PCTKR2022016628-appb-img-000010
Figure PCTKR2022016628-appb-img-000011
;
Figure PCTKR2022016628-appb-img-000010
Figure PCTKR2022016628-appb-img-000011
;
R4는 수소이다.R 4 is hydrogen.
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1에서,In Formula 1,
R5는 수소 또는 메틸이고;R 5 is hydrogen or methyl;
R6는 수소, 메틸, CF3, 이소프로필,-C(=O)NH2, ,에틸옥시카보닐, 또는 1-메틸프로필옥시이다.R 6 is hydrogen, methyl, CF 3 , isopropyl,-C(=O)NH 2 , ethyloxycarbonyl, or 1-methylpropyloxy.
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1로 표시되는 화합물은 하기 화합물 군으로부터 선택된다.The compound represented by Formula 1 is selected from the following compound groups.
<1> 2-(6-((2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<1> 2-(6-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridine -2-yl)propan-2-ol;
<2> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<2> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)thieno[2,3-d]pyridine midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<3> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<3> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<4> 2-(6-((5-메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<4> 2-(6-((5-methyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl )amino)pyridin-2-yl)propan-2-ol;
<5> 2-(6-((5,6-디메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<5> 2-(6-((5,6-dimethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol;
<6> 2-(6-((5,6-디메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<6> 2-(6-((5,6-dimethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol;
<7> 2-(6-((5,6-디메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<7> 2-(6-((5,6-dimethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol;
<8> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-2-메톡시페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<8> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)thieno[2,3-d]pyridine midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<9> 2-(6-((2-((3-메톡시-4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<9> 2-(6-((2-((3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4- yl)amino)pyridin-2-yl)propan-2-ol;
<10> 2-(6-((2-((1-(테트라하이드로-2H-피란-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<10> 2-(6-((2-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<11> 2-(6-((2-((4-(4-(4-메틸피페라진-1-일)피페리딘-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<11> 2-(6-((2-((4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)thieno[2,3-d ]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<12> 2-(6-((2-((4-((2-(디메틸아미노)에틸)(메틸)아미노)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<12> 2-(6-((2-((4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl )amino)pyridin-2-yl)propan-2-ol;
<13> 2-(6-((2-((4-(4-에틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<13> 2-(6-((2-((4-(4-ethylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridine -2-yl)propan-2-ol;
<14> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-이소프로필티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<14> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-isopropylthieno[2, 3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<15> 2-(6-((5-이소프로필-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<15> 2-(6-((5-isopropyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4- yl)amino)pyridin-2-yl)propan-2-ol;
<16> 2-(6-((2-((3-메톡시-4-(4-메틸피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<16> 2-(6-((2-((3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<17> 2-(6-((5-메틸-2-((1-(테트라하이드로-2H-피란-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<17> 2-(6-((5-methyl-2-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<18> 2-(6-((2-((3-메톡시-4-(피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<18> 2-(6-((2-((3-methoxy-4-(piperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol;
<19> sec-부틸 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트;<19> sec-butyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropane- 2-yl)pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxylate;
<20> sec-부틸 4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-5-카복실레이트;<20> sec-butyl 4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-2-((4-(4-methylpiperazin-1-yl)phenyl )amino)thieno[2,3-d]pyrimidine-5-carboxylate;
<21> 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카르복사미드;<21> 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl )pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxamide;
<22> 4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-5-카르복사미드;<22> 4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-2-((4-(4-methylpiperazin-1-yl)phenyl)amino) thieno[2,3-d]pyrimidine-5-carboxamide;
<23> (1R,4R)-4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)시클로헥산-1-올;<23> (1R,4R)-4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d ]pyrimidin-2-yl)amino)cyclohexan-1-ol;
<24> 에틸 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트;<24> Ethyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2- yl)pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxylate;
<25> 2-(6-((5-메틸-2-(((1R,4R)-4-모르폴리노시클로헥실)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<25> 2-(6-((5-methyl-2-(((1R,4R)-4-morpholinocyclohexyl)amino)thieno[2,3-d]pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol;
<26> 2-(6-((5-메틸-2-(((1R,4R)-4-(피페리딘-1-일)시클로헥실)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<26> 2-(6-((5-methyl-2-(((1R,4R)-4-(piperidin-1-yl)cyclohexyl)amino)thieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<27> (1S,2R,3R,5R)-3-(하이드록시메틸)-5-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)시클펜탄-1,2-디올;<27> (1S,2R,3R,5R)-3-(hydroxymethyl)-5-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino) -5-methylthieno[2,3-d]pyrimidin-2-yl)amino)cyclopentane-1,2-diol;
<28> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-(트리플루오로메틸)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<28> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-(trifluoromethyl)thie no[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<29> 2-(6-((2-((4-(4-메틸피페라진-1-일)페닐)아미노)-5-(트리플루오로메틸)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<29> 2-(6-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)thieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<30> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(피리딘-2-일)티에노[2,3-d]피리미딘-2,4-디아민;<30> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(pyridin-2-yl)thieno[2,3 -d] pyrimidine-2,4-diamine;
<31> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-페닐티에노[2,3-d]피리미딘-2,4-디아민;<31> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-phenylthieno[2,3-d]pyrimidine- 2,4-diamine;
<32> 2-(6-((5-메틸-2-((1-(옥세탄-3-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<32> 2-(6-((5-methyl-2-((1-(oxetan-3-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<33> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<33> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<34> N4-(6-(터트-부틸)피리딘-2-일)-N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<34> N4-(6-(tert-butyl)pyridin-2-yl)-N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5- methylthieno[2,3-d]pyrimidine-2,4-diamine;
<35> 2-(6-((5-메틸-2-((1-(테트라하이드로퓨란-3-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<35> 2-(6-((5-methyl-2-((1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<36> 2-(6-((2-((3-플루오로-4-(4-메틸피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<36> 2-(6-((2-((3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<37> 2-(6-((5-메틸-2-((4-(4-메틸피페라진-1-일)-3-(트리플루오로메틸)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<37> 2-(6-((5-methyl-2-((4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<38> 4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시-N-(1-메틸피페리딘-4-일)벤즈아미드;<38> 4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine-2- yl)amino)-2-methoxy-N-(1-methylpiperidin-4-yl)benzamide;
<39> 메틸 5-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-(4-메틸피페라진-1-일)벤조에이트;<39> Methyl 5-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine-2 -yl)amino)-2-(4-methylpiperazin-1-yl)benzoate;
<40> 2-(6-((2-((3-(하이드록시메틸)-4-(4-메틸피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<40> 2-(6-((2-((3-(hydroxymethyl)-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<41> 2-(6-((2-((1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<41> 2-(6-((2-((1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<42> 2-(6-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<42> 2-(6-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<43> 2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<43> 2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<44> 2-(3-((2-((1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<44> 2-(3-((2-((1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<45> 5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)-N4-페닐티에노[2,3-d]피리미딘-2,4-디아민;<45> 5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-N4-phenylthieno[2,3-d]pyrimidine- 2,4-diamine;
<46> N2-(1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)-5-메틸-N4-페닐티에노[2,3-d]피리미딘-2,4-디아민;<46> N2-(1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-methyl-N4-phenylthieno[2,3-d]pyrimidine- 2,4-diamine;
<47> 2-(6-((2-((4-(4-(디에틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<47> 2-(6-((2-((4-(4-(diethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<48> 2-(6-((2-((3-메톡시-4-(1,4-디옥사-8-아자스피로[4.5]데칸-8-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<48> 2-(6-((2-((3-methoxy-4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)phenyl)amino)-5-methyl thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<49> (4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)(4-메틸피페라진-1-일)메타논;<49> (4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine-2 -yl)amino)-2-methoxyphenyl)(4-methylpiperazin-1-yl)methanone;
<50> 2-메틸-2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판니트릴;<50> 2-methyl-2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propanenitrile;
<51> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)-2-메틸프로판니트릴;<51> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)-2-methylpropanenitrile;
<52> 5-메틸-N4-(1-메틸-1H-피라졸-4-일)-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<52> 5-methyl-N4-(1-methyl-1H-pyrazol-4-yl)-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d ]pyrimidine-2,4-diamine;
<53> N4-(5-(터트-부틸)이속사졸-3-일)-5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<53> N4-(5-(tert-butyl)isoxazol-3-yl)-5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3- d] pyrimidine-2,4-diamine;
<54> N4-(1H-인다졸-6-일)-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<54> N4-(1H-indazol-6-yl)-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyrimidine-2,4- diamine;
<55> 5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)-N4-(퀴놀린-7-일)티에노[2,3-d]피리미딘-2,4-디아민;<55> 5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)-N4-(quinolin-7-yl)thieno[2,3-d]pyrimidine-2,4 -diamine;
<56> N4-(1H-인다졸-6-일)-5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<56> N4-(1H-indazol-6-yl)-5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyrimidine- 2,4-diamine;
<57> 5-메틸-4-(4-메틸-1H-이미다졸-1-일)-N-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2-아민;<57> 5-methyl-4- (4-methyl-1H-imidazol-1-yl) -N- (4- (4-methylpiperazin-1-yl) phenyl) thieno [2,3-d ]pyrimidin-2-amine;
<58> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-1-메틸-1H-피라졸-5-일)프로판-2-올;<58> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)-1-methyl-1H-pyrazol-5-yl)propan-2-ol;
<59> 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤즈아마이드;<59> 3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)benzamide;
<60>2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<60> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<61> 2-(6-((2-((4-(3-(디메틸아미노)피롤리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<61> 2-(6-((2-((4-(3-(dimethylamino)pyrrolidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<62> 2-(3-((2-((4-(3-(디메틸아미노)피롤리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<62> 2-(3-((2-((4-(3-(dimethylamino)pyrrolidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<63> 2-(6-((2-((3-메톡시-4-(4-(피롤리딘-1-일)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<63> 2-(6-((2-((3-methoxy-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<64> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<64> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<65> 2-(3-((2-((3-메톡시-4-(4-(피롤리딘-1-일)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<65> 2-(3-((2-((3-methoxy-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<66> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-메톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<66> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-methoxypropan-2-yl)pyridin-2 -yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
<67> 2-(3-((2-((4-(4-(디메틸아미노)아제판-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<67> 2-(3-((2-((4-(4-(dimethylamino)azepan-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<68> 2-(6-((2-((4-(4-(디메틸아미노)아제판-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<68> 2-(6-((2-((4-(4-(dimethylamino)azepan-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<69> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-메톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<69> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-methoxypropan-2-yl) )pyridin-2-yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
<70> 터트-부틸(1-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)피페리딘-4-일)카바메이트;<70> tert-butyl(1-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3- d]pyrimidin-2-yl)amino)-2-methoxyphenyl)piperidin-4-yl)carbamate;
<71> 터트-부틸(1-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)피페리딘-4-일)카바메이트;<71> tert-butyl(1-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine -2-yl)amino)-2-methoxyphenyl)piperidin-4-yl)carbamate;
<72> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-에톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<72> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-ethoxypropan-2-yl)pyridin-2 -yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
<73> 2-(4-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<73> 2-(4-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<74> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-에톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<74> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-ethoxypropan-2-yl) )pyridin-2-yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
<75> 2-(2-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-4-일)프로판-2-올;<75> 2-(2-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-4-yl)propan-2-ol;
<76> 2-(3-((2-((4-(4-(아지리딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<76> 2-(3-((2-((4-(4-(aziridin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<77> 2-(2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-4-일)프로판-2-올;<77> 2-(2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-4-yl)propan-2-ol;
<78> 1-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)시클로부탄-1-올;<78> 1-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)cyclobutan-1-ol;
<79> 2-(6-((2-((4-(4-(아지리딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<79> 2-(6-((2-((4-(4-(aziridin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<80> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)-2-메틸프로판니트릴;<80> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)-2-methylpropanenitrile;
<81> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)-2-메틸프로판니트릴;<81> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)-2-methylpropanenitrile;
<82> 2-(6-((2-((3-메톡시-4-(4-(메틸아미노)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<82> 2-(6-((2-((3-methoxy-4-(4-(methylamino)piperidin-1-yl)phenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<83> 2-(6-((2-((3-메톡시-4-(4-메톡시피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<83> 2-(6-((2-((3-methoxy-4-(4-methoxypiperidin-1-yl)phenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<84> 2-(3-((2-((3-메톡시-4-(4-메톡시피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<84> 2-(3-((2-((3-methoxy-4-(4-methoxypiperidin-1-yl)phenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<85> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(3-(2-메톡시프로판-2-일)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<85> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-(2-methoxypropan-2-yl)phenyl)- 5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
<86> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3-(2-메톡시프로판-2-일)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<86> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-(2-methoxypropan-2-yl) )phenyl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
<87> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<87> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno[2,3 -d] pyrimidine-2,4-diamine;
<88> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<88> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
<89> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(3-(트리플루오로메틸)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<89> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(3-(trifluoromethyl) phenyl)thieno[2,3-d]pyrimidine-2,4-diamine;
<90> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(3-(트리플루오로메틸)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<90> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(3-(trifluoromethyl)phenyl)thieno [2,3-d]pyrimidine-2,4-diamine;
<91> 2-(6-((2-((1-(3-(디메틸아미노)프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<91> 2-(6-((2-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<92> 2-(6-((2-((1-(2-(디메틸아미노)에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<92> 2-(6-((2-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<93> 2-(3-((2-((1-(2-(디메틸아미노)에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<93> 2-(3-((2-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<94> 2-(6-((2-((1-(2-메톡시에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<94> 2-(6-((2-((1-(2-methoxyethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl)amino)pyridin-2-yl)propan-2-ol;
<95> 2-(3-((2-((1-(2-메톡시에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<95> 2-(3-((2-((1-(2-methoxyethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl)amino)phenyl)propan-2-ol;
<96> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-플루오로피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<96> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-fluoropyridin-2-yl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
<97> 2-(3-((2-((1-(3-(디메틸아미노)프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<97> 2-(3-((2-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<98> 2-(6-((2-((4-(4-아미노피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<98> 2-(6-((2-((4-(4-aminopiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<99> 2-(3-((2-((4-(4-아미노피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<99> 2-(3-((2-((4-(4-aminopiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<100> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(3-메톡시페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<100> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-methoxyphenyl)-5-methylthieno[2,3 -d] pyrimidine-2,4-diamine;
<101> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3-메톡시페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<101> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-methoxyphenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
<102> 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페놀;<102> 3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenol;
<103> 3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페놀;<103> 3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenol;
<104> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(2-(이소프로필설포닐)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<104> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(2-(isopropylsulfonyl)phenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
<105> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(2-(이소프로필설포닐)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<105> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(2-(isopropylsulfonyl)phenyl)-5 -Methylthieno[2,3-d]pyrimidine-2,4-diamine;
<106> N4-(2-(이소프로필설포닐)페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<106> N4-(2-(isopropylsulfonyl)phenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno [2,3-d]pyrimidine-2,4-diamine;
<107> 2-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-N,N-디메틸벤젠설폰아미드;<107> 2-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide;
<108> 2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-N,N-디메틸벤젠설폰아미드;<108> 2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide;
<109> N,N-디메틸-2-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤젠설폰아미드;<109> N,N-dimethyl-2-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[ 2,3-d]pyrimidin-4-yl)amino)benzenesulfonamide;
<110> N4-(3-메톡시페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<110> N4-(3-methoxyphenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[2,3 -d] pyrimidine-2,4-diamine;
<111> 메틸 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트;<111> methyl 3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)benzoate;
<112> 메틸 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트;<112> methyl 3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d ]pyrimidin-4-yl)amino)benzoate;
<113> 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페놀;<113> 3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] pyrimidin-4-yl)amino)phenol;
<114> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올;<114> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol;
<115> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올;<115> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol;
<116> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-(트리플루오로메틸)페닐)프로판-2-올;<116> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)-5-(trifluoromethyl)phenyl)propan-2-ol;
<117> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-(트리플루오로메틸)페닐)프로판-2-올;<117> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)-5-(trifluoromethyl)phenyl)propan-2-ol;
<118> 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-3,5-디메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<118> 2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-3,5-dimethyl-1H-pyrazol-4-yl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<119> 2-(6-((2-((1-(1-시클로프로필피페리딘-4-일)-3,5-디메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<119> 2-(6-((2-((1-(1-cyclopropylpiperidin-4-yl)-3,5-dimethyl-1H-pyrazol-4-yl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<120> (2-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<120> (2-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide;
<121> (2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<121> (2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide;
<122> 디메틸(2-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)포스핀옥사이드<122> Dimethyl(2-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3- d] pyrimidin-4-yl) amino) phenyl) phosphine oxide
<123> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(6-(트리플루오로메틸)피리딘-2-일)티에노[2,3-d]피리미딘-2,4-디아민<123> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(6-(trifluoromethyl)pyridine-2- yl)thieno[2,3-d]pyrimidine-2,4-diamine
<124> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(6-플루오로피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<124> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-fluoropyridin-2-yl)-5 -Methylthieno[2,3-d]pyrimidine-2,4-diamine;
<125> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(6-(트리플루오로메틸)피리딘-2-일)티에노[2,3-d]피리미딘-2,4-디아민;<125> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(6-(trifluoromethyl) pyridin-2-yl)thieno[2,3-d]pyrimidine-2,4-diamine;
<126> 2-(6-((2-((1-(3-메톡시프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<126> 2-(6-((2-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl)amino)pyridin-2-yl)propan-2-ol;
<127> 2-(3-((2-((1-(3-메톡시프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<127> 2-(3-((2-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl)amino)phenyl)propan-2-ol;
<128> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<128> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-fluorophenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<129> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<129> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-fluorophenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<130> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-플루오로페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<130> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-fluorophenyl)-N4-(3-fluorophenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
<131> N2-(3,5-디메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<131> N2-(3,5-dimethyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-N4-(3-fluorophenyl)-5-methyl thieno[2,3-d]pyrimidine-2,4-diamine;
<132> 2-(3-((2-((3,5-디메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<132> 2-(3-((2-((3,5-dimethyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methyl thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<133> 2-(6-((5-메틸-2-((3-메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<133> 2-(6-((5-methyl-2-((3-methyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<134> 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤조산;<134> 3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] pyrimidin-4-yl)amino)benzoic acid;
<135> 3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조산;<135> 3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)benzoic acid;
<136> N4-(3-플루오로페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<136> N4-(3-fluorophenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[2,3 -d] pyrimidine-2,4-diamine;
<137> N2-(1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<137> N2-(1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)-N4-(3-fluorophenyl)-5-methylthieno[2, 3-d] pyrimidine-2,4-diamine;
<138> 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올;<138> 2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol;
<139> 2-(3-플루오로-5-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<139> 2-(3-fluoro-5-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thie no[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<140> 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<140> 2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<141> 2-(6-((2-((1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<141> 2-(6-((2-((1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<142> 2-(6-((2-((1-(1-시클로프로필피페리딘-4-일)-3-메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<142> 2-(6-((2-((1-(1-cyclopropylpiperidin-4-yl)-3-methyl-1H-pyrazol-4-yl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<143> 2-(3-((2-((5-클로로-1-((3S,4S)-3-플루오로-1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<143> 2-(3-((2-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl) -1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<144> 2-(3-((2-((5-클로로-1-((3S,4S)-3-플루오로-1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<144> 2-(3-((2-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl) -1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<145> 2-(3-((2-((3-메톡시-4-(2,6-디아자스피로[3.3]헵탄-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<145> 2-(3-((2-((3-methoxy-4-(2,6-diazaspiro[3.3]heptan-2-yl)phenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<146> 2-(6-((2-((3-메톡시-4-(2,6-디아자스피로[3.3]헵탄-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<146> 2-(6-((2-((3-methoxy-4-(2,6-diazaspiro[3.3]heptan-2-yl)phenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<147> 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-3-메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<147> 2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-3-methyl-1H-pyrazol-4-yl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<148> 메틸 3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트;<148> Methyl 3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)benzoate;
<149> 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조산;<149> 3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)benzoic acid;
<150> 2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)-5-(트리플루오로메틸)페닐)프로판-2-올;<150> 2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)-5-(trifluoromethyl)phenyl)propan-2-ol;
<151> 2-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-3-메틸-1H-피라졸-1-일)-2-메틸프로판아미드;<151> 2-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine -2-yl)amino)-3-methyl-1H-pyrazol-1-yl)-2-methylpropanamide;
<152> 2-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-3-메틸-1H-피라졸-1-일)-2-메틸프로판아미드;<152> 2-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl )amino)-3-methyl-1H-pyrazol-1-yl)-2-methylpropanamide;
<153> 1-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)시클로부탄-1-올;<153> 1-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)cyclobutan-1-ol;
<154> 1-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)시클로부탄-1-올;<154> 1-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)cyclobutan-1-ol;
<155> 2-(3-((5-메틸-2-((3-메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<155> 2-(3-((5-methyl-2-((3-methyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<156> 2-(6-((2-((4-(4-시클로프로필피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<156> 2-(6-((2-((4-(4-cyclopropylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<157> 2-(3-((2-((4-(4-시클로프로필피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<157> 2-(3-((2-((4-(4-cyclopropylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<158> 메틸 2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)벤조에이트;<158> Methyl 2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3-fluorophenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-2-yl)amino)benzoate;
<159> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-플루오로프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<159> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-fluoropropan-2-yl)pyridin-2 -yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
<160> 2-(6-((2-((4-(4-시클로부틸피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<160> 2-(6-((2-((4-(4-cyclobutylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<161> 2-(3-((2-((4-(4-시클로부틸피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<161> 2-(3-((2-((4-(4-cyclobutylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<162> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<162> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<163> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<163> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<164> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<164> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
<165> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<165> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<166> (2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)페닐)메탄올;<166> (2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3-fluorophenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-2-yl)amino)phenyl)methanol;
<167> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-이소프로폭시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<167> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropoxyphenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<168> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-이소프로폭시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<168> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropoxyphenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<169> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-이소프로폭시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<169> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropoxyphenyl)-N4-(3-fluorophenyl)-5-methylthier no[2,3-d]pyrimidine-2,4-diamine;
<170> 2-(6-((2-((3,5-디메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<170> 2-(6-((2-((3,5-dimethyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methyl thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<171> 3-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)옥세탄-3-올;<171> 3-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)oxetan-3-ol;
<172> 3-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)옥세탄-3-올;<172> 3-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)oxetan-3-ol;
<173> 2-(3-((2-((3-메톡시-4-(2-옥사-6-아자스피로[3.3]헵탄-6-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<173> 2-(3-((2-((3-methoxy-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)amino)-5-methylthieno[ 2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<174> 2-(6-((2-((3-메톡시-4-(2-옥사-6-아자스피로[3.3]헵탄-6-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<174> 2-(6-((2-((3-methoxy-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)amino)-5-methylthieno[ 2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<175> 2-(3-((5-메틸-2-((1-메틸-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<175> 2-(3-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino )phenyl)propan-2-ol;
<176> 2-(6-((5-메틸-2-((1-메틸-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<176> 2-(6-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino )pyridin-2-yl)propan-2-ol;
<177> 2-(3-((2-((1-(2-옥사스피로[3.3]헵탄-6-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<177> 2-(3-((2-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<178> 2-(6-((2-((1-(2-옥사스피로[3.3]헵탄-6-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<178> 2-(6-((2-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<179> 2-(3-((2-((1-((3S,4R)-3-플루오로피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<179> 2-(3-((2-((1-((3S,4R)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<180> 2-(6-((2-((1-((3S,4R)-3-플루오로피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<180> 2-(6-((2-((1-((3S,4R)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<181> 메틸 2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)벤조에이트;<181> Methyl 2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((6-(2-hydroxypropan-2-yl)pyridin-2 -yl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl)amino)benzoate;
<182> 메틸 2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)벤조에이트;<182> methyl 2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino )-5-methylthieno[2,3-d]pyrimidin-2-yl)amino)benzoate;
<183> 2-(6-((5-메틸-2-((1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<183> 2-(6-((5-methyl-2-((1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino )thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<184> 2-(3-((5-메틸-2-((1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<184> 2-(3-((5-methyl-2-((1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino )thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<185> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<185> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<186> N4-(3-플루오로페닐)-5-메틸-N2-(1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<186> N4-(3-fluorophenyl)-5-methyl-N2-(1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl ) thieno[2,3-d]pyrimidine-2,4-diamine;
<187> 2-(3-플루오로-5-((5-메틸-2-((1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<187> 2-(3-fluoro-5-((5-methyl-2-((1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol- 4-yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<188> 2-(6-((2-((1-((3S, 4R)-3-플루오로-1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<188> 2-(6-((2-((1-((3S, 4R)-3-fluoro-1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino )-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<189> 2-(3-((2-((1-((3S,4R)-3-플루오로-1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<189> 2-(3-((2-((1-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino )-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<190> (2-((2-((1-((3S,4R)-3-플루오로-1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<190> (2-((2-((1-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)- 5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphineoxide;
<191> 1-(4-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)피페리딘-1-일)에탄-1-온;<191> 1-(4-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine- 2-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;
<192> 1-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)시클로부탄-1-올;<192> 1-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)cyclobutan-1-ol;
<193> (2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<193> (2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide;
<194> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)-1,1,1-트리플루오로프로판-2-올;<194> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)-1,1,1-trifluoropropan-2-ol;
<195> 1,1,1-트리플루오로-2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<195> 1,1,1-trifluoro-2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4- yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
<196> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)-1,1,1-트리플루오로프로판-2-올;<196> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)-1,1,1-trifluoropropan-2-ol;
<197> 1-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)-2-메틸프로판-2-올;<197> 1-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine -2-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol;
<198> 1-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)-2-메틸프로판-2-올;<198> 1-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl )amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol;
<199> (2-((2-((1-(2-하이드록시-2-메틸프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<199> (2-((2-((1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl) amino) phenyl) dimethylphosphine oxide;
<200> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)-1,1,1-트리플루오로프로판-2-올;<200> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)-1,1,1-trifluoropropan-2-ol;
<201> 1,1,1-트리플루오로-2-(6-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<201> 1,1,1-trifluoro-2-(6-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4- yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
<202> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올;<202> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol;
<203> (2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3,5-디플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)페닐)메탄올;<203> (2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3,5-difluorophenyl)amino)-5-methylthier no[2,3-d]pyrimidin-2-yl)amino)phenyl)methanol;
<204> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3,5-디플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<204> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3,5-difluorophenyl)-5- methylthieno[2,3-d]pyrimidine-2,4-diamine;
<205> N4-(3,5-디플루오로페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<205> N4-(3,5-difluorophenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[ 2,3-d] pyrimidine-2,4-diamine;
<206> (2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<206> (2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphineoxide;
<207> (2-((2-((1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<207> (2-((2-((1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide;
<208> 1-(4-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)피페리딘-1-일)에탄-1-온;<208> 1-(4-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d ]pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;
<209> 1-(4-(4-((4-((2-(디메틸포스포릴)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)피페리딘-1-일)에탄-1-온.<209> 1-(4-(4-((4-((2-(dimethylphosphoryl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl)amino) -1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one.
본 발명의 다른 측면에서,In another aspect of the invention,
하기 반응식 1에 나타낸 바와 같이,As shown in Scheme 1 below,
화학식 2로 표시되는 화합물과 화학식 3으로 표시되는 화합물을 반응시켜 화학식 1로 표시되는 화합물을 제조하는 단계를 포함하는 화학식 1로 표시되는 화합물의 제조방법을 제공한다.Provided is a method for preparing a compound represented by Chemical Formula 1 comprising the step of preparing a compound represented by Chemical Formula 1 by reacting a compound represented by Chemical Formula 2 with a compound represented by Chemical Formula 3.
[반응식 1][Scheme 1]
상기 반응식 1에서,In Scheme 1 above,
R1, R2, R3, R4, R5 및 R6는 상기 화학식 1에서 정의한 바와 같다.R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in Formula 1 above.
이하, 상기 반응식 1의 제조방법을 상세히 설명한다.Hereinafter, the preparation method of Scheme 1 will be described in detail.
상기 반응식 1의 제조방법에서, 단계 1은 화학식 2로 표시되는 화합물과 화학식 3으로 표시되는 화합물을 친핵성 치환반응 시키는 단계로서, 화학식 2로 표시되는 화합물과 화학식 3으로 표시되는 화합물을 반응시켜 화학식 1포 표시되는 화합물을 제조하는 단계이다. 이때 용매로는 유기용매, 예를 들면 DMF나 sec-부탄올 등이 사용될수 있으며, 친핵성 치환반응을 위해 통상적으로 사용되는 조건을 사용하여 수행할 수 있다.In the preparation method of Reaction Scheme 1, Step 1 is a step of subjecting a compound represented by Chemical Formula 2 to a compound represented by Chemical Formula 3 by a nucleophilic substitution reaction, wherein the compound represented by Chemical Formula 2 is reacted with a compound represented by Chemical Formula 3 to obtain Chemical Formula This is a step for preparing a compound displayed in 1 package. In this case, an organic solvent such as DMF or sec-butanol may be used as the solvent, and conditions commonly used for nucleophilic substitution reactions may be used.
상기 제조방법은 하나의 예시로서 제시된 본 발명의 일 실시예에 한정되는 것은 아니며, 통상의 유기화학적인 지식 하에 용매, 반응 물질, 온도 조건 등을 변형하여 수행 가능하다.The preparation method is not limited to one embodiment of the present invention presented as an example, and can be performed by modifying solvents, reactants, temperature conditions, etc. under conventional organic chemistry knowledge.
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염은 암 또는 자가면역질환의 예방 또는 치료에 사용하기 위한 것이다.The compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof is intended for use in the prevention or treatment of cancer or autoimmune diseases.
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는, 암 또는 자가면역질환의 예방 또는 치료용 약학적 조성물을 제공한다.Provided is a pharmaceutical composition for preventing or treating cancer or autoimmune disease, containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
상기 화학식 1로 표시되는 화합물은 IRAK4를 억제하는 것을 특징으로 한다.The compound represented by Formula 1 is characterized in that it inhibits IRAK4.
상기 화학식 1로 표시되는 화합물은 염증인자로서 자가면역질환과 관련된 염증성 사이토카인인 TNF-α, IL-6 의 발현을 억제하는 것을 특징으로 한다.The compound represented by Formula 1 is characterized by suppressing the expression of TNF-α and IL-6, which are inflammatory cytokines related to autoimmune diseases, as inflammatory factors.
상기 암은 백혈병, 림프종, 다발성 골수종, 방광암, 유방암, 결장암, 신장암, 간암, 폐암, 소세포폐암, 식도암, 담낭암, 난소암, 췌장암, 위암, 자궁 경부암, 갑상선암, 전립선암, 또는 피부암 중 어느 하나인 것일 수 있다.The cancer is any one of leukemia, lymphoma, multiple myeloma, bladder cancer, breast cancer, colon cancer, kidney cancer, liver cancer, lung cancer, small cell lung cancer, esophageal cancer, gallbladder cancer, ovarian cancer, pancreatic cancer, stomach cancer, cervical cancer, thyroid cancer, prostate cancer, or skin cancer. may be
상기 자가면역질환은 건선, 류마티스성 관절염, 혈관염, 염증성 장 질환, 피부염, 골관절염, 천식, 염증성 근육 질환, 알러지성 질환, 질염, 간질 방광염, 경피증, 골다공증, 습진, 동종이계 또는 이종발생성 이식 거부, 이식편대숙주질환(GVHD), 홍반성 낭창, 염증성 질환, I형 당뇨병, 폐 섬유증, 피부근염, 쇼그렌 증후군, 갑상선염, 중증 근무력증, 자가면역 용혈성 빈혈, 다발성 경화증, 낭포성 섬유증, 만성적 재발성 간염, 원발성 담도성 간경변증, 알러지성 결막염 또는 아토피 피부염 중 어느 하나인 것일 수 있다.The autoimmune disease is psoriasis, rheumatoid arthritis, vasculitis, inflammatory bowel disease, dermatitis, osteoarthritis, asthma, inflammatory muscle disease, allergic disease, vaginitis, interstitial cystitis, scleroderma, osteoporosis, eczema, allogeneic or xenogeneic transplant rejection , Graft-versus-host disease (GVHD), lupus erythematosus, inflammatory disease, type I diabetes, pulmonary fibrosis, dermatomyositis, Sjogren's syndrome, thyroiditis, myasthenia gravis, autoimmune hemolytic anemia, multiple sclerosis, cystic fibrosis, chronic recurrent hepatitis , primary biliary cirrhosis, allergic conjunctivitis, or atopic dermatitis.
본 발명에 있어서, 용어 “유효성분으로 함유하는”이란, 암 또는 자가면역질환의 예방, 개선, 또는 치료의 효과를 가져오는 용량 범위로 함유하는 것을 의미하고, 중증도 및 제형에 따라 용량 범위는 변할 수 있으며, 적용 횟수도 적용 대상의 연령, 체중 및 체질에 따라 변할 수 있다. 본 발명의 한 구체예에서, 본 발명의 약학적 조성물 내에서 화학식 1로 표시되는 화합물은 예를 들어, 0.001 mg/kg 이상, 바람직하게는 0.1 mg/kg 이상, 보다 바람직하게는 10 mg/kg 이상, 보다 더 바람직하게는 100 mg/kg 이상, 보다 더욱 더 바람직하게는 250 mg/kg 이상, 가장 바람직하게는 0.1 g/kg 이상 포함된다. 본 발명의 약학적 조성물 내에 포함되는 화학식 1로 표시되는 화합물의 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.In the present invention, the term "contained as an active ingredient" means that it is contained in a dosage range that results in the prevention, improvement, or treatment of cancer or autoimmune disease, and the dosage range may vary depending on the severity and formulation. The number of times of application may also vary according to the age, weight and constitution of the target subject. In one embodiment of the present invention, the compound represented by Formula 1 in the pharmaceutical composition of the present invention is, for example, 0.001 mg/kg or more, preferably 0.1 mg/kg or more, more preferably 10 mg/kg or more, more preferably 100 mg/kg or more, even more preferably 250 mg/kg or more, and most preferably 0.1 g/kg or more. The upper limit of the amount of the compound represented by Formula 1 included in the pharmaceutical composition of the present invention can be selected and implemented within an appropriate range by those skilled in the art.
본 발명에 따른 약학적 조성물은 유효량의 화학식 1로 표시되는 화합물을 단독으로 포함하거나 하나 이상의 약학적으로 허용되는 담체, 부형제 또는 희석제를 포함할 수 있다.The pharmaceutical composition according to the present invention may include an effective amount of the compound represented by Formula 1 alone or may include one or more pharmaceutically acceptable carriers, excipients, or diluents.
상기 약학적으로 허용되는 담체, 부형제 또는 희석제는 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 위장 장애, 현기증과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 물질을 말한다. 상기 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있으며, 이에 제한되는 것은 아니다. 또한, 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제 및 방부제 등을 추가로 포함할 수 있다.The pharmaceutically acceptable carrier, excipient or diluent refers to a material that is physiologically acceptable and does not cause an allergic reaction such as gastrointestinal disorder or dizziness or similar reaction when administered to humans. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, but are not limited thereto. In addition, fillers, anti-coagulants, lubricants, wetting agents, flavoring agents, emulsifiers and preservatives may be further included.
상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염은 임상 투여시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로오스 (sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용된다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테로 등이 사용될 수 있다.The compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be administered in various oral and parenteral dosage forms during clinical administration. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in one or more compounds, such as starch, calcium carbonate, sucrose or lactose ( lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. there is. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, and emulsions. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염을 유효 성분으로 하는 약학적 조성물은 비경구 투여할 수 있으며, 비경구 투여는 피하주사, 정맥주사, 근육 내 주사 또는 흉부 내 주사를 주입하는 방법에 의한다. A pharmaceutical composition comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient may be administered parenterally, and parenteral administration is performed by subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection. depending on how
이때, 비경구 투여용 제형으로 제제화하기 위하여 상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염을 안정제 또는 완충제와 함께 물에 혼합하여 용액 또는 현탁액으로 제조하고, 이를 앰플 또는 바이알 단위 투여형으로 제조할 수 있다. 상기 조성물은 멸균되고/되거나 방부제, 안정화제, 수화제 또는 유화 촉진제, 삼투압 조절을 위한 염 및/또는 완충제 등의 보조제, 및 기타 치료적으로 유용한 물질을 함유할 수 있으며, 통상적인 방법인 혼합, 과립화 또는 코팅 방법에 따라 제제화할 수 있다.At this time, in order to formulate a formulation for parenteral administration, the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof is mixed in water together with a stabilizer or buffer to prepare a solution or suspension, which is prepared in an ampoule or vial unit dosage form can be manufactured with The composition may be sterilized and/or contain preservatives, stabilizers, hydration agents or emulsification accelerators, salts and/or buffers for osmotic pressure control, and other therapeutically useful substances, and may contain conventional methods such as mixing and granulation. It can be formulated according to the coating or coating method.
본 발명에 있어서, 용어 “예방”이란, 본 발명의 약학적 조성물, 건강기능식품 조성물을 암 또는 자가면역질환의 투병중이지 않은 개체에게 투여, 섭취 또는 적용하여 암 또는 자가면역질환의 증세를 억제 또는 차단함으로써, 암 또는 자가면역질환의 증세가 사전에 발생되지 않도록 하는 것을 의미한다.In the present invention, the term “prevention” means suppressing the symptoms of cancer or autoimmune disease by administering, ingesting, or applying the pharmaceutical composition or health functional food composition of the present invention to a subject not suffering from cancer or autoimmune disease. Or by blocking, it means preventing symptoms of cancer or autoimmune disease from occurring in advance.
본 발명에 있어서, 용어 “치료”란, 본 발명의 약학적 조성물을 암 또는 자가면역질환 투병중인 개체에게 투여한 결과로서 암 또는 자가면역질환의 증세의 완치는 물론 암 또는 자가면역질환의 증세의 부분적 완치, 호전 및 경감을 포함한다.In the present invention, the term "treatment" refers to the cure of symptoms of cancer or autoimmune disease as well as the treatment of symptoms of cancer or autoimmune disease as a result of administering the pharmaceutical composition of the present invention to an individual suffering from cancer or autoimmune disease. It includes partial cure, improvement and remission.
본 발명의 약학적 조성물은 약학적으로 유효한 양으로 투여한다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
본 발명에 있어서, 용어 “약학적으로 유효한 양”이란, 의학적 치료 또는 개선에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 예를 들어, 0.001 mg/kg 이상, 0.1 mg/kg 이상, 10 mg/kg 이상, 100 mg/kg 이상, 250 mg/kg 이상, 0.1 g/kg 이상 포함된다. 본 발명의 약학적 조성물의 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.In the present invention, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment or improvement, and the effective dose level is the type and severity of the subject, age, It may be determined according to factors including sex, activity of drug, sensitivity to drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used concurrently, and other factors well known in the medical field. Examples include 0.001 mg/kg or more, 0.1 mg/kg or more, 10 mg/kg or more, 100 mg/kg or more, 250 mg/kg or more, and 0.1 g/kg or more. The upper limit of the amount of the pharmaceutical composition of the present invention can be selected and implemented by those skilled in the art within an appropriate range.
나아가, 상기 화학식 1로 표시되는 화합물은 이의 약학적으로 허용가능한 염뿐만 아니라, 이로부터 제조될 수 있는 입체이성질체, 용매화물, 수화물 등의 형태로 사용될 수 있다.Furthermore, the compound represented by Formula 1 may be used in the form of not only pharmaceutically acceptable salts thereof, but also stereoisomers, solvates, and hydrates that may be prepared therefrom.
또한, 상기 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물은 개별 치료제로 투여하거나, 사용중인 다른 항암제와 병용투여하여 사용할 수 있다.In addition, a pharmaceutical composition for preventing or treating cancer containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient is administered as an individual therapeutic agent, It can be used in combination with other anticancer drugs currently in use.
또한, 상기 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물은 항암제와 병용투여함으로써 항암 효과를 증진시킬 수 있다.In addition, a pharmaceutical composition for preventing or treating cancer containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient is administered in combination with an anticancer agent. effect can be enhanced.
본 발명의 다른 측면에서,In another aspect of the invention,
상기 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 암 또는 자가면역질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다.Provided is a health functional food composition for preventing or improving cancer or autoimmune diseases, containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 있어서, 용어 “개선”이란, 본 발명의 약학적 조성물, 식품 조성물을 암 또는 자가면역질환 투병 개체에게 투여, 섭취 또는 적용하여 암 또는 자가면역질환의 증세의 경감 또는 완화를 포함하는 의미이다.In the present invention, the term "improvement" means that the pharmaceutical composition or food composition of the present invention is administered, ingested, or applied to a subject suffering from cancer or autoimmune disease to reduce or alleviate the symptoms of cancer or autoimmune disease. am.
본 발명의 약학적 조성물 및 건강기능식품 조성물에서 언급된 사항은 서로 모순되지 않는 한 동일하게 적용된다.Matters mentioned in the pharmaceutical composition and health functional food composition of the present invention are equally applied unless they contradict each other.
본 발명의 다른 측면에서, 본 명세서에 기재된 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 필요한 대상에게 투여하는 단계를 포함하는 암 또는 자가면역질환의 예방 또는 치료 방법이 제공된다.In another aspect of the present invention, cancer or autoimmunity comprising the step of administering to a subject in need of a compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof described herein. A method for preventing or treating a disease is provided.
본 발명의 다른 측면에서, 암 또는 자가면역질환의 예방 또는 치료에 있어서의, 본 명세서에 기재된 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염의 사용을 제공한다.In another aspect of the present invention, use of the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof described herein in the prevention or treatment of cancer or autoimmune disease. provides
본 발명의 다른 측면에서, 본 명세서에 기재된 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염의 암 또는 자가면역질환의 예방 또는 치료를 위한 약제 제조에 있어서의 사용을 제공한다.In another aspect of the present invention, a compound represented by Formula 1 described herein, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof is used to prepare a medicament for preventing or treating cancer or autoimmune diseases. provide use in
상기 방법, 사용에 있어서, 전술한 약학적 조성물에 대한 상세한 설명이 적용될 수 있다.In the methods and uses, the detailed description of the pharmaceutical composition described above can be applied.
이하, 본 발명을 제조예, 실시예 및 실험예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by production examples, examples and experimental examples.
단, 하기 제조예, 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 제조예, 실시예 및 실험예에 한정되는 것은 아니다.However, the following Preparation Examples, Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Preparation Examples, Examples and Experimental Examples.
<분석 및 정제 조건><Analysis and purification conditions>
본 발명의 실시예에서 합성된 화합물은 하기의 방법으로 정제하거나 또는 구조 분석을 실시하였다.Compounds synthesized in Examples of the present invention were purified or structurally analyzed by the following methods.
1. LC-MS 분석 조건1. LC-MS Analysis Conditions
기기명: Shimadzu LCMS-2020Device Name: Shimadzu LCMS-2020
컬럼: ACE Excel2 C18, 75x2.1 mmColumn: ACE Excel2 C18, 75x2.1 mm
이동상: 아세토니트릴/H2O + 0.1% TFAMobile Phase: Acetonitrile/H 2 O + 0.1% TFA
유속 : 1mL/minFlow rate: 1mL/min
UV detector: 254nmUV detector: 254nm
2. 2. MPLCMPLC 정제 조건 purification conditions
기기명: CombiFlash®Device Name: CombiFlash®
UV detector: 254nmUV detector: 254nm
3. Prep-3. Prep- HPLCHPLC 정제 조건 purification conditions
기기명: Gilson GX-281, 321 pump, UV/VIS-155Device name: Gilson GX-281, 321 pump, UV/VIS-155
컬럼: Luna®10 νÅmmColumn: Luna®10 νÅmm
이동상: 아세토니트릴/ 0.1% TFA H2OMobile Phase: Acetonitrile/ 0.1% TFA H2O
유속 : 15mL/minFlow rate: 15mL/min
UV detector: 254nmUV detector: 254nm
4. 1H NMR4. 1 H NMR
기기명: Brucker Avance (400 MHz)Device Name: Brucker Avance (400 MHz)
<< 실시예Example 1> 2-(6-((2- 1> 2-(6-((2- (( (4-(4-(4-(4- 메틸피페라진Methylpiperazine -1-일)페닐)아미노)-1-yl) phenyl) amino) 티에노[2,3-d]피리미딘Thieno[2,3-d]pyrimidine -4-일)아미노)피리딘-2-일)프로판-2-올의 제조Preparation of -4-yl) amino) pyridin-2-yl) propan-2-ol
Figure PCTKR2022016628-appb-img-000012
Figure PCTKR2022016628-appb-img-000012
단계 1 : 2-(6-((2-클로로티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올의 제조Step 1: Preparation of 2-(6-((2-chlorothieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol
Figure PCTKR2022016628-appb-img-000013
Figure PCTKR2022016628-appb-img-000013
2,4-디클로로티에노[2,3-d]피리미딘(0.3 g, 1.463 mmol)을 N,N-디메틸포름아미드 (5 mL)에 녹인 후, 2-(6-아미노피리딘-2-일)프로판-2-올 (0.223 g, 1.463 mmol)와 DIPEA (0.774 ml, 4.39 mmol)을 상온에서 첨가한 후, 80 °C에서 16시간 동안 교반하였다.After dissolving 2,4-dichlorothieno[2,3-d]pyrimidine (0.3 g, 1.463 mmol) in N,N-dimethylformamide (5 mL), 2-(6-aminopyridin-2-yl ) After adding propan-2-ol (0.223 g, 1.463 mmol) and DIPEA (0.774 ml, 4.39 mmol) at room temperature, the mixture was stirred at 80 °C for 16 hours.
상기 반응 혼합액을 실온으로 냉각시킨 후, 에틸아세테이트로 희석시키고 물과 소금물로 씻어주었다. 유기층의 잔류물은 무수 황산나트륨으로 건조하고, 여과 및 농축한 후 MPLC로 정제하여 목적하는 화합물 (0.21 g, 45%)을 제조하였다 MS m/z : 321[M+H]+ After cooling the reaction mixture to room temperature, it was diluted with ethyl acetate and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (0.21 g, 45%) MS m/z: 321 [M+H] +
단계 2 : 2-(6-((2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올Step 2: 2-(6-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridine -2-yl)propan-2-ol
상기 단계 1에서 제조한 화합물(0.05g, 0.156 mmol)을 sec-부탄올(1.5 mL)에 녹인 후, 4-(4-메틸피페라진-1-일)아닐린 (0.033 g, 0.171 mmol) 그리고 탄산 칼륨(0.108 g, 0.779 mmol)을 첨가한 후, 약 1분간 탈기하였다. 상기 혼합액에 Pd2(dba)3 (0.014 g, 0.016 mmol) 그리고 Xphos(7.4 mg, 0.016 mmol)을 넣고 80 ℃ 에서 1시간 동안 교반하였다. 상기 반응 혼합액을 실온으로 냉각시켜 셀라이트를 통해 여과한 후, 에틸아세테이트로 희석시키고 물과 소금물로 씻어주었다. 유기층의 잔류물은 무수 황산나트륨으로 건조하고, 여과 및 농축한 후 Prep HPLC로 정제하고 포화 탄산수소나트륨 수용액을 첨가하여 중화 시킨 후, 목적하는 화합물 (34.4 mg, 46%, 흰색고체)을 제조하였다. MS m/z : 476[M+H]+ After dissolving the compound (0.05g, 0.156 mmol) prepared in step 1 in sec-butanol (1.5 mL), 4-(4-methylpiperazin-1-yl)aniline (0.033 g, 0.171 mmol) and potassium carbonate (0.108 g, 0.779 mmol) was added, followed by degassing for about 1 minute. Pd 2 (dba) 3 (0.014 g, 0.016 mmol) and Xphos (7.4 mg, 0.016 mmol) were added to the mixture and stirred at 80 °C for 1 hour. The reaction mixture was cooled to room temperature, filtered through celite, diluted with ethyl acetate, and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, purified by Prep HPLC, and neutralized by adding saturated aqueous sodium bicarbonate solution to obtain the desired compound (34.4 mg, 46%, white solid). MS m/z : 476 [M+H] +
<< 실시예Example 2 내지 2 to 실시예Example 18> 18>
상기 실시예 1의 제조방법과 동일한 방법으로, 반응물만 달리하여 실시예 2 내지 실시예 18의 화합물을 제조하였다.The compounds of Examples 2 to 18 were prepared in the same manner as in the preparation method of Example 1, except for the reactants.
<< 실시예Example 19> sec-부틸 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트의 제조 19> sec-Butyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2 Preparation of -yl) pyridin-2-yl) amino) thieno [2,3-d] pyrimidine-5-carboxylate
Figure PCTKR2022016628-appb-img-000014
Figure PCTKR2022016628-appb-img-000014
단계 1 : 메틸2-클로로-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트의 제조Step 1: Methyl2-chloro-4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxylate manufacturing
Figure PCTKR2022016628-appb-img-000015
Figure PCTKR2022016628-appb-img-000015
상기 실시예 1의 단계 1과 동일한 방법을 수행하여 목적화합물을 제조하였다. MS m/z : 393[M+H]+ A target compound was prepared by performing the same method as in step 1 of Example 1 above. MS m/z : 393 [M+H] +
단계 2 : sec-부틸 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트의 제조Step 2: sec-butyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropane- Preparation of 2-yl) pyridin-2-yl) amino) thieno [2,3-d] pyrimidine-5-carboxylate
Figure PCTKR2022016628-appb-img-000016
Figure PCTKR2022016628-appb-img-000016
상기 실시예 1의 단계 2와 동일한 방법을 수행하여 목적화합물을 제조하였다. MS m/z : 634 [M+H]+ A target compound was prepared by performing the same method as in step 2 of Example 1 above. MS m/z : 634 [M+H] +
<< 실시예Example 20> sec-부틸 4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-5-카복실레이트의 제조 20> sec-butyl 4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-2-((4-(4-methylpiperazin-1-yl)phenyl) Preparation of amino) thieno [2,3-d] pyrimidine-5-carboxylate
상기 실시예 19의 제조방법과 동일한 방법으로, 반응물만 달리하여 실시예 20의 화합물을 제조하였다.The compound of Example 20 was prepared in the same manner as in the preparation method of Example 19, except for the reactants.
<< 실시예Example 21> 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카르복사미드의 제조 21> 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl) Preparation of pyridin-2-yl) amino) thieno [2,3-d] pyrimidine-5-carboxamide
Figure PCTKR2022016628-appb-img-000017
Figure PCTKR2022016628-appb-img-000017
단계 1: 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카르복실산의 제조Step 1: 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl) Preparation of )pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxylic acid
Figure PCTKR2022016628-appb-img-000018
Figure PCTKR2022016628-appb-img-000018
상기 실시예 19의 단계 2에서 제조한 화합물 (0.1039 g, 0.164 mmol)을 테트라하이드로퓨란(0.5 mL), 메탄올(0.5 mL)에 녹인 후, 물 (0.5 mL)에 녹인 수산화 리튬(0.012 g, 0.492 mmol)을 첨가한 후, 상온에서 1시간 동안 교반하였다. 상기 반응 혼합액에 1N 염산 수용액을 PH3이 될 때까지 첨가 하고, 디클로로메탄으로 희석시키고 물과 소금물로 씻어주었다. 유기층의 잔류물은 무수 황산나트륨으로 건조하고 여과 및 농축한 후, 정제단계 없이 노란색 고체의 목적화합물 (0.095 g, quant)을 수득하였다. MS m/z : 578[M+H]+ After dissolving the compound (0.1039 g, 0.164 mmol) prepared in step 2 of Example 19 in tetrahydrofuran (0.5 mL) and methanol (0.5 mL), lithium hydroxide (0.012 g, 0.492 g) dissolved in water (0.5 mL) mmol) was added, and the mixture was stirred at room temperature for 1 hour. 1N aqueous hydrochloric acid solution was added to the reaction mixture until PH3 was reached, diluted with dichloromethane, and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a target compound (0.095 g, quant) as a yellow solid without purification. MS m/z : 578 [M+H] +
단계 2 : 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카르복사미드의 제조Step 2: 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl) Preparation of )pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxamide
Figure PCTKR2022016628-appb-img-000019
Figure PCTKR2022016628-appb-img-000019
상기 단계 1에서 제조한 화합물(0.095 g, 0.164 mmol)을 N,N-디메틸포름아미드(1 mL)에 녹인 후, 염화 암모늄 (0.044 g, 0.822 mmol), DIPEA (0.287 ml, 1.644 mmol),HOBT (0.028 g, 0.181 mmol) 그리고 EDCI (0.035 g, 0.181 mmol)을 첨가한 후, 상온에서 16시간 동안 교반하였다. 상기 반응 혼합액을 디클로로메탄으로 희석시키고 물과 소금물로 씻어주었다. 유기층의 잔류물은 무수 황산나트륨으로 건조하고, 여과 및 농축한 후, MPLC로 정제하고 목적하는 화합물 (7.6 mg, 8%, 흰색고체)을 제조하였다. MS m/z : 577[M+H]+ After dissolving the compound prepared in step 1 (0.095 g, 0.164 mmol) in N, N-dimethylformamide (1 mL), ammonium chloride (0.044 g, 0.822 mmol), DIPEA (0.287 ml, 1.644 mmol), HOBT (0.028 g, 0.181 mmol) and EDCI (0.035 g, 0.181 mmol) were added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with dichloromethane and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (7.6 mg, 8%, white solid). MS m/z : 577[M+H] +
< 실시예 22> 상기 실시예 21의 제조방법과 동일한 방법으로, 반응물만 달리하여 실시예 22의 화합물을 제조하였다. < Example 22> The compound of Example 22 was prepared in the same manner as in Example 21, except for the reactants.
<< 실시예Example 23> ( 23> ( 1R,4R1R,4R )-4-((4-((6-(2-)-4-((4-((6-(2- 하이드록시프로판hydroxypropane -2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)시클로헥산-1-올의 제조Preparation of -2-yl) pyridin-2-yl) amino) -5-methylthieno [2,3-d] pyrimidin-2-yl) amino) cyclohexan-1-ol
단계 1 : 2-(6-((2-클로로-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올의 제조Step 1: Preparation of 2-(6-((2-chloro-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol
Figure PCTKR2022016628-appb-img-000020
Figure PCTKR2022016628-appb-img-000020
상기 실시예 1의 단계 1과 유사한 방법으로 수행하여 목적화합물을 제조하였다.A target compound was prepared in a manner similar to step 1 of Example 1 above.
MS m/z : 335 [M+H]+ MS m/z : 335 [M+H] +
단계 2 : (1R,4R)-4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)시클로헥산-1-올의 제조Step 2: (1R,4R)-4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d Preparation of ]pyrimidin-2-yl)amino)cyclohexan-1-ol
Figure PCTKR2022016628-appb-img-000021
Figure PCTKR2022016628-appb-img-000021
상기 단계 1에서 제조한 화합물(0.03 g, 0.090 mmol)을 N,N-디메틸포름아미드 (1 mL)에 녹인 후, (Rr,4R)-4-아미노시클로헥산올 (10.32 mg, 0.090 mmol)과 DIPEA (0.023 ml, 0.134 mmol) 을 상온에서 첨가한 후, 120 °C에서 16시간 동안 교반하였다. 상기 반응 혼합액을 실온으로 냉각시킨 후, 에틸아세테이트로 희석시키고 물과 소금물로 씻어주었다. 유기층의 잔류물은 무수 황산나트륨으로 건조하고, 여과 및 농축한 후 MPLC로 정제하여 목적하는 화합물 (7.8 mg, 21%)을 제조하였다. MS m/z : 414[M+H]+ After dissolving the compound (0.03 g, 0.090 mmol) prepared in step 1 in N, N-dimethylformamide (1 mL), (Rr, 4R) -4-aminocyclohexanol (10.32 mg, 0.090 mmol) and After adding DIPEA (0.023 ml, 0.134 mmol) at room temperature, the mixture was stirred at 120 °C for 16 hours. After cooling the reaction mixture to room temperature, it was diluted with ethyl acetate and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (7.8 mg, 21%). MS m/z : 414 [M+H] +
<< 실시예Example 24> 24> 메틸methyl 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트의 제조 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl)pyridin- Preparation of 2-yl) amino) thieno [2,3-d] pyrimidine-5-carboxylate
Figure PCTKR2022016628-appb-img-000022
Figure PCTKR2022016628-appb-img-000022
단계 1 : 메틸 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트의 제조Step 1: Methyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2- Preparation of yl) pyridin-2-yl) amino) thieno [2,3-d] pyrimidine-5-carboxylate
Figure PCTKR2022016628-appb-img-000023
Figure PCTKR2022016628-appb-img-000023
상기 실시예 19의 단계2 에서 제조한 화합물(0.29 g, 0.749 mmol)을 N,N-디메틸포름아미드(1.5 mL)에 녹인 후, 1-(4-아미노-2-메톡시페닐)-N,N-디메틸피페리딘-4-아민 (0.187 g, 0.749 mmol) 그리고 탄산 칼륨(0.518 g, 3.74 mmol)을 첨가한 후, 약 1분간 탈기하였다. 상기 혼합액에 Pd2(dba)3 (0.069 g, 0.075 mmol) 그리고 Xphos(0.036 g, 0.075 mmol)을 넣고 80 ℃ 에서 1시간 동안 교반하였다. 상기 반응 혼합액을 실온으로 냉각시켜 셀라이트를 통해 여과한 후, 에틸아세테이트로 희석시키고 물과 소금물로 씻어주었다. 유기층의 잔류물은 무수 황산나트륨으로 건조하고, 여과 및 농축한 후 Prep HPLC로 정제하고 포화 탄산수소나트륨 수용액을 첨가하여 중화 시킨 후, 목적하는 화합물 (0.0705 g, 16%, 흰색고체)을 제조하였다. MS m/z : 606[M+H]+ After dissolving the compound (0.29 g, 0.749 mmol) prepared in step 2 of Example 19 in N, N-dimethylformamide (1.5 mL), 1-(4-amino-2-methoxyphenyl)-N, After adding N-dimethylpiperidin-4-amine (0.187 g, 0.749 mmol) and potassium carbonate (0.518 g, 3.74 mmol), it was degassed for about 1 minute. Pd2(dba)3 (0.069 g, 0.075 mmol) and Xphos (0.036 g, 0.075 mmol) were added to the mixture and stirred at 80 °C for 1 hour. The reaction mixture was cooled to room temperature, filtered through celite, diluted with ethyl acetate, and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, purified by Prep HPLC, and neutralized by adding saturated sodium bicarbonate aqueous solution to obtain the desired compound (0.0705 g, 16%, white solid). MS m/z : 606 [M+H] +
<< 실시예Example 25 내지 25 to 실시예Example 27> 27>
상기 실시예 23의 제조방법과 동일한 방법으로, 반응물만 달리하여 실시예 25 내지 실시예 27의 화합물을 제조하였다.The compounds of Examples 25 to 27 were prepared in the same manner as in the preparation method of Example 23, except for the reactants.
<< 실시예Example 28 내지 28 to 실시예Example 52> 52>
상기 실시예 1의 제조방법과 동일한 방법으로, 반응물만 달리하여 실시예 28 내지 실시예 52의 화합물을 제조하였다.The compounds of Examples 28 to 52 were prepared in the same manner as in the preparation method of Example 1, except for the reactants.
<< 실시예Example 53> N4-(5-( 53> N4-(5-( 터트tut -부틸)-butyl) 이속사졸Isoxazole -3-일)-5--3- days)-5- 메틸methyl -N2--N2- (4-(4-메틸피페라진-1-일)페닐)티에노(4-(4-methylpiperazin-1-yl)phenyl)thieno [2,3-d]피리미딘-2,4-디아민의 제조Preparation of [2,3-d]pyrimidine-2,4-diamine
Figure PCTKR2022016628-appb-img-000024
Figure PCTKR2022016628-appb-img-000024
단계 1: 5-(터트-부틸)-N-(2-클로로-5-메틸티에노[2,3-d]피리미딘-4-일)이속사졸-3-아민의 제조Step 1: Preparation of 5-(tert-butyl)-N-(2-chloro-5-methylthieno[2,3-d]pyrimidin-4-yl)isoxazol-3-amine
Figure PCTKR2022016628-appb-img-000025
Figure PCTKR2022016628-appb-img-000025
5-(터트-부틸)이속사졸-3-아민(0.141 g, 1 mmol) 을 N,N-디메틸포름아미드 (5 mL)에 녹인 후, 0 ℃ 에서 소듐하이드라이드 (44 mg, 1.8 mmol)와 2,4-디클로로-5-메틸티에노[2,3-d]피리미딘(0.2 g, 0.9 mmol)을 첨가한 후, 상온에서 22 시간 동안 교반하였다. 반응이 종결된 후, 에틸아세테이트로 희석시키고 물과 소금물로 씻어주었다. 유기층의 잔류물은 무수 황산나트륨으로 건조하고, 여과 및 농축한 후 MPLC로 정제하여 목적하는 화합물 (0.14 g, 47%, 흰색 고체)을 제조하였다. MS m/z : 323[M+H]+ After dissolving 5-(tert-butyl)isoxazol-3-amine (0.141 g, 1 mmol) in N,N-dimethylformamide (5 mL), sodium hydride (44 mg, 1.8 mmol) and After adding 2,4-dichloro-5-methylthieno[2,3-d]pyrimidine (0.2 g, 0.9 mmol), the mixture was stirred at room temperature for 22 hours. After the reaction was completed, the mixture was diluted with ethyl acetate and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and then purified by MPLC to obtain the desired compound (0.14 g, 47%, white solid). MS m/z : 323[M+H] +
단계 2: N4-(5-(터트-부틸)이속사졸-3-일)-5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민의 제조Step 2: N4-(5-(tert-butyl)isoxazol-3-yl)-5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3- d] Preparation of pyrimidine-2,4-diamine
Figure PCTKR2022016628-appb-img-000026
Figure PCTKR2022016628-appb-img-000026
상기 실시예 1의 단계 2 와 유사하게 수행하여 목적화합물을 제조하였다. MS m/z : 478[M+H]+ A target compound was prepared by performing similarly to step 2 of Example 1 above. MS m/z : 478 [M+H] +
< 실시예 54 내지 실시예 63> 실시예 1과 유사한 방법으로 실시예 54-63의 화합물을 제조하였다. < Examples 54 to 63 > Compounds of Examples 54-63 were prepared in a similar manner to Example 1.
< 실시예 64> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올의 제조 < Example 64> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methyl Preparation of thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol
Figure PCTKR2022016628-appb-img-000027
Figure PCTKR2022016628-appb-img-000027
단계 1: 2-(3-((2-클로로-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올의 제조Step 1: Preparation of 2-(3-((2-chloro-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol
Figure PCTKR2022016628-appb-img-000028
Figure PCTKR2022016628-appb-img-000028
상기 실시예 1 단계 1과 유사하게 수행하여 목적화합물을 제조하였다. MS m/z : 334[M+H]+ A target compound was prepared in the same manner as in Example 1, step 1. MS m/z : 334 [M+H] +
단계 2 : 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올의 제조Step 2: 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno Preparation of [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol
Figure PCTKR2022016628-appb-img-000029
Figure PCTKR2022016628-appb-img-000029
상기 단계 1에서 제조한 화합물(0.3 g, 0.899 mmol)을 tert-부탄올(1 mL)에 녹인 후, 4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시아닐린 (0.282 g, 1.078 mmol) 그리고 탄산 세슘(0.586 g, 1.797 mmol)을 첨가한 후, 약 1분간 탈기하였다. 상기혼합액에 Xphos Pd G2 (0.071 g, 0.090 mmol)을 넣고 80 oC에서 16시간 동안 교반하였다. 상기 반응 혼합액을 실온으로 냉각시켜 셀라이트를 통해 여과한 후, 에틸아세테이트로 희석시키고 물과 소금물로 씻어주었다. 유기층의 잔류물은 무수 황산나트륨으로 건조하고, 여과 및 농축한 후 Prep HPLC로 정제하고 포화 탄산수소나트륨 수용액을 첨가하여 중화 시킨 후, 목적하는 화합물 (185 mg, 37%, 노란색고체)을 제조하였다. MS m/z : 559[M+H]+ After dissolving the compound (0.3 g, 0.899 mmol) prepared in step 1 in tert-butanol (1 mL), 4-(4-(azetidin-1-yl)piperidin-1-yl)-3- After adding methoxyaniline (0.282 g, 1.078 mmol) and cesium carbonate (0.586 g, 1.797 mmol), the mixture was degassed for about 1 minute. Xphos Pd G2 (0.071 g, 0.090 mmol) was added to the mixture and stirred at 80 ° C for 16 hours. The reaction mixture was cooled to room temperature, filtered through celite, diluted with ethyl acetate, and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, purified by Prep HPLC, and neutralized by adding saturated sodium bicarbonate aqueous solution to obtain the desired compound (185 mg, 37%, yellow solid). MS m/z : 559 [M+H] +
<< 실시예Example 65 내지 81> 65 to 81>
상기 실시예 1과 유사한 방법으로 실시예 65-68, 70-73, 75-76, 78-80의 화합물을 제조하였다.The compounds of Examples 65-68, 70-73, 75-76, and 78-80 were prepared in a similar manner to Example 1.
상기 실시예 64와 유사한 방법으로 실시예 69, 74, 77, 81의 화합물을 제조하였다. 실시예 81의 화합물은 Prep HPLC로 정제 후 그대로 2,2,2-트리플루오로아세트산 염의 형태로 수득하였다.The compounds of Examples 69, 74, 77 and 81 were prepared in a similar manner to Example 64. The compound of Example 81 was obtained in the form of a 2,2,2-trifluoroacetic acid salt as it was after purification by Prep HPLC.
< 실시예 82> 2-(6-((2-((3-메톡시-4-(4-(메틸아미노)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올의 2,2,2-트리플루오로아세트산 염의 제조 < Example 82> 2-(6-((2-((3-methoxy-4-(4-(methylamino)piperidin-1-yl)phenyl)amino)-5-methylthieno[2 Preparation of 2,2,2-trifluoroacetic acid salt of ,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol
Figure PCTKR2022016628-appb-img-000030
Figure PCTKR2022016628-appb-img-000030
단계 1: 2-(6-((2-((3-메톡시-4-(4-(메틸아미노)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올 , 2,2,2-트리플루오로아세트산의 제조Step 1: 2-(6-((2-((3-methoxy-4-(4-(methylamino)piperidin-1-yl)phenyl)amino)-5-methylthieno[2,3 -d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol, the preparation of 2,2,2-trifluoroacetic acid
Figure PCTKR2022016628-appb-img-000031
Figure PCTKR2022016628-appb-img-000031
상기 실시예 1과 유사하게 수행하여 제조한 터트-부틸(1-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)피페리딘-4-일)(메틸)카바메이트(0.095 g, 0.150 mmol)을 디클로로메탄(2 mL)에 녹인 후, 트리플루오로아세트산 (1 ml, 12.98 mmol)을 첨가 하고 상온에서 1시간 동안 교반 하였다. 반응 혼합물을 농축한 후, Prep HPLC로 정제하여 목적하는 화합물 (22.5 mg, 23%, 노란색고체)을 제조하였다. MS m/z : 648[M+H]+ tert-Butyl(1-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-prepared by conducting similarly to Example 1 above Methylthieno[2,3-d]pyrimidin-2-yl)amino)-2-methoxyphenyl)piperidin-4-yl)(methyl)carbamate (0.095 g, 0.150 mmol) was dissolved in dichloromethane ( 2 mL), trifluoroacetic acid (1 ml, 12.98 mmol) was added and stirred at room temperature for 1 hour. After concentrating the reaction mixture, it was purified by Prep HPLC to give the desired compound (22.5 mg, 23%, yellow solid). MS m/z : 648 [M+H] +
<< 실시예Example 83 내지 83 to 실시예Example 133> 133>
상기 실시예 1과 유사한 방법으로 실시예 83-85, 87, 90-97, 100, 102, 107, 109-114, 116, 118-120, 122-123, 126-127, 131-133의 화합물을 제조하였다.The compounds of Examples 83-85, 87, 90-97, 100, 102, 107, 109-114, 116, 118-120, 122-123, 126-127 and 131-133 were prepared in a similar manner to Example 1. manufactured.
상기 실시예 64와 유사한 방법으로 실시예 86, 88-89, 101, 103, 108, 115, 117, 121, 124-125, 128-130의 화합물을 제조하였다.The compounds of Examples 86, 88-89, 101, 103, 108, 115, 117, 121, 124-125, and 128-130 were prepared in a similar manner to Example 64.
상기 실시예 53과 유사한 방법으로 실시예 104-106의 화합물을 제조하였다.Compounds of Examples 104-106 were prepared in a similar manner to Example 53 above.
상기 실시예 82와 유사한 방법으로 실시예 98-99의 화합물을 제조하였다.The compounds of Examples 98-99 were prepared in a similar manner to Example 82.
< 실시예 134> 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤조산의 2,2,2-트리플루오로아세트산 염의 제조 < Example 134> 3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3- Preparation of 2,2,2-trifluoroacetic acid salt of d]pyrimidin-4-yl)amino)benzoic acid
Figure PCTKR2022016628-appb-img-000032
Figure PCTKR2022016628-appb-img-000032
단계 1: 5-(터트-부틸)-N-(2-클로로-5-메틸티에노[2,3-d]피리미딘-4-일)이속사졸-3-아민의 제조Step 1: Preparation of 5-(tert-butyl)-N-(2-chloro-5-methylthieno[2,3-d]pyrimidin-4-yl)isoxazol-3-amine
Figure PCTKR2022016628-appb-img-000033
Figure PCTKR2022016628-appb-img-000033
상기 실시예 1과 유사한 방법으로 합성한 메틸 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트 (32 mg, 0.067 mmol)을 테트라히드로퓨란/메탄올/물 (1 mL)에 용해 시킨 후, 상온에서 수산화리튬 (6.42 mg, 0.268 mmol)을 첨가하였다. 반응 혼합물을 50 oC에서 3시간 동안 가열 교반 하였다. 반응이 종결된 후 혼합물을 감압하에 농축한 다음 Prep HPLC로 정제하여, 2,2,2-트리플루오로아세트산 염 형태의 목적하는 화합물 (22 mg, 71%, 연한 노란색 고체)을 제조하였다. MS m/z : 464[M+H]+ Methyl 3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thiere synthesized in a similar manner to Example 1 After dissolving no[2,3-d]pyrimidin-4-yl)amino)benzoate (32 mg, 0.067 mmol) in tetrahydrofuran/methanol/water (1 mL), lithium hydroxide (6.42 mg , 0.268 mmol) was added. The reaction mixture was heated and stirred at 50 ° C for 3 hours. After the reaction was completed, the mixture was concentrated under reduced pressure and then purified by Prep HPLC to obtain the desired compound (22 mg, 71%, pale yellow solid) in the form of a 2,2,2-trifluoroacetic acid salt. MS m/z : 464 [M+H] +
< 실시예 135> 상기 실시예 134와 유사한 방법으로 실시예 135의 화합물을 제조하였다. < Example 135> The compound of Example 135 was prepared in a similar manner to Example 134.
<< 실시예Example 136 내지 136 to 실시예Example 209> 209>
상기 실시예 1과 유사한 방법으로 실시예 136-144, 147, 150-153, 155-161, 170, 172-178, 183-184, 186-191, 194-199, 201, 205, 207-209의 화합물을 제조하였다.Examples 136-144, 147, 150-153, 155-161, 170, 172-178, 183-184, 186-191, 194-199, 201, 205, 207-209 in a similar manner to Example 1 compound was prepared.
상기 실시예 64와 유사한 방법으로 실시예 148, 154, 162-169, 171, 181-182, 185, 192-193, 200, 202-204, 206의 화합물을 제조하였다.Compounds of Examples 148, 154, 162-169, 171, 181-182, 185, 192-193, 200, 202-204, and 206 were prepared in a similar manner to Example 64.
상기 실시예 82와 유사한 방법으로 실시예 145-146, 179-180의 화합물을 제조하였다.The compounds of Examples 145-146 and 179-180 were prepared in a similar manner to Example 82.
상기 실시예 134와 유사한 방법으로 실시예 149의 화합물을 제조하였다.The compound of Example 149 was prepared in a similar manner to Example 134 above.
아래 표 1 내지 2에 실시예 1 내지 209 화합물의 구조를 제시한다. Tables 1-2 below show the structures of the compounds of Examples 1-209.
Figure PCTKR2022016628-appb-img-000034
Figure PCTKR2022016628-appb-img-000034
Figure PCTKR2022016628-appb-img-000035
Figure PCTKR2022016628-appb-img-000035
Figure PCTKR2022016628-appb-img-000036
Figure PCTKR2022016628-appb-img-000036
Figure PCTKR2022016628-appb-img-000037
Figure PCTKR2022016628-appb-img-000037
Figure PCTKR2022016628-appb-img-000038
Figure PCTKR2022016628-appb-img-000038
Figure PCTKR2022016628-appb-img-000039
Figure PCTKR2022016628-appb-img-000039
Figure PCTKR2022016628-appb-img-000040
Figure PCTKR2022016628-appb-img-000040
Figure PCTKR2022016628-appb-img-000041
Figure PCTKR2022016628-appb-img-000041
Figure PCTKR2022016628-appb-img-000042
Figure PCTKR2022016628-appb-img-000042
Figure PCTKR2022016628-appb-img-000043
Figure PCTKR2022016628-appb-img-000043
Figure PCTKR2022016628-appb-img-000044
Figure PCTKR2022016628-appb-img-000044
Figure PCTKR2022016628-appb-img-000045
Figure PCTKR2022016628-appb-img-000045
Figure PCTKR2022016628-appb-img-000046
Figure PCTKR2022016628-appb-img-000046
Figure PCTKR2022016628-appb-img-000047
Figure PCTKR2022016628-appb-img-000047
Figure PCTKR2022016628-appb-img-000048
Figure PCTKR2022016628-appb-img-000048
Figure PCTKR2022016628-appb-img-000049
Figure PCTKR2022016628-appb-img-000049
Figure PCTKR2022016628-appb-img-000050
Figure PCTKR2022016628-appb-img-000050
Figure PCTKR2022016628-appb-img-000051
Figure PCTKR2022016628-appb-img-000051
Figure PCTKR2022016628-appb-img-000052
Figure PCTKR2022016628-appb-img-000052
Figure PCTKR2022016628-appb-img-000053
Figure PCTKR2022016628-appb-img-000053
Figure PCTKR2022016628-appb-img-000054
Figure PCTKR2022016628-appb-img-000054
Figure PCTKR2022016628-appb-img-000055
Figure PCTKR2022016628-appb-img-000055
Figure PCTKR2022016628-appb-img-000056
Figure PCTKR2022016628-appb-img-000056
Figure PCTKR2022016628-appb-img-000057
Figure PCTKR2022016628-appb-img-000057
Figure PCTKR2022016628-appb-img-000058
Figure PCTKR2022016628-appb-img-000058
Figure PCTKR2022016628-appb-img-000059
Figure PCTKR2022016628-appb-img-000059
Figure PCTKR2022016628-appb-img-000060
Figure PCTKR2022016628-appb-img-000060
아래 표 3 내지 6에는 화합물의 이름과 분석 결과이다.Tables 3 to 6 below show the names of compounds and analysis results.
실시예Example 화합물명compound name 1H NMR and/or Mass 1 H NMR and/or Mass
1One 2-(6-((2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2- 1) propan-2-ol 1H NMR (400MHz, DMSO) δ9.69 (s, 1H), 9.12 (s, 1H), 8.31 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 6.0 Hz, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.54 (d, J = 8.6 Hz, 2H), 7.33 (d, J = 7.5 Hz, 1H), 7.19 (d, J = 6.0 Hz, 1H), 6.92 - 6.86 (m, 2H), 5.24 (s, 1H), 3.06 (t, J = 5.0 Hz, 4H), 2.45 (t, J = 4.9 Hz, 4H), 2.22 (s, 3H), 1.47 (s, 6H); 476 [M+H]+ 1 H NMR (400 MHz, DMSO) δ9.69 (s, 1H), 9.12 (s, 1H), 8.31 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 6.0 Hz, 1H), 7.74 ( t, J = 7.9 Hz, 1H), 7.54 (d, J = 8.6 Hz, 2H), 7.33 (d, J = 7.5 Hz, 1H), 7.19 (d, J = 6.0 Hz, 1H), 6.92 - 6.86 ( m, 2H), 5.24 (s, 1H), 3.06 (t, J = 5.0 Hz, 4H), 2.45 (t, J = 4.9 Hz, 4H), 2.22 (s, 3H), 1.47 (s, 6H); 476 [M+H] +
22 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.37 (d, J = 8.2 Hz, 1H), 7.67 (t, J = 7.9 Hz, 1H), 7.60 (s, 1H), 7.26 - 7.22 (m, 2H), 7.13 - 7.03 (m, 3H), 6.97 - 6.90 (m, 2H), 4.60 (s, 1H), 3.86 (s, 3H), 3.53 (d, J = 10.9 Hz, 2H), 2.64 - 2.53 (m, 2H), 2.40 - 2.28 (m, 7H), 1.96 - 1.87 (m, 2H), 1.87 - 1.74 (m, 2H), 1.55 (s, 6H) ; 534 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.37 (d, J = 8.2 Hz, 1H), 7.67 (t, J = 7.9 Hz, 1H), 7.60 (s, 1H), 7.26 - 7.22 (m, 2H), 7.13 - 7.03 (m, 3H), 6.97 - 6.90 (m, 2H), 4.60 (s, 1H), 3.86 (s, 3H), 3.53 (d, J = 10.9 Hz, 2H), 2.64 - 2.53 (m, 2H), 2.40 - 2.28 (m, 7H), 1.96 - 1.87 (m, 2H), 1.87 - 1.74 (m, 2H), 1.55 (s, 6H); 534 [M+H] +
33 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.10 - 7.01 (m, 2H), 6.93 (d, J = 8.5 Hz, 1H), 6.88 (s, 1H), 6.64 (d, J = 1.4 Hz, 1H), 3.84 (s, 3H), 3.65 (br s, 1H), 3.54 (d, J = 11.4 Hz, 2H), 2.73 (s, 3H), 2.63 - 2.54 (m, 2H), 2.52 - 2.29 (m, 7H), 1.94 (d, J = 12.6 Hz, 2H), 1.87 - 1.80 (m, 2H), 1.55 (s, 6H); 538 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.10 - 7.01 (m, 2H), 6.93 (d, J = 8.5 Hz, 1H), 6.88 (s, 1H), 6.64 (d, J = 1.4 Hz, 1H), 3.84 (s, 3H), 3.65 (br s, 1H), 3.54 (d, J = 11.4 Hz, 2H), 2.73 (s, 3H), 2.63 - 2.54 (m, 2H), 2.52 - 2.29 (m, 7H), 1.94 (d, J = 12.6 Hz, 2H), 1.87 - 1.80 (m , 2H), 1.55 (s, 6H); 538 [M+H] +
44 2-(6-((5-메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino) Pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.30 (d, J = 8.3 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.51 - 7.46 (m, 2H), 7.03 (dd, J = 7.6, 0.7 Hz, 1H), 6.99 - 6.93 (m, 2H), 6.84 (s, 1H), 6.62 (s, 1H), 4.75 (br s, 1H), 3.26 - 3.15 (m, 4H), 2.72 (s, 3H), 2.67 - 2.59 (m, 4H), 2.38 (s, 3H), 1.54 (s, 6H); 490[M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.30 (d, J = 8.3 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.51 - 7.46 (m, 2H), 7.03 (dd, J = 7.6, 0.7 Hz, 1H), 6.99 - 6.93 (m, 2H), 6.84 (s, 1H), 6.62 (s, 1H), 4.75 (br s, 1H), 3.26 - 3.15 (m , 4H), 2.72 (s, 3H), 2.67 - 2.59 (m, 4H), 2.38 (s, 3H), 1.54 (s, 6H); 490 [M+H] +
55 2-(6-((5,6-디메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5,6-dimethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ8.28 (d, J = 8.2 Hz, 1H), 7.96 (s, 1H), 7.62 (t, J = 7.9 Hz, 1H), 7.51 - 7.43 (m, 2H), 7.01 (d, J = 7.6 Hz, 1H), 6.98 - 6.92 (m, 2H), 6.76 (s, 1H), 4.82 (br s, 1H), 3.24 - 3.18 (m, 4H), 2.63 (t, J = 5.0 Hz, 4H), 2.58 (s, 3H), 2.40 (s, 3H), 2.38 (s, 3H), 1.54 (s, 6H); 504 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.28 (d, J = 8.2 Hz, 1H), 7.96 (s, 1H), 7.62 (t, J = 7.9 Hz, 1H), 7.51 - 7.43 (m, 2H) , 7.01 (d, J = 7.6 Hz, 1H), 6.98 - 6.92 (m, 2H), 6.76 (s, 1H), 4.82 (br s, 1H), 3.24 - 3.18 (m, 4H), 2.63 (t, J = 5.0 Hz, 4H), 2.58 (s, 3H), 2.40 (s, 3H), 2.38 (s, 3H), 1.54 (s, 6H); 504 [M+H] +
66 2-(6-((5,6-디메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5,6-dimethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ8.35 - 8.28 (m, 1H), 7.97 (s, 1H), 7.64 (t, J = 7.9 Hz, 1H), 7.25 - 7.22 (m, 1H), 7.06 (dd, J = 8.5, 2.4 Hz, 1H), 7.04 - 7.01 (m, 1H), 6.92 (d, J = 8.5 Hz, 1H), 6.81 (s, 1H), 4.80 (s, 1H), 3.83 (s, 3H), 3.53 (d, J = 11.5 Hz, 2H), 2.65 - 2.52 (m, 5H), 2.44 - 2.40 (m, 3H), 2.37 (s, 7H), 1.93 (d, J = 12.2 Hz, 2H), 1.86 - 1.76 (m, 2H), 1.54 (s, 6H); 562 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.35 - 8.28 (m, 1H), 7.97 (s, 1H), 7.64 (t, J = 7.9 Hz, 1H), 7.25 - 7.22 (m, 1H), 7.06 ( dd, J = 8.5, 2.4 Hz, 1H), 7.04 - 7.01 (m, 1H), 6.92 (d, J = 8.5 Hz, 1H), 6.81 (s, 1H), 4.80 (s, 1H), 3.83 (s , 3H), 3.53 (d, J = 11.5 Hz, 2H), 2.65 - 2.52 (m, 5H), 2.44 - 2.40 (m, 3H), 2.37 (s, 7H), 1.93 (d, J = 12.2 Hz, 2H), 1.86 - 1.76 (m, 2H), 1.54 (s, 6H); 562 [M+H] +
77 2-(6-((5,6-디메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5,6-dimethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.37 (d, J = 8.2 Hz, 1H), 7.73 (s, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.32 - 7.26 (m, 2H), 7.14 - 7.02 (m, 4H), 6.91 (d, J = 8.5 Hz, 1H), 3.83 (s, 3H), 3.51 (dd, J = 9.2, 6.5 Hz, 2H), 2.85 - 2.69 (m, 6H), 2.62 - 2.51 (m, 5H), 2.37 (s, 3H), 1.99 - 1.90 (m, 2H), 1.88 - 1.78 (m, 2H), 1.54 (s, 6H); 589[M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.37 (d, J = 8.2 Hz, 1H), 7.73 (s, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.32 - 7.26 (m, 2H), 7.14 - 7.02 (m, 4H), 6.91 (d, J = 8.5 Hz, 1H), 3.83 (s, 3H), 3.51 (dd, J = 9.2, 6.5 Hz, 2H), 2.85 - 2.69 (m, 6H) , 2.62 - 2.51 (m, 5H), 2.37 (s, 3H), 1.99 - 1.90 (m, 2H), 1.88 - 1.78 (m, 2H), 1.54 (s, 6H); 589[M+H] +
88 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-2-메톡시페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.42 (d, J = 8.2 Hz, 1H), 8.25 (d, J = 9.1 Hz, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.57 (s, 1H), 7.32 (s, 1H), 7.23 (d, J = 6.0 Hz, 1H), 7.05 (t, J = 6.4 Hz, 2H), 6.63 - 6.56 (m, 2H), 3.90 (s, 3H), 3.72 - 3.62 (m, 2H), 2.76 - 2.67 (m, 2H), 2.37 - 2.25 (m, 7H), 2.02 - 1.92 (m, 2H), 1.75 - 1.66 (m, 2H), 1.56 (s, 6H); 534 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.42 (d, J = 8.2 Hz, 1H), 8.25 (d, J = 9.1 Hz, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.57 (s, 1H), 7.32 (s, 1H), 7.23 (d, J = 6.0 Hz, 1H), 7.05 (t, J = 6.4 Hz, 2H), 6.63 - 6.56 (m, 2H), 3.90 (s, 3H), 3.72 - 3.62 (m, 2H), 2.76 - 2.67 (m, 2H), 2.37 - 2.25 (m, 7H), 2.02 - 1.92 (m, 2H), 1.75 - 1.66 (m, 2H), 1.56 (s, 6H) ); 534 [M+H] +
99 2-(6-((2-((3-메톡시-4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino )pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.37 (d, J = 8.2 Hz, 1H), 7.70 - 7.63 (m, 2H), 7.30 - 7.28 (m, 1H), 7.25 (s, 1H), 7.11 (dd, J = 8.5, 2.4 Hz, 1H), 7.05 (t, J = 6.7 Hz, 2H), 6.99 (s, 1H), 6.94 (d, J = 8.5 Hz, 1H), 3.85 (s, 3H), 3.22 - 3.07 (m, 4H), 2.78 - 2.68 (m, 4H), 2.43 (s, 3H), 1.55 (s, 6H); 506 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 8.37 (d, J = 8.2 Hz, 1H), 7.70 - 7.63 (m, 2H), 7.30 - 7.28 (m, 1H), 7.25 (s, 1H), 7.11 (dd , J = 8.5, 2.4 Hz, 1H), 7.05 (t, J = 6.7 Hz, 2H), 6.99 (s, 1H), 6.94 (d, J = 8.5 Hz, 1H), 3.85 (s, 3H), 3.22 - 3.07 (m, 4H), 2.78 - 2.68 (m, 4H), 2.43 (s, 3H), 1.55 (s, 6H); 506 [M+H] +
1010 2-(6-((2-((1-(테트라하이드로-2H-피란-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ8.35 (d, J = 8.3 Hz, 1H), 7.98 (br s, 1H), 7.76 - 7.65 (m, 2H), 7.55 (s, 1H), 7.24 (s, 1H), 7.08 - 7.02 (m, 2H), 6.87 (s, 1H), 4.68 (br s, 1H), 4.39 - 4.29 (m, 1H), 4.17 - 4.08 (m, 2H), 3.60 - 3.51 (m, 2H), 2.17 - 2.09 (m, 4H), 1.55 (s, 6H); 482 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.35 (d, J = 8.3 Hz, 1H), 7.98 (br s, 1H), 7.76 - 7.65 (m, 2H), 7.55 (s, 1H), 7.24 (s , 1H), 7.08 - 7.02 (m, 2H), 6.87 (s, 1H), 4.68 (br s, 1H), 4.39 - 4.29 (m, 1H), 4.17 - 4.08 (m, 2H), 3.60 - 3.51 ( m, 2H), 2.17 - 2.09 (m, 4H), 1.55 (s, 6H); 482 [M+H] +
1111 2-(6-((2-((4-(4-(4-메틸피페라진-1-일)피페리딘-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine -4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.35 (d, J = 8.2 Hz, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.59 (s, 1H), 7.52 - 7.46 (m, 2H), 7.23 (d, J = 6.0 Hz, 1H), 7.07 - 7.02 (m, 2H), 7.00 - 6.94 (m, 2H), 6.88 (s, 1H), 3.75 - 3.66 (m, 2H), 2.80 - 2.59 (m, 6H), 2.58 - 2.43 (m, 3H), 2.43 - 2.34 (m, 2H), 2.31 (s, 3H), 1.99 - 1.93 (m, 2H), 1.71 - 1.66 (m, 2H), 1.55 (s, 6H); 559 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.35 (d, J = 8.2 Hz, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.59 (s, 1H), 7.52 - 7.46 (m, 2H), 7.23 (d, J = 6.0 Hz, 1H), 7.07 - 7.02 (m, 2H), 7.00 - 6.94 (m, 2H), 6.88 (s, 1H), 3.75 - 3.66 (m, 2H), 2.80 - 2.59 ( m, 6H), 2.58 - 2.43 (m, 3H), 2.43 - 2.34 (m, 2H), 2.31 (s, 3H), 1.99 - 1.93 (m, 2H), 1.71 - 1.66 (m, 2H), 1.55 ( s, 6H); 559 [M+H] +
1212 2-(6-((2-((4-((2-(디메틸아미노)에틸)(메틸)아미노)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino) Pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.35 (d, J = 8.3 Hz, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.59 (s, 1H), 7.47 - 7.40 (m, 2H), 7.22 (d, J = 6.0 Hz, 1H), 7.06 - 6.99 (m, 2H), 6.82 (s, 1H), 6.78 - 6.72 (m, 2H), 3.50 - 3.42 (m, 2H), 2.97 (s, 3H), 2.55 - 2.47 (m, 2H), 2.31 (s, 6H); 478 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.35 (d, J = 8.3 Hz, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.59 (s, 1H), 7.47 - 7.40 (m, 2H), 7.22 (d, J = 6.0 Hz, 1H), 7.06 - 6.99 (m, 2H), 6.82 (s, 1H), 6.78 - 6.72 (m, 2H), 3.50 - 3.42 (m, 2H), 2.97 (s, 3H), 2.55 - 2.47 (m, 2H), 2.31 (s, 6H); 478 [M+H] +
1313 2-(6-((2-((4-(4-에틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-ethylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2- 1) propan-2-ol 1H NMR (400MHz, CDCl3) δ8.34 (d, J = 8.2 Hz, 1H), 7.70 - 7.60 (m, 2H), 7.52 - 7.46 (m, 2H), 7.24 (d, J = 6.0 Hz, 1H), 7.06 - 7.00 (m, 2H), 7.00 - 6.93 (m, 3H), 3.21 (dd, J = 6.2, 3.8 Hz, 4H), 2.65 (t, J = 5.0 Hz, 4H), 2.50 (q, J = 7.2 Hz, 2H), 1.54 (s, 6H), 1.15 (t, J = 7.2 Hz, 3H); 490 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.34 (d, J = 8.2 Hz, 1H), 7.70 - 7.60 (m, 2H), 7.52 - 7.46 (m, 2H), 7.24 (d, J = 6.0 Hz, 1H), 7.06 - 7.00 (m, 2H), 7.00 - 6.93 (m, 3H), 3.21 (dd, J = 6.2, 3.8 Hz, 4H), 2.65 (t, J = 5.0 Hz, 4H), 2.50 (q , J = 7.2 Hz, 2H), 1.54 (s, 6H), 1.15 (t, J = 7.2 Hz, 3H); 490 [M+H] +
1414 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-이소프로필티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-isopropylthieno[2,3-d ]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.2 Hz, 1H), 7.96 (s, 1H), 7.68 - 7.61 (m, 1H), 7.26 - 7.21 (m, 1H), 7.09 - 7.01 (m, 2H), 6.93 (d, J = 8.5 Hz, 1H), 6.89 (s, 1H), 6.71 (s, 1H), 4.80 (s, 1H), 3.83 (s, 3H), 3.53 (d, J = 11.4 Hz, 2H), 3.35 (p, J = 6.7 Hz, 1H), 2.62 - 2.53 (m, 2H), 2.35 (s, 7H), 1.91 (d, J = 12.2 Hz, 2H), 1.85 - 1.76 (m, 2H), 1.55 (s, 6H), 1.49 (s, 3H), 1.47 (s, 3H); 576 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 1 H NMR (400 MHz, CDCl 3 ) δ 8.32 (d, J = 8.2 Hz, 1H), 7.96 (s, 1H), 7.68 - 7.61 (m, 1H), 7.26 - 7.21 ( m, 1H), 7.09 - 7.01 (m, 2H), 6.93 (d, J = 8.5 Hz, 1H), 6.89 (s, 1H), 6.71 (s, 1H), 4.80 (s, 1H), 3.83 (s , 3H), 3.53 (d, J = 11.4 Hz, 2H), 3.35 (p, J = 6.7 Hz, 1H), 2.62 - 2.53 (m, 2H), 2.35 (s, 7H), 1.91 (d, J = 12.2 Hz, 2H), 1.85 - 1.76 (m, 2H), 1.55 (s, 6H), 1.49 (s, 3H), 1.47 (s, 3H); 576 [M+H] +
1515 2-(6-((5-이소프로필-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-isopropyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino )pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.29 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.52 - 7.45 (m, 2H), 7.02 (d, J = 7.6 Hz, 1H), 7.00 - 6.93 (m, 2H), 6.82 (s, 1H), 6.69 (s, 1H), 4.82 (br s, 1H), 3.34 (p, J = 6.7 Hz, 1H), 3.21 (t, J = 5.0 Hz, 4H), 2.64 (t, J = 5.0 Hz, 4H), 2.39 (s, 3H), 1.54 (s, 6H), 1.48 (s, 3H), 1.47 (s, 3H); 518 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.29 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.52 - 7.45 (m, 2H), 7.02 (d, J = 7.6 Hz, 1H), 7.00 - 6.93 (m, 2H), 6.82 (s, 1H), 6.69 (s, 1H), 4.82 (br s, 1H), 3.34 (p, J = 6.7 Hz, 1H), 3.21 (t, J = 5.0 Hz, 4H), 2.64 (t, J = 5.0 Hz, 4H), 2.39 (s, 3H), 1.54 (s, 6H), 1.48 (s, 3H), 1.47 (s, 3H); 518 [M+H] +
1616 2-(6-((2-((3-메톡시-4-(4-메틸피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ8.32 (d, J = 8.2 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.24 (d, J = 2.3 Hz, 1H), 7.09 (dd, J = 8.5, 2.4 Hz, 1H), 7.05 - 6.98 (m, 2H), 6.93 (d, J = 8.5 Hz, 1H), 6.62 (s, 1H), 4.74 (br s, 1H), 3.82 (s, 3H), 3.24 - 2.95 (m, 4H), 2.71 (s, 3H), 2.70 - 2.56 (m, 4H), 2.37 (s, 3H), 1.54 (s, 6H); 520 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.32 (d, J = 8.2 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.24 (d, J = 2.3 Hz) , 1H), 7.09 (dd, J = 8.5, 2.4 Hz, 1H), 7.05 - 6.98 (m, 2H), 6.93 (d, J = 8.5 Hz, 1H), 6.62 (s, 1H), 4.74 (br s , 1H), 3.82 (s, 3H), 3.24 - 2.95 (m, 4H), 2.71 (s, 3H), 2.70 - 2.56 (m, 4H), 2.37 (s, 3H), 1.54 (s, 6H); 520 [M+H] +
1717 2-(6-((5-메틸-2-((1-(테트라하이드로-2H-피란-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] Pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ8.31 (d, J = 8.3 Hz, 1H), 8.00 - 7.88 (m, 2H), 7.70 (t, J = 7.9 Hz, 1H), 7.53 (s, 1H), 7.05 (d, J = 7.6 Hz, 1H), 6.80 (s, 1H), 6.63 (s, 1H), 4.72 (s, 1H), 4.38 - 4.28 (m, 1H), 4.17 - 4.08 (m, 2H), 3.60 - 3.50 (m, 2H), 2.72 (s, 3H), 2.15 - 2.07 (m, 4H), 1.55 (s, 6H); 466 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.31 (d, J = 8.3 Hz, 1H), 8.00 - 7.88 (m, 2H), 7.70 (t, J = 7.9 Hz, 1H), 7.53 (s, 1H) , 7.05 (d, J = 7.6 Hz, 1H), 6.80 (s, 1H), 6.63 (s, 1H), 4.72 (s, 1H), 4.38 - 4.28 (m, 1H), 4.17 - 4.08 (m, 2H) ), 3.60 - 3.50 (m, 2H), 2.72 (s, 3H), 2.15 - 2.07 (m, 4H), 1.55 (s, 6H); 466 [M+H] +
1818 2-(6-((2-((3-메톡시-4-(피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-methoxy-4-(piperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.29 - 7.27 (m, 1H), 7.09 (dd, J = 8.5, 2.4 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.94 (s, 1H), 6.91 (d, J = 2.3 Hz, 1H), 6.64 (d, J = 1.3 Hz, 1H), 3.84 (s, 3H), 3.14 - 3.07 (m, 4H), 3.07 - 2.99 (m, 4H), 2.73 (s, 3H), 1.54 (s, 6H), 0.92 - 0.82 (m, 1H); 506 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.29 - 7.27 (m, 1H), 7.09 (dd, J = 8.5, 2.4 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.94 (s, 1H), 6.91 (d, J = 2.3 Hz, 1H), 6.64 (d, J = 1.3 Hz, 1H), 3.84 (s, 3H), 3.14 - 3.07 (m, 4H), 3.07 - 2.99 (m, 4H), 2.73 (s, 3H), 1.54 (s, 6H), 0.92 - 0.82 ( m, 1H); 506 [M+H] +
1919 sec-부틸 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트sec-butyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl )pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxylate 1H NMR (400MHz, CDCl3) δ12.19 (s, 1H), 8.35 (d, J = 8.2 Hz, 1H), 8.02 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.26 - 7.23 (m, 1H), 7.08 (dd, J = 8.5, 2.3 Hz, 1H), 7.00 (d, J = 7.5 Hz, 1H), 6.94 (s, 1H), 6.92 (s, 1H), 5.36 (s, 1H), 5.24 - 5.13 (m, 1H), 3.83 (s, 3H), 3.53 (d, J = 11.2 Hz, 2H), 2.64 - 2.54 (m, 2H), 2.35 (s, 7H), 1.92 (d, J = 12.1 Hz, 2H), 1.85 - 1.70 (m, 4H), 1.55 (s, 6H), 1.38 (d, J = 6.2 Hz, 3H), 1.00 (t, J = 7.4 Hz, 3H); 634 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ12.19 (s, 1H), 8.35 (d, J = 8.2 Hz, 1H), 8.02 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.26 - 7.23 (m, 1H), 7.08 (dd, J = 8.5, 2.3 Hz, 1H), 7.00 (d, J = 7.5 Hz, 1H), 6.94 (s, 1H), 6.92 (s, 1H), 5.36 ( s, 1H), 5.24 - 5.13 (m, 1H), 3.83 (s, 3H), 3.53 (d, J = 11.2 Hz, 2H), 2.64 - 2.54 (m, 2H), 2.35 (s, 7H), 1.92 (d, J = 12.1 Hz, 2H), 1.85 - 1.70 (m, 4H), 1.55 (s, 6H), 1.38 (d, J = 6.2 Hz, 3H), 1.00 (t, J = 7.4 Hz, 3H) ; 634 [M+H] +
2020 sec-부틸 4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-5-카복실레이트sec-butyl 4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-2-((4-(4-methylpiperazin-1-yl)phenyl)amino) Thieno[2,3-d]pyrimidine-5-carboxylate 1H NMR (400MHz, CDCl3) δ12.17 (s, 1H), 8.32 (d, J = 8.2 Hz, 1H), 8.00 (s, 1H), 7.60 (t, J = 7.9 Hz, 1H), 7.54 - 7.43 (m, 2H), 7.04 - 6.92 (m, 3H), 6.88 (s, 1H), 5.38 (s, 1H), 5.25 - 5.10 (m, 1H), 3.26 - 3.14 (m, 4H), 2.61 (t, J = 5.0 Hz, 4H), 2.37 (s, 3H), 1.81 - 1.67 (m, 2H), 1.53 (s, 6H), 1.37 (d, J = 6.3 Hz, 3H), 1.00 (t, J = 7.4 Hz, 3H); 576 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ12.17 (s, 1H), 8.32 (d, J = 8.2 Hz, 1H), 8.00 (s, 1H), 7.60 (t, J = 7.9 Hz, 1H), 7.54 - 7.43 (m, 2H), 7.04 - 6.92 (m, 3H), 6.88 (s, 1H), 5.38 (s, 1H), 5.25 - 5.10 (m, 1H), 3.26 - 3.14 (m, 4H), 2.61 (t, J = 5.0 Hz, 4H), 2.37 (s, 3H), 1.81 - 1.67 (m, 2H), 1.53 (s, 6H), 1.37 (d, J = 6.3 Hz, 3H), 1.00 (t, J = 7.4 Hz, 3H); 576 [M+H] +
2121 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카르복사미드2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl)pyridin- 2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxamide 1H NMR (400MHz, CDCl3) δ12.36 (s, 1H), 8.33 (d, J = 8.2 Hz, 1H), 7.70 - 7.58 (m, 2H), 7.54 - 7.30 (m, 1H), 7.27 - 7.21 (m, 2H), 7.08 (dd, J = 8.5, 2.4 Hz, 1H), 6.99 - 6.90 (m, 3H), 5.45 (s, 1H), 3.83 (s, 3H), 3.53 (d, J = 10.8 Hz, 2H), 2.63 - 2.53 (m, 2H), 2.36 (s, 7H), 1.91 (d, J = 15.2 Hz, 2H), 1.87 - 1.73 (m, 2H), 1.55 (s, 6H); 577 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ12.36 (s, 1H), 8.33 (d, J = 8.2 Hz, 1H), 7.70 - 7.58 (m, 2H), 7.54 - 7.30 (m, 1H), 7.27 - 7.21 (m, 2H), 7.08 (dd, J = 8.5, 2.4 Hz, 1H), 6.99 - 6.90 (m, 3H), 5.45 (s, 1H), 3.83 (s, 3H), 3.53 (d, J = 10.8 Hz, 2H), 2.63 - 2.53 (m, 2H), 2.36 (s, 7H), 1.91 (d, J = 15.2 Hz, 2H), 1.87 - 1.73 (m, 2H), 1.55 (s, 6H); 577 [M+H] +
2222 4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-5-카르복사미드4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[ 2,3-d] pyrimidine-5-carboxamide 1H NMR (400MHz, MEOD) δ1H NMR (400 MHz, MeOD) δ 8.44 (d, J = 8.3 Hz, 1H), 7.87 (s, 1H), 7.65 (t, J = 8.0 Hz, 1H), 7.55 - 7.47 (m, 2H), 7.19 (d, J = 7.6 Hz, 1H), 7.05 - 6.95 (m, 2H), 4.64 (br s, 1H), 3.19 (t, J = 5.0 Hz, 4H), 2.65 (t, J = 5.0 Hz, 4H), 2.36 (s, 3H), 1.54 (s, 6H); 519 [M+H]+ - _ _ 7.47 (m, 2H), 7.19 (d, J = 7.6 Hz, 1H), 7.05 - 6.95 (m, 2H), 4.64 (br s, 1H), 3.19 (t, J = 5.0 Hz, 4H), 2.65 ( t, J = 5.0 Hz, 4H), 2.36 (s, 3H), 1.54 (s, 6H); 519 [M+H] +
2323 (1r,4r)-4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)시클로헥산-1-올(1r,4r)-4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine -2-yl) amino) cyclohexan-1-ol 1H NMR (400MHz, CDCl3) δ8.41 (d, J = 8.3 Hz, 1H), 7.89 (s, 1H), 7.73 (t, J = 7.9 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.52 (s, 1H), 4.95 - 4.83 (m, 1H), 4.76 (s, 1H), 3.95 - 3.82 (m, 1H), 3.76 - 3.64 (m, 1H), 2.69 (d, J = 1.3 Hz, 3H), 2.26 - 2.17 (m, 2H), 2.10 - 2.00 (m, 2H), 1.54 (s, 6H), 1.53 - 1.43 (m, 2H), 1.38 - 1.28 (m, 2H); 414 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.41 (d, J = 8.3 Hz, 1H), 7.89 (s, 1H), 7.73 (t, J = 7.9 Hz, 1H), 7.04 (d, J = 7.6 Hz) , 1H), 6.52 (s, 1H), 4.95 - 4.83 (m, 1H), 4.76 (s, 1H), 3.95 - 3.82 (m, 1H), 3.76 - 3.64 (m, 1H), 2.69 (d, J = 1.3 Hz, 3H), 2.26 - 2.17 (m, 2H), 2.10 - 2.00 (m, 2H), 1.54 (s, 6H), 1.53 - 1.43 (m, 2H), 1.38 - 1.28 (m, 2H); 414 [M+H] +
2424 에틸 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트Ethyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl)pyridine -2-yl) amino) thieno [2,3-d] pyrimidine-5-carboxylate 1H NMR (400MHz,DMSO) δ 11.69 (s, 1H), 9.39 (s, 1H), 8.51 (br s, 1H), 8.35 (s, 1H), 7.73 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 7.5 Hz, 1H), 7.33 - 7.21 (m, 2H), 6.86 (d, J = 8.3 Hz, 1H), 5.19 (s, 1H), 4.42 (q, J = 7.1 Hz, 2H), 3.74 (s, 3H), 2.26 - 2.04 (m, 7H), 1.87 - 1.76 (m, 2H), 1.59 - 1.50 (m, 2H), 1.46 (s, 6H), 1.38 (t, J = 7.1 Hz, 3H); 606 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 11.69 (s, 1H), 9.39 (s, 1H), 8.51 (br s, 1H), 8.35 (s, 1H), 7.73 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 7.5 Hz, 1H), 7.33 - 7.21 (m, 2H), 6.86 (d, J = 8.3 Hz, 1H), 5.19 (s, 1H), 4.42 (q, J = 7.1 Hz, 2H) ), 3.74 (s, 3H), 2.26 - 2.04 (m, 7H), 1.87 - 1.76 (m, 2H), 1.59 - 1.50 (m, 2H), 1.46 (s, 6H), 1.38 (t, J = 7.1 Hz, 3H); 606 [M+H] +
2525 2-(6-((5-메틸-2-(((1r,4r)-4-모르폴리노시클로헥실)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-(((1r,4r)-4-morpholinocyclohexyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridine -2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.39 (d, J = 8.2 Hz, 1H), 7.89 (s, 1H), 7.73 (t, J = 7.9 Hz, 1H), 7.04 (d, J = 7.5 Hz, 1H), 6.52 (d, J = 1.4 Hz, 1H), 4.87 (d, J = 7.9 Hz, 1H), 4.75 (s, 1H), 3.78 (t, J = 4.7 Hz, 4H), 2.73 - 2.64 (m, 5H), 2.30 (d, J = 11.2 Hz, 2H), 2.05 (d, J = 12.5 Hz, 2H), 1.54 (s, 6H), 1.42 (d, J = 28.6 Hz, 3H), 1.26 (d, J = 12.5 Hz, 5H); 483 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.39 (d, J = 8.2 Hz, 1H), 7.89 (s, 1H), 7.73 (t, J = 7.9 Hz, 1H), 7.04 (d, J = 7.5 Hz, 1H), 6.52 (d, J = 1.4 Hz, 1H), 4.87 (d, J = 7.9 Hz, 1H), 4.75 (s, 1H), 3.78 (t, J = 4.7 Hz, 4H), 2.73 - 2.64 ( m, 5H), 2.30 (d, J = 11.2 Hz, 2H), 2.05 (d, J = 12.5 Hz, 2H), 1.54 (s, 6H), 1.42 (d, J = 28.6 Hz, 3H), 1.26 ( d, J = 12.5 Hz, 5H); 483 [M+H] +
2626 2-(6-((5-메틸-2-(((1r,4r)-4-(피페리딘-1-일)시클로헥실)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-(((1r,4r)-4-(piperidin-1-yl)cyclohexyl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.41 (d, J = 8.2 Hz, 1H), 7.88 (s, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.51 (s, 1H), 4.84 (d, J = 7.9 Hz, 1H), 4.75 (s, 1H), 3.90 - 3.73 (m, 1H), 2.69 (s, 3H), 2.60 (br s, 4H), 2.40 (br s, 1H), 2.32 - 2.22 (m, 2H), 2.02 (d, J = 13.0 Hz, 2H), 1.66 - 1.63 (m, 2H), 1.54 (s, 6H), 1.53 - 1.44 (m, 4H), 1.32 - 1.21 (m, 4H); 481 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.41 (d, J = 8.2 Hz, 1H), 7.88 (s, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.51 (s, 1H), 4.84 (d, J = 7.9 Hz, 1H), 4.75 (s, 1H), 3.90 - 3.73 (m, 1H), 2.69 (s, 3H), 2.60 (br s, 4H), 2.40 (br s, 1H), 2.32 - 2.22 (m, 2H), 2.02 (d, J = 13.0 Hz, 2H), 1.66 - 1.63 (m, 2H), 1.54 (s, 6H), 1.53 - 1.44 (m, 4H), 1.32 - 1.21 (m, 4H); 481 [M+H] +
2727 (1S,2R,3R,5R)-3-(하이드록시메틸)-5-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)시클펜탄-1,2-디올(1S,2R,3R,5R)-3-(hydroxymethyl)-5-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5- Methylthieno[2,3-d]pyrimidin-2-yl)amino)cyclopentane-1,2-diol 1H NMR (400MHz, CDCl3) δ8.33 (d, J = 8.2 Hz, 1H), 7.90 (s, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.07 (d, J = 7.6 Hz, 1H), 6.57 (s, 1H), 5.26 (s, 1H), 4.66 (s, 1H), 4.24 (s, 1H), 4.06 - 3.99 (m, 1H), 3.97 - 3.90 (m, 1H), 3.79 - 3.66 (m, 2H), 2.68 (s, 3H), 2.44 - 2.29 (m, 2H), 1.54 (s, 6H), 1.47 - 1.32 (m, 2H); 446 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.33 (d, J = 8.2 Hz, 1H), 7.90 (s, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.07 (d, J = 7.6 Hz) , 1H), 6.57 (s, 1H), 5.26 (s, 1H), 4.66 (s, 1H), 4.24 (s, 1H), 4.06 - 3.99 (m, 1H), 3.97 - 3.90 (m, 1H), 3.79 - 3.66 (m, 2H), 2.68 (s, 3H), 2.44 - 2.29 (m, 2H), 1.54 (s, 6H), 1.47 - 1.32 (m, 2H); 446 [M+H] +
2828 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-(트리플루오로메틸)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-(trifluoromethyl)thieno[2 ,3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.24 (d, J = 8.2 Hz, 1H), 8.11 - 8.04 (m, 1H), 7.64 (t, J = 7.9 Hz, 1H), 7.55 (s, 1H), 7.20 (s, 1H), 7.11 - 7.05 (m, 2H), 6.98 - 6.90 (m, 2H), 4.62 (s, 1H), 3.83 (s, 3H), 3.55 (d, J = 10.9 Hz, 2H), 2.65 - 2.56 (m, 2H), 2.51 - 2.36 (m, 7H), 1.96 (s, 2H), 1.88 - 1.76 (m, 2H), 1.55 (s, 6H); 602 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.24 (d, J = 8.2 Hz, 1H), 8.11 - 8.04 (m, 1H), 7.64 (t, J = 7.9 Hz, 1H), 7.55 (s, 1H), 7.20 (s, 1H), 7.11 - 7.05 (m, 2H), 6.98 - 6.90 (m, 2H), 4.62 (s, 1H), 3.83 (s, 3H), 3.55 (d, J = 10.9 Hz, 2H) , 2.65 - 2.56 (m, 2H), 2.51 - 2.36 (m, 7H), 1.96 (s, 2H), 1.88 - 1.76 (m, 2H), 1.55 (s, 6H); 602 [M+H] +
2929 2-(6-((2-((4-(4-메틸피페라진-1-일)페닐)아미노)-5-(트리플루오로메틸)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.20 (d, J = 8.2 Hz, 1H), 8.06 (q, J = 3.8 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.51 (d, J = 1.2 Hz, 1H), 7.52 - 7.42 (m, 3H), 7.06 (d, J = 7.6 Hz, 1H), 7.00 - 6.90 (m, 3H), 3.22 (dd, J = 6.2, 3.8 Hz, 4H), 2.66 - 2.58 (m, 4H), 2.38 (s, 3H), 1.54 (s, 6H); 544 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.20 (d, J = 8.2 Hz, 1H), 8.06 (q, J = 3.8 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.51 (d, J = 1.2 Hz, 1H), 7.52 - 7.42 (m, 3H), 7.06 (d, J = 7.6 Hz, 1H), 7.00 - 6.90 (m, 3H), 3.22 (dd, J = 6.2, 3.8 Hz, 4H) ), 2.66 - 2.58 (m, 4H), 2.38 (s, 3H), 1.54 (s, 6H); 544 [M+H] +
3030 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(피리딘-2-일)티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(pyridin-2-yl)thieno[2,3-d] Pyrimidine-2,4-diamine 1H NMR (400MHz, CDCl3) δ8.45 (d, J = 8.4 Hz, 1H), 8.31 - 8.26 (m, 1H), 7.96 (s, 1H), 7.66 - 7.59 (m, 1H), 7.26 - 7.19 (m, 1H), 7.07 (dd, J = 8.4, 2.3 Hz, 1H), 6.99 (dd, J = 7.3, 4.9 Hz, 1H), 6.96 - 6.89 (m, 2H), 6.61 (s, 1H), 3.83 (s, 3H), 3.53 (d, J = 11.1 Hz, 2H), 2.72 (s, 3H), 2.63 - 2.54 (m, 2H), 2.35 (s, 7H), 1.96 - 1.88 (m, 2H), 1.86 - 1.74 (m, 2H); 490 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.45 (d, J = 8.4 Hz, 1H), 8.31 - 8.26 (m, 1H), 7.96 (s, 1H), 7.66 - 7.59 (m, 1H), 7.26 - 7.19 (m, 1H), 7.07 (dd, J = 8.4, 2.3 Hz, 1H), 6.99 (dd, J = 7.3, 4.9 Hz, 1H), 6.96 - 6.89 (m, 2H), 6.61 (s, 1H) , 3.83 (s, 3H), 3.53 (d, J = 11.1 Hz, 2H), 2.72 (s, 3H), 2.63 - 2.54 (m, 2H), 2.35 (s, 7H), 1.96 - 1.88 (m, 2H) ), 1.86 - 1.74 (m, 2H); 490 [M+H] +
3131 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-페닐티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-phenylthieno[2,3-d]pyrimidine-2,4 -Diamine 1H NMR (400MHz, CDCl3) δ7.67 - 7.57 (m, 2H), 7.39 - 7.30 (m, 2H), 7.29 - 7.22 (m, 1H), 7.14 - 7.09 (m, 2H), 7.04 (dd, J = 8.5, 2.4 Hz, 1H), 6.97 (s, 1H), 6.89 - 6.81 (m, 1H), 6.56 (s, 1H), 3.73 (s, 3H), 3.54 - 3.46 (m, 2H), 2.64 (s, 3H), 2.59 - 2.51 (m, 2H), 2.40 - 2.28 (m, 7H), 1.94 - 1.87 (m, 2H), 1.84 - 1.73 (m, 2H); 489 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.67 - 7.57 (m, 2H), 7.39 - 7.30 (m, 2H), 7.29 - 7.22 (m, 1H), 7.14 - 7.09 (m, 2H), 7.04 (dd , J = 8.5, 2.4 Hz, 1H), 6.97 (s, 1H), 6.89 - 6.81 (m, 1H), 6.56 (s, 1H), 3.73 (s, 3H), 3.54 - 3.46 (m, 2H), 2.64 (s, 3H), 2.59 - 2.51 (m, 2H), 2.40 - 2.28 (m, 7H), 1.94 - 1.87 (m, 2H), 1.84 - 1.73 (m, 2H); 489 [M+H] +
3232 2-(6-((5-메틸-2-((1-(옥세탄-3-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-((1-(oxetan-3-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.32 (d, J = 8.2 Hz, 1H), 8.13 (s, 1H), 7.93 (s, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.59 (s, 1H), 7.11 - 7.02 (m, 1H), 6.81 (s, 1H), 6.64 (s, 1H), 5.52 - 5.40 (m, 1H), 5.11 (t, J = 6.6 Hz, 2H), 5.05 (t, J = 7.4 Hz, 2H), 4.67 (s, 1H), 2.72 (d, J = 1.4 Hz, 3H), 1.55 (s, 6H); 438 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.32 (d, J = 8.2 Hz, 1H), 8.13 (s, 1H), 7.93 (s, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.59 ( s, 1H), 7.11 - 7.02 (m, 1H), 6.81 (s, 1H), 6.64 (s, 1H), 5.52 - 5.40 (m, 1H), 5.11 (t, J = 6.6 Hz, 2H), 5.05 (t, J = 7.4 Hz, 2H), 4.67 (s, 1H), 2.72 (d, J = 1.4 Hz, 3H), 1.55 (s, 6H); 438 [M+H] +
3333 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400MHz, CDCl3) δ7.67 - 7.62 (m, 1H), 7.57 (t, J = 2.0 Hz, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.25 (d, J = 2.4 Hz, 1H), 7.23 - 7.18 (m, 1H), 7.15 (s, 1H), 6.98 (dd, J = 8.5, 2.4 Hz, 1H), 6.93 (s, 1H), 6.83 (d, J = 8.5 Hz, 1H), 6.59 - 6.54 (m, 1H), 3.66 (s, 3H), 3.51 - 3.43 (m, 2H), 2.65 (s, 3H), 2.58 - 2.48 (m, 2H), 2.35 - 2.25 (m, 7H), 1.92 - 1.83 (m, 2H), 1.81 - 1.70 (m, 2H), 1.55 (s, 6H); 547 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ7.67 - 7.62 (m, 1H), 7.57 (t, J = 2.0 Hz, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.25 (d, J = 2.4 Hz, 1H), 7.23 - 7.18 (m, 1H), 7.15 (s, 1H), 6.98 (dd, J = 8.5, 2.4 Hz, 1H), 6.93 (s, 1H), 6.83 (d, J = 8.5 Hz, 1H), 6.59 - 6.54 (m, 1H), 3.66 (s, 3H), 3.51 - 3.43 (m, 2H), 2.65 (s, 3H), 2.58 - 2.48 (m, 2H), 2.35 - 2.25 ( m, 7H), 1.92 - 1.83 (m, 2H), 1.81 - 1.70 (m, 2H), 1.55 (s, 6H); 547 [M+H] +
3434 N4-(6-(터트-부틸)피리딘-2-일)-N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N4-(6-(tert-butyl)pyridin-2-yl)-N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine 1H NMR (400MHz, CDCl3) δ8.18 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.27 - 7.24 (m, 1H), 7.07 (dd, J = 8.4, 2.4 Hz, 1H), 7.04 - 6.99 (m, 1H), 6.97 - 6.87 (m, 2H), 6.63 - 6.56 (m, 1H), 3.82 (s, 3H), 3.56 - 3.48 (m, 2H), 2.72 (d, J = 1.3 Hz, 3H), 2.62 - 2.52 (m, 2H), 2.33 (s, 7H), 1.94 - 1.87 (m, 2H), 1.84 - 1.73 (m, 2H), 1.34 (s, 9H); 546 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.18 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.27 - 7.24 (m, 1H) , 7.07 (dd, J = 8.4, 2.4 Hz, 1H), 7.04 - 6.99 (m, 1H), 6.97 - 6.87 (m, 2H), 6.63 - 6.56 (m, 1H), 3.82 (s, 3H), 3.56 - 3.48 (m, 2H), 2.72 (d, J = 1.3 Hz, 3H), 2.62 - 2.52 (m, 2H), 2.33 (s, 7H), 1.94 - 1.87 (m, 2H), 1.84 - 1.73 (m , 2H), 1.34 (s, 9H); 546 [M+H] +
3535 2-(6-((5-메틸-2-((1-(테트라하이드로퓨란-3-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-((1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidine- 4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ8.29 (d, J = 8.2 Hz, 1H), 7.97 - 7.87 (m, 2H), 7.68 (t, J = 7.9 Hz, 1H), 7.56 - 7.51 (m, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.94 (s, 1H), 6.60 (s, 1H), 4.99 - 4.89 (m, 1H), 4.70 (s, 1H), 4.17 - 4.04 (m, 3H), 3.98 - 3.89 (m, 1H), 2.70 (s, 3H), 2.51 - 2.32 (m, 2H), 1.54 (s, 6H); 452 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.29 (d, J = 8.2 Hz, 1H), 7.97 - 7.87 (m, 2H), 7.68 (t, J = 7.9 Hz, 1H), 7.56 - 7.51 (m, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.94 (s, 1H), 6.60 (s, 1H), 4.99 - 4.89 (m, 1H), 4.70 (s, 1H), 4.17 - 4.04 (m , 3H), 3.98 - 3.89 (m, 1H), 2.70 (s, 3H), 2.51 - 2.32 (m, 2H), 1.54 (s, 6H); 452 [M+H] +
3636 2-(6-((2-((3-플루오로-4-(4-메틸피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.31 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.62 (dd, J = 14.5, 2.5 Hz, 1H), 7.17 - 7.09 (m, 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.99 - 6.89 (m, 2H), 6.65 (s, 1H), 4.69 (s, 1H), 3.19 - 3.03 (m, 4H), 2.72 (d, J = 1.3 Hz, 3H), 2.69 - 2.55 (m, 4H), 2.37 (s, 3H), 1.55 (s, 6H); 508 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.31 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.62 (dd, J = 14.5, 2.5 Hz, 1H), 7.17 - 7.09 (m, 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.99 - 6.89 (m, 2H), 6.65 (s, 1H), 4.69 (s, 1H), 3.19 - 3.03 (m, 4H), 2.72 (d, J = 1.3 Hz, 3H), 2.69 - 2.55 (m, 4H), 2.37 (s, 3H), 1.55 (s, 6H); 508 [M+H] +
3737 2-(6-((5-메틸-2-((4-(4-메틸피페라진-1-일)-3-(트리플루오로메틸)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-((4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)amino)thieno[2,3-d] Pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ8.26 (d, J = 8.1 Hz, 1H), 7.97 (s, 1H), 7.83 (d, J = 2.6 Hz, 1H), 7.79 (dd, J = 8.6, 2.7 Hz, 1H), 7.67 (t, J = 7.9 Hz, 1H), 7.38 (d, J = 8.6 Hz, 1H), 7.15 (s, 1H), 7.06 (d, J = 7.6 Hz, 1H), 6.67 (s, 1H), 4.69 (s, 1H), 2.95 (t, J = 4.8 Hz, 4H), 2.72 (d, J = 1.3 Hz, 3H), 2.58 (s, 4H), 2.36 (s, 3H), 1.55 (s, 6H); 558 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.26 (d, J = 8.1 Hz, 1H), 7.97 (s, 1H), 7.83 (d, J = 2.6 Hz, 1H), 7.79 (dd, J = 8.6, 2.7 Hz, 1H), 7.67 (t, J = 7.9 Hz, 1H), 7.38 (d, J = 8.6 Hz, 1H), 7.15 (s, 1H), 7.06 (d, J = 7.6 Hz, 1H), 6.67 (s, 1H), 4.69 (s, 1H), 2.95 (t, J = 4.8 Hz, 4H), 2.72 (d, J = 1.3 Hz, 3H), 2.58 (s, 4H), 2.36 (s, 3H) , 1.55 (s, 6H); 558 [M+H] +
3838 4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시-N-(1-메틸피페리딘-4-일)벤즈아미드4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl)amino )-2-methoxy-N-(1-methylpiperidin-4-yl)benzamide 1H NMR (400MHz, CDCl3) δ8.34 (d, J = 8.1 Hz, 1H), 8.14 (d, J = 8.6 Hz, 1H), 7.96 (s, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.77 - 7.70 (m, 2H), 7.24 (s, 1H), 7.15 - 7.05 (m, 2H), 6.72 (d, J = 1.4 Hz, 1H), 4.64 (s, 1H), 4.11 (s, 1H), 3.93 (s, 3H), 2.74 (d, J = 1.2 Hz, 5H), 2.31 (s, 3H), 2.27 - 2.17 (m, 2H), 2.11 - 2.01 (m, 2H), 1.67 - 1.58 (m, 2H), 1.56 (s, 6H), 1.25 (s, 1H); 562 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.34 (d, J = 8.1 Hz, 1H), 8.14 (d, J = 8.6 Hz, 1H), 7.96 (s, 1H), 7.81 (d, J = 7.8 Hz , 1H), 7.77 - 7.70 (m, 2H), 7.24 (s, 1H), 7.15 - 7.05 (m, 2H), 6.72 (d, J = 1.4 Hz, 1H), 4.64 (s, 1H), 4.11 ( s, 1H), 3.93 (s, 3H), 2.74 (d, J = 1.2 Hz, 5H), 2.31 (s, 3H), 2.27 - 2.17 (m, 2H), 2.11 - 2.01 (m, 2H), 1.67 - 1.58 (m, 2H), 1.56 (s, 6H), 1.25 (s, 1H); 562 [M+H] +
3939 메틸 5-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-(4-메틸피페라진-1-일)벤조에이트methyl 5-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl) Amino)-2-(4-methylpiperazin-1-yl)benzoate 1H NMR (400MHz, CDCl3) δ8.27 (d, J = 8.3 Hz, 1H), 7.95 (s, 1H), 7.90 (d, J = 2.7 Hz, 1H), 7.72 (dd, J = 8.8, 2.8 Hz, 1H), 7.64 (t, J = 7.9 Hz, 1H), 7.09 (d, J = 8.8 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.97 (s, 1H), 6.64 (s, 1H), 4.68 (s, 1H), 3.85 (s, 3H), 3.08 (t, J = 4.8 Hz, 4H), 2.72 (s, 3H), 2.62 (t, J = 4.9 Hz, 4H), 2.37 (s, 3H), 1.54 (s, 6H); 548 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.27 (d, J = 8.3 Hz, 1H), 7.95 (s, 1H), 7.90 (d, J = 2.7 Hz, 1H), 7.72 (dd, J = 8.8, 2.8 Hz, 1H), 7.64 (t, J = 7.9 Hz, 1H), 7.09 (d, J = 8.8 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.97 (s, 1H), 6.64 (s, 1H), 4.68 (s, 1H), 3.85 (s, 3H), 3.08 (t, J = 4.8 Hz, 4H), 2.72 (s, 3H), 2.62 (t, J = 4.9 Hz, 4H) , 2.37 (s, 3H), 1.54 (s, 6H); 548 [M+H] +
4040 2-(6-((2-((3-(하이드록시메틸)-4-(4-메틸피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-(hydroxymethyl)-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.31 (d, J = 8.3 Hz, 1H), 7.94 (s, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.50 (dd, J = 8.6, 2.7 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.22 (d, J = 8.6 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 7.00 (s, 1H), 6.65 (s, 1H), 4.78 (s, 2H), 4.69 (s, 1H), 3.03 (t, J = 4.8 Hz, 4H), 2.72 (s, 3H), 2.63 (s, 4H), 2.38 (s, 3H), 1.55 (s, 6H); 520 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.31 (d, J = 8.3 Hz, 1H), 7.94 (s, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.50 (dd, J = 8.6, 2.7 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.22 (d, J = 8.6 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 7.00 (s, 1H), 6.65 ( s, 1H), 4.78 (s, 2H), 4.69 (s, 1H), 3.03 (t, J = 4.8 Hz, 4H), 2.72 (s, 3H), 2.63 (s, 4H), 2.38 (s, 3H) ), 1.55 (s, 6H); 520 [M+H] +
4141 2-(6-((2-((1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ8.30 (d, J = 8.2 Hz, 1H), 7.99 - 7.87 (m, 2H), 7.70 (t, J = 7.9 Hz, 1H), 7.51 (s, 1H), 7.04 (d, J = 7.6, 0.8 Hz, 1H), 6.74 (s, 1H), 6.62 (s, 1H), 4.69 (s, 1H), 4.22 - 4.07 (m, 1H), 3.15 - 3.05 (m, 2H), 2.71 (d, J = 1.3 Hz, 3H), 2.47 (q, J = 7.2 Hz, 2H), 2.22 - 2.13 (m, 2H), 2.13 - 2.01 (m, 4H), 1.54 (s, 6H), 1.13 (t, J = 7.2 Hz, 3H); 493 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.30 (d, J = 8.2 Hz, 1H), 7.99 - 7.87 (m, 2H), 7.70 (t, J = 7.9 Hz, 1H), 7.51 (s, 1H) , 7.04 (d, J = 7.6, 0.8 Hz, 1H), 6.74 (s, 1H), 6.62 (s, 1H), 4.69 (s, 1H), 4.22 - 4.07 (m, 1H), 3.15 - 3.05 (m , 2H), 2.71 (d, J = 1.3 Hz, 3H), 2.47 (q, J = 7.2 Hz, 2H), 2.22 - 2.13 (m, 2H), 2.13 - 2.01 (m, 4H), 1.54 (s, 6H), 1.13 (t, J = 7.2 Hz, 3H); 493 [M+H] +
4242 2-(6-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] Pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, CDCl3) δ8.30 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 5.6 Hz, 2H), 7.69 (t, J = 7.9 Hz, 1H), 7.52 (s, 1H), 7.08 - 7.02 (m, 1H), 6.73 (s, 1H), 6.61 (s, 1H), 4.72 (s, 1H), 4.18 - 4.06 (m, 1H), 3.03 - 2.95 (m, 2H), 2.71 (s, 3H), 2.33 (s, 3H), 2.20 - 2.05 (m, 6H), 1.54 (s, 6H); 479 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.30 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 5.6 Hz, 2H), 7.69 (t, J = 7.9 Hz, 1H), 7.52 (s , 1H), 7.08 - 7.02 (m, 1H), 6.73 (s, 1H), 6.61 (s, 1H), 4.72 (s, 1H), 4.18 - 4.06 (m, 1H), 3.03 - 2.95 (m, 2H) ), 2.71 (s, 3H), 2.33 (s, 3H), 2.20 - 2.05 (m, 6H), 1.54 (s, 6H); 479 [M+H] +
4343 2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400MHz, CDCl3) δ7.58 - 7.45 (m, 3H), 7.42 - 7.35 (m, 2H), 7.28 (s, 1H), 7.03 (s, 1H), 6.80 - 6.74 (m, 1H), 6.55 (s, 1H), 4.06 - 3.94 (m, 1H), 2.99 - 2.89 (m, 2H), 2.65 (s, 3H), 2.32 (s, 3H), 2.13 - 2.02 (m, 2H), 1.98 - 1.89 (m, 2H), 1.77 - 1.64 (m, 2H), 1.59 (s, 6H); 478 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ7.58 - 7.45 (m, 3H), 7.42 - 7.35 (m, 2H), 7.28 (s, 1H), 7.03 (s, 1H), 6.80 - 6.74 (m, 1H) ), 6.55 (s, 1H), 4.06 - 3.94 (m, 1H), 2.99 - 2.89 (m, 2H), 2.65 (s, 3H), 2.32 (s, 3H), 2.13 - 2.02 (m, 2H), 1.98 - 1.89 (m, 2H), 1.77 - 1.64 (m, 2H), 1.59 (s, 6H); 478 [M+H] +
4444 2-(3-((2-((1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400MHz, CDCl3) δ7.64 - 7.50 (m, 2H), 7.48 - 7.41 (m, 2H), 7.41 - 7.35 (m, 1H), 7.32 (s, 1H), 7.06 (s, 1H), 6.70 (s, 1H), 6.56 (s, 1H), 4.11 - 3.97 (m, 1H), 3.06 (d, J = 11.5 Hz, 2H), 2.65 (s, 3H), 2.47 (q, J = 7.2 Hz, 2H), 2.11 - 1.98 (m, 4H), 1.77 (s, 2H), 1.59 (s, 6H), 1.15 (t, J = 7.2 Hz, 3H); 492 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.64 - 7.50 (m, 2H), 7.48 - 7.41 (m, 2H), 7.41 - 7.35 (m, 1H), 7.32 (s, 1H), 7.06 (s, 1H) ), 6.70 (s, 1H), 6.56 (s, 1H), 4.11 - 3.97 (m, 1H), 3.06 (d, J = 11.5 Hz, 2H), 2.65 (s, 3H), 2.47 (q, J = 7.2 Hz, 2H), 2.11 - 1.98 (m, 4H), 1.77 (s, 2H), 1.59 (s, 6H), 1.15 (t, J = 7.2 Hz, 3H); 492 [M+H] +
4545 5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)-N4-페닐티에노[2,3-d]피리미딘-2,4-디아민5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-N4-phenylthieno[2,3-d]pyrimidine-2,4 -Diamine 1H NMR (400MHz, CDCl3) δ7.90 - 7.76 (m, 1H), 7.63 - 7.55 (m, 2H), 7.45 - 7.34 (m, 3H), 7.20 - 7.08 (m, 2H), 6.72 (s, 1H), 6.60 - 6.53 (m, 1H), 4.08 - 3.96 (m, 1H), 3.02 - 2.91 (m, 2H), 2.65 (s, 3H), 2.33 (s, 3H), 2.17 - 1.96 (m, 6H); 420 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ7.90 - 7.76 (m, 1H), 7.63 - 7.55 (m, 2H), 7.45 - 7.34 (m, 3H), 7.20 - 7.08 (m, 2H), 6.72 (s , 1H), 6.60 - 6.53 (m, 1H), 4.08 - 3.96 (m, 1H), 3.02 - 2.91 (m, 2H), 2.65 (s, 3H), 2.33 (s, 3H), 2.17 - 1.96 (m , 6H); 420 [M+H] +
4646 N2-(1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)-5-메틸-N4-페닐티에노[2,3-d]피리미딘-2,4-디아민N2-(1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-methyl-N4-phenylthieno[2,3-d]pyrimidine-2,4 -Diamine 1H NMR (400MHz, CDCl3) δ7.84 (s, 1H), 7.64 - 7.53 (m, 2H), 7.45 - 7.34 (m, 3H), 7.20 - 7.14 (m, 1H), 7.12 (s, 1H), 6.67 (s, 1H), 6.61 - 6.53 (m, 1H), 4.12 - 3.98 (m, 1H), 3.13 - 3.01 (m, 2H), 2.66 (s, 3H), 2.47 (q, J = 7.2 Hz, 2H), 2.16 - 1.95 (m, 6H), 1.13 (t, J = 7.2 Hz, 3H); 434 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.84 (s, 1H), 7.64 - 7.53 (m, 2H), 7.45 - 7.34 (m, 3H), 7.20 - 7.14 (m, 1H), 7.12 (s, 1H) ), 6.67 (s, 1H), 6.61 - 6.53 (m, 1H), 4.12 - 3.98 (m, 1H), 3.13 - 3.01 (m, 2H), 2.66 (s, 3H), 2.47 (q, J = 7.2 Hz, 2H), 2.16 - 1.95 (m, 6H), 1.13 (t, J = 7.2 Hz, 3H); 434 [M+H] +
4747 2-(6-((2-((4-(4-(디에틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(diethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.65 (t, J = 7.9 Hz, 1H), 7.25 (d, J = 2.4 Hz, 1H), 7.09 - 7.02 (m, 2H), 6.92 (d, J = 8.5 Hz, 1H), 6.88 (s, 1H), 6.66 - 6.61 (m, 1H), 4.70 (s, 1H), 3.84 (s, 3H), 3.53 (d, J = 11.3 Hz, 2H), 2.73 (s, 4H), 2.66 (q, J = 7.2 Hz, 4H), 2.61 - 2.53 (m, 2H), 1.90 - 1.76 (m, 5H), 1.54 (s, 6H), 1.10 (t, J = 7.1 Hz, 6H); 576 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.65 (t, J = 7.9 Hz, 1H), 7.25 (d, J = 2.4 Hz) , 1H), 7.09 - 7.02 (m, 2H), 6.92 (d, J = 8.5 Hz, 1H), 6.88 (s, 1H), 6.66 - 6.61 (m, 1H), 4.70 (s, 1H), 3.84 ( s, 3H), 3.53 (d, J = 11.3 Hz, 2H), 2.73 (s, 4H), 2.66 (q, J = 7.2 Hz, 4H), 2.61 - 2.53 (m, 2H), 1.90 - 1.76 (m , 5H), 1.54 (s, 6H), 1.10 (t, J = 7.1 Hz, 6H); 576 [M+H] +
4848 2-(6-((2-((3-메톡시-4-(1,4-디옥사-8-아자스피로[4.5]데칸-8-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-methoxy-4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)phenyl)amino)-5-methylthieno[ 2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.33 (d, J = 8.3 Hz, 1H), 7.93 (s, 1H), 7.65 (t, J = 7.9 Hz, 1H), 7.25 (d, J = 2.3 Hz, 1H), 7.07 (dd, J = 8.4, 2.4 Hz, 1H), 7.04 (dd, J = 7.6, 0.7 Hz, 1H), 6.97 - 6.90 (m, 2H), 6.63 (d, J = 1.3 Hz, 1H), 4.71 (s, 1H), 4.01 (s, 4H), 3.84 (s, 3H), 3.17 - 3.08 (m, 4H), 2.72 (d, J = 1.3 Hz, 3H), 1.94 (t, J = 5.6 Hz, 4H), 1.54 (s, 6H); 563 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.33 (d, J = 8.3 Hz, 1H), 7.93 (s, 1H), 7.65 (t, J = 7.9 Hz, 1H), 7.25 (d, J = 2.3 Hz, 1H), 7.07 (dd, J = 8.4, 2.4 Hz, 1H), 7.04 (dd, J = 7.6, 0.7 Hz, 1H), 6.97 - 6.90 (m, 2H), 6.63 (d, J = 1.3 Hz, 1H) ), 4.71 (s, 1H), 4.01 (s, 4H), 3.84 (s, 3H), 3.17 - 3.08 (m, 4H), 2.72 (d, J = 1.3 Hz, 3H), 1.94 (t, J = 5.6 Hz, 4H), 1.54 (s, 6H); 563 [M+H] +
4949 (4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)(4-메틸피페라진-1-일)메타논(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl) Amino)-2-methoxyphenyl)(4-methylpiperazin-1-yl)methanone 1H NMR (400MHz, CDCl3) δ8.38 - 8.30 (m, 1H), 7.96 (s, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.50 (d, J = 1.9 Hz, 1H), 7.21 (d, J = 8.2 Hz, 1H), 7.14 (s, 1H), 7.11 (dd, J = 8.2, 1.9 Hz, 1H), 7.09 - 7.05 (m, 1H), 6.70 - 6.68 (m, 1H), 4.66 (s, 1H), 3.87 (s, 1H), 3.83 - 3.70 (m, 4H), 3.42 - 3.27 (m, 2H), 2.74 (s, 3H), 2.56 - 2.35 (m, 3H), 2.35 - 2.21 (m, 4H), 1.55 (s, 6H); 548 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.38 - 8.30 (m, 1H), 7.96 (s, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.50 (d, J = 1.9 Hz, 1H) , 7.21 (d, J = 8.2 Hz, 1H), 7.14 (s, 1H), 7.11 (dd, J = 8.2, 1.9 Hz, 1H), 7.09 - 7.05 (m, 1H), 6.70 - 6.68 (m, 1H) ), 4.66 (s, 1H), 3.87 (s, 1H), 3.83 - 3.70 (m, 4H), 3.42 - 3.27 (m, 2H), 2.74 (s, 3H), 2.56 - 2.35 (m, 3H), 2.35 - 2.21 (m, 4H), 1.55 (s, 6H); 548 [M+H] +
5050 2-메틸-2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판니트릴2-methyl-2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)propanenitrile 1H NMR (400MHz, CDCl3) δ8.03 (s, 1H), 7.87 (s, 1H), 7.51 (d, J = 8.2 Hz, 1H), 7.45 (s, 1H), 7.38 (t, J = 8.0 Hz, 1H), 7.16 (s, 2H), 6.88 (s, 1H), 6.60 - 6.55 (m, 1H), 4.10 - 4.00 (m, 1H), 3.01 - 2.92 (m, 2H), 2.67 (s, 3H), 2.33 (s, 3H), 2.17 - 1.98 (m, 6H), 1.74 (s, 6H); 487 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.03 (s, 1H), 7.87 (s, 1H), 7.51 (d, J = 8.2 Hz, 1H), 7.45 (s, 1H), 7.38 (t, J = 8.0 Hz, 1H), 7.16 (s, 2H), 6.88 (s, 1H), 6.60 - 6.55 (m, 1H), 4.10 - 4.00 (m, 1H), 3.01 - 2.92 (m, 2H), 2.67 (s , 3H), 2.33 (s, 3H), 2.17 - 1.98 (m, 6H), 1.74 (s, 6H); 487 [M+H] +
실시예Example 화합물명compound name 1H NMR and/or Mass 1 H NMR and/or Mass
5151 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)-2-메틸프로판니트릴2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl)amino)phenyl)-2-methylpropanenitrile 1H NMR (400MHz, CDCl3) δ8.17 (s, 1H), 7.51 - 7.44 (m, 1H), 7.35 (t, J = 7.9 Hz, 1H), 7.28 (d, J = 2.4 Hz, 1H), 7.19 (s, 1H), 7.17 - 7.12 (m, 1H), 7.11 - 7.04 (m, 2H), 6.87 (d, J = 8.5 Hz, 1H), 6.62 - 6.57 (m, 1H), 3.78 (s, 3H), 3.54 - 3.44 (m, 2H), 2.67 (d, J = 1.3 Hz, 3H), 2.59 - 2.50 (m, 2H), 2.38 - 2.28 (m, 7H), 1.92 - 1.84 (m, 2H), 1.83 - 1.74 (m, 2H), 1.72 (s, 6H); 556 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ8.17 (s, 1H), 7.51 - 7.44 (m, 1H), 7.35 (t, J = 7.9 Hz, 1H), 7.28 (d, J = 2.4 Hz, 1H) , 7.19 (s, 1H), 7.17 - 7.12 (m, 1H), 7.11 - 7.04 (m, 2H), 6.87 (d, J = 8.5 Hz, 1H), 6.62 - 6.57 (m, 1H), 3.78 (s , 3H), 3.54 - 3.44 (m, 2H), 2.67 (d, J = 1.3 Hz, 3H), 2.59 - 2.50 (m, 2H), 2.38 - 2.28 (m, 7H), 1.92 - 1.84 (m, 2H) ), 1.83 - 1.74 (m, 2H), 1.72 (s, 6H); 556 [M+H] +
5252 5-메틸-N4-(1-메틸-1H-피라졸-4-일)-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민5-methyl-N4-(1-methyl-1H-pyrazol-4-yl)-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyrimidine -2,4-diamine 1H NMR (400 MHz, CDCl3) 7.79 (s, 1H), 7.44-7.40 (m, 3H), 6.93 (dd, J = 6.9, 2.0 Hz, 2H), 6.88 (s, 1H), 6.71 (s, 1H), 6.2 (s, 1H), 3.82 (s, 3H), 3.19 (t, J = 4.8 Hz, 4H), 2.61 (s, 3H), 2.58 (t, J = 4.8 Hz, 4H), 2.36 (s, 3H); 435 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) 7.79 (s, 1H), 7.44-7.40 (m, 3H), 6.93 (dd, J = 6.9, 2.0 Hz, 2H), 6.88 (s, 1H), 6.71 (s , 1H), 6.2 (s, 1H), 3.82 (s, 3H), 3.19 (t, J = 4.8 Hz, 4H), 2.61 (s, 3H), 2.58 (t, J = 4.8 Hz, 4H), 2.36 (s, 3H); 435 [M+H] +
5353 N4-(5-(터트-부틸)이속사졸-3-일)-5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민N4-(5-(tert-butyl)isoxazol-3-yl)-5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyryl Midine-2,4-diamine 1H NMR (400 MHz, CDCl3) 7.96 (s, 1H), 7.65 (dd, J = 6.8, 2.2 Hz, 2H), 6.99 (dd, J = 6.8, 2.2 Hz, 2H), 6.78 (s, 1H), 4.22 (s, 2H), 3.22 (t, J = 4.9 Hz, 4H), 2.68 (s, 3H), 2.60 (t, J= Hz, 4H), 2.37 (s, 3H), 1.30 (s, 9H); 478 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) 7.96 (s, 1H), 7.65 (dd, J = 6.8, 2.2 Hz, 2H), 6.99 (dd, J = 6.8, 2.2 Hz, 2H), 6.78 (s, 1H) ), 4.22 (s, 2H), 3.22 (t, J = 4.9 Hz, 4H), 2.68 (s, 3H), 2.60 (t, J = Hz, 4H), 2.37 (s, 3H), 1.30 (s, 9H); 478 [M+H] +
5454 N4-(1H-인다졸-6-일)-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민N4-(1H-indazol-6-yl)-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400MHz,DMSO) δ12.90 (s, 1H), 9.48 (s, 1H), 9.03 (s, 1H), 8.02 (s, 1H), 7.97 (s, 1H), 7.75 - 7.65 (m, 2H), 7.59 - 7.50 (m, 3H), 7.20 (d, J = 6.0 Hz, 1H), 6.86 - 6.76 (m, 2H), 3.08 - 2.94 (m, 4H), 2.48 - 2.41 (m, 4H), 2.22 (s, 3H); 457 [M+H]+ 1H NMR (400MHz,DMSO) δ12.90 (s, 1H), 9.48 (s, 1H), 9.03 (s, 1H), 8.02 (s, 1H), 7.97 (s, 1H), 7.75 - 7.65 (m , 2H), 7.59 - 7.50 (m, 3H), 7.20 (d, J = 6.0 Hz, 1H), 6.86 - 6.76 (m, 2H), 3.08 - 2.94 (m, 4H), 2.48 - 2.41 (m, 4H) ), 2.22 (s, 3H); 457 [M+H] +
5555 5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)-N4-(퀴놀린-7-일)티에노[2,3-d]피리미딘-2,4-디아민5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)-N4-(quinolin-7-yl)thieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 8.88 (d, J = 2.96 Hz, 1H), 8.54 (br s, 1H), 8.11 (d, J = 8.08 Hz, 1H), 7.77 (dd, J = 13.82, 10.12 Hz, 2H), 7.55 (d, J = 8.88 Hz, 2H), 7.42 (s, 1H), 7.32 (q, J = 3.96 Hz, 1H), 7.06 (s, 1H), 6.91 (d, J = 8.92 Hz, 2H), 6.60 (d, J = 0.84 Hz, 1H), 3.18 (t, J = 4.8 Hz, 4H), 2.70 (s, 3H), 2.62 (t, J = 4.88 Hz, 4H), 2.37 (s, 3H) ; 482 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.88 (d, J = 2.96 Hz, 1H), 8.54 (br s, 1H), 8.11 (d, J = 8.08 Hz, 1H), 7.77 (dd, J = 13.82 , 10.12 Hz, 2H), 7.55 (d, J = 8.88 Hz, 2H), 7.42 (s, 1H), 7.32 (q, J = 3.96 Hz, 1H), 7.06 (s, 1H), 6.91 (d, J = 8.92 Hz, 2H), 6.60 (d, J = 0.84 Hz, 1H), 3.18 (t, J = 4.8 Hz, 4H), 2.70 (s, 3H), 2.62 (t, J = 4.88 Hz, 4H), 2.37 (s, 3H); 482 [M+H] +
5656 N4-(1H-인다졸-6-일)-5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민N4-(1H-indazol-6-yl)-5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyrimidine-2,4 -Diamine 1H NMR (400 MHz, MeOD) 8.15 (br s, 1H), 7.81 (d, J = 8.36 Hz, 2H), 7.26 (dd, J = 8.72, 1.28 Hz, 3H), 6.93 (br s, 1H), 6.70 (br s, 2H), 3.64 - 3.59 (m, 4H), 3.28 - 3.20 (m, 4H), 2.98 (s, 3H), 2.72 (s, 3H); 471 [M+H]+ 1H NMR (400 MHz, MeOD) 8.15 (br s, 1H), 7.81 (d, J = 8.36 Hz, 2H), 7.26 (dd, J = 8.72, 1.28 Hz, 3H), 6.93 (br s, 1H) , 6.70 (br s, 2H), 3.64 - 3.59 (m, 4H), 3.28 - 3.20 (m, 4H), 2.98 (s, 3H), 2.72 (s, 3H); 471 [M+H] +
5757 5-메틸-4-(4-메틸-1H-이미다졸-1-일)-N-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2-아민5-methyl-4-(4-methyl-1H-imidazol-1-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyrimidine -2-amine 1H NMR (400 MHz, MeOD) δ 9.22 (br s, 1H), 7.77 (br s, 1H), 7.65 (d, J = 8.96 Hz, 2H), 7.10 (d, J = 1.24 Hz, 1H), 7.04 (d, J = 6.92 Hz, 2H), 3.80 - 3.77 (m, 4H), 3.62 - 3.59 (m, 4H), 3.03 (br s, 1H), 2.98 (s, 3H), 2.46 (s, 3H), 2.05 (s, 3H); 420 [M+H]+ 1H NMR (400 MHz, MeOD) δ 9.22 (br s, 1H), 7.77 (br s, 1H), 7.65 (d, J = 8.96 Hz, 2H), 7.10 (d, J = 1.24 Hz, 1H), 7.04 (d, J = 6.92 Hz, 2H), 3.80 - 3.77 (m, 4H), 3.62 - 3.59 (m, 4H), 3.03 (br s, 1H), 2.98 (s, 3H), 2.46 (s, 3H) ), 2.05 (s, 3H); 420 [M+H] +
5858 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-1-메틸-1H-피라졸-5-일)프로판-2-올2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl)amino)-1-methyl-1H-pyrazol-5-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.08 (s, 1H), 8.01 (s, 1H), 7.28 (dd, J = 8.5, 2.3 Hz, 1H), 7.15 (br s, 1H), 6.84 - 6.76 (m, 2H), 6.55 (br s, 1H), 5.31 (s, 1H), 3.90 (s, 3H), 3.70 (s, 3H), 3.33 - 3.29 (m, 2H), 2.60 (s, 3H), 2.48 - 2.41 (m, 2H), 2.19 (s, 6H), 2.16 - 2.07 (m, 1H), 1.84 - 1.74 (m, 2H), 1.58 - 1.49 (m, 2H), 1.48 (s, 6H) ); 551 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.08 (s, 1H), 8.01 (s, 1H), 7.28 (dd, J = 8.5, 2.3 Hz, 1H), 7.15 (br s, 1H), 6.84 - 6.76 ( m, 2H), 6.55 (br s, 1H), 5.31 (s, 1H), 3.90 (s, 3H), 3.70 (s, 3H), 3.33 - 3.29 (m, 2H), 2.60 (s, 3H), 2.48 - 2.41 (m, 2H), 2.19 (s, 6H), 2.16 - 2.07 (m, 1H), 1.84 - 1.74 (m, 2H), 1.58 - 1.49 (m, 2H), 1.48 (s, 6H) ) ; 551 [M+H] +
5959 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤즈아마이드3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)benzamide 1H NMR (400 MHz, DMSO) δ 9.09 (s, 1H), 8.20 (s, 1H), 8.05 - 7.90 (m, 3H), 7.64 - 7.56 (m, 1H), 7.46 - 7.35 (m, 2H), 7.23 (d, J = 8.7 Hz, 1H), 7.18 (br s, 1H), 6.83 (s, 1H), 6.70 (d, J = 8.6 Hz, 1H), 3.60 (s, 3H), 3.27 (d, J = 11.4 Hz, 2H), 2.64 (s, 3H), 2.47 - 2.38 (m, 2H), 2.18 (s, 6H), 2.16 - 2.07 (m, 1H), 1.78 (d, J = 12.2 Hz, 2H), 1.56 - 1.40 (m, 2H); 532 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.09 (s, 1H), 8.20 (s, 1H), 8.05 - 7.90 (m, 3H), 7.64 - 7.56 (m, 1H), 7.46 - 7.35 (m, 2H) , 7.23 (d, J = 8.7 Hz, 1H), 7.18 (br s, 1H), 6.83 (s, 1H), 6.70 (d, J = 8.6 Hz, 1H), 3.60 (s, 3H), 3.27 (d , J = 11.4 Hz, 2H), 2.64 (s, 3H), 2.47 - 2.38 (m, 2H), 2.18 (s, 6H), 2.16 - 2.07 (m, 1H), 1.78 (d, J = 12.2 Hz, 2H), 1.56 - 1.40 (m, 2H); 532 [M+H] +
6060 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.28 (s, 1H), 8.35 - 8.26 (m, 1H), 8.24 (s, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.37 - 7.22 (m, 3H), 6.90 (s, 1H), 6.82 (d, J = 8.4 Hz, 1H), 5.21 (s, 1H), 3.70 (s, 3H), 3.22 - 3.14 (m, 2H), 3.06 (t, J = 6.8 Hz, 4H), 2.65 (s, 3H), 2.61 - 2.54 (m, 2H), 2.09 - 1.97 (m, 1H), 1.91 (p, J = 6.8 Hz, 2H), 1.75 - 1.62 (m, 2H), 1.43 (s, 6H), 1.32 - 1.18 (m, 2H); 560 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.28 (s, 1H), 8.35 - 8.26 (m, 1H), 8.24 (s, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.37 - 7.22 (m , 3H), 6.90 (s, 1H), 6.82 (d, J = 8.4 Hz, 1H), 5.21 (s, 1H), 3.70 (s, 3H), 3.22 - 3.14 (m, 2H), 3.06 (t, J = 6.8 Hz, 4H), 2.65 (s, 3H), 2.61 - 2.54 (m, 2H), 2.09 - 1.97 (m, 1H), 1.91 (p, J = 6.8 Hz, 2H), 1.75 - 1.62 (m , 2H), 1.43 (s, 6H), 1.32 - 1.18 (m, 2H); 560 [M+H] +
6161 2-(6-((2-((4-(3-(디메틸아미노)피롤리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(3-(dimethylamino)pyrrolidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.2 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.21 (s, 1H), 7.04 - 7.02 (m, 2H), 6.88 (s, 1H), 6.76 (d, J = 8.48 Hz, 1H), 6.61 (s, 1H), 4.78 (s, 1H), 3.80 (s, 3H), 3.61 - 3.55 (m, 1H), 3.46 - 3.41 (m, 1H), 3.24 - 3.12 (m, 2H), 2.89 - 2.83 (m, 1H), 2.25 (s, 3H), 2.19 - 2.04 (m, 1H), 1.90 - 1.81 (m, 1H), 1.54 (s, 6H) ; 534 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.33 (d, J = 8.2 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.21 (s, 1H), 7.04 - 7.02 (m, 2H), 6.88 (s, 1H), 6.76 (d, J = 8.48 Hz, 1H), 6.61 (s, 1H), 4.78 (s, 1H), 3.80 (s, 3H), 3.61 - 3.55 (m, 1H), 3.46 - 3.41 (m, 1H), 3.24 - 3.12 (m , 2H), 2.89 - 2.83 (m, 1H), 2.25 (s, 3H), 2.19 - 2.04 (m, 1H), 1.90 - 1.81 (m, 1H), 1.54 (s, 6H); 534 [M+H] +
6262 2-(3-((2-((4-(3-(디메틸아미노)피롤리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(3-(dimethylamino)pyrrolidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 7.88 Hz, 1H),7.58 (s, 1H), 7.31 (t, J = 7.84 Hz, 1H), 7.25 (s, 1H), 7.20 (d, J = 7.96 Hz, 1H), 7.15 (s, 1H), 6.92 (dd, J = 8.48, 2.24 Hz, 1H), 6.84 (s, 1H), 6.69 (d, J = 8.52 Hz, 1H), 6.55 (d, J = 0.96 Hz, 1H), 3.61 (s, 3H), 3.54 - 3.48 (m, 1H), 3.40 - 3.37 (m, 1H), 3.22 - 3.08 (m, 2H), 2.87 - 2.83 (m, 1H), 2.65 (s, 3H), 2.30 (s, 6H), 2.15 - 2.11 (m, 1H), 1.87 - 1.80 (m, 1H), 1.54 (s, 3H), 1.53 (s, 3H) ; 533 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.63 (d, J = 7.88 Hz, 1H), 7.58 (s, 1H), 7.31 (t, J = 7.84 Hz, 1H), 7.25 (s, 1H), 7.20 (d, J = 7.96 Hz, 1H), 7.15 (s, 1H), 6.92 (dd, J = 8.48, 2.24 Hz, 1H), 6.84 (s, 1H), 6.69 (d, J = 8.52 Hz, 1H) , 6.55 (d, J = 0.96 Hz, 1H), 3.61 (s, 3H), 3.54 - 3.48 (m, 1H), 3.40 - 3.37 (m, 1H), 3.22 - 3.08 (m, 2H), 2.87 - 2.83 (m, 1H), 2.65 (s, 3H), 2.30 (s, 6H), 2.15 - 2.11 (m, 1H), 1.87 - 1.80 (m, 1H), 1.54 (s, 3H), 1.53 (s, 3H) ) ; 533 [M+H] +
6363 2-(6-((2-((3-메톡시-4-(4-(피롤리딘-1-일)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-methoxy-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)-5-methylthieno[2 ,3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.24 Hz, 1H), 7.94 (s, 1H), 7.65 (t, J = 7.88 Hz, 1H), 7.23 (s, 1H), 7.08 - 7.03 (m, 2H), 6.92 (d, J = 8.44 Hz, 1H), 6.88 (s, 1H), 6.63 (s, 1H), 4.75 (s, 1H), 3.82 (s, 3H), 3.49 - 3.47 (m, 2H), 2.72 (s,3H), 2.63 - 2.61 (m, 6H), 2.18 - 2.16 (m, 1H), 2.00 - 1.98 (m, 2H), 1.81 - 1.69 (m, 6H), 1.54 (s, 6H) ; 574 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.33 (d, J = 8.24 Hz, 1H), 7.94 (s, 1H), 7.65 (t, J = 7.88 Hz, 1H), 7.23 (s, 1H), 7.08 - 7.03 (m, 2H), 6.92 (d, J = 8.44 Hz, 1H), 6.88 (s, 1H), 6.63 (s, 1H), 4.75 (s, 1H), 3.82 (s, 3H), 3.49 - 3.47 (m, 2H), 2.72 (s,3H), 2.63 - 2.61 (m, 6H), 2.18 - 2.16 (m, 1H), 2.00 - 1.98 (m, 2H), 1.81 - 1.69 (m, 6H), 1.54 (s, 6H) ; 574 [M+H] +
6464 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.03 (s, 1H), 8.05 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.52 (s, 1H), 7.31 - 7.21 (m, 2H), 7.21 - 7.13 (m, 2H), 6.81 (s, 1H), 6.70 (d, J = 8.6 Hz, 1H), 5.00 (s, 1H), 3.53 (s, 3H), 3.18 - 3.09 (m, 2H), 3.06 (t, J = 6.8 Hz, 4H), 2.64 (s, 3H), 2.48 - 2.41 (m, 2H), 2.06 - 1.96 (m, 1H), 1.90 (p, J = 6.8 Hz, 2H), 1.70 - 1.60 (m, 2H), 1.41 (s, 6H), 1.30 - 1.15 (m, 2H); 559 [M+H]+ 1H NMR (400 MHz, DMSO) δ 9.03 (s, 1H), 8.05 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.52 (s, 1H), 7.31 - 7.21 (m, 2H) ), 7.21 - 7.13 (m, 2H), 6.81 (s, 1H), 6.70 (d, J = 8.6 Hz, 1H), 5.00 (s, 1H), 3.53 (s, 3H), 3.18 - 3.09 (m, 2H), 3.06 (t, J = 6.8 Hz, 4H), 2.64 (s, 3H), 2.48 - 2.41 (m, 2H), 2.06 - 1.96 (m, 1H), 1.90 (p, J = 6.8 Hz, 2H) ), 1.70 - 1.60 (m, 2H), 1.41 (s, 6H), 1.30 - 1.15 (m, 2H); 559 [M+H] +
6565 2-(3-((2-((3-메톡시-4-(4-(피롤리딘-1-일)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((3-methoxy-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)-5-methylthieno[2 ,3-d] pyrimidin-4-yl) amino) phenyl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 9.04 (s,1H), 8.06 (s,1H), 7.70 (d, J = 6.8 Hz, 1H), 7.52 (s, 1H), 7.28 - 7.25 (m, 2H), 7.19 (d, J = 7.84 Hz, 2H), 6.80 (s, 1H), 6.70 (d, J = 8.6 Hz, 1H), 5.01 (s, 1H), 4.14 (bs, 1H), 3.54 (s, 3H), 3.23 - 3.20 (m, 2H), 3.16 (s, 3H), 2.64 (s, 3H), 2.00 - 1.98 (m, 1H), 1.89 - 1.86 (m, 2H), 1.67 - 1.65 (m, 4H),1.55 - 1.45 (m,3H), 1.42 (s, 6H), 1.26 - 1.15 (m, 1H) ; 573 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 9.04 (s, 1H), 8.06 (s, 1H), 7.70 (d, J = 6.8 Hz, 1H), 7.52 (s, 1H), 7.28 - 7.25 (m, 2H), 7.19 (d, J = 7.84 Hz, 2H), 6.80 (s, 1H), 6.70 (d, J = 8.6 Hz, 1H), 5.01 (s, 1H), 4.14 (bs, 1H), 3.54 ( s, 3H), 3.23 - 3.20 (m, 2H), 3.16 (s, 3H), 2.64 (s, 3H), 2.00 - 1.98 (m, 1H), 1.89 - 1.86 (m, 2H), 1.67 - 1.65 ( m, 4H), 1.55 - 1.45 (m, 3H), 1.42 (s, 6H), 1.26 - 1.15 (m, 1H); 573 [M+H] +
6666 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-메톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-methoxypropan-2-yl)pyridin-2-yl) -5-Methylthieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 8.12 Hz, 1H), 7.94 (s, 1H), 7.64 (t, J = 7.88 Hz, 1H), 7.27 (s, 1H), 7.23 (d, J = 7.56 Hz, 1H), 7.08 (dd, J = 8.48, 2.24 Hz, 1H), 6.93 (d, J = 8.48 Hz, 1H), 6.86 (s, 1H), 6.62 (s, 1H), 3.84 (s, 3H), 3.55 - 3.52 (m, 2H), 3.18 (s, 3H), 2.73 (s, 3H), 2.61 - 2.56 (m, 2H), 2.36 (s, 6H), 1.93 - 1.90 (m, 2H), 1.85 - 1.77 (m, 3H), 1.54 (s, 6H) ; 562 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.26 (d, J = 8.12 Hz, 1H), 7.94 (s, 1H), 7.64 (t, J = 7.88 Hz, 1H), 7.27 (s, 1H), 7.23 (d, J = 7.56 Hz, 1H), 7.08 (dd, J = 8.48, 2.24 Hz, 1H), 6.93 (d, J = 8.48 Hz, 1H), 6.86 (s, 1H), 6.62 (s, 1H) , 3.84 (s, 3H), 3.55 - 3.52 (m, 2H), 3.18 (s, 3H), 2.73 (s, 3H), 2.61 - 2.56 (m, 2H), 2.36 (s, 6H), 1.93 - 1.90 (m, 2H), 1.85 - 1.77 (m, 3H), 1.54 (s, 6H); 562 [M+H] +
6767 2-(3-((2-((4-(4-(디메틸아미노)아제판-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-(dimethylamino)azepan-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyryl midin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.60 - 7.58 (m, 2H), 7.31 (t, J = 8.0 Hz, 1H), 7.26-7.20 (m, 2H), 7.15 (s, 1H), 6.94 (s, 1H), 6.91 (dd, J = 8.48, 2,0 Hz, 1H), 6.80 (d, J = 8.52 Hz, 1H), 6.55 (s, 1H), 3.59 (s, 3H), 3.28 - 3.22 (m, 2H), 3.09 - 3.03 (m, 2H), 2.83 - 2.81 (m, 1H), 2.82 (s, 3H), 2.03 (s, 6H), 2.02 - 1.91 (m, 1H) 1.86 - 1.55 (m, 6H), 1.53 (s, 3H), 1.52 (s, 3H) ; 561 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.60 - 7.58 (m, 2H), 7.31 (t, J = 8.0 Hz, 1H), 7.26-7.20 (m, 2H), 7.15 (s, 1H), 6.94 ( s, 1H), 6.91 (dd, J = 8.48, 2,0 Hz, 1H), 6.80 (d, J = 8.52 Hz, 1H), 6.55 (s, 1H), 3.59 (s, 3H), 3.28 - 3.22 (m, 2H), 3.09 - 3.03 (m, 2H), 2.83 - 2.81 (m, 1H), 2.82 (s, 3H), 2.03 (s, 6H), 2.02 - 1.91 (m, 1H) 1.86 - 1.55 ( m, 6H), 1.53 (s, 3H), 1.52 (s, 3H); 561 [M+H] +
6868 2-(6-((2-((4-(4-(디메틸아미노)아제판-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(dimethylamino)azepan-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.24 Hz, 1H), 7.94 (s, 1H), 7.65 (t, J = 7.92 Hz, 1H), 7.21 (s,1H), 7.03 (dd, J = 7.52, 2.64 Hz, 2H), 6.90 (d, J = 8.52 Hz, 1H), 6.84 (s, 1H), 6.62 (s, 1H), 4.75 (s, 1H), 3.82 (s, 3H), 3.34 - 3.27 (m, 2H), 3.16 - 3.09 (m, 2H), 2.90 - 2.85 (m, 1H), 2.83 (s,3H), 2.34 (s, 6H), 2.04 - 1.93 (m, 1H), 1.90 - 1.77 (m, 6H), 1.54 (s, 6H) ; 562 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.33 (d, J = 8.24 Hz, 1H), 7.94 (s, 1H), 7.65 (t, J = 7.92 Hz, 1H), 7.21 (s, 1H), 7.03 (dd, J = 7.52, 2.64 Hz, 2H), 6.90 (d, J = 8.52 Hz, 1H), 6.84 (s, 1H), 6.62 (s, 1H), 4.75 (s, 1H), 3.82 (s, 3H), 3.34 - 3.27 (m, 2H), 3.16 - 3.09 (m, 2H), 2.90 - 2.85 (m, 1H), 2.83 (s,3H), 2.34 (s, 6H), 2.04 - 1.93 (m, 1H), 1.90 - 1.77 (m, 6H), 1.54 (s, 6H); 562 [M+H] +
6969 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-메톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-methoxypropan-2-yl)pyridin- 2-yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, DMSO) δ 9.31 (s, 1H), 8.35 (bs, 1H), 8.28 (s, 1H), 7.78 (t, J = 7.8 Hz, 1H), 7.32 - 7.29 (m, 2H), 7.22 (d, J = 7.6 Hz, 1H), 6.92 (s, 1H), 6.83 (d, J = 8.44 Hz, 1H), 3.71 (s, 3H), 3.21 - 3.18 (m, 2H), 3.09 - 3.07 (m, 6H), 2.66 (s, 3H), 2.09 - 2.05 (m, 1H), 1.99 - 1.89 (m, 2H), 1.70 - 1.67 (m, 2H), 1.47 (s, 6H), 1.28 - 1.23 (m, 2H) ; 574 [M+H]+ 1H NMR (400 MHz, DMSO) δ 9.31 (s, 1H), 8.35 (bs, 1H), 8.28 (s, 1H), 7.78 (t, J = 7.8 Hz, 1H), 7.32 - 7.29 (m, 2H) ), 7.22 (d, J = 7.6 Hz, 1H), 6.92 (s, 1H), 6.83 (d, J = 8.44 Hz, 1H), 3.71 (s, 3H), 3.21 - 3.18 (m, 2H), 3.09 - 3.07 (m, 6H), 2.66 (s, 3H), 2.09 - 2.05 (m, 1H), 1.99 - 1.89 (m, 2H), 1.70 - 1.67 (m, 2H), 1.47 (s, 6H), 1.28 - 1.23 (m, 2H) ; 574 [M+H] +
7070 터트-부틸(1-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)피페리딘-4-일)카바메이트tert-butyl(1-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyridine midin-2-yl)amino)-2-methoxyphenyl)piperidin-4-yl)carbamate 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.66 (dd, J = 8.7, 7.1 Hz, 1H), 7.29 (s, 1H), 7.08 - 7.03 (m, 2H), 6.93 (s, 2H), 6.64 (s, 1H), 4.72 (s, 1H), 4.54 - 4.51 (m, 1H), 3.83 (s, 3H), 3.62 (s, 3H), 3.66 - 3.61 (m, 1H), 3.41 - 3.38 (m, 2H), 2.73 - 2.69 (m, 5H), 2.07 - 2.04 (m, 2H), 1.69 - 1.65 (m, 2H), 1.55 (s, 6H), 1.47 (s, 9H); 620 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.66 (dd, J = 8.7, 7.1 Hz, 1H), 7.29 (s, 1H) , 7.08 - 7.03 (m, 2H), 6.93 (s, 2H), 6.64 (s, 1H), 4.72 (s, 1H), 4.54 - 4.51 (m, 1H), 3.83 (s, 3H), 3.62 (s , 3H), 3.66 - 3.61 (m, 1H), 3.41 - 3.38 (m, 2H), 2.73 - 2.69 (m, 5H), 2.07 - 2.04 (m, 2H), 1.69 - 1.65 (m, 2H), 1.55 (s, 6H), 1.47 (s, 9H); 620 [M+H] +
7171 터트-부틸(1-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)피페리딘-4-일)카바메이트tert-butyl(1-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine-2- yl)amino)-2-methoxyphenyl)piperidin-4-yl)carbamate 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 7.9 Hz, 1H), 7.58 (s, 1H), 7.29 (dd, J = 7.8, 7.9 Hz, 1H), 7.24 (d, J = 1.3 Hz, 1H), 7.19 (dd, J = 1.3, 7.8 Hz, 1H), 7.15 (s, 1H), 7.07 (s, 1H), 6.96 (d, J = 8.4 Hz, 1H), 6.82 (d, J = 8.4 Hz, 1H), 6.56 (s, 1H), 4.54 (d, J = 7.5 Hz, 1H), 3.63 - 3.60 (m, 4H), 3.32 (d, J = 11.4 Hz, 2H), 2.68 - 2.63 (m, 5H), 2.24 (s, 1H), 2.04-2.01 (m, 2H), 1.68 - 1.62 (m, 2H), 1.53 (s, 6H), 1.46 (s, 9H); 619 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.61 (d, J = 7.9 Hz, 1H), 7.58 (s, 1H), 7.29 (dd, J = 7.8, 7.9 Hz, 1H), 7.24 (d, J = 1.3 Hz, 1H), 7.19 (dd, J = 1.3, 7.8 Hz, 1H), 7.15 (s, 1H), 7.07 (s, 1H), 6.96 (d, J = 8.4 Hz, 1H), 6.82 (d, J = 8.4 Hz, 1H), 6.56 (s, 1H), 4.54 (d, J = 7.5 Hz, 1H), 3.63 - 3.60 (m, 4H), 3.32 (d, J = 11.4 Hz, 2H), 2.68 - 2.63 (m, 5H), 2.24 (s, 1H), 2.04-2.01 (m, 2H), 1.68 - 1.62 (m, 2H), 1.53 (s, 6H), 1.46 (s, 9H); 619 [M+H] +
7272 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-에톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-ethoxypropan-2-yl)pyridin-2-yl) -5-Methylthieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.16 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.92 Hz, 1H), 7.27 - 7.24 (m, 2H), 7.08 (dd, J = 8.48, 2.28 Hz, 1H), 6.93 (d, J = 8.52 Hz, 1H), 6.87 (s, 1H), 6.61 (s, 1H), 3.84 (s, 3H), 3.55 - 3.52 (m, 2H), 3.35 - 3.30 (m, 2H), 2.72 (s, 3H), 2.61 - 2.56 (m, 2H), 2.36 (s, 6H), 1.93 - 1.90 (m, 2H), 1.85 - 1.76 (m, 3H), 1.23 (s, 6H), 1.23 - 1.20 (m, 3H) ; 576 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.25 (d, J = 8.16 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.92 Hz, 1H), 7.27 - 7.24 (m, 2H) , 7.08 (dd, J = 8.48, 2.28 Hz, 1H), 6.93 (d, J = 8.52 Hz, 1H), 6.87 (s, 1H), 6.61 (s, 1H), 3.84 (s, 3H), 3.55 - 3.52 (m, 2H), 3.35 - 3.30 (m, 2H), 2.72 (s, 3H), 2.61 - 2.56 (m, 2H), 2.36 (s, 6H), 1.93 - 1.90 (m, 2H), 1.85 - 1.76 (m, 3H), 1.23 (s, 6H), 1.23 - 1.20 (m, 3H); 576 [M+H] +
7373 2-(4-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(4-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 5.44 Hz, 1H), 7.77 (d, J = 4.48 Hz, 1H), 7.39 (s, 1H), 7.32 (s, 1H), 7.20(s, 1H), 7.08 (d, J = 7.4 Hz, 1H), 6.92 - 6.90 (m, 2H), 6.65 (s, 1H), 4.74 (bs. 1H), 3.80 (s, 3H), 3.54 - 3.48 (m, 2H), 2.69 (s, 3H), 2.61 - 2.54 (m, 3H), 2.36 (s, 6H), 1.93 - 1.89 (m, 2H), 1.83 - 1.75 (m, 2H), 1.53 (s, 6H) ; 548 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.36 (d, J = 5.44 Hz, 1H), 7.77 (d, J = 4.48 Hz, 1H), 7.39 (s, 1H), 7.32 (s, 1H), 7.20 (s, 1H), 7.08 (d, J = 7.4 Hz, 1H), 6.92 - 6.90 (m, 2H), 6.65 (s, 1H), 4.74 (bs. 1H), 3.80 (s, 3H), 3.54 - 3.48 (m, 2H), 2.69 (s, 3H), 2.61 - 2.54 (m, 3H), 2.36 (s, 6H), 1.93 - 1.89 (m, 2H), 1.83 - 1.75 (m, 2H), 1.53 ( s, 6H); 548 [M+H] +
7474 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-에톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-ethoxypropan-2-yl)pyridin- 2-yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.16 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.88 Hz, 1H), 7.25 - 7.23 (m, 2H), 7.07 (dd, J = 8.48, 2.16 Hz, 1H), 6.92 (d, J = 8.44 Hz, 1H), 6.85 (s, 1H), 6.61 (s, 1H), 3.82 (s, 3H), 3.43 - 3.40 (m, 2H), 3.35 - 3.30 (m, 5H), 2.72 (s, 3H), 2.66 - 2.61 (m, 2H), 2.31 - 2.12 (m, 3H), 1.84 - 1.81 (m, 3H), 1.61 - 1.56 (m, 3H), 1.54 (s, 3H), 1.21 (t, J = 6.96 Hz, 3H) ; 588 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.25 (d, J = 8.16 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 7.88 Hz, 1H), 7.25 - 7.23 (m, 2H) , 7.07 (dd, J = 8.48, 2.16 Hz, 1H), 6.92 (d, J = 8.44 Hz, 1H), 6.85 (s, 1H), 6.61 (s, 1H), 3.82 (s, 3H), 3.43 - 3.40 (m, 2H), 3.35 - 3.30 (m, 5H), 2.72 (s, 3H), 2.66 - 2.61 (m, 2H), 2.31 - 2.12 (m, 3H), 1.84 - 1.81 (m, 3H), 1.61 - 1.56 (m, 3H), 1.54 (s, 3H), 1.21 (t, J = 6.96 Hz, 3H); 588 [M+H] +
7575 2-(2-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-4-일)프로판-2-올2-(2-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl) amino) pyridin-4-yl) propan-2-ol 1H NMR (400 MHz, MeOD) δ 7.93 (d, J = 7.04 Hz, 1H), 7.32 (s, 1H), 7.28 (s, 1H), 7.15 (d, J = 8.24 Hz, 1H), 7.07 (dd, J = 7.04, 1.4 Hz, 1H), 7.02 (d, 1.08 Hz, 1H), 6.87 (d, J = 8.64 Hz, 1H), 3.77 (s, 3H), 3.37 - 3.34 (m, 2H), 2.51 - 2.46 (m, 2H), 2.24 (s, 6H), 1.89 - 1.84 (m, 2H), 1.79(s, 3H), 1.79 - 1.77 (m, 1H), 1.66 - 1.57 (m, 2H), 1.48 (s, 6H) ; 548 [M+H]+ 1H NMR (400 MHz, MeOD) δ 7.93 (d, J = 7.04 Hz, 1H), 7.32 (s, 1H), 7.28 (s, 1H), 7.15 (d, J = 8.24 Hz, 1H), 7.07 ( dd, J = 7.04, 1.4 Hz, 1H), 7.02 (d, 1.08 Hz, 1H), 6.87 (d, J = 8.64 Hz, 1H), 3.77 (s, 3H), 3.37 - 3.34 (m, 2H), 2.51 - 2.46 (m, 2H), 2.24 (s, 6H), 1.89 - 1.84 (m, 2H), 1.79(s, 3H), 1.79 - 1.77 (m, 1H), 1.66 - 1.57 (m, 2H), 1.48 (s, 6H) ; 548 [M+H] +
7676 2-(3-((2-((4-(4-(아지리딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-(aziridin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.63 (dd, J = 7.8, 1.2 Hz, 7.57 (d, J = 1.6 Hz, 1H), 7.32 (dd, J = 7.8, 7.9 Hz, 1H), 7.26 - 7.25 (m, 1H), 7.21 (d, J = 7.9 Hz, 1H), 6.97 (dd, J = 2.3, 8.5 Hz, 1H), 6.88 (s, 1H), 6.84 (d, J = 8.5 Hz, 1H), 6.59 - 6.57 (m, 1H), 3.67 (s, 3H), 3.53 - 3.50 (m, 1H), 3.40 - 3.37 (m, 2H), 2.66 (s, 3H), 2.62 - 2.55 (m, 2H), 1.91 - 1.85 (m, 5H), 1.76 - 1.74 (m, 2H), 1.55 (s, 6H), 1.18 - 1.14 (m, 2H); 545 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.63 (dd, J = 7.8, 1.2 Hz, 7.57 (d, J = 1.6 Hz, 1H), 7.32 (dd, J = 7.8, 7.9 Hz, 1H), 7.26 - 7.25 (m, 1H), 7.21 (d, J = 7.9 Hz, 1H), 6.97 (dd, J = 2.3, 8.5 Hz, 1H), 6.88 (s, 1H), 6.84 (d, J = 8.5 Hz, 1H) ), 6.59 - 6.57 (m, 1H), 3.67 (s, 3H), 3.53 - 3.50 (m, 1H), 3.40 - 3.37 (m, 2H), 2.66 (s, 3H), 2.62 - 2.55 (m, 2H) ), 1.91 - 1.85 (m, 5H), 1.76 - 1.74 (m, 2H), 1.55 (s, 6H), 1.18 - 1.14 (m, 2H) ;
7777 2-(2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-4-일)프로판-2-올2-(2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d] pyrimidin-4-yl) amino) pyridin-4-yl) propan-2-ol 1H NMR (400 MHz, MeOD) δ 7.94 (d, J = 7.08 Hz, 1H), 7.32 (s, 1H), 7.28 (s, 1H), 7.15 (d, J = 7.68 Hz, 1H), 7.08 (dd, J = 7.08, 1.68 Hz, 1H), 7.02 (s, 1H), 6.87 (d, J = 8.6 Hz, 1H), 3.77 (s, 3H), 3.58 - 3.55 (m, 2H), 3.32 - 3.30 (m, 2H), 2.78 - 2.74 (m, 2H), 2.58 - 2.51 (m, 2H), 1.94 - 1.89 (m, 5H), 1.88 (s, 3H), 1.57 - 1.48 (m, 2H), 1.48 (s, 6H) ; 560 [M+H]+ 1H NMR (400 MHz, MeOD) δ 7.94 (d, J = 7.08 Hz, 1H), 7.32 (s, 1H), 7.28 (s, 1H), 7.15 (d, J = 7.68 Hz, 1H), 7.08 ( dd, J = 7.08, 1.68 Hz, 1H), 7.02 (s, 1H), 6.87 (d, J = 8.6 Hz, 1H), 3.77 (s, 3H), 3.58 - 3.55 (m, 2H), 3.32 - 3.30 (m, 2H), 2.78 - 2.74 (m, 2H), 2.58 - 2.51 (m, 2H), 1.94 - 1.89 (m, 5H), 1.88 (s, 3H), 1.57 - 1.48 (m, 2H), 1.48 (s, 6H) ; 560 [M+H] +
7878 1-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)시클로부탄-1-올1-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl) amino) pyridin-2-yl) cyclobutan-1-ol 1H NMR (400 MHz, CDCl3) δ 12.57 (s, 1H), 8.34 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.73 (dd, J = 8.0, 7.9 Hz, 1H), 7.37 (s, 1H), 7.30 - 7.27 (m, 1H), 7.10 - 7.08 (m, 1H), 6.99 - 6.91 (m, 1H), 6.66 (s, 1H), 4.84 (s, 1H), 3.85 (s, 3H), 3.63 - 3.59 (m, 2H), 3.21 - 3.19 (m, 1H), 2.80 (s, 6H), 2.75 - 2.69 (m, 5H), 2.57 - 2.46 (m, 4H), 2.32 - 2.29 (m, 2H), 2.10 - 2.02 (m, 4H); 560 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 12.57 (s, 1H), 8.34 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.73 (dd, J = 8.0, 7.9 Hz, 1H) , 7.37 (s, 1H), 7.30 - 7.27 (m, 1H), 7.10 - 7.08 (m, 1H), 6.99 - 6.91 (m, 1H), 6.66 (s, 1H), 4.84 (s, 1H), 3.85 (s, 3H), 3.63 - 3.59 (m, 2H), 3.21 - 3.19 (m, 1H), 2.80 (s, 6H), 2.75 - 2.69 (m, 5H), 2.57 - 2.46 (m, 4H), 2.32 - 2.29 (m, 2H), 2.10 - 2.02 (m, 4H); 560 [M+H] +
7979 2-(6-((2-((4-(4-(아지리딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(aziridin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.65 (dd, J = 7.9, 8.0 Hz,1H), 7.27 - 7.24 (m, 1H), 7.08 - 7.03 (m, 2H), 6.92 (d, J = 8.4 Hz, 1H), 6.89 (s, 1H), 6.63 (s, 1H), 4.71 (s, 1H), 3.84 (s, 3H), 3.44 - 3.41 (m, 2H), 2.72 (s, 3H), 2.66 - 2.60 (m, 2H), 1.94 - 1.88 (m, 4H), 1.77 - 1.70 (m, 2H), 1.64 (s, 6H), 1.19 - 1.16 (m, 2H); 546 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.65 (dd, J = 7.9, 8.0 Hz, 1H), 7.27 - 7.24 (m, 1H), 7.08 - 7.03 (m, 2H), 6.92 (d, J = 8.4 Hz, 1H), 6.89 (s, 1H), 6.63 (s, 1H), 4.71 (s, 1H), 3.84 (s, 3H) ), 3.44 - 3.41 (m, 2H), 2.72 (s, 3H), 2.66 - 2.60 (m, 2H), 1.94 - 1.88 (m, 4H), 1.77 - 1.70 (m, 2H), 1.64 (s, 6H) ), 1.19 - 1.16 (m, 2H); 546 [M+H] +
8080 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)-2-메틸프로판니트릴2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl)amino)pyridin-2-yl)-2-methylpropanenitrile 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.3 Hz, 1H), 7.97 (s, 1H), 7.66 (t, J = 8.0 Hz, 1H), 7.25 - 7.21 (m, 2H), 7.08 (dd, J = 8.4, 2.3 Hz, 1H), 6.93 (d, J = 8.5 Hz, 1H), 6.86 (s, 1H), 6.64 (s, 1H), 3.85 (s, 3H), 3.53 (d, J = 11.3 Hz, 2H), 2.72 (s, 3H), 2.63 - 2.53 (m, 2H), 2.36 (s, 6H), 1.94 - 1.87 (m, 2H), 1.85 - 1.77 (m, 2H), 1.75 (s, 6H); 557 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.37 (d, J = 8.3 Hz, 1H), 7.97 (s, 1H), 7.66 (t, J = 8.0 Hz, 1H), 7.25 - 7.21 (m, 2H) , 7.08 (dd, J = 8.4, 2.3 Hz, 1H), 6.93 (d, J = 8.5 Hz, 1H), 6.86 (s, 1H), 6.64 (s, 1H), 3.85 (s, 3H), 3.53 ( d, J = 11.3 Hz, 2H), 2.72 (s, 3H), 2.63 - 2.53 (m, 2H), 2.36 (s, 6H), 1.94 - 1.87 (m, 2H), 1.85 - 1.77 (m, 2H) , 1.75 (s, 6H); 557 [M+H] +
8181 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)-2-메틸프로판니트릴, 2,2,2-트리플루오로아세트산2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d] pyrimidin-4-yl) amino) pyridin-2-yl) -2-methylpropanenitrile, 2,2,2-trifluoroacetic acid 1H NMR (400 MHz, MeOD) δ 8.53 (d, J = 8.4 Hz, 1H), 7.85 (t, J = 8.0 Hz, 1H), 7.74 (s, 1H), 7.48 - 7.23 (m, 3H), 6.90 (s, 1H), 4.26 (s, 3H), 4.02 - 3.86 (m, 2H), 3.82 - 3.48 (m, 4H), 2.74 (s, 3H), 2.70 - 2.56 (m, 1H), 2.51 - 2.21 (m, 4H), 1.99 - 1.85 (m, 2H), 1.77 (s, 6H); 569 [M+H]+ 1H NMR (400 MHz, MeOD) δ 8.53 (d, J = 8.4 Hz, 1H), 7.85 (t, J = 8.0 Hz, 1H), 7.74 (s, 1H), 7.48 - 7.23 (m, 3H), 6.90 (s, 1H), 4.26 (s, 3H), 4.02 - 3.86 (m, 2H), 3.82 - 3.48 (m, 4H), 2.74 (s, 3H), 2.70 - 2.56 (m, 1H), 2.51 - 2.21 (m, 4H), 1.99 - 1.85 (m, 2H), 1.77 (s, 6H); 569 [M+H] +
8282 2-(6-((2-((3-메톡시-4-(4-(메틸아미노)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올, 2,2,2-트리플루오로아세트산2-(6-((2-((3-methoxy-4-(4-(methylamino)piperidin-1-yl)phenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol, 2,2,2-trifluoroacetic acid 1H NMR (400 MHz, MeOD) δ 8.26 (t, J = 8.1 Hz, 1H), 7.90 (d, J = 8.5 Hz, 1H), 7.72 (s, 1H), 7.53 (d, J = 7.7 Hz, 1H), 7.32 (dd, J = 8.7, 2.3 Hz, 1H), 7.23 (d, J = 8.7 Hz, 1H), 7.02 (s, 1H), 3.98 (s, 3H), 3.65 (d, J = 12.0 Hz, 2H), 3.14 (t, J = 12.0 Hz, 2H), 2.83 - 2.71 (m, 6H), 2.37 - 2.25 (m, 2H), 2.05 - 1.91 (m, 2H), 1.72 (s, 6H); 534 [M+H]+ 1H NMR (400 MHz, MeOD) δ 8.26 (t, J = 8.1 Hz, 1H), 7.90 (d, J = 8.5 Hz, 1H), 7.72 (s, 1H), 7.53 (d, J = 7.7 Hz, 1H), 7.32 (dd, J = 8.7, 2.3 Hz, 1H), 7.23 (d, J = 8.7 Hz, 1H), 7.02 (s, 1H), 3.98 (s, 3H), 3.65 (d, J = 12.0 Hz, 2H), 3.14 (t, J = 12.0 Hz, 2H), 2.83 - 2.71 (m, 6H), 2.37 - 2.25 (m, 2H), 2.05 - 1.91 (m, 2H), 1.72 (s, 6H) ; 534 [M+H] +
8383 2-(6-((2-((3-메톡시-4-(4-메톡시피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-methoxy-4-(4-methoxypiperidin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.10 - 7.01 (m, 2H), 6.94 (d, J = 8.5 Hz, 1H), 6.87 (s, 1H), 6.64 (s, 1H), 4.71 (s, 1H), 3.84 (s, 3H), 3.40 (s, 3H), 3.38 - 3.27 (m, 3H), 2.82 - 2.74 (m, 2H), 2.73 (s, 3H), 2.11 - 2.02 (m, 2H), 1.87 - 1.75 (m, 2H), 1.55 (s, 6H); 535 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.33 (d, J = 8.2 Hz, 1H), 7.94 (s, 1H), 7.66 (t, J = 7.9 Hz, 1H), 7.10 - 7.01 (m, 2H) , 6.94 (d, J = 8.5 Hz, 1H), 6.87 (s, 1H), 6.64 (s, 1H), 4.71 (s, 1H), 3.84 (s, 3H), 3.40 (s, 3H), 3.38 - 3.27 (m, 3H), 2.82 - 2.74 (m, 2H), 2.73 (s, 3H), 2.11 - 2.02 (m, 2H), 1.87 - 1.75 (m, 2H), 1.55 (s, 6H); 535 [M+H] +
8484 2-(3-((2-((3-메톡시-4-(4-메톡시피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((3-methoxy-4-(4-methoxypiperidin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.64 (dd, J = 8.0, 2.2 Hz, 1H), 7.56 (s, 1H), 7.33 (t, J = 7.9 Hz, 1H), 7.29 - 7.26 (m, 1H), 7.24 - 7.20 (m, 1H), 7.16 (s, 1H), 6.98 (dd, J = 8.5, 2.4 Hz, 1H), 6.89 - 6.81 (m, 2H), 6.59 (s, 1H), 3.66 (s, 3H), 3.39 (s, 3H), 3.34 - 3.25 (m, 2H), 2.79 - 2.69 (m, 2H), 2.67 (s, 3H), 2.11 - 1.99 (m, 2H), 1.83 - 1.74 (m, 2H), 1.55 (s, 6H); 534 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.64 (dd, J = 8.0, 2.2 Hz, 1H), 7.56 (s, 1H), 7.33 (t, J = 7.9 Hz, 1H), 7.29 - 7.26 (m, 1H), 7.24 - 7.20 (m, 1H), 7.16 (s, 1H), 6.98 (dd, J = 8.5, 2.4 Hz, 1H), 6.89 - 6.81 (m, 2H), 6.59 (s, 1H), 3.66 (s, 3H), 3.39 (s, 3H), 3.34 - 3.25 (m, 2H), 2.79 - 2.69 (m, 2H), 2.67 (s, 3H), 2.11 - 1.99 (m, 2H), 1.83 - 1.74 (m, 2H), 1.55 (s, 6H); 534 [M+H] +
8585 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(3-(2-메톡시프로판-2-일)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-(2-methoxypropan-2-yl)phenyl)-5-methyl Thieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.79 (dd, J = 7.92, 1.68 Hz, 1H), 7.38 (s, 1H), 7.34 (t, J = 7.88 Hz, 1H), 7.28 (d, J = 2.16 Hz, 1H), 7.17 - 7.16 (m, 2H), 7. 01 (dd, J = 8.48, 2.28 Hz, 1H), 6.87 (s, 1H), 6.84 (d, J = 6.08 Hz, 1H), 6.59 (s, 1H), 3.74 (s, 3H), 3.50 - 3.47 (m, 2H), 3.12 (s, 3H), 2.68 (s, 3H), 2.57 - 2.52 (m, 2H), 2.35 (s, 6H), 2.32 - 2.30 (m, 1H), 1.91 - 1.88 (m, 2H), 1.83 - 1.76 (m, 2H), 1.53 (s, 6H) ; 561 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.79 (dd, J = 7.92, 1.68 Hz, 1H), 7.38 (s, 1H), 7.34 (t, J = 7.88 Hz, 1H), 7.28 (d, J = 2.16 Hz, 1H), 7.17 - 7.16 (m, 2H), 7.01 (dd, J = 8.48, 2.28 Hz, 1H), 6.87 (s, 1H), 6.84 (d, J = 6.08 Hz, 1H), 6.59 (s, 1H), 3.74 (s, 3H), 3.50 - 3.47 (m, 2H), 3.12 (s, 3H), 2.68 (s, 3H), 2.57 - 2.52 (m, 2H), 2.35 (s, 6H), 2.32 - 2.30 (m, 1H), 1.91 - 1.88 (m, 2H), 1.83 - 1.76 (m, 2H), 1.53 (s, 6H); 561 [M+H] +
8686 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3-(2-메톡시프로판-2-일)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-(2-methoxypropan-2-yl)phenyl) -5-Methylthieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.79 (dd, J = 8.0, 1.32 Hz, 1H), 7.38 (s, 1H), 7.34 (t, J = 7.88 Hz, 1H), 7.17 - 7.15 (m, 2H), 7.00 (dd, J = 8.44, 2.28 Hz, 1H), 6.86 (d, J = 8.52 Hz, 1H), 6.82 (s, 1H), 6.58 (s, 1H), 3.72 (s, 1H), 3.38 - 3.35 (m, 2H), 3.29 - 3.23 (m, 4H), 3.11 (s, 3H), 2.68 (s, 3H), 2.62 - 2.57 (m, 2H), 2.10 - 2.05 (m, 3H), 1.81 - 1.78 (m, 2H), 1.53 (s, 6H), 1.49 - 1.47 (m, 2H) ; 573 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.79 (dd, J = 8.0, 1.32 Hz, 1H), 7.38 (s, 1H), 7.34 (t, J = 7.88 Hz, 1H), 7.17 - 7.15 (m, 2H), 7.00 (dd, J = 8.44, 2.28 Hz, 1H), 6.86 (d, J = 8.52 Hz, 1H), 6.82 (s, 1H), 6.58 (s, 1H), 3.72 (s, 1H), 3.38 - 3.35 (m, 2H), 3.29 - 3.23 (m, 4H), 3.11 (s, 3H), 2.68 (s, 3H), 2.62 - 2.57 (m, 2H), 2.10 - 2.05 (m, 3H), 1.81 - 1.78 (m, 2H), 1.53 (s, 6H), 1.49 - 1.47 (m, 2H); 573 [M+H] +
8787 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno[2,3-d] Pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 2.2 Hz, 1H), 7.31 - 7.29 (m, 1H), 7.27 - 7.22 (m, 2H), 7.21 - 7.15 (m, 1H), 7.12 (dd, J = 8.48, 2.32 Hz, 1H), 6.92 (d, J = 8.48 Hz, 1H), 6.87 (s, 1H), 6.80 (td, J = 8.24, 1.84 Hz, 1H), 6.60 (s, 1H), 3.81 (s, 3H), 3.53 - 3.51 (m, 2H), 2.67 (s, 3H), 2.59 - 2.54 (m, 2H), 2.36 - 2.34 (m, 1H), 2.35 (s, 6H), 1.92 - 1.89 (m, 2H), 1.84 - 1.74 (m, 2H) ; 507 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 2.2 Hz, 1H), 7.31 - 7.29 (m, 1H), 7.27 - 7.22 (m, 2H), 7.21 - 7.15 (m, 1H), 7.12 (dd, J = 8.48, 2.32 Hz, 1H), 6.92 (d, J = 8.48 Hz, 1H), 6.87 (s, 1H), 6.80 (td, J = 8.24, 1.84 Hz, 1H), 6.60 (s , 1H), 3.81 (s, 3H), 3.53 - 3.51 (m, 2H), 2.67 (s, 3H), 2.59 - 2.54 (m, 2H), 2.36 - 2.34 (m, 1H), 2.35 (s, 6H) ), 1.92 - 1.89 (m, 2H), 1.84 - 1.74 (m, 2H); 507 [M+H] +
8888 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno[2, 3-d] pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.73 - 7.70 (m, 1H), 7.30 - 7.28 (m, 1H), 7.20 - 7.16 (m, 3H), 7.10 (dd, J = 8.48, 2.36 Hz, 1H), 6.91 (d, J = 8.52 Hz, 1H), 6.87 (s, 1H), 6.82 - 6.78 (m, 1H), 6.59 (d, J = 1.08 Hz, 1H), 3.79 (s, 3H), 3.41 - 3.38 (m, 2H), 3.23 - 3.20 (m, 4H), 2.66 (s, 3H), 2.63 - 2.58 (m, 2H), 2.12 - 2.05 (m, 3H), 1.81 - 1.78 (m, 2H), 1.56 - 1.47 (m, 2H) ; 519 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.73 - 7.70 (m, 1H), 7.30 - 7.28 (m, 1H), 7.20 - 7.16 (m, 3H), 7.10 (dd, J = 8.48, 2.36 Hz, 1H ), 6.91 (d, J = 8.52 Hz, 1H), 6.87 (s, 1H), 6.82 - 6.78 (m, 1H), 6.59 (d, J = 1.08 Hz, 1H), 3.79 (s, 3H), 3.41 - 3.38 (m, 2H), 3.23 - 3.20 (m, 4H), 2.66 (s, 3H), 2.63 - 2.58 (m, 2H), 2.12 - 2.05 (m, 3H), 1.81 - 1.78 (m, 2H) , 1.56 - 1.47 (m, 2H); 519 [M+H] +
8989 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(3-(트리플루오로메틸)페닐)티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(3-(trifluoromethyl)phenyl)thie no[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.12 Hz, 1H), 7.80 (s, 1H), 7.46 (t, J = 7.92 Hz, 1H), 7.37 (d, J = 7.68 Hz, 1H), 7.23 (s, 1H), 7.18 (d, J = 1.64 Hz, 1H), 7.07 (dd, J = 8.44, 2.32 Hz, 1H), 6.88 (d, J = 8.52 Hz, 1H), 6.83 (s, 1H), 6.62 (d, J = 0.96 Hz, 1H), 3.76 (s, 3H), 3.39 - 3.37 (m, 2H), 3.25 - 3.22 (m, 4H), 2.69 (s, 3H), 2.64 - 2.58 (m, 2H), 2.12 - 2.05 (m, 3H), 1.81 - 1.79 (m, 2H), 1.57 - 1.48 (m, 2H) ; 569 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, J = 8.12 Hz, 1H), 7.80 (s, 1H), 7.46 (t, J = 7.92 Hz, 1H), 7.37 (d, J = 7.68 Hz , 1H), 7.23 (s, 1H), 7.18 (d, J = 1.64 Hz, 1H), 7.07 (dd, J = 8.44, 2.32 Hz, 1H), 6.88 (d, J = 8.52 Hz, 1H), 6.83 (s, 1H), 6.62 (d, J = 0.96 Hz, 1H), 3.76 (s, 3H), 3.39 - 3.37 (m, 2H), 3.25 - 3.22 (m, 4H), 2.69 (s, 3H), 2.64 - 2.58 (m, 2H), 2.12 - 2.05 (m, 3H), 1.81 - 1.79 (m, 2H), 1.57 - 1.48 (m, 2H); 569 [M+H] +
9090 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(3-(트리플루오로메틸)페닐)티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(3-(trifluoromethyl)phenyl)thieno[2, 3-d] pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.16 Hz, 1H), 7.81 (s, 1H), 7.46 (t, J = 7.88 Hz, 1H), 7.37 (d, J = 7.76 Hz, 1H), 7.23 (s, 1H), 7.19 (d, J = 1.72 Hz, 1H), 7.08 (dd, J = 8.48, 2.32 Hz, 1H), 6.88 (d, J = 8.52 Hz, 1H), 6.84 (s, 1H), 6.62 (d, J = 1.04 Hz, 1H), 3.78 (s, 3H), 3.52 - 3.49 (m, 2H), 2.69 (s, 3H), 2.59 - 2.53 (2H), 2.35 (s, 6H), 2.34 - 2.33 (m, 1H), 1.91 - 1.89 (m, 2H), 1.84 - 1.73 (m, 2H) ; 557 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, J = 8.16 Hz, 1H), 7.81 (s, 1H), 7.46 (t, J = 7.88 Hz, 1H), 7.37 (d, J = 7.76 Hz , 1H), 7.23 (s, 1H), 7.19 (d, J = 1.72 Hz, 1H), 7.08 (dd, J = 8.48, 2.32 Hz, 1H), 6.88 (d, J = 8.52 Hz, 1H), 6.84 (s, 1H), 6.62 (d, J = 1.04 Hz, 1H), 3.78 (s, 3H), 3.52 - 3.49 (m, 2H), 2.69 (s, 3H), 2.59 - 2.53 (2H), 2.35 ( s, 6H), 2.34 - 2.33 (m, 1H), 1.91 - 1.89 (m, 2H), 1.84 - 1.73 (m, 2H); 557 [M+H] +
9191 2-(6-((2-((1-(3-(디메틸아미노)프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 7.88 Hz, 1H), 7.92 - 7.91 (m, 2H), 7.72 (t, J = 7.92 Hz, 1H), 7.52 (s, 1H), 7.05 (d, J = 7.52 Hz, 1H), 6.68 (s, 1H), 6.62 (d, J = 1.04 Hz, 1H), 4.17 (t, J = 6.96 Hz, 2H), 2.72 (s, 3H), 2.32 - 2.29 (m, 2H), 2.24 (s, 6H), 2.08 - 2.01 (m, 2H), 1.55 (s, 6H) ; 467 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.31 (d, J = 7.88 Hz, 1H), 7.92 - 7.91 (m, 2H), 7.72 (t, J = 7.92 Hz, 1H), 7.52 (s, 1H) , 7.05 (d, J = 7.52 Hz, 1H), 6.68 (s, 1H), 6.62 (d, J = 1.04 Hz, 1H), 4.17 (t, J = 6.96 Hz, 2H), 2.72 (s, 3H) , 2.32 - 2.29 (m, 2H), 2.24 (s, 6H), 2.08 - 2.01 (m, 2H), 1.55 (s, 6H); 467 [M+H] +
9292 2-(6-((2-((1-(2-(디메틸아미노)에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.29 (br s, 1H), 8.24 (br s, 2H), 7.93 (br s, 1H), 7.79 (t, J = 7.9 Hz, 1H), 7.48 (s, 1H), 7.34 (d, J = 7.7 Hz, 1H), 6.86 (s, 1H), 5.20 (s, 1H), 4.23 - 4.01 (m, 2H), 2.72 - 2.57 (m, 5H), 2.16 (s, 6H), 1.44 (s, 6H); 453 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.29 (br s, 1H), 8.24 (br s, 2H), 7.93 (br s, 1H), 7.79 (t, J = 7.9 Hz, 1H), 7.48 (s, 1H), 7.34 (d, J = 7.7 Hz, 1H), 6.86 (s, 1H), 5.20 (s, 1H), 4.23 - 4.01 (m, 2H), 2.72 - 2.57 (m, 5H), 2.16 (s , 6H), 1.44 (s, 6H); 453 [M+H] +
9393 2-(3-((2-((1-(2-(디메틸아미노)에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.0(br s, 1H), 8.10 (br s, 1H), 7.74 - 7.13 (m, 6H), 6.75 (s, 1H), 5.03 (s, 1H), 4.23 - 3.87 (m, 2H), 2.69 - 2.59 (m, 3H), 2.13 (s, 6H), 1.44 (s, 6H); 452 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.0 (br s, 1H), 8.10 (br s, 1H), 7.74 - 7.13 (m, 6H), 6.75 (s, 1H), 5.03 (s, 1H), 4.23 - 3.87 (m, 2H), 2.69 - 2.59 (m, 3H), 2.13 (s, 6H), 1.44 (s, 6H); 452 [M+H] +
9494 2-(6-((2-((1-(2-메톡시에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(2-methoxyethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine-4- yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.31 (br s, 1H), 8.57 - 8.10 (m, 2H), 7.93 (br s, 1H), 7.79 (t, J = 7.9 Hz, 1H), 7.50 (br s, 1H), 7.39 - 7.28 (m, 1H), 6.87 (s, 1H), 5.20 (s, 1H), 4.28 - 4.10 (m, 2H), 3.66 (t, J = 5.4 Hz, 2H), 3.23 (s, 3H), 2.64 (s, 3H), 1.44 (s, 6H); 440 [M+H]+ 1H NMR (400 MHz, DMSO) δ 9.31 (br s, 1H), 8.57 - 8.10 (m, 2H), 7.93 (br s, 1H), 7.79 (t, J = 7.9 Hz, 1H), 7.50 (br s, 1H), 7.39 - 7.28 (m, 1H), 6.87 (s, 1H), 5.20 (s, 1H), 4.28 - 4.10 (m, 2H), 3.66 (t, J = 5.4 Hz, 2H), 3.23 (s, 3H), 2.64 (s, 3H), 1.44 (s, 6H); 440 [M+H] +
9595 2-(3-((2-((1-(2-메톡시에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-(2-methoxyethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine-4- yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.03 (br s, 1H), 8.08 (br s, 1H), 7.74 - 7.29 (m, 5H), 7.25 (br s, 1H), 6.75 (s, 1H), 5.00 (s, 1H), 4.17 - 3.92 (m, 2H), 3.69 - 3.48 (m, 2H), 3.19 (s, 3H), 2.62 (s, 3H), 1.44 (s, 6H); 439 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.03 (br s, 1H), 8.08 (br s, 1H), 7.74 - 7.29 (m, 5H), 7.25 (br s, 1H), 6.75 (s, 1H), 5.00 (s, 1H), 4.17 - 3.92 (m, 2H), 3.69 - 3.48 (m, 2H), 3.19 (s, 3H), 2.62 (s, 3H), 1.44 (s, 6H); 439 [M+H] +
9696 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-플루오로피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-fluoropyridin-2-yl)-5-methylthieno[2, 3-d] pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 7.96 Hz, 1H), 7.82 (s, 1H), 7.68 (q, J = 8.04 Hz, 1H), 7.25 (s, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.94 - 6.92 (m, 2H), 6.62 (s, 1H), 6.58 (d, J = 7.8 Hz, 1H), 3.84 (s, 3H), 3.54 - 3.51 (m, 2H), 2.69 (s, 3H), 2.61 - 2.55 (m, 2H), 2.35 (s, 6H), 2.32 - 2.31 (m, 1H), 1.92 - 1.90 (m, 2H), 1.84 - 1.74 (m, 2H) ; 508 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.32 (d, J = 7.96 Hz, 1H), 7.82 (s, 1H), 7.68 (q, J = 8.04 Hz, 1H), 7.25 (s, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.94 - 6.92 (m, 2H), 6.62 (s, 1H), 6.58 (d, J = 7.8 Hz, 1H), 3.84 (s, 3H), 3.54 - 3.51 ( m, 2H), 2.69 (s, 3H), 2.61 - 2.55 (m, 2H), 2.35 (s, 6H), 2.32 - 2.31 (m, 1H), 1.92 - 1.90 (m, 2H), 1.84 - 1.74 ( m, 2H); 508 [M+H] +
9797 2-(3-((2-((1-(3-(디메틸아미노)프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.52 - 7.38 (m, 5H), 7.29 (s, 1H), 7.08 (s, 1H), 6.81 (s, 1H), 6.55 (d, J = 1.16 Hz, 1H), 3.98 (t, J = 7.04 Hz, 2H), 2.66 (s, 3H), 2.27 - 2.23 (m, 2H), 2.23 (s, 6H), 1.84 - 1.81 (m, 2H), 1.56 (s, 6H) ; 466 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.52 - 7.38 (m, 5H), 7.29 (s, 1H), 7.08 (s, 1H), 6.81 (s, 1H), 6.55 (d, J = 1.16 Hz, 1H), 3.98 (t, J = 7.04 Hz, 2H), 2.66 (s, 3H), 2.27 - 2.23 (m, 2H), 2.23 (s, 6H), 1.84 - 1.81 (m, 2H), 1.56 (s , 6H); 466 [M+H] +
9898 2-(6-((2-((4-(4-아미노피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올, 2,2,2-트리플루오로아세트산2-(6-((2-((4-(4-aminopiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)pyridin-2-yl)propan-2-ol, 2,2,2-trifluoroacetic acid 1H NMR (400MHz,DMSO) δ 9.41 (s, 1H), 8.41 (s, 1H), 8.26 (d, J = 7.9 Hz, 1H), 8.01 - 7.95 (m, 3H), 7.80 (dd, J = 7.8, 8.0 Hz, 1H), 7.47 (s, 1H), 7.39 - 7.35 (m, 2H), 7.07 (s, 1H), 6.96 (s, 1H), 3.78 (s, 3H), 3.25 - 3.22 (m, 3H), 2.93 - 2.90 (m, 2H), 2.67 (s, 3H), 2.07 - 2.01 (m, 2H), 1.80 - 1.75 (m, 2H), 1.46 (s, 6H); 520 [M+H]+ 1H NMR (400MHz,DMSO) δ 9.41 (s, 1H), 8.41 (s, 1H), 8.26 (d, J = 7.9 Hz, 1H), 8.01 - 7.95 (m, 3H), 7.80 (dd, J = 7.8, 8.0 Hz, 1H), 7.47 (s, 1H), 7.39 - 7.35 (m, 2H), 7.07 (s, 1H), 6.96 (s, 1H), 3.78 (s, 3H), 3.25 - 3.22 (m , 3H), 2.93 - 2.90 (m, 2H), 2.67 (s, 3H), 2.07 - 2.01 (m, 2H), 1.80 - 1.75 (m, 2H), 1.46 (s, 6H); 520 [M+H] +
9999 2-(3-((2-((4-(4-아미노피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올, 2,2,2-트리플루오로아세트산2-(3-((2-((4-(4-aminopiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)phenyl)propan-2-ol, 2,2,2-trifluoroacetic acid 1H NMR (400MHz,DMSO) δ 9.19 (s, 1H), 8.11 (s, 1H), 7.92 - 7.89 (m, 3H), 7.68 (d, J = 7.7 Hz, 1H), 7.53 (s, 1H), 7.40 (s, 1H), 7.30 - 7.19 (m, 3H), 6.85 (s, 2H), 5.32 (t, J = 4.6 Hz, 1H), 3.57 (s, 3H), 2.68 - 2.65 (m, 5H), 2.34-2.31 (m, 2H), 2.01 - 1.97 (m, 3H),1.77 - 1.74 (m, 2H), 1.42 (s, 6H); 519 [M+H]+ 1H NMR (400MHz,DMSO) δ 9.19 (s, 1H), 8.11 (s, 1H), 7.92 - 7.89 (m, 3H), 7.68 (d, J = 7.7 Hz, 1H), 7.53 (s, 1H) , 7.40 (s, 1H), 7.30 - 7.19 (m, 3H), 6.85 (s, 2H), 5.32 (t, J = 4.6 Hz, 1H), 3.57 (s, 3H), 2.68 - 2.65 (m, 5H) ), 2.34-2.31 (m, 2H), 2.01 - 1.97 (m, 3H), 1.77 - 1.74 (m, 2H), 1.42 (s, 6H); 519 [M+H] +
100100 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(3-메톡시페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-methoxyphenyl)-5-methylthieno[2,3-d] Pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ7.34 (s, 1H), 7.15 (s, 1H), 7.08 (dd, J = 19.6, 7.5 Hz, 2H), 6.87 (d, J = 12.2 Hz, 2H), 6.69 (d, J = 7.2 Hz, 1H), 6.59 (s, 1H), 3.75 (s, 6H), 3.50 (d, J = 9.8 Hz, 2H), 2.66 (s, 3H), 2.55 (t, J = 11.3 Hz, 2H), 2.35 (s, 6H), 1.89 (s, 2H), 1.79 (d, J = 8.4 Hz, 3H); 519 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ7.34 (s, 1H), 7.15 (s, 1H), 7.08 (dd, J = 19.6, 7.5 Hz, 2H), 6.87 (d, J = 12.2 Hz, 2H) ), 6.69 (d, J = 7.2 Hz, 1H), 6.59 (s, 1H), 3.75 (s, 6H), 3.50 (d, J = 9.8 Hz, 2H), 2.66 (s, 3H), 2.55 (t , J = 11.3 Hz, 2H), 2.35 (s, 6H), 1.89 (s, 2H), 1.79 (d, J = 8.4 Hz, 3H); 519 [M+H] +
실시예Example 화합물명compound name 1H NMR and/or Mass 1 H NMR and/or Mass
101101 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3-메톡시페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-methoxyphenyl)-5-methylthieno[2, 3-d] pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ7.34 (t, J = 2.2 Hz, 1H), 7.27 (s, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.15 (s, 1H), 7.10 (dd, J = 8.0, 1.3 Hz, 1H), 7.04 (dd, J = 8.5, 2.4 Hz, 1H), 6.85 (d, J = 8.6 Hz, 2H), 6.69 (dd, J = 8.0, 2.2 Hz, 1H), 6.59 (d, J = 1.1 Hz, 1H), 3.74 (d, J = 6.0 Hz, 6H), 3.52 - 3.40 (m, 4H), 2.66 (s, 3H), 2.60 (t, J = 10.4 Hz, 2H), 2.19 (d, J = 15.9 Hz, 4H), 2.04 (s, 1H), 1.86 (d, J = 10.7 Hz, 4H); 531 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ7.34 (t, J = 2.2 Hz, 1H), 7.27 (s, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.15 (s, 1H), 7.10 (dd, J = 8.0, 1.3 Hz, 1H), 7.04 (dd, J = 8.5, 2.4 Hz, 1H), 6.85 (d, J = 8.6 Hz, 2H), 6.69 (dd, J = 8.0, 2.2 Hz) , 1H), 6.59 (d, J = 1.1 Hz, 1H), 3.74 (d, J = 6.0 Hz, 6H), 3.52 - 3.40 (m, 4H), 2.66 (s, 3H), 2.60 (t, J = 10.4 Hz, 2H), 2.19 (d, J = 15.9 Hz, 4H), 2.04 (s, 1H), 1.86 (d, J = 10.7 Hz, 4H); 531 [M+H] +
102102 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페놀3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)phenol 1H NMR (400 MHz, CDCl3) δ7.61 (t, J = 2.1 Hz, 1H), 7.21 (d, J = 2.2 Hz, 1H), 7.19 - 7.12 (m, 2H), 7.04 (dd, J = 8.5, 2.3 Hz, 1H), 6.92 - 6.87 (m, 2H), 6.73 (d, J = 9.3 Hz, 1H), 6.59 - 6.54 (m, 2H), 3.78 (s, 3H), 3.53 (d, J = 11.9 Hz, 2H), 2.65 (s, 3H), 2.60 (d, J = 11.9 Hz, 2H), 2.39 (s, 6H), 1.90 (d, J = 10.3 Hz, 2H), 1.85 - 1.74 (m, 3H); 505 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ7.61 (t, J = 2.1 Hz, 1H), 7.21 (d, J = 2.2 Hz, 1H), 7.19 - 7.12 (m, 2H), 7.04 (dd, J = 8.5, 2.3 Hz, 1H), 6.92 - 6.87 (m, 2H), 6.73 (d, J = 9.3 Hz, 1H), 6.59 - 6.54 (m, 2H), 3.78 (s, 3H), 3.53 (d, J = 11.9 Hz, 2H), 2.65 (s, 3H), 2.60 (d, J = 11.9 Hz, 2H), 2.39 (s, 6H), 1.90 (d, J = 10.3 Hz, 2H), 1.85 - 1.74 ( m, 3H); 505 [M+H] +
103103 3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페놀3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenol 1H NMR (400 MHz, CDCl3) δ 7.66 (t, J = 2.1 Hz, 1H), 7.15 (d, J = 8.0 Hz, 2H), 7.12 - 7.10 (m, 1H), 7.04 (dd, J = 8.5, 2.3 Hz, 1H), 6.93 (d, J = 8.5 Hz, 1H), 6.88 (s, 1H), 6.66 (d, J = 7.7 Hz, 1H), 6.59 - 6.55 (m, 2H), 3.78 (s, 3H), 3.50 (d, J = 12.1 Hz, 2H), 3.40 (s, 3H), 2.72 (t, J = 10.9 Hz, 2H), 2.64 (s, 3H), 2.33 (s, 2H), 2.20 - 2.15 (m, 2H), 1.73 (d, J = 9.9 Hz, 2H), 1.62 (d, J = 9.1 Hz, 3H); 517 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.66 (t, J = 2.1 Hz, 1H), 7.15 (d, J = 8.0 Hz, 2H), 7.12 - 7.10 (m, 1H), 7.04 (dd, J = 8.5, 2.3 Hz, 1H), 6.93 (d, J = 8.5 Hz, 1H), 6.88 (s, 1H), 6.66 (d, J = 7.7 Hz, 1H), 6.59 - 6.55 (m, 2H), 3.78 ( s, 3H), 3.50 (d, J = 12.1 Hz, 2H), 3.40 (s, 3H), 2.72 (t, J = 10.9 Hz, 2H), 2.64 (s, 3H), 2.33 (s, 2H), 2.20 - 2.15 (m, 2H), 1.73 (d, J = 9.9 Hz, 2H), 1.62 (d, J = 9.1 Hz, 3H); 517 [M+H] +
104104 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(2-(이소프로필설포닐)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(2-(isopropylsulfonyl)phenyl)-5-methylthieno[2, 3-d] pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ9.17 (s, 1H), 8.23 (d, J = 7.8 Hz, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.64 - 7.56 (m, 1H), 7.29 - 7.27 (m, 1H), 7.02 (dd, J = 8.5, 2.4 Hz, 1H), 6.87 - 6.79 (m, 2H), 6.63 (s, 1H), 3.71 (s, 3H), 3.53 - 3.48 (m, 2H), 3.28 - 3.15 (m, 1H), 2.67 (s, 3H), 2.62 - 2.55 (m, 2H), 2.47 (s, 6H), 2.02 - 1.95 (m, 2H), 1.87 - 1.80 (m, 2H), 1.28 (d, J = 7.1 Hz, 6H), 1.27 - 1.25 (m, 1H); 595 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ9.17 (s, 1H), 8.23 (d, J = 7.8 Hz, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.64 - 7.56 (m, 1H) ), 7.29 - 7.27 (m, 1H), 7.02 (dd, J = 8.5, 2.4 Hz, 1H), 6.87 - 6.79 (m, 2H), 6.63 (s, 1H), 3.71 (s, 3H), 3.53 - 3.48 (m, 2H), 3.28 - 3.15 (m, 1H), 2.67 (s, 3H), 2.62 - 2.55 (m, 2H), 2.47 (s, 6H), 2.02 - 1.95 (m, 2H), 1.87 - 1.80 (m, 2H), 1.28 (d, J = 7.1 Hz, 6H), 1.27 - 1.25 (m, 1H); 595 [M+H] +
105105 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(2-(이소프로필설포닐)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(2-(isopropylsulfonyl)phenyl)-5-methylthier no[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ9.18 (s, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.61 (dd, J = 8.0 Hz, 8.0 Hz, 1H), 7.30 - 7.26 (m, 2H), 7.00 (dd, J = 8.5, 2.3 Hz, 1H), 6.86 - 6.77 (m, 2H), 6.63 (s, 1H), 3.68 (s, 3H), 3.47 - 3.45 (m, 2H), 3.29 - 3.15 (m, 1H), 2.67 (s, 3H), 2.64 - 2.58 (m, 2H), 1.97 - 1.90 (m, 2H), 1.55 - 1.51 (m, 4H), 1.28 (d, J = 7.1 Hz, 6H), 1.25 - 1.20 (m, 4H) ; 607 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ9.18 (s, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.61 (dd, J = 8.0 Hz, 8.0 Hz, 1H), 7.30 - 7.26 (m, 2H), 7.00 (dd, J = 8.5, 2.3 Hz, 1H), 6.86 - 6.77 (m, 2H), 6.63 (s, 1H), 3.68 (s , 3H), 3.47 - 3.45 (m, 2H), 3.29 - 3.15 (m, 1H), 2.67 (s, 3H), 2.64 - 2.58 (m, 2H), 1.97 - 1.90 (m, 2H), 1.55 - 1.51 (m, 4H), 1.28 (d, J = 7.1 Hz, 6H), 1.25 - 1.20 (m, 4H); 607 [M+H] +
106106 N4-(2-(이소프로필설포닐)페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민N4-(2-(isopropylsulfonyl)phenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[2, 3-d] pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ9.11 (s, 1H), 8.18 (d, J = 8.3 Hz, 1H), 7.93 (dd, J = 8.0, 1.5 Hz, 1H), 7.84 (s, 1H), 7.68 - 7.60 (m, 1H), 7.43 (s, 1H), 7.30 - 7.26 (m, 1H), 6.61 (s, 2H), 4.05 (s, 1H), 3.24 - 3.17 (m, 1H), 2.99 (s, 2H), 2.66 (s, 3H), 2.37 (s, 3H), 2.10 - 2.00 (m, 6H), 1.26 (d, J = 6.3 Hz, 6H), 1.25 - 1.20 (m, 1H); 526 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ9.11 (s, 1H), 8.18 (d, J = 8.3 Hz, 1H), 7.93 (dd, J = 8.0, 1.5 Hz, 1H), 7.84 (s, 1H) ), 7.68 - 7.60 (m, 1H), 7.43 (s, 1H), 7.30 - 7.26 (m, 1H), 6.61 (s, 2H), 4.05 (s, 1H), 3.24 - 3.17 (m, 1H), 2.99 (s, 2H), 2.66 (s, 3H), 2.37 (s, 3H), 2.10 - 2.00 (m, 6H), 1.26 (d, J = 6.3 Hz, 6H), 1.25 - 1.20 (m, 1H) ; 526 [M+H] +
107107 2-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-N,N-디메틸벤젠설폰아미드2-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl)amino)-N,N-dimethylbenzenesulfonamide 1H NMR (400 MHz, CDCl3) δ9.09 (s, 1H), 8.18 (d, J = 7.7 Hz, 1H), 7.85 (dd, J = 8.0, 1.5 Hz, 1H), 7.60 - 7.54 (m, 1H), 7.36 (d, J = 2.3 Hz, 1H), 7.29 - 7.23 (m, 1H), 7.02 (dd, J = 8.5, 2.4 Hz, 1H), 6.88 - 6.78 (m, 2H), 6.63 (d, J = 1.2 Hz, 1H), 3.72 (s, 3H), 3.55 (d, J = 12.1 Hz, 2H), 3.16 - 3.07 (m, 1H), 2.77 - 2.57 (m, 17H), 2.25 (d, J = 10.4 Hz, 2H), 2.03 - 1.93 (m, 2H); 596 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ9.09 (s, 1H), 8.18 (d, J = 7.7 Hz, 1H), 7.85 (dd, J = 8.0, 1.5 Hz, 1H), 7.60 - 7.54 (m , 1H), 7.36 (d, J = 2.3 Hz, 1H), 7.29 - 7.23 (m, 1H), 7.02 (dd, J = 8.5, 2.4 Hz, 1H), 6.88 - 6.78 (m, 2H), 6.63 ( d, J = 1.2 Hz, 1H), 3.72 (s, 3H), 3.55 (d, J = 12.1 Hz, 2H), 3.16 - 3.07 (m, 1H), 2.77 - 2.57 (m, 17H), 2.25 (d , J = 10.4 Hz, 2H), 2.03 - 1.93 (m, 2H); 596 [M+H] +
108108 2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-N,N-디메틸벤젠설폰아미드2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide 1H NMR (400 MHz, CDCl3) δ9.08 (s, 1H), 8.18 (d, J = 7.9 Hz, 1H), 7.85 (dd, J = 8.0, 1.4 Hz, 1H), 7.60 - 7.53 (m, 1H), 7.30 (d, J = 2.2 Hz, 1H), 7.29 - 7.22 (m, 1H), 7.00 (dd, J = 8.5, 2.3 Hz, 1H), 6.90 - 6.76 (m, 2H), 6.62 (d, J = 0.8 Hz, 1H), 3.93 - 3.73 (m, 4H), 3.67 (s, 3H), 3.46 (d, J = 11.9 Hz, 2H), 2.83 - 2.47 (m, 13H), 2.47 - 2.33 (m, 2H), 1.99 - 1.93 (m, 2H), 1.90 - 1.81 (m, 2H); 608 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ9.08 (s, 1H), 8.18 (d, J = 7.9 Hz, 1H), 7.85 (dd, J = 8.0, 1.4 Hz, 1H), 7.60 - 7.53 (m , 1H), 7.30 (d, J = 2.2 Hz, 1H), 7.29 - 7.22 (m, 1H), 7.00 (dd, J = 8.5, 2.3 Hz, 1H), 6.90 - 6.76 (m, 2H), 6.62 ( d, J = 0.8 Hz, 1H), 3.93 - 3.73 (m, 4H), 3.67 (s, 3H), 3.46 (d, J = 11.9 Hz, 2H), 2.83 - 2.47 (m, 13H), 2.47 - 2.33 (m, 2H), 1.99 - 1.93 (m, 2H), 1.90 - 1.81 (m, 2H); 608 [M+H] +
109109 N,N-디메틸-2-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤젠설폰아미드N,N-dimethyl-2-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3 -d] pyrimidin-4-yl) amino) benzenesulfonamide 1H NMR (400 MHz, CDCl3) δ9.01 (s, 1H), 8.13 (d, J = 8.2 Hz, 1H), 7.86 (dd, J = 8.0, 1.5 Hz, 2H), 7.63 - 7.57 (m, 1H), 7.42 (m, 1H), 7.29 - 7.23 (m, 1H), 6.60 (s, 2H), 4.11 - 4.01 (m, 1H), 3.05 - 2.93 (m, 2H), 2.72 - 2.59 (m, 9H), 2.42 - 2.30 (m, 3H), 2.21 - 1.96 (m, 6H); 527 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ9.01 (s, 1H), 8.13 (d, J = 8.2 Hz, 1H), 7.86 (dd, J = 8.0, 1.5 Hz, 2H), 7.63 - 7.57 (m , 1H), 7.42 (m, 1H), 7.29 - 7.23 (m, 1H), 6.60 (s, 2H), 4.11 - 4.01 (m, 1H), 3.05 - 2.93 (m, 2H), 2.72 - 2.59 (m , 9H), 2.42 - 2.30 (m, 3H), 2.21 - 1.96 (m, 6H); 527 [M+H] +
110110 N4-(3-메톡시페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민N4-(3-methoxyphenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[2,3-d] Pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ7.87 (s, 1H), 7.42 (s, 1H), 7.34 - 7.26 (m, 2H), 7.14 - 7.06 (m, 2H), 6.71 (dd, J = 8.1, 2.2 Hz, 1H), 6.64 (s, 1H), 6.67 - 6.59 (m, 1H), 4.07 - 3.98 (m, 1H), 3.80 (s, 3H), 2.96 (d, J = 11.1 Hz, 2H), 2.65 (s, 3H), 2.33 (s, 3H), 2.19 - 1.96 (m, 6H); 450 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.87 (s, 1H), 7.42 (s, 1H), 7.34 - 7.26 (m, 2H), 7.14 - 7.06 (m, 2H), 6.71 (dd, J = 8.1, 2.2 Hz, 1H), 6.64 (s, 1H), 6.67 - 6.59 (m, 1H), 4.07 - 3.98 (m, 1H), 3.80 (s, 3H), 2.96 (d, J = 11.1 Hz, 2H) ), 2.65 (s, 3H), 2.33 (s, 3H), 2.19 - 1.96 (m, 6H); 450 [M+H] +
111111 메틸 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트Methyl 3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl) amino) benzoate 1H NMR (400 MHz, CDCl3) δ8.13 - 8.07 (m, 1H), 8.06 - 8.02 (m, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.42 (t, J = 7.9 Hz, 1H), 7.25 - 7.19 (m, 2H), 7.07 (dd, J = 8.5, 2.3 Hz, 1H), 6.89 - 6.82 (m, 2H), 6.61 (d, J = 1.0 Hz, 1H), 3.93 (s, 3H), 3.77 (s, 3H), 3.55 - 3.46 (m, 2H), 2.69 (s, 3H), 2.57 (t, J = 10.9 Hz, 2H), 2.50 - 2.32 (m, 7H), 1.98 - 1.91 (m, 2H), 1.85 - 1.77 (m, 3H); 547 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ8.13 - 8.07 (m, 1H), 8.06 - 8.02 (m, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.42 (t, J = 7.9 Hz , 1H), 7.25 - 7.19 (m, 2H), 7.07 (dd, J = 8.5, 2.3 Hz, 1H), 6.89 - 6.82 (m, 2H), 6.61 (d, J = 1.0 Hz, 1H), 3.93 ( s, 3H), 3.77 (s, 3H), 3.55 - 3.46 (m, 2H), 2.69 (s, 3H), 2.57 (t, J = 10.9 Hz, 2H), 2.50 - 2.32 (m, 7H), 1.98 - 1.91 (m, 2H), 1.85 - 1.77 (m, 3H); 547 [M+H] +
112112 메틸 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트Methyl 3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidine -4-yl) amino) benzoate 1H NMR (400 MHz, CDCl3) δ8.08 (s, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.92 - 7.78 (m, 2H), 7.49 - 7.42 (m, 2H), 7.19 (s, 1H), 6.70 (s, 1H), 6.60 (d, J = 1.0 Hz, 1H), 4.11 - 3.99 (m, 1H), 3.94 (s, 3H), 3.08 - 2.93 (m, 2H), 2.68 (s, 3H), 2.37 (s, 3H), 2.21 - 1.99 (m, 6H); 478 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ8.08 (s, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.92 - 7.78 (m, 2H), 7.49 - 7.42 (m, 2H), 7.19 (s, 1H), 6.70 (s, 1H), 6.60 (d, J = 1.0 Hz, 1H), 4.11 - 3.99 (m, 1H), 3.94 (s, 3H), 3.08 - 2.93 (m, 2H), 2.68 (s, 3H), 2.37 (s, 3H), 2.21 - 1.99 (m, 6H); 478 [M+H] +
113113 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페놀3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidine- 4-yl)amino)phenol 1H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.38 (s, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.18 (s, 1H), 7.04 (s, 1H), 6.74 (s, 1H), 6.70 (d, J = 7.6 Hz, 1H), 6.66 (dd, J = 8.0, 1.7 Hz, 1H), 6.54 (d, J = 1.2 Hz, 1H), 4.18 (dd, J = 11.4, 5.6 Hz, 1H), 3.03 (d, J = 11.7 Hz, 2H), 2.64 (d, J = 0.7 Hz, 3H), 2.48 (s, 3H), 2.18 (d, J = 9.5 Hz, 2H), 2.09 - 2.05 (m, 1H), 2.00 (dd, J = 11.5, 3.9 Hz, 4H) ; 436 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.89 (s, 1H), 7.38 (s, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.18 (s, 1H), 7.04 (s, 1H) , 6.74 (s, 1H), 6.70 (d, J = 7.6 Hz, 1H), 6.66 (dd, J = 8.0, 1.7 Hz, 1H), 6.54 (d, J = 1.2 Hz, 1H), 4.18 (dd, J = 11.4, 5.6 Hz, 1H), 3.03 (d, J = 11.7 Hz, 2H), 2.64 (d, J = 0.7 Hz, 3H), 2.48 (s, 3H), 2.18 (d, J = 9.5 Hz, 2H), 2.09 - 2.05 (m, 1H), 2.00 (dd, J = 11.5, 3.9 Hz, 4H); 436 [M+H] +
114114 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.75 - 7.73 (m, 1H), 7.23 (s, 1H), 7.19 (d, J = 2.08 Hz, 1H), 7.16 (d, J = 1.56 Hz, 1H), 7.08 (dd, J = 8.44, 2.32 Hz, 1H), 6.92 - 6.87 (m, 2H), 6.85 (s, 1H), 6.60 (d, J = 1.12 Hz, 1H), 3.78 (s, 3H), 3.52 - 3.49 (m, 2H), 2.67 (s, 3H), 2.59 - 2.53 (m, 2H), 2.33 (s, 6H), 2.32 - 2.31 (m, 1H), 1.90 - 1.87 (m, 2H), 1.82 - 1.72 (m, 2H), 1.55 (s, 6H) ; 565 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.75 - 7.73 (m, 1H), 7.23 (s, 1H), 7.19 (d, J = 2.08 Hz, 1H), 7.16 (d, J = 1.56 Hz, 1H) , 7.08 (dd, J = 8.44, 2.32 Hz, 1H), 6.92 - 6.87 (m, 2H), 6.85 (s, 1H), 6.60 (d, J = 1.12 Hz, 1H), 3.78 (s, 3H), 3.52 - 3.49 (m, 2H), 2.67 (s, 3H), 2.59 - 2.53 (m, 2H), 2.33 (s, 6H), 2.32 - 2.31 (m, 1H), 1.90 - 1.87 (m, 2H), 1.82 - 1.72 (m, 2H), 1.55 (s, 6H) ; 565 [M+H] +
115115 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.73 - 7.70 (m, 1H), 7.22 (s, 1H), 7.19 (d, J = 2.12 Hz, 1H), 7.17 (d, J = 1.52 Hz, 1H), 7.06 (dd, J = 8.44, 2.32 Hz, 1H), 6.90 - 6.87 (m, 1H), 6.84 (s, 1H), 6.59 (d, J = 1.08 Hz, 1H), 3.75 (s, 3H), 3.40 - 3.38 (m, 2H), 3.35 - 3.20 (m, 4H), 2.67 (s, 3H), 2.63 - 2.58 (m, 2H), 2.17 - 2.04 (m, 3H), 1.81 - 1.79 (m, 2H), 1.57 (s, 6H), 1.55 - 1.49 (m, 2H) ; 577 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.73 - 7.70 (m, 1H), 7.22 (s, 1H), 7.19 (d, J = 2.12 Hz, 1H), 7.17 (d, J = 1.52 Hz, 1H) , 7.06 (dd, J = 8.44, 2.32 Hz, 1H), 6.90 - 6.87 (m, 1H), 6.84 (s, 1H), 6.59 (d, J = 1.08 Hz, 1H), 3.75 (s, 3H), 3.40 - 3.38 (m, 2H), 3.35 - 3.20 (m, 4H), 2.67 (s, 3H), 2.63 - 2.58 (m, 2H), 2.17 - 2.04 (m, 3H), 1.81 - 1.79 (m, 2H) ), 1.57 (s, 6H), 1.55 - 1.49 (m, 2H); 577 [M+H] +
116116 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-(트리플루오로메틸)페닐)프로판-2-올2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] Pyrimidin-4-yl)amino)-5-(trifluoromethyl)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H), 7.80 (s, 1H), 7.47 (s, 1H), 7.22 (s, 1H), 7.17 (d, J = 1.8 Hz, 1H), 7.01 (dd, J = 8.48, 2.24 Hz, 1H), 6.88 (s, 1H), 6.83 (d, J = 8.52 Hz, 1H), 6.61 (d, J = 1.0 Hz, 1H), 3.67 (s,3H), 3.51 - 3.48 (m, 2H), 2.68 (s, 3H), 2.61 - 2.54 (m, 3H), 2.48 (s, 6H), 1.97 - 1.94 (m, 2H), 1.87 - 1.77 (m, 2H), 1.55 (s, 6H) ; 615 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.86 (s, 1H), 7.80 (s, 1H), 7.47 (s, 1H), 7.22 (s, 1H), 7.17 (d, J = 1.8 Hz, 1H) , 7.01 (dd, J = 8.48, 2.24 Hz, 1H), 6.88 (s, 1H), 6.83 (d, J = 8.52 Hz, 1H), 6.61 (d, J = 1.0 Hz, 1H), 3.67 (s, 3H), 3.51 - 3.48 (m, 2H), 2.68 (s, 3H), 2.61 - 2.54 (m, 3H), 2.48 (s, 6H), 1.97 - 1.94 (m, 2H), 1.87 - 1.77 (m, 2H), 1.55 (s, 6H); 615 [M+H] +
117117 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-(트리플루오로메틸)페닐)프로판-2-올2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)-5-(trifluoromethyl)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 5.6 Hz, 1H), 7.48 (s, 1H), 7.20 (s, 1H), 7.16 (d, J = 1.96 Hz, 1H), 6.97 (dd, J = 8.44, 2.28 Hz, 1H), 6.85 - 6.83 (m, 2H), 6.60 (d, J = 1.04 Hz, 1H), 3.63 (s, 3H), 3.37 - 3.34 (m, 2H), 3.25 - 3.22 (m, 4H), 2.68 (s, 3H), 2.62 - 2.56 (m, 2H), 2.11 - 2.04 (m, 3H), 1.79 - 1.77 (m, 2H), 1.52 (s, 6H), 1.49 - 1.46 (m, 2H) ; 627 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.82 (d, J = 5.6 Hz, 1H), 7.48 (s, 1H), 7.20 (s, 1H), 7.16 (d, J = 1.96 Hz, 1H), 6.97 (dd, J = 8.44, 2.28 Hz, 1H), 6.85 - 6.83 (m, 2H), 6.60 (d, J = 1.04 Hz, 1H), 3.63 (s, 3H), 3.37 - 3.34 (m, 2H), 3.25 - 3.22 (m, 4H), 2.68 (s, 3H), 2.62 - 2.56 (m, 2H), 2.11 - 2.04 (m, 3H), 1.79 - 1.77 (m, 2H), 1.52 (s, 6H), 1.49 - 1.46 (m, 2H) ; 627 [M+H] +
118118 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-3,5-디메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-3,5-dimethyl-1H-pyrazol-4-yl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 7.95 (br s, 1H), 7.83 (s, 1H), 7.73 (br s, 1H), 7.47 (br s, 1H), 7.26 - 6.96 (m, 2H), 6.70 (s, 1H), 4.94 (s, 1H), 4.14 - 3.93 (m, 1H), 3.17 - 2.92 (m, 2H), 2.62 (s, 3H), 2.42 - 2.25 (m, 2H), 2.05 (s, 3H), 2.04 - 1.96 (m, 2H), 1.93 (s, 3H), 1.82 - 1.66 (m, 3H), 1.42 (s, 6H), 0.59 - 0.41 (m, 2H), 0.41 - 0.23 (m, 2H); 532 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 7.95 (br s, 1H), 7.83 (s, 1H), 7.73 (br s, 1H), 7.47 (br s, 1H), 7.26 - 6.96 (m, 2H), 6.70 (s, 1H), 4.94 (s, 1H), 4.14 - 3.93 (m, 1H), 3.17 - 2.92 (m, 2H), 2.62 (s, 3H), 2.42 - 2.25 (m, 2H), 2.05 ( s, 3H), 2.04 - 1.96 (m, 2H), 1.93 (s, 3H), 1.82 - 1.66 (m, 3H), 1.42 (s, 6H), 0.59 - 0.41 (m, 2H), 0.41 - 0.23 ( m, 2H); 532 [M+H] +
119119 2-(6-((2-((1-(1-시클로프로필피페리딘-4-일)-3,5-디메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(1-cyclopropylpiperidin-4-yl)-3,5-dimethyl-1H-pyrazol-4-yl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 8.24 (s, 1H), 8.07 (s, 1H), 7.96 - 7.31 (m, 2H), 7.26 (d, 1H), 6.79 (s, 1H), 5.15 (s, 1H), 4.16 - 3.96 (m, 1H), 3.14 - 2.97 (m, 2H), 2.62 (s, 3H), 2.44 - 2.30 (m, 2H), 2.08 (s, 3H), 2.06 - 1.98 (m, 2H), 1.95 (s, 3H), 1.82 - 1.73 (m, 2H), 1.68 (s, 1H), 1.41 (s, 6H), 0.51 - 0.40 (m, 2H), 0.40 - 0.29 (m, 2H); 533 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 8.24 (s, 1H), 8.07 (s, 1H), 7.96 - 7.31 (m, 2H), 7.26 (d, 1H), 6.79 (s, 1H), 5.15 (s , 1H), 4.16 - 3.96 (m, 1H), 3.14 - 2.97 (m, 2H), 2.62 (s, 3H), 2.44 - 2.30 (m, 2H), 2.08 (s, 3H), 2.06 - 1.98 (m , 2H), 1.95 (s, 3H), 1.82 - 1.73 (m, 2H), 1.68 (s, 1H), 1.41 (s, 6H), 0.51 - 0.40 (m, 2H), 0.40 - 0.29 (m, 2H) ); 533 [M+H] +
120120 (2-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드(2-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl) amino) phenyl) dimethylphosphine oxide 1H NMR (400 MHz, CDCl3) δ 10.00 (s, 1H), 8.14 (dd, J = 8.2, 4.2 Hz, 1H), 7.50 (t, J = 7.8 Hz, 1H), 7.35 - 7.31 (m, 1H), 7.29 (d, J = 2.3 Hz, 1H), 7.15 (td, J = 7.4, 2.0 Hz, 1H), 7.03 (dd, J = 8.5, 2.4 Hz, 1H), 6.85 - 6.80 (m, 2H), 6.56 (d, J = 1.2 Hz, 1H), 3.70 (s, 3H), 3.47 (d, J = 11.5 Hz, 2H), 2.72 (d, J = 0.9 Hz, 3H), 2.54 (t, J = 10.8 Hz, 2H), 2.34 (s, 6H), 1.89 (d, J = 11.3 Hz, 2H), 1.82 (s, 3H), 1.79 (s, 3H), 1.77 - 1.72 (m, 3H) ; 565 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 10.00 (s, 1H), 8.14 (dd, J = 8.2, 4.2 Hz, 1H), 7.50 (t, J = 7.8 Hz, 1H), 7.35 - 7.31 (m, 1H), 7.29 (d, J = 2.3 Hz, 1H), 7.15 (td, J = 7.4, 2.0 Hz, 1H), 7.03 (dd, J = 8.5, 2.4 Hz, 1H), 6.85 - 6.80 (m, 2H) ), 6.56 (d, J = 1.2 Hz, 1H), 3.70 (s, 3H), 3.47 (d, J = 11.5 Hz, 2H), 2.72 (d, J = 0.9 Hz, 3H), 2.54 (t, J = 10.8 Hz, 2H), 2.34 (s, 6H), 1.89 (d, J = 11.3 Hz, 2H), 1.82 (s, 3H), 1.79 (s, 3H), 1.77 - 1.72 (m, 3H); 565 [M+H] +
121121 (2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드(2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)phenyl)dimethylphosphineoxide 1H NMR (400 MHz, CDCl3) δ9.99 (s, 1H), 8.13 (dd, J = 8.2, 4.3 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.35 - 7.27 (m, 2H), 7.15 (td, J = 7.5, 1.6 Hz, 1H), 7.02 (dd, J = 8.5, 2.4 Hz, 1H), 6.83 (d, J = 8.5 Hz, 1H), 6.79 (s, 1H), 6.56 (d, J = 1.1 Hz, 1H), 3.68 (s, 3H), 3.35 (d, J = 11.7 Hz, 2H), 3.26 (s, 3H), 2.72 (d, J = 0.8 Hz, 3H), 2.59 (t, J = 10.2 Hz, 2H), 2.11 (d, J = 7.0 Hz, 3H), 1.80 (d, J = 13.1 Hz, 8H), 1.58 - 1.50 (m, 3H) ; 577 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ9.99 (s, 1H), 8.13 (dd, J = 8.2, 4.3 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.35 - 7.27 (m , 2H), 7.15 (td, J = 7.5, 1.6 Hz, 1H), 7.02 (dd, J = 8.5, 2.4 Hz, 1H), 6.83 (d, J = 8.5 Hz, 1H), 6.79 (s, 1H) , 6.56 (d, J = 1.1 Hz, 1H), 3.68 (s, 3H), 3.35 (d, J = 11.7 Hz, 2H), 3.26 (s, 3H), 2.72 (d, J = 0.8 Hz, 3H) , 2.59 (t, J = 10.2 Hz, 2H), 2.11 (d, J = 7.0 Hz, 3H), 1.80 (d, J = 13.1 Hz, 8H), 1.58 - 1.50 (m, 3H); 577 [M+H] +
122122 디메틸(2-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)포스핀옥사이드Dimethyl(2-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyridine Midin-4-yl) amino) phenyl) phosphine oxide 1H NMR (400 MHz, CDCl3) δ9.95 (s, 1H), 8.10 (dd, J = 8.2, 4.2 Hz, 1H), 7.86 (s, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.41 (s, 1H), 7.34 (ddd, J = 13.5, 7.7, 1.3 Hz, 1H), 7.17 (td, J = 7.5, 1.5 Hz, 1H), 6.63 (s, 1H), 6.55 (d, J = 1.2 Hz, 1H), 4.06 (s, 1H), 3.03 (d, J = 10.1 Hz, 2H), 2.72 (d, J = 0.9 Hz, 3H), 2.39 (s, 3H), 2.12 (dd, J = 34.6, 9.6 Hz, 4H), 1.80 (d, J = 13.1 Hz, 8H) ; 496 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ9.95 (s, 1H), 8.10 (dd, J = 8.2, 4.2 Hz, 1H), 7.86 (s, 1H), 7.53 (t, J = 7.8 Hz, 1H) ), 7.41 (s, 1H), 7.34 (ddd, J = 13.5, 7.7, 1.3 Hz, 1H), 7.17 (td, J = 7.5, 1.5 Hz, 1H), 6.63 (s, 1H), 6.55 (d, J = 1.2 Hz, 1H), 4.06 (s, 1H), 3.03 (d, J = 10.1 Hz, 2H), 2.72 (d, J = 0.9 Hz, 3H), 2.39 (s, 3H), 2.12 (dd, J = 34.6, 9.6 Hz, 4H), 1.80 (d, J = 13.1 Hz, 8H); 496 [M+H] +
123123 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(6-(트리플루오로메틸)피리딘-2-일)티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(6-(trifluoromethyl)pyridin-2-yl)thie no[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.16 Hz, 1H), 7.81 (s, 1H), 7.46 (t, J = 7.88 Hz, 1H), 7.37 (d, J = 7.76 Hz, 1H), 7.23 (s, 1H), 7.19 (d, J = 1.72 Hz, 1H), 7.08 (dd, J = 8.48, 2.32 Hz, 1H), 6.88 (d, J = 8.52 Hz, 1H), 6.84 (s, 1H), 6.62 (dd, J = 1.04 Hz, 1H), 3.78 (s, 3H), 3.52 - 3.49 (m, 2H), 2.69 (s, 3H), 2.59 - 2.53 (m, 2H), 2.35 (s, 6H), 2.35 - 2.34 (m, 1H), 1.91 - 1.89 (m, 2H), 1.84 - 1.74 (m, 2H) ; 558 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, J = 8.16 Hz, 1H), 7.81 (s, 1H), 7.46 (t, J = 7.88 Hz, 1H), 7.37 (d, J = 7.76 Hz , 1H), 7.23 (s, 1H), 7.19 (d, J = 1.72 Hz, 1H), 7.08 (dd, J = 8.48, 2.32 Hz, 1H), 6.88 (d, J = 8.52 Hz, 1H), 6.84 (s, 1H), 6.62 (dd, J = 1.04 Hz, 1H), 3.78 (s, 3H), 3.52 - 3.49 (m, 2H), 2.69 (s, 3H), 2.59 - 2.53 (m, 2H), 2.35 (s, 6H), 2.35 - 2.34 (m, 1H), 1.91 - 1.89 (m, 2H), 1.84 - 1.74 (m, 2H); 558 [M+H] +
124124 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(6-플루오로피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-fluoropyridin-2-yl)-5-methylthier no[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 8.32 (dd, J = 8.04, 2.0 Hz, 1H), 7.82 (s, 1H), 7.69 (q, J = 8.12 Hz, 1H), 7.22 (dd, J = 2.2 Hz, 1H), 7.05 (dd, J = 8.48, 2.32 Hz, 1H), 6.94 (s, 1H), 6.91 (d, J = 5.52 Hz, 1H), 6.62 (d, J = 1.08 Hz, 1H), 6.59 (dd, J = 7.88, 2.28 Hz), 3.82 (s, 3H), 3.42 - 3.39 (m, 2H), 3.27 - 3.23 (m, 4H), 2.70 (s, 3H), 2.67 - 2.61 (m, 2H), 2.17 - 2.04 (m, 3H), 1.83 - 1.80 (m, 2H), 1.59 - 1.50 (m, 2H) ; 520 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.32 (dd, J = 8.04, 2.0 Hz, 1H), 7.82 (s, 1H), 7.69 (q, J = 8.12 Hz, 1H), 7.22 (dd, J = 2.2 Hz, 1H), 7.05 (dd, J = 8.48, 2.32 Hz, 1H), 6.94 (s, 1H), 6.91 (d, J = 5.52 Hz, 1H), 6.62 (d, J = 1.08 Hz, 1H) , 6.59 (dd, J = 7.88, 2.28 Hz), 3.82 (s, 3H), 3.42 - 3.39 (m, 2H), 3.27 - 3.23 (m, 4H), 2.70 (s, 3H), 2.67 - 2.61 (m , 2H), 2.17 - 2.04 (m, 3H), 1.83 - 1.80 (m, 2H), 1.59 - 1.50 (m, 2H); 520 [M+H] +
125125 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(6-(트리플루오로메틸)피리딘-2-일)티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(6-(trifluoromethyl)pyridine-2 -yl)thieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.52 Hz, 1H), 8.04 (s, 1H), 7.75 (t, J = 7.92 Hz, 1H), 7.34 (d, J = 7.36 Hz, 1H), 7.20 (d, J = 2.2 Hz, 1H), 7.05 (dd, J = 8.44, 2.32 Hz), 6.92 (d, J = 8.48 Hz, 1H), 6.88 (s, 1H), 6.64 (d, J = 1.16 Hz, 1H), 3.82 (s, 3H), 3.43 - 3.40 (m, 2H), 3.29 - 3.26 (m, 4H), 2.73 (s, 3H), 2.67 - 2.61 (m, 2H), 2.17 - 2.00 (m, 3H), 1.83 - 1.81 (m, 2H), 1.60 - 1.51 (m, 2H) ; 570 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.62 (d, J = 8.52 Hz, 1H), 8.04 (s, 1H), 7.75 (t, J = 7.92 Hz, 1H), 7.34 (d, J = 7.36 Hz , 1H), 7.20 (d, J = 2.2 Hz, 1H), 7.05 (dd, J = 8.44, 2.32 Hz), 6.92 (d, J = 8.48 Hz, 1H), 6.88 (s, 1H), 6.64 (d , J = 1.16 Hz, 1H), 3.82 (s, 3H), 3.43 - 3.40 (m, 2H), 3.29 - 3.26 (m, 4H), 2.73 (s, 3H), 2.67 - 2.61 (m, 2H), 2.17 - 2.00 (m, 3H), 1.83 - 1.81 (m, 2H), 1.60 - 1.51 (m, 2H) ; 570 [M+H] +
126126 2-(6-((2-((1-(3-메톡시프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine-4- yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.29 (s, 1H), 8.43 - 8.16 (m, 2H), 7.89 (br s, 1H), 7.77 (t, J = 7.9 Hz, 1H), 7.47 (s, 1H), 7.36 - 7.30 (m, 1H), 6.85 (s, 1H), 5.18 (s, 1H), 4.12 - 4.05 (m, 2H), 3.27 (t, J = 6.2 Hz, 2H), 3.22 (s, 3H), 2.62 (s, 3H), 1.95 (p, J = 6.5 Hz, 2H), 1.43 (s, 6H); 454 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.29 (s, 1H), 8.43 - 8.16 (m, 2H), 7.89 (br s, 1H), 7.77 (t, J = 7.9 Hz, 1H), 7.47 (s, 1H), 7.36 - 7.30 (m, 1H), 6.85 (s, 1H), 5.18 (s, 1H), 4.12 - 4.05 (m, 2H), 3.27 (t, J = 6.2 Hz, 2H), 3.22 (s , 3H), 2.62 (s, 3H), 1.95 (p, J = 6.5 Hz, 2H), 1.43 (s, 6H); 454 [M+H] +
127127 2-(3-((2-((1-(3-메톡시프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine-4- yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.04 (s, 1H), 8.10 (br s, 1H), 7.87 - 7.48 (m, 2H), 7.45 - 7.10 (m, 4H), 6.75 (s, 1H), 5.02 (s, 1H), 3.99 - 3.84 (m, 2H), 3.28 - 3.21 (m, 5H), 2.63 (s, 3H), 1.96 - 1.80 (m, 2H), 1.45 (s, 6H); 453 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.04 (s, 1H), 8.10 (br s, 1H), 7.87 - 7.48 (m, 2H), 7.45 - 7.10 (m, 4H), 6.75 (s, 1H), 5.02 (s, 1H), 3.99 - 3.84 (m, 2H), 3.28 - 3.21 (m, 5H), 2.63 (s, 3H), 1.96 - 1.80 (m, 2H), 1.45 (s, 6H); 453 [M+H] +
128128 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-fluorophenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400MHz, DMSO) δ 9.19 (s, 1H), 8.11 (s, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.55 - 7.51 (m, 2H), 7.31 (dd, J = 7.8, 7.8 Hz, 1H), 7.24 - 7.22 (m, 2H), 6.85 (dd, J = 7.5, 7.5 Hz, 1H), 5.04 (s, 1H), 3.11 - 3.06 (m, 6H), 2.68 - 2.58 (m, 5H), 2.07 - 2.04 (m, 1H), 1.94 - 1.90 (m, 2H), 1.69 - 1.66 (m, 2H), 1.44 (s, 6H), 1.29 - 1.23 (m, 2H); 547 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.19 (s, 1H), 8.11 (s, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.55 - 7.51 (m, 2H), 7.31 (dd, J = 7.8, 7.8 Hz, 1H), 7.24 - 7.22 (m, 2H), 6.85 (dd, J = 7.5, 7.5 Hz, 1H), 5.04 (s, 1H), 3.11 - 3.06 (m, 6H), 2.68 - 2.58 (m, 5H), 2.07 - 2.04 (m, 1H), 1.94 - 1.90 (m, 2H), 1.69 - 1.66 (m, 2H), 1.44 (s, 6H), 1.29 - 1.23 (m, 2H); 547 [M+H] +
129129 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-fluorophenyl)amino)-5-methylthieno[2, 3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400MHz, DMSO) δ 9.44 (s, 1H), 8.29 (s, 1H), 8.23 (d, J = 8.5 Hz, 1H), 7.78 (dd, J = 7.8, 8.0 Hz, 1H), 7.65 (dd, J = 2.1, 15.2 Hz, 1H), 7.36 - 7.32 (m, 2H), 7.00 - 6.93 (m, 2H), 5.25 (s, 1H), 3.20 - 3.06 (m, 6H), 2.68 - 2.63 (m, 5H), 2.09 - 2.06 (m, 1H), 1.94 - 1.90 (m, 2H), 1.72 - 1.69 (m, 2H), 1.44 (s, 6H), 1.31 - 1.23 (m, 2H); 548 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.44 (s, 1H), 8.29 (s, 1H), 8.23 (d, J = 8.5 Hz, 1H), 7.78 (dd, J = 7.8, 8.0 Hz, 1H), 7.65 (dd, J = 2.1, 15.2 Hz, 1H), 7.36 - 7.32 (m, 2H), 7.00 - 6.93 (m, 2H), 5.25 (s, 1H), 3.20 - 3.06 (m, 6H), 2.68 - 2.63 (m, 5H), 2.09 - 2.06 (m, 1H), 1.94 - 1.90 (m, 2H), 1.72 - 1.69 (m, 2H), 1.44 (s, 6H), 1.31 - 1.23 (m, 2H); 548 [M+H] +
130130 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-플루오로페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-fluorophenyl)-N4-(3-fluorophenyl)-5-methylthieno[2, 3-d] pyrimidine-2,4-diamine 1H NMR (400MHz, DMSO) δ 9.36 (s, 1H), 8.24 (s, 1H), 7.69 (d, J = 11.5 Hz, 1H), 7.58 (dd, J = 15.4, 1.9 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.41 - 7.35 (m, 1H), 7.28 (d, J= 8.8 Hz, 1H), 6.95 - 6.87 (m, 3H), 3.83 - 3.10 (m, 6H), 2.68 - 2.59 (m, 5H), 2.11 - 2.08 (m, 1H), 2.01 - 1.90 (m, 2H), 1.72 - 1.69 (m, 2H), 1.45 - 1.32 (m, 2H); 507 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.36 (s, 1H), 8.24 (s, 1H), 7.69 (d, J = 11.5 Hz, 1H), 7.58 (dd, J = 15.4, 1.9 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.41 - 7.35 (m, 1H), 7.28 (d, J = 8.8 Hz, 1H), 6.95 - 6.87 (m, 3H), 3.83 - 3.10 (m, 6H), 2.68 - 2.59 (m, 5H), 2.11 - 2.08 (m, 1H), 2.01 - 1.90 (m, 2H), 1.72 - 1.69 (m, 2H), 1.45 - 1.32 (m, 2H); 507 [M+H] +
131131 N2-(3,5-디메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(3,5-dimethyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-N4-(3-fluorophenyl)-5-methylthieno[ 2,3-d] pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 9.68 Hz, 1H), 7.22 - 7.15 (m, 3H), 7.06 - 7.05 (m, 1H), 6.71 (t, J = 6.92 Hz, 1H), 6.54 (d, J = 1.0 Hz, 1H), 6.04 (s, 1H), 3.97 (bs, 1H), 3.06 (bs, 2H), 2.64 (s, 3H), 2.36 - 2.31 (m, 2H), 2.16 (s, 3H), 2.13 (s, 3H), 1.98 - 1.96 (m, 2H), 1.76 - 1.72 (m, 2H) ; 466 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.61 (d, J = 9.68 Hz, 1H), 7.22 - 7.15 (m, 3H), 7.06 - 7.05 (m, 1H), 6.71 (t, J = 6.92 Hz, 1H), 6.54 (d, J = 1.0 Hz, 1H), 6.04 (s, 1H), 3.97 (bs, 1H), 3.06 (bs, 2H), 2.64 (s, 3H), 2.36 - 2.31 (m, 2H) ), 2.16 (s, 3H), 2.13 (s, 3H), 1.98 - 1.96 (m, 2H), 1.76 - 1.72 (m, 2H); 466 [M+H] +
132132 2-(3-((2-((3,5-디메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((3,5-dimethyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[ 2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.57 (s, 1H), 7.55 (s, 1H), 7.19 - 7.18 (m,2H), 7.08 (d, J = 7.52 Hz, 1H), 6.52 (s, 1H), 6.15 (s, 1H), 3.96 - 3.90 (m, 1H), 3.05 - 3.02 (m, 2H), 2.65 (s, 3H), 2.37 (s, 3H), 2.36 - 2.31 (m, 2H), 2.13 (s, 3H), 2.06 (s, 3H), 1.93 - 1.90 (m, 4H), 1.56 (s, 6H) ; 506 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.57 (s, 1H), 7.55 (s, 1H), 7.19 - 7.18 (m, 2H), 7.08 (d, J = 7.52 Hz, 1H), 6.52 (s, 1H), 6.15 (s, 1H), 3.96 - 3.90 (m, 1H), 3.05 - 3.02 (m, 2H), 2.65 (s, 3H), 2.37 (s, 3H), 2.36 - 2.31 (m, 2H) , 2.13 (s, 3H), 2.06 (s, 3H), 1.93 - 1.90 (m, 4H), 1.56 (s, 6H); 506 [M+H] +
133133 2-(6-((5-메틸-2-((3-메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-((3-methyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2, 3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ8.19 (s, 1H), 7.92 (s, 1H), 7.81 (s, 1H), 7.66 (d, J = 7.5 Hz, 1H), 7.04 (d, J = 7.5 Hz, 1H), 6.61 (s, 1H), 6.29 (s, 1H), 4.09 - 4.03 (m, 1H), 3.00 - 2.97 (m, 2H), 2.72 (s, 3H), 2.34 (s, 3H), 2.24 (s, 3H), 2.20 - 2.02 (m, 6H), 1.54 (s, 6H); 493 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ8.19 (s, 1H), 7.92 (s, 1H), 7.81 (s, 1H), 7.66 (d, J = 7.5 Hz, 1H), 7.04 (d, J = 7.5 Hz, 1H), 6.61 (s, 1H), 6.29 (s, 1H), 4.09 - 4.03 (m, 1H), 3.00 - 2.97 (m, 2H), 2.72 (s, 3H), 2.34 (s, 3H), 2.24 (s, 3H), 2.20 - 2.02 (m, 6H), 1.54 (s, 6H); 493 [M+H] +
134134 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤조산, 2,2,2-트리플루오로아세트산3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidine- 4-yl)amino)benzoic acid, 2,2,2-trifluoroacetic acid 1H NMR (400 MHz, DMSO) δ9.53 - 9.36 (m, 1H), 9.17 (s, 1H), 8.41 - 8.24 (m, 1H), 8.04 (s, 1H), 7.83 - 7.69 (m, 1H), 7.58 - 7.50 (m, 1H), 7.49 - 7.32 (m, 1H), 6.81 (s, 1H), 3.56 (s, 3H), 3.15 - 3.06 (m, 2H), 2.86 - 2.79 (m, 3H), 2.63 (s, 3H), 2.18 - 1.96 (m, 4H); 464 [M+H]+ 1 H NMR (400 MHz, DMSO) δ9.53 - 9.36 (m, 1H), 9.17 (s, 1H), 8.41 - 8.24 (m, 1H), 8.04 (s, 1H), 7.83 - 7.69 (m, 1H) ), 7.58 - 7.50 (m, 1H), 7.49 - 7.32 (m, 1H), 6.81 (s, 1H), 3.56 (s, 3H), 3.15 - 3.06 (m, 2H), 2.86 - 2.79 (m, 3H) ), 2.63 (s, 3H), 2.18 - 1.96 (m, 4H); 464 [M+H] +
135135 3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조산, 2,2,2-트리플루오로아세트산3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)benzoic acid, 2,2,2-trifluoroacetic acid 1H NMR (400 MHz, DMSO) δ9.90 (br s, 1H), 9.16 (s, 1H), 8.30 (s, 1H), 8.12 - 8.00 (m, 2H), 7.68 (d, J = 7.7 Hz, 1H), 7.46 (t, J = 7.9 Hz, 1H), 7.32 - 7.21 (m, 2H), 6.88 - 6.84 (m, 1H), 6.83 - 6.74 (m, 1H), 4.19 - 4.01 (m, 4H), 3.62 (s, 3H), 2.69 - 2.59 (m, 5H), 2.55 - 2.51 (m, 2H), 2.48 - 2.40 (m, 2H), 2.28 - 2.18 (m, 1H), 2.03 - 1.94 (m, 2H), 1.54 - 1.43 (m, 2H); 545 [M+H]+ 1 H NMR (400 MHz, DMSO) δ9.90 (br s, 1H), 9.16 (s, 1H), 8.30 (s, 1H), 8.12 - 8.00 (m, 2H), 7.68 (d, J = 7.7 Hz , 1H), 7.46 (t, J = 7.9 Hz, 1H), 7.32 - 7.21 (m, 2H), 6.88 - 6.84 (m, 1H), 6.83 - 6.74 (m, 1H), 4.19 - 4.01 (m, 4H) ), 3.62 (s, 3H), 2.69 - 2.59 (m, 5H), 2.55 - 2.51 (m, 2H), 2.48 - 2.40 (m, 2H), 2.28 - 2.18 (m, 1H), 2.03 - 1.94 (m , 2H), 1.54 - 1.43 (m, 2H); 545 [M+H] +
136136 N4-(3-플루오로페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민N4-(3-fluorophenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[2,3-d] Pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.67 (d, J = 10.96 Hz, 1H), 7.47 (s, 1H), 7.33 - 7.29 (m, 1H), 7.17 - 7.15 (m, 2H), 6.85 - 6.68 (m, 1H), 6.59 (s,1H), 6.59 (s, 1H), 4.13 - 4.05 (m, 1H), 3.01 - 2.98 (m, 2H), 2.66 (s, 3H), 2.35 (s, 3H), 2.17 - 2.04 (m, 6H) ; 438 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.90 (s, 1H), 7.67 (d, J = 10.96 Hz, 1H), 7.47 (s, 1H), 7.33 - 7.29 (m, 1H), 7.17 - 7.15 ( m, 2H), 6.85 - 6.68 (m, 1H), 6.59 (s, 1H), 6.59 (s, 1H), 4.13 - 4.05 (m, 1H), 3.01 - 2.98 (m, 2H), 2.66 (s, 3H), 2.35 (s, 3H), 2.17 - 2.04 (m, 6H); 438 [M+H] +
137137 N2-(1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)-N4-(3-fluorophenyl)-5-methylthieno[2,3-d ]Pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.64 (d, J = 10.56 Hz, 1H), 7.44 (s, 1H), 7.32 - 7.29 (m, 1H), 7.18 - 7.17 (m, 2H), 6.84 - 6.80 (m, 1H), 6.73 (s, 1H), 6.58 (s, 1H), 4.13 - 4.08 (m, 1H), 3.17 - 3.14 (m, 2H), 2.65 (s, 3H), 2.39 - 2.33 (m, 2H), 2.12 - 2.09 (m, 2H), 1.99 - 1.91 (m, 2H), 1.67 - 1.64 (m, 1H), 0.50 - 0.46 (m, 4H) ; 464 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.87 (s, 1H), 7.64 (d, J = 10.56 Hz, 1H), 7.44 (s, 1H), 7.32 - 7.29 (m, 1H), 7.18 - 7.17 ( m, 2H), 6.84 - 6.80 (m, 1H), 6.73 (s, 1H), 6.58 (s, 1H), 4.13 - 4.08 (m, 1H), 3.17 - 3.14 (m, 2H), 2.65 (s, 3H), 2.39 - 2.33 (m, 2H), 2.12 - 2.09 (m, 2H), 1.99 - 1.91 (m, 2H), 1.67 - 1.64 (m, 1H), 0.50 - 0.46 (m, 4H); 464 [M+H] +
138138 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.76 - 7.73 (m, 1H), 7.53 - 7.51 (m, 1H), 7.49 (s, 1H), 7.42 (s, 1H), 7.20 (s, 1H), 7.16 (s, 1H), 6.95 (d, J = 9.12 Hz, 1H), 6.81 (s, 1H), 6.57 (s, 1H), 4.12 - 4.10 (m, 1H), 3.19 - 3.17 (m, 2H), 2.65 (s, 3H), 2.38 - 2.36 (m, 2H), 2.09 - 2.02 (m, 3H), 1.91 - 1.89 (m, 2H), 1.56 (s, 6H), 0.53 - 0.51 (m, 4H) ; 522 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.76 - 7.73 (m, 1H), 7.53 - 7.51 (m, 1H), 7.49 (s, 1H), 7.42 (s, 1H), 7.20 (s, 1H), 7.16 (s, 1H), 6.95 (d, J = 9.12 Hz, 1H), 6.81 (s, 1H), 6.57 (s, 1H), 4.12 - 4.10 (m, 1H), 3.19 - 3.17 (m, 2H) , 2.65 (s, 3H), 2.38 - 2.36 (m, 2H), 2.09 - 2.02 (m, 3H), 1.91 - 1.89 (m, 2H), 1.56 (s, 6H), 0.53 - 0.51 (m, 4H) ; 522 [M+H] +
139139 2-(3-플루오로-5-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-fluoro-5-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2 ,3-d] pyrimidin-4-yl) amino) phenyl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.63 - 7.61 (m, 1H), 7.42 - 7.37 (m, 1H), 7.34 (s, 1H), 7.21 (s, 1H), 7.10 - 7.08 (m, 2H), 6.88 (s, 1H), 6.56 (s, 1H), 4.08 - 4.03 (m, 1H), 3.01 - 2.98 (m, 2H), 2.64 (s, 3H), 2.35 (s, 3H), 2.17 - 2.04 (m, 6H), 1.57 (s, 6H) ; 496 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.63 - 7.61 (m, 1H), 7.42 - 7.37 (m, 1H), 7.34 (s, 1H), 7.21 (s, 1H), 7.10 - 7.08 (m, 2H) ), 6.88 (s, 1H), 6.56 (s, 1H), 4.08 - 4.03 (m, 1H), 3.01 - 2.98 (m, 2H), 2.64 (s, 3H), 2.35 (s, 3H), 2.17 - 2.04 (m, 6H), 1.57 (s, 6H); 496 [M+H] +
140140 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.03 (s, 1H), 8.12 (br s, 1H), 7.65 - 7.47 (m, 2H), 7.47 - 7.12 (m, 4H), 6.74 (s, 1H), 5.02 (s, 1H), 3.96 - 3.76 (m, 1H), 2.99 (d, J = 11.2 Hz, 2H), 2.62 (s, 3H), 2.36 - 2.22 (m, 2H), 1.93 - 1.57 (m, 5H), 1.45 (s, 6H), 0.51 - 0.40 (m, 2H), 0.37 - 0.29 (m, 2H); 504 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.03 (s, 1H), 8.12 (br s, 1H), 7.65 - 7.47 (m, 2H), 7.47 - 7.12 (m, 4H), 6.74 (s, 1H), 5.02 (s, 1H), 3.96 - 3.76 (m, 1H), 2.99 (d, J = 11.2 Hz, 2H), 2.62 (s, 3H), 2.36 - 2.22 (m, 2H), 1.93 - 1.57 (m, 5H), 1.45 (s, 6H), 0.51 - 0.40 (m, 2H), 0.37 - 0.29 (m, 2H); 504 [M+H] +
141141 2-(6-((2-((1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.27 (s, 1H), 8.62 - 8.08 (m, 2H), 7.90 (br s, 1H), 7.77 (t, J = 7.9 Hz, 1H), 7.48 (br s, 1H), 7.34 (d, J = 7.7 Hz, 1H), 6.86 (s, 1H), 5.20 (s, 1H), 4.16 - 4.08 (m, 1H), 3.11 - 3.02 (m, 2H), 2.63 (s, 3H), 2.42 - 2.28 (m, 2H), 2.01 - 1.90 (m, 2H), 1.89 - 1.77 (m, 2H), 1.74 - 1.64 (m, 1H), 1.45 (s, 6H), 0.54 - 0.42 (m, 2H), 0.42 - 0.28 (m, 2H); 505 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.27 (s, 1H), 8.62 - 8.08 (m, 2H), 7.90 (br s, 1H), 7.77 (t, J = 7.9 Hz, 1H), 7.48 (br s , 1H), 7.34 (d, J = 7.7 Hz, 1H), 6.86 (s, 1H), 5.20 (s, 1H), 4.16 - 4.08 (m, 1H), 3.11 - 3.02 (m, 2H), 2.63 ( s, 3H), 2.42 - 2.28 (m, 2H), 2.01 - 1.90 (m, 2H), 1.89 - 1.77 (m, 2H), 1.74 - 1.64 (m, 1H), 1.45 (s, 6H), 0.54 - 0.42 (m, 2H), 0.42 - 0.28 (m, 2H); 505 [M+H] +
142142 2-(6-((2-((1-(1-시클로프로필피페리딘-4-일)-3-메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(1-cyclopropylpiperidin-4-yl)-3-methyl-1H-pyrazol-4-yl)amino)-5-methylthieno[2 ,3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, DMSO) δ 8.53 (s, 1H), 8.20 (s, 1H), 7.87 - 7.58 (m, 3H), 7.30 (d, J = 7.6 Hz, 1H), 6.83 (s, 1H), 5.18 (s, 1H), 4.03 - 3.99 (m, 1H), 3.01 (d, J = 11.6 Hz, 2H), 2.62 (s, 3H), 2.34 - 2.26 (m, 2H), 2.08 (s, 3H), 1.96 - 1.89 (m, 2H), 1.85 - 1.75 (m, 2H), 1.68 - 1.59 (m, 1H), 1.43 (s, 6H), 0.48 - 0.39 (m, 2H), 0.35 - 0.28 (m, 2H); 519 [M+H]+ 1H NMR (400 MHz, DMSO) δ 8.53 (s, 1H), 8.20 (s, 1H), 7.87 - 7.58 (m, 3H), 7.30 (d, J = 7.6 Hz, 1H), 6.83 (s, 1H) ), 5.18 (s, 1H), 4.03 - 3.99 (m, 1H), 3.01 (d, J = 11.6 Hz, 2H), 2.62 (s, 3H), 2.34 - 2.26 (m, 2H), 2.08 (s, 3H), 1.96 - 1.89 (m, 2H), 1.85 - 1.75 (m, 2H), 1.68 - 1.59 (m, 1H), 1.43 (s, 6H), 0.48 - 0.39 (m, 2H), 0.35 - 0.28 ( m, 2H); 519 [M+H] +
143143 2-(3-((2-((5-클로로-1-((3S,4S)-3-플루오로-1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H- pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 8.44 (s, 1H), 8.00 (s, 1H), 7.75 (s, 1H), 7.70 - 7.63 (m, 1H), 7.52 (s, 1H), 7.24 - 7.13 (m, 2H), 6.79 (s, 1H), 5.01 - 4.96 (m, 0.5H), 4.95 (s, 1H), 4.89 - 4.81 (m, 0.5H), 4.61 - 4.53 (m, 2H), 4.51 - 4.44 (m, 2H), 4.44 - 4.35 (m, 1H), 3.59 (p, J = 6.3 Hz, 1H), 3.24 - 3.17 (m, 1H), 2.82 - 2.76 (m, 1H), 2.64 (s, 3H), 2.17 - 2.05 (m, 3H), 1.96 - 1.92 (m, 1H), 1.43 (s, 6H); 573 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 8.44 (s, 1H), 8.00 (s, 1H), 7.75 (s, 1H), 7.70 - 7.63 (m, 1H), 7.52 (s, 1H), 7.24 - 7.13 (m, 2H), 6.79 (s, 1H), 5.01 - 4.96 (m, 0.5H), 4.95 (s, 1H), 4.89 - 4.81 (m, 0.5H), 4.61 - 4.53 (m, 2H), 4.51 - 4.44 (m, 2H), 4.44 - 4.35 (m, 1H), 3.59 (p, J = 6.3 Hz, 1H), 3.24 - 3.17 (m, 1H), 2.82 - 2.76 (m, 1H), 2.64 (s , 3H), 2.17 - 2.05 (m, 3H), 1.96 - 1.92 (m, 1H), 1.43 (s, 6H); 573 [M+H] +
144144 2-(6-((2-((5-클로로-1-((3S,4S)-3-플루오로-1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H- pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 8.72 (s, 1H), 8.40 - 7.96 (m, 2H), 7.84 (s, 1H), 7.62 (br s, 1H), 7.29 (d, J = 7.6 Hz, 1H), 6.88 (s, 1H), 5.16 (s, 1H), 5.09 - 5.00 (m, 0.5H), 4.96 - 4.88 (m, 0.5H), 4.64 - 4.54 (m, 2H), 4.54 - 4.43 (m, 3H), 3.61 (p, J = 6.3 Hz, 1H), 3.27 - 3.19 (m, 1H), 2.87 - 2.76 (m, 1H), 2.64 (s, 3H), 2.20 - 2.09 (m, 3H), 2.03 - 1.95 (m, 1H), 1.43 (s, 6H); 574 [M+H]+ 1H NMR (400 MHz, DMSO) δ 8.72 (s, 1H), 8.40 - 7.96 (m, 2H), 7.84 (s, 1H), 7.62 (br s, 1H), 7.29 (d, J = 7.6 Hz, 1H), 6.88 (s, 1H), 5.16 (s, 1H), 5.09 - 5.00 (m, 0.5H), 4.96 - 4.88 (m, 0.5H), 4.64 - 4.54 (m, 2H), 4.54 - 4.43 ( m, 3H), 3.61 (p, J = 6.3 Hz, 1H), 3.27 - 3.19 (m, 1H), 2.87 - 2.76 (m, 1H), 2.64 (s, 3H), 2.20 - 2.09 (m, 3H) , 2.03 - 1.95 (m, 1H), 1.43 (s, 6H); 574 [M+H] +
145145 2-(3-((2-((3-메톡시-4-(2,6-디아자스피로[3.3]헵탄-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((3-methoxy-4-(2,6-diazaspiro[3.3]heptan-2-yl)phenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 8.86 (s, 1H), 7.99 (s, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.57 - 7.49 (m, 1H), 7.28 - 7.16 (m, 3H), 7.10 (d, J = 8.6 Hz, 1H), 6.77 (s, 1H), 6.23 (d, J = 8.5 Hz, 1H), 4.96 (s, 1H), 3.77 (s, 3H), 3.61 (s, 4H), 3.51 (s, 4H), 2.63 (s, 3H), 1.42 (s, 6H); 517 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 8.86 (s, 1H), 7.99 (s, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.57 - 7.49 (m, 1H), 7.28 - 7.16 (m , 3H), 7.10 (d, J = 8.6 Hz, 1H), 6.77 (s, 1H), 6.23 (d, J = 8.5 Hz, 1H), 4.96 (s, 1H), 3.77 (s, 3H), 3.61 (s, 4H), 3.51 (s, 4H), 2.63 (s, 3H), 1.42 (s, 6H); 517 [M+H] +
146146 2-(6-((2-((3-메톡시-4-(2,6-디아자스피로[3.3]헵탄-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-methoxy-4-(2,6-diazaspiro[3.3]heptan-2-yl)phenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.13 (s, 1H), 8.41 - 8.13 (m, 2H), 7.72 (t, J = 7.9 Hz, 1H), 7.33 (d, J = 7.5 Hz, 1H), 7.24 (s, 1H), 7.19 (d, J = 8.3 Hz, 1H), 6.87 (s, 1H), 6.40 - 6.31 (m, 1H), 5.18 (s, 1H), 3.83 (s, 3H), 3.79 - 3.56 (m, 8H), 2.65 (s, 3H), 1.44 (s, 6H); 518 [M+H]+ 1H NMR (400 MHz, DMSO) δ 9.13 (s, 1H), 8.41 - 8.13 (m, 2H), 7.72 (t, J = 7.9 Hz, 1H), 7.33 (d, J = 7.5 Hz, 1H), 7.24 (s, 1H), 7.19 (d, J = 8.3 Hz, 1H), 6.87 (s, 1H), 6.40 - 6.31 (m, 1H), 5.18 (s, 1H), 3.83 (s, 3H), 3.79 - 3.56 (m, 8H), 2.65 (s, 3H), 1.44 (s, 6H); 518 [M+H] +
147147 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-3-메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-3-methyl-1H-pyrazol-4-yl)amino)-5-methylthieno[2 ,3-d] pyrimidin-4-yl) amino) phenyl) propan-2-ol 1H NMR (400 MHz, DMSO) δ 8.35 (br s, 2H), 8.06 (br s, 1H), 7.60 - 7.44 (m, 2H), 7.27 (t, J = 7.8 Hz, 1H), 7.25 - 7.19 (m, 1H), 6.73 (s, 1H), 5.00 (s, 1H), 3.82 - 3.73 (m, 1H), 3.02 - 2.96 (m, 2H), 2.62 (s, 3H), 2.34 - 2.24 (m, 2H), 2.08 (s, 3H), 1.81 - 1.72 (m, 2H), 1.70 - 1.61 (m, 2H), 1.43 (s, 6H), 0.49 - 0.40 (m, 2H), 0.36 - 0.28 (m, 2H); 518 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 8.35 (br s, 2H), 8.06 (br s, 1H), 7.60 - 7.44 (m, 2H), 7.27 (t, J = 7.8 Hz, 1H), 7.25 - 7.19 (m, 1H), 6.73 (s, 1H), 5.00 (s, 1H), 3.82 - 3.73 (m, 1H), 3.02 - 2.96 (m, 2H), 2.62 (s, 3H), 2.34 - 2.24 (m , 2H), 2.08 (s, 3H), 1.81 - 1.72 (m, 2H), 1.70 - 1.61 (m, 2H), 1.43 (s, 6H), 0.49 - 0.40 (m, 2H), 0.36 - 0.28 (m , 2H); 518 [M+H] +
148148 메틸 3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트Methyl 3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)benzoate 1H NMR (400 MHz, CDCl3) δ8.12 - 8.02 (m, 2H), 7.79 (d, J = 7.8 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 7.24 - 7.18 (m, 2H), 7.06 (dd, J = 8.5, 2.3 Hz, 1H), 6.88 - 6.81 (m, 2H), 6.61 (d, J = 1.0 Hz, 1H), 3.92 (s, 3H), 3.75 (s, 3H), 3.50 - 3.25 (m, 6H), 2.68 (s, 3H), 2.60 (t, J = 10.4 Hz, 2H), 2.32 - 2.11 (m, 3H), 1.87 - 1.81 (m, 2H), 1.65 - 1.57 (m, 2H); 559 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ8.12 - 8.02 (m, 2H), 7.79 (d, J = 7.8 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 7.24 - 7.18 (m , 2H), 7.06 (dd, J = 8.5, 2.3 Hz, 1H), 6.88 - 6.81 (m, 2H), 6.61 (d, J = 1.0 Hz, 1H), 3.92 (s, 3H), 3.75 (s, 3H), 3.50 - 3.25 (m, 6H), 2.68 (s, 3H), 2.60 (t, J = 10.4 Hz, 2H), 2.32 - 2.11 (m, 3H), 1.87 - 1.81 (m, 2H), 1.65 - 1.57 (m, 2H); 559 [M+H] +
149149 -3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조산, 2,2,2-트리플루오로아세트산-3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl) amino) benzoic acid, 2,2,2-trifluoroacetic acid 1H NMR (400 MHz, DMSO) δ9.54 (br s, 1H), 9.16 (s, 1H), 8.30 (s, 1H), 8.14 - 8.02 (m, 2H), 7.68 (d, J = 7.8 Hz, 1H), 7.46 (t, J = 7.9 Hz, 1H), 7.32 - 7.21 (m, 2H), 6.89 - 6.83 (m, 1H), 6.83 - 6.74 (m, 1H), 3.62 (s, 3H), 3.33 - 3.28 (m, 2H), 2.80 (d, J = 4.5 Hz, 6H), 2.73 - 2.57 (m, 5H), 2.13 - 1.97 (m, 2H), 1.85 - 1.71 (m, 2H); 533 [M+H]+ 1 H NMR (400 MHz, DMSO) δ9.54 (br s, 1H), 9.16 (s, 1H), 8.30 (s, 1H), 8.14 - 8.02 (m, 2H), 7.68 (d, J = 7.8 Hz , 1H), 7.46 (t, J = 7.9 Hz, 1H), 7.32 - 7.21 (m, 2H), 6.89 - 6.83 (m, 1H), 6.83 - 6.74 (m, 1H), 3.62 (s, 3H), 3.33 - 3.28 (m, 2H), 2.80 (d, J = 4.5 Hz, 6H), 2.73 - 2.57 (m, 5H), 2.13 - 1.97 (m, 2H), 1.85 - 1.71 (m, 2H); 533 [M+H] +
150150 2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)-5-(트리플루오로메틸)페닐)프로판-2-올2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] Pyrimidin-4-yl)amino)-5-(trifluoromethyl)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.75 - 7.74 (m, 2H), 7.65 (s, 1H), 7.48 (bs, 1H), 7.32 (s, 1H), 7.07 (s, 1H), 6.09 - 6.84 (m, 1H), 6.58 (s, 1H) 4.04 - 3.99 (m, 1H), 2.97 - 2.95 (m, 2H), 2.66 (s, 3H), 2.34 - 1.98 (m, 6H), 1.59 (s, 6H) ; 546 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.75 - 7.74 (m, 2H), 7.65 (s, 1H), 7.48 (bs, 1H), 7.32 (s, 1H), 7.07 (s, 1H), 6.09 - 6.84 (m, 1H), 6.58 (s, 1H) 4.04 - 3.99 (m, 1H), 2.97 - 2.95 (m, 2H), 2.66 (s, 3H), 2.34 - 1.98 (m, 6H), 1.59 (s , 6H); 546 [M+H] +
실시예Example 화합물명compound name 1H NMR and/or Mass 1 H NMR and/or Mass
151151 2-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-3-메틸-1H-피라졸-1-일)-2-메틸프로판아미드2-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine-2- yl)amino)-3-methyl-1H-pyrazol-1-yl)-2-methylpropanamide 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 7.12 Hz, 1H), 7.99 (s, 1H), 7.95 (s, 1H), 7.67 (t, J = 7.76 Hz, 1H), 7.05 (d, J = 7.56 Hz, 1H), 6.63 (s,1H), 6.46 (d, J = 12.4 Hz, 1H), 6.30 (s, 1H), 5.38 (d, J = 17.92 Hz, 1H), 4.64 (s, 1H), 2.72 (s, 3H), 2.29 (s, 3H), 1.84 (s, 6H), 1.54 (s, 6H) ; 481 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.18 (d, J = 7.12 Hz, 1H), 7.99 (s, 1H), 7.95 (s, 1H), 7.67 (t, J = 7.76 Hz, 1H), 7.05 (d, J = 7.56 Hz, 1H), 6.63 (s, 1H), 6.46 (d, J = 12.4 Hz, 1H), 6.30 (s, 1H), 5.38 (d, J = 17.92 Hz, 1H), 4.64 (s, 1H), 2.72 (s, 3H), 2.29 (s, 3H), 1.84 (s, 6H), 1.54 (s, 6H); 481 [M+H] +
152152 2-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-3-메틸-1H-피라졸-1-일)-2-메틸프로판아미드2-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl)amino) -3-methyl-1H-pyrazol-1-yl)-2-methylpropanamide 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.57 (d, J = 7.68 Hz, 1H), 7.51 (s, 1H), 7.33 (t, J = 7.8 Hz, 1H), 7.28 (s, 1H), 7.14 (s, 1H), 6.57 (s, 1H), 6.44 (s, 1H), 6.14 (s, 1H), 5.26 (s, 1H), 2.66 (s, 3H), 2.24 (s, 3H), 1.71 (s, 6H), 1.58 (s, 6H) ; 480 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.85 (s, 1H), 7.57 (d, J = 7.68 Hz, 1H), 7.51 (s, 1H), 7.33 (t, J = 7.8 Hz, 1H), 7.28 (s, 1H), 7.14 (s, 1H), 6.57 (s, 1H), 6.44 (s, 1H), 6.14 (s, 1H), 5.26 (s, 1H), 2.66 (s, 3H), 2.24 ( s, 3H), 1.71 (s, 6H), 1.58 (s, 6H); 480 [M+H] +
153153 1-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)시클로부탄-1-올1-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)cyclobutan-1-ol 1H NMR (400 MHz, CDCl3) δ7.64 - 7.56 (m, 2H), 7.37 (t, J = 7.8 Hz, 1H), 7.32 - 7.27 (m, 2H), 7.17 (s, 1H), 6.98 (dd, J = 8.4, 2.2 Hz, 1H), 6.88 (s, 1H), 6.83 (d, J = 8.5 Hz, 1H), 6.60 (d, J = 1.1 Hz, 1H), 3.66 (s, 3H), 3.56 - 3.46 (m, 2H), 2.67 (s, 3H), 2.64 - 2.42 (m, 11H), 2.36 - 2.28 (m, 2H), 2.04 - 1.95 (m, 2H), 1.89 - 1.83 (m, 2H), 1.72 - 1.64 (m, 2H); 559 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.64 - 7.56 (m, 2H), 7.37 (t, J = 7.8 Hz, 1H), 7.32 - 7.27 (m, 2H), 7.17 (s, 1H), 6.98 (dd, J = 8.4, 2.2 Hz, 1H), 6.88 (s, 1H), 6.83 (d, J = 8.5 Hz, 1H), 6.60 (d, J = 1.1 Hz, 1H), 3.66 (s, 3H) , 3.56 - 3.46 (m, 2H), 2.67 (s, 3H), 2.64 - 2.42 (m, 11H), 2.36 - 2.28 (m, 2H), 2.04 - 1.95 (m, 2H), 1.89 - 1.83 (m, 2H), 1.72 - 1.64 (m, 2H); 559 [M+H] +
154154 1-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)시클로부탄-1-올1-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)cyclobutan-1-ol 1H NMR (400 MHz, CDCl3) δ7.65 - 7.56 (m, 2H), 7.37 (t, J = 7.8 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H), 7.16 (s, 1H), 6.96 (dd, J = 8.4, 2.3 Hz, 1H), 6.88 - 6.79 (m, 2H), 6.58 (d, J = 1.1 Hz, 1H), 3.64 (s, 3H), 3.44 - 3.25 (m, 5H), 2.67 (s, 3H), 2.65 - 2.56 (m, 2H), 2.53 - 2.43 (m, 2H), 2.36 - 2.27 (m, 2H), 2.20 - 2.08 (m, 2H), 2.08 - 1.94 (m, 2H), 1.86 - 1.78 (m, 2H), 1.73 - 1.62 (m, 4H); 571 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.65 - 7.56 (m, 2H), 7.37 (t, J = 7.8 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H), 7.16 (s, 1H) ), 6.96 (dd, J = 8.4, 2.3 Hz, 1H), 6.88 - 6.79 (m, 2H), 6.58 (d, J = 1.1 Hz, 1H), 3.64 (s, 3H), 3.44 - 3.25 (m, 5H), 2.67 (s, 3H), 2.65 - 2.56 (m, 2H), 2.53 - 2.43 (m, 2H), 2.36 - 2.27 (m, 2H), 2.20 - 2.08 (m, 2H), 2.08 - 1.94 ( m, 2H), 1.86 - 1.78 (m, 2H), 1.73 - 1.62 (m, 4H); 571 [M+H] +
155155 2-(3-((5-메틸-2-((3-메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((5-methyl-2-((3-methyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ7.71 (s, 1H), 7.63 (s, 1H), 7.31 - 7.29 (m, 2H), 7.25 - 7.17 (m, 2H), 6.54 (s, 1H), 6.21 (s, 1H), 3.96 - 3.91 (m, 1H), 3.02 (d, J = 10.8 Hz, 2H), 2.66 (s, 3H), 2.33 (s, 3H), 2.32 - 2.25 (m, 2H), 2.22 (s, 3H), 2.19 - 2.08 (m, 2H), 1.89 (d, J = 12.8 Hz, 2H), 1.56 (s, 6H), 1.31 - 1.28 (m, 2H); 492 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.71 (s, 1H), 7.63 (s, 1H), 7.31 - 7.29 (m, 2H), 7.25 - 7.17 (m, 2H), 6.54 (s, 1H) , 6.21 (s, 1H), 3.96 - 3.91 (m, 1H), 3.02 (d, J = 10.8 Hz, 2H), 2.66 (s, 3H), 2.33 (s, 3H), 2.32 - 2.25 (m, 2H) ), 2.22 (s, 3H), 2.19 - 2.08 (m, 2H), 1.89 (d, J = 12.8 Hz, 2H), 1.56 (s, 6H), 1.31 - 1.28 (m, 2H); 492 [M+H] +
156156 2-(6-((2-((4-(4-시클로프로필피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-cyclopropylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.66 (dd, J = 7.9, 7.8 Hz, 1H), 7.08 - 7.03 (m, 2H), 6.99 (s, 1H), 6.65 (s, 1H), 4.67 (s, 1H), 3.85 (s, 3H), 3.46 (d, J = 9.5 Hz, 2H), 2.73 (s, 3H), 1.88 - 1.70 (m, 4H), 1.55 (s, 6H), 0.89 - 0.65 (m, 4H), 0.44 - 0.40 (m, 2H), 0.13 - 0.11 (m, 2H); 545 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.32 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.66 (dd, J = 7.9, 7.8 Hz, 1H), 7.08 - 7.03 (m, 2H), 6.99 (s, 1H), 6.65 (s, 1H), 4.67 (s, 1H), 3.85 (s, 3H), 3.46 (d, J = 9.5 Hz, 2H), 2.73 (s, 3H), 1.88 - 1.70 (m, 4H), 1.55 (s, 6H), 0.89 - 0.65 (m, 4H), 0.44 - 0.40 (m, 2H), 0.13 - 0.11 (m, 2H); 545 [M+H] +
157157 2-(3-((2-((4-(4-시클로프로필피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-cyclopropylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl) amino) phenyl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.64 (dd, J = 1.3, 7.9 Hz, 1H), 7.57 (dd, J = 11.8, 1.9 Hz, 1H), 7.32 (dd, J = 7.9, 7.9 Hz, 1H), 7.25 - 7.21 (m, 2H), 7.16 (s, 1H), 6.98 (dd, J = 2.4, 8.5 Hz, 1H), 6.86 - 6.84 (m, 2H), 6.57 (d, J = 1.3 Hz, 1H), 3.67 (s, 3H), 3.41 - 3.37 (m, 2H), 2.67 (s, 3H), 2.47 (t, J = 4.4 Hz, 2H), 1.82 (d, J = 13.5 Hz, 2H), 1.65 - 1.56 (m, 8H), 0.63 - 0.59 (m, 2H), 0.43 - 0.38 (m, 2H), 0.12 - 0.09 (m, 2H); 544 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.64 (dd, J = 1.3, 7.9 Hz, 1H), 7.57 (dd, J = 11.8, 1.9 Hz, 1H), 7.32 (dd, J = 7.9, 7.9 Hz, 1H), 7.25 - 7.21 (m, 2H), 7.16 (s, 1H), 6.98 (dd, J = 2.4, 8.5 Hz, 1H), 6.86 - 6.84 (m, 2H), 6.57 (d, J = 1.3 Hz) , 1H), 3.67 (s, 3H), 3.41 - 3.37 (m, 2H), 2.67 (s, 3H), 2.47 (t, J = 4.4 Hz, 2H), 1.82 (d, J = 13.5 Hz, 2H) , 1.65 - 1.56 (m, 8H), 0.63 - 0.59 (m, 2H), 0.43 - 0.38 (m, 2H), 0.12 - 0.09 (m, 2H); 544 [M+H] +
158158 메틸 2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)벤조에이트Methyl 2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3-fluorophenyl)amino)-5-methylthieno[2,3- d]pyrimidin-2-yl)amino)benzoate 1H NMR (400 MHz, CDCl3) δ 7.79 - 7.76 (m, 2H), 7.67 (ddd, J = 2.2, 2.2, 11.2 Hz, 1H), 7.31 - 7.28 (m, 1H), 7.25 - 7.23 (m, 1H), 7.17 (dd, J = 1.1, 8.1 Hz, 1H), 7.04 (d, J = 8.6 Hz, 1H), 6.87 (s, 1H), 6.80 (ddd, J = 1.8, 8.1, 8.2 Hz, 1H), 6.61 (d, J = 1.1 Hz, 1H), 3.86 (s, 3H), 3.29 - 3.20 (m, 6H), 2.75 - 2.68 (m, 2H), 2.67 (s, 3H), 2.12 - 2.06 (m, 3H), 1.78 (d, J = 11.5 Hz, 2H), 1.48 - 1.40 (m, 2H); 547 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.79 - 7.76 (m, 2H), 7.67 (ddd, J = 2.2, 2.2, 11.2 Hz, 1H), 7.31 - 7.28 (m, 1H), 7.25 - 7.23 (m , 1H), 7.17 (dd, J = 1.1, 8.1 Hz, 1H), 7.04 (d, J = 8.6 Hz, 1H), 6.87 (s, 1H), 6.80 (ddd, J = 1.8, 8.1, 8.2 Hz, 1H), 6.61 (d, J = 1.1 Hz, 1H), 3.86 (s, 3H), 3.29 - 3.20 (m, 6H), 2.75 - 2.68 (m, 2H), 2.67 (s, 3H), 2.12 - 2.06 (m, 3H), 1.78 (d, J = 11.5 Hz, 2H), 1.48 - 1.40 (m, 2H); 547 [M+H] +
159159 N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-플루오로프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-fluoropropan-2-yl)pyridin-2-yl) -5-Methylthieno[2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ8.29 (d, J = 8.1 Hz, 1H), 7.91 (s, 1H), 7.65 (dd, J = 7.9, 8.0 Hz, 1H), 7.25 - 7.22 (m, 2H), 7.08 (dd, J = 2.3, 8.5 Hz, 1H), 6.92 (d, J = 8.5 Hz, 1H), 6.88 (s, 1H), 6.62 (d, J = 1.1 Hz, 1H), 3.83 (s, 3H), 3.52 (d, J = 11.7 Hz, 2H), 2.72 (s, 3H), 2.62 - 2.55 (m, 2H), 2.35 - 2.31 (m, 5H), 1.90 - 1.72 (m, 4H), 1.66 (s, 6H); 550 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ8.29 (d, J = 8.1 Hz, 1H), 7.91 (s, 1H), 7.65 (dd, J = 7.9, 8.0 Hz, 1H), 7.25 - 7.22 (m , 2H), 7.08 (dd, J = 2.3, 8.5 Hz, 1H), 6.92 (d, J = 8.5 Hz, 1H), 6.88 (s, 1H), 6.62 (d, J = 1.1 Hz, 1H), 3.83 (s, 3H), 3.52 (d, J = 11.7 Hz, 2H), 2.72 (s, 3H), 2.62 - 2.55 (m, 2H), 2.35 - 2.31 (m, 5H), 1.90 - 1.72 (m, 4H) ), 1.66 (s, 6H); 550 [M+H] +
160160 2-(6-((2-((4-(4-시클로부틸피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-cyclobutylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ8.32 (d, J = 8.0 Hz, 1H), 7394 (s, 1H), 7.65 (dd, J = 7.9, 8.0 Hz, 1H), 7.25 - 7.22 (m, 1H), 7.08 - 7.02 (m, 2H), 6.93 (d, J = 8.5 Hz, 1H), 6.63 (d, J = 1.1 Hz, 1H), 4.72 (s, 1H), 3.82 (s, 3H), 3.49 - 3.42 (m, 2H), 2.73 (s, 3H), 2.50 (t, J = 11.4 Hz, 2H), 2.12 - 1.98 (m, 3H), 1.89 - 1.67 (m, 6H), 1.54 (s, 6H), 1.37 - 1.30 (m, 3H); 559 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ8.32 (d, J = 8.0 Hz, 1H), 7394 (s, 1H), 7.65 (dd, J = 7.9, 8.0 Hz, 1H), 7.25 - 7.22 (m , 1H), 7.08 - 7.02 (m, 2H), 6.93 (d, J = 8.5 Hz, 1H), 6.63 (d, J = 1.1 Hz, 1H), 4.72 (s, 1H), 3.82 (s, 3H) , 3.49 - 3.42 (m, 2H), 2.73 (s, 3H), 2.50 (t, J = 11.4 Hz, 2H), 2.12 - 1.98 (m, 3H), 1.89 - 1.67 (m, 6H), 1.54 (s , 6H), 1.37 - 1.30 (m, 3H); 559 [M+H] +
161161 2-(3-((2-((4-(4-시클로부틸피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-cyclobutylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl) amino) phenyl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ7.64 (dd, J = 1.3, 8.0 Hz, 1H), 7.57 (dd, J = 1.8, 1.9 Hz, 1H), 7.32 (dd, J = 7.8, 8.0 Hz, 1H), 7.25 - 7.21 (m, 1H), 6.98 (dd, J = 2.2, 8.3 Hz, 1H), 6.85 (d, J = 8.6 Hz, 1H), 6.84 (s, 1H), 6.58 (d, J = 1.3 Hz, 1H), 3.66 (s, 3H), 3.38 (d, J = 11.6 Hz, 2H), 2.67 (s, 3H), 2.47 (t, J = 11.0 Hz, 2H), 2.12 - 1.96 (m, 3H), 1.88 - 1.83 (m, 2H), 1.76 - 1.66 (m, 4H), 1.55 (s, 6H), 1.34 - 1.25 (m, 4H); 558 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ7.64 (dd, J = 1.3, 8.0 Hz, 1H), 7.57 (dd, J = 1.8, 1.9 Hz, 1H), 7.32 (dd, J = 7.8, 8.0 Hz) , 1H), 7.25 - 7.21 (m, 1H), 6.98 (dd, J = 2.2, 8.3 Hz, 1H), 6.85 (d, J = 8.6 Hz, 1H), 6.84 (s, 1H), 6.58 (d, J = 1.3 Hz, 1H), 3.66 (s, 3H), 3.38 (d, J = 11.6 Hz, 2H), 2.67 (s, 3H), 2.47 (t, J = 11.0 Hz, 2H), 2.12 - 1.96 ( m, 3H), 1.88 - 1.83 (m, 2H), 1.76 - 1.66 (m, 4H), 1.55 (s, 6H), 1.34 - 1.25 (m, 4H); 558 [M+H] +
162162 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)amino)-5-methylthieno[2, 3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ8.31 (d, J = 8.2 Hz, 1H), 7.93 (s, 1H), 7.65 (dd, J = 7.9, 8.0 Hz, 1H), 7.19 (d, J = 2.3 Hz, 1H), 7.08 - 7.02 (m, 2H), 6.89 (d, J = 8.5 Hz, 1H), 6.83 (s, 1H), 6.63 (d, J = 1.2 Hz, 1H), 4.72 (s, 1H), 4.01 (q, J = 7.0 Hz, 2H), 3.44 (d, J = 11.8 HZ, 2H), 3.22 (t, J = 7.0 Hz, 4H), 2.72 (s, 3H), 2.65 - 2.60 (m, 2H), 2.13 - 2.04 (m, 3H), 1.80 (d, J = 11.8 Hz, 2H), 1.54 - 1.50 (m, 8H), 1.41 (t, J = 7.0 Hz, 3H); 574 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ8.31 (d, J = 8.2 Hz, 1H), 7.93 (s, 1H), 7.65 (dd, J = 7.9, 8.0 Hz, 1H), 7.19 (d, J = 2.3 Hz, 1H), 7.08 - 7.02 (m, 2H), 6.89 (d, J = 8.5 Hz, 1H), 6.83 (s, 1H), 6.63 (d, J = 1.2 Hz, 1H), 4.72 (s , 1H), 4.01 (q, J = 7.0 Hz, 2H), 3.44 (d, J = 11.8 HZ, 2H), 3.22 (t, J = 7.0 Hz, 4H), 2.72 (s, 3H), 2.65 - 2.60 (m, 2H), 2.13 - 2.04 (m, 3H), 1.80 (d, J = 11.8 Hz, 2H), 1.54 - 1.50 (m, 8H), 1.41 (t, J = 7.0 Hz, 3H); 574 [M+H] +
163163 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ7.60 - 7.56 (m, 2H), 7.32 (dd, J = 7.8, 7.8 Hz, 1H), 7.25 - 7.22 (m, 2H), 7.15 (s, 1H), 6.94 (dd, J = 2.3, 8.6 Hz, 1H), 6.81 (d, J = 8.2 Hz, 2H), 6.57 (d, J = 1.1 Hz, 1H), 3.76 (q, J = 7.0 Hz, 2H), 3.38 (d, J = 11.6 Hz, 2H), 3.21 (t, J = 6.9 Hz, 4H), 2.67 (s, 3H), 2.62 - 2.56 (m, 2H), 2.11 - 1.96 (m, 3H), 1.78 (d, J = 11.6 Hz, 2H), 1.53 (s, 6H), 1.50 - 1.46 (m, 2H), 1.33 (t, J = 7.0 Hz, 3H); 573 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.60 - 7.56 (m, 2H), 7.32 (dd, J = 7.8, 7.8 Hz, 1H), 7.25 - 7.22 (m, 2H), 7.15 (s, 1H) , 6.94 (dd, J = 2.3, 8.6 Hz, 1H), 6.81 (d, J = 8.2 Hz, 2H), 6.57 (d, J = 1.1 Hz, 1H), 3.76 (q, J = 7.0 Hz, 2H) , 3.38 (d, J = 11.6 Hz, 2H), 3.21 (t, J = 6.9 Hz, 4H), 2.67 (s, 3H), 2.62 - 2.56 (m, 2H), 2.11 - 1.96 (m, 3H), 1.78 (d, J = 11.6 Hz, 2H), 1.53 (s, 6H), 1.50 - 1.46 (m, 2H), 1.33 (t, J = 7.0 Hz, 3H); 573 [M+H] +
164164 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno[2, 3-d] pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ7.71 (ddd, J = 2.2, 2.2, 11.2 Hz, 1H), 7.29 - 7.24 (m, 1H), 77.21 - 7.15 (m, 3HH), 7.10 (dd, J = 2.3. 8.5 Hz, 1H), 6.88 (d, J = 8.5 Hz, 1H), 6.83 - 6.80 (m, 2H), 6.59 (d, J = 1.1 Hz, 1H), 3.97 (q, J = 6.9 Hz, 2H), 3.43 (d, J = 11.8 Hz, 2H), 3.22 (t, J = 6.9 Hz, 4H), 2.67 (s, 3H), 2.59 (dt, J = 1.8, 11.2 Hz, 2H), 2.11 - 2.06 (m, 3H), 1.80 (d, J = 11.4 Hz, 2H), 1.55 - 1.49 (m, 2H), 1.41 (t, J = 6.9 Hz, 3H); 533 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.71 (ddd, J = 2.2, 2.2, 11.2 Hz, 1H), 7.29 - 7.24 (m, 1H), 77.21 - 7.15 (m, 3HH), 7.10 (dd, J = 2.3.8.5 Hz, 1H), 6.88 (d, J = 8.5 Hz, 1H), 6.83 - 6.80 (m, 2H), 6.59 (d, J = 1.1 Hz, 1H), 3.97 (q, J = 6.9 Hz, 2H), 3.43 (d, J = 11.8 Hz, 2H), 3.22 (t, J = 6.9 Hz, 4H), 2.67 (s, 3H), 2.59 (dt, J = 1.8, 11.2 Hz, 2H), 2.11 - 2.06 (m, 3H), 1.80 (d, J = 11.4 Hz, 2H), 1.55 - 1.49 (m, 2H), 1.41 (t, J = 6.9 Hz, 3H); 533 [M+H] +
165165 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.09 (s, 1H), 7.51 - 7.50 (m, 1H), 7.44 (d, J = 2.36 Hz, 1H), 7.37 (d, J = 4.88 Hz, 2H), 7.24 (dd, J = 8.48, 1.92 Hz, 1H), 7.14 (s, 1H), 7.06 (d, J = 8.56 Hz, 1H), 7.01 (s, 1H), 6.57 (d, J = 0.84 Hz, 1H), 4.47 (s, 1H), 3.32 - 3.28 (m, 4H), 3.08 - 3.05 (m, 2H), 2.70 - 2.67 (m, 2H), 2.65 (s, 3H), 2.13 - 2.09 (m, 1H), 2.05 - 2.03 (m, 2H), 1.84 - 1.81 (m, 2H), 1.46 (s, 6H), 1.27 - 1.23 (m, 2H) ; 559 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.09 (s, 1H), 7.51 - 7.50 (m, 1H), 7.44 (d, J = 2.36 Hz, 1H), 7.37 (d, J = 4.88 Hz, 2H) , 7.24 (dd, J = 8.48, 1.92 Hz, 1H), 7.14 (s, 1H), 7.06 (d, J = 8.56 Hz, 1H), 7.01 (s, 1H), 6.57 (d, J = 0.84 Hz, 1H), 4.47 (s, 1H), 3.32 - 3.28 (m, 4H), 3.08 - 3.05 (m, 2H), 2.70 - 2.67 (m, 2H), 2.65 (s, 3H), 2.13 - 2.09 (m, 1H), 2.05 - 2.03 (m, 2H), 1.84 - 1.81 (m, 2H), 1.46 (s, 6H), 1.27 - 1.23 (m, 2H); 559 [M+H] +
166166 (2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)페닐)메탄올(2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3-fluorophenyl)amino)-5-methylthieno[2,3- d]pyrimidin-2-yl)amino)phenyl)methanol 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.26 Hz, 1H), 7.49 (dd, J = 8.6, 2.48 Hz, 1H), 7.34 (d, J = 2.52 Hz, 1H), 7.31 - 7.28 (m,1H), 7.23 (s, 1H), 7.16 (dd, J = 8.68, 3.48 Hz, 2H), 6.92 (s, 1H), 6.83 (td, J = 8.28, 1.92 Hz, 1H), 6.61 (d, J = 1.08 Hz, 1H), 4.73 (s, 2H), 3.29 - 3.27 (m, 4H), 3.15 - 3.12 (m, 2H), 2.76 - 2.70 (m, 2H), 2.66 (s, 3H), 2.23 - 2.21 (m, 1H), 2.15 - 2.08 (m, 2H), 1.87 - 1.84 (m, 2H), 1.56 - 1.47 (m, 2H) ; 519 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.67 (d, J = 8.26 Hz, 1H), 7.49 (dd, J = 8.6, 2.48 Hz, 1H), 7.34 (d, J = 2.52 Hz, 1H), 7.31 - 7.28 (m, 1H), 7.23 (s, 1H), 7.16 (dd, J = 8.68, 3.48 Hz, 2H), 6.92 (s, 1H), 6.83 (td, J = 8.28, 1.92 Hz, 1H), 6.61 (d, J = 1.08 Hz, 1H), 4.73 (s, 2H), 3.29 - 3.27 (m, 4H), 3.15 - 3.12 (m, 2H), 2.76 - 2.70 (m, 2H), 2.66 (s, 3H), 2.23 - 2.21 (m, 1H), 2.15 - 2.08 (m, 2H), 1.87 - 1.84 (m, 2H), 1.56 - 1.47 (m, 2H); 519 [M+H] +
167167 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-이소프로폭시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropoxyphenyl)amino)-5-methylthieno[2 ,3-d] pyrimidin-4-yl) amino) phenyl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 1.64 Hz, 1H), 7.57 (d, J = 7.88 Hz, 1H), 7.34 (t, J = 7.88 Hz, 1H), 7.28 (d, J = 2.36 Hz, 1H), 7.24 (s, 1H), 7.15 (s, 1H), 6.96 (dd, J = 8.48, 2.32 Hz, 1H), 6.84 (s, 1H), 6.79 (d, J = 8.52 Hz, 1H), 6.56 (d, J = 1.0 Hz, 1H), 4.42 - 4.36 (m, 1H), 3.42 - 3.33 (m, 5H), 2.66 (s,3H), 2.61 - 2.53 (m, 3H), 2.15 - 2.13 (m, 3H), 1.82 - 1.79 (m, 2H), 1.54 (s, 6H), 1.53 - 1.51 (m, 2H), 1.23 (s, 3H), 1.21 (s, 3H) ; 587 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 7.61 (d, J = 1.64 Hz, 1H), 7.57 (d, J = 7.88 Hz, 1H), 7.34 (t, J = 7.88 Hz, 1H), 7.28 (d , J = 2.36 Hz, 1H), 7.24 (s, 1H), 7.15 (s, 1H), 6.96 (dd, J = 8.48, 2.32 Hz, 1H), 6.84 (s, 1H), 6.79 (d, J = 8.52 Hz, 1H), 6.56 (d, J = 1.0 Hz, 1H), 4.42 - 4.36 (m, 1H), 3.42 - 3.33 (m, 5H), 2.66 (s, 3H), 2.61 - 2.53 (m, 3H) ), 2.15 - 2.13 (m, 3H), 1.82 - 1.79 (m, 2H), 1.54 (s, 6H), 1.53 - 1.51 (m, 2H), 1.23 (s, 3H), 1.21 (s, 3H); 587 [M+H] +
168168 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-이소프로폭시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropoxyphenyl)amino)-5-methylthieno[2 ,3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.24 Hz, 1H), 7.92 (s, 1H), 7.68 (t, J = 7.96 Hz, 1H), 7.24 (d, J = 1.6 Hz, 1H), 7.09 - 7.03 (m, 2H), 6.88 (s, 1H), 6.84 (d, J = 6.68 Hz, 1H), 6.63 (s, 1H), 4.73 (bs, 1H), 4.58 - 4.52 (m, 1H), 3.51 - 3.48 (m, 6H), 2.72 (s, 3H), 2.63 - 2.57 (m, 3H), 2.24 - 2.20 (m, 2H), 1.88 - 1.85 (m, 2H), 1.70 - 1.60 (m, 2H), 1.54 (s, 6H), 1.33 (s, 3H), 1.31 (s, 3H) ; 588 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.32 (d, J = 8.24 Hz, 1H), 7.92 (s, 1H), 7.68 (t, J = 7.96 Hz, 1H), 7.24 (d, J = 1.6 Hz , 1H), 7.09 - 7.03 (m, 2H), 6.88 (s, 1H), 6.84 (d, J = 6.68 Hz, 1H), 6.63 (s, 1H), 4.73 (bs, 1H), 4.58 - 4.52 ( m, 1H), 3.51 - 3.48 (m, 6H), 2.72 (s, 3H), 2.63 - 2.57 (m, 3H), 2.24 - 2.20 (m, 2H), 1.88 - 1.85 (m, 2H), 1.70 - 1.60 (m, 2H), 1.54 (s, 6H), 1.33 (s, 3H), 1.31 (s, 3H); 588 [M+H] +
169169 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-이소프로폭시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno[2 ,3-d] pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.74 - 7.70 (m, 1H), 7.31 - 7.27 (m, 1H), 7.25 - 7.17 (m, 3H), 7.15 - 7.11 (m, 1H), 6.86 - 6.78 (m, 3H), 6.59 (d, J = 1.08 Hz, 1H), 4.55 - 4.49 (m, 1H), 3.80 - 3.60 (m, 3H), 3.53 - 3.50 (m, 2H), 2.66 (s, 3H), 2.61 - 2.55 (m, 3H), 2.35 - 2.25 (m, 2H), 1.91 - 1.88 (m, 2H), 1.70 - 1.68 (m, 2H), 1.33 (s, 3H), 1.32 (s, 3H); 547 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.74 - 7.70 (m, 1H), 7.31 - 7.27 (m, 1H), 7.25 - 7.17 (m, 3H), 7.15 - 7.11 (m, 1H), 6.86 - 6.78 (m, 3H), 6.59 (d, J = 1.08 Hz, 1H), 4.55 - 4.49 (m, 1H), 3.80 - 3.60 (m, 3H), 3.53 - 3.50 (m, 2H), 2.66 (s, 3H) ), 2.61 - 2.55 (m, 3H), 2.35 - 2.25 (m, 2H), 1.91 - 1.88 (m, 2H), 1.70 - 1.68 (m, 2H), 1.33 (s, 3H), 1.32 (s, 3H) ); 547 [M+H] +
170170 2-(6-((2-((3,5-디메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3,5-dimethyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[ 2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.49 (bs, 1H), 6.96 (d, J = 7.56 Hz, 1H), 6.57 (d, J = 1.08 Hz, 1H), 6.14 (s, 1H), 4.74 (bs, 1H), 3.99 - 3.97 (m, 1H), 3.12 - 3.10 (m, 2H), 2.69 (s, 3H), 2.39 (s, 3H), 2.35 - 2.23 (m, 4H), 2.15 (s, 3H), 2.13 (s, 3H), 1.98 - 1.96 (m, 2H), 1.51 (s, 6H) ; 507 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.92 (s, 1H), 7.49 (bs, 1H), 6.96 (d, J = 7.56 Hz, 1H), 6.57 (d, J = 1.08 Hz, 1H), 6.14 (s, 1H), 4.74 (bs, 1H), 3.99 - 3.97 (m, 1H), 3.12 - 3.10 (m, 2H), 2.69 (s, 3H), 2.39 (s, 3H), 2.35 - 2.23 (m , 4H), 2.15 (s, 3H), 2.13 (s, 3H), 1.98 - 1.96 (m, 2H), 1.51 (s, 6H); 507 [M+H] +
171171 3-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)옥세탄-3-올3-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)oxetan-3-ol 1H NMR (400 MHz, CDCl3) δ7.85 (s, 1H), 7.50 - 7.38 (m, 3H), 7.22 - 7.15 (m, 2H), 6.95 - 6.86 (m, 2H), 6.81 (d, J = 8.5 Hz, 1H), 6.59 (d, J = 1.1 Hz, 1H), 4.82 (d, J = 7.0 Hz, 2H), 4.71 (d, J = 6.9 Hz, 2H), 3.53 (s, 3H), 3.41 - 3.24 (m, 6H), 2.67 (s, 3H), 2.64 - 2.57 (m, 2H), 2.25 - 2.18 (m, 1H), 2.16 - 2.09 (m, 2H), 1.83 - 1.79 (m, 3H), 1.58 - 1.54 (m, 2H); 573 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.85 (s, 1H), 7.50 - 7.38 (m, 3H), 7.22 - 7.15 (m, 2H), 6.95 - 6.86 (m, 2H), 6.81 (d, J = 8.5 Hz, 1H), 6.59 (d, J = 1.1 Hz, 1H), 4.82 (d, J = 7.0 Hz, 2H), 4.71 (d, J = 6.9 Hz, 2H), 3.53 (s, 3H) , 3.41 - 3.24 (m, 6H), 2.67 (s, 3H), 2.64 - 2.57 (m, 2H), 2.25 - 2.18 (m, 1H), 2.16 - 2.09 (m, 2H), 1.83 - 1.79 (m, 3H), 1.58 - 1.54 (m, 2H); 573 [M+H] +
172172 DN300786LSY-023-80
3-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)옥세탄-3-올DN300786LSY-023-80
3-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)oxetan-3-ol 		1H NMR (400 MHz, CDCl3) δ7.81 (s, 1H), 7.59 - 7.52 (m, 1H), 7.41 (d, J = 5.2 Hz, 2H), 7.24 - 7.16 (m, 2H), 6.95 (dd, J = 8.5, 2.3 Hz, 1H), 6.89 (s, 1H), 6.83 (d, J = 8.5 Hz, 1H), 6.60 (d, J = 1.1 Hz, 1H), 4.84 (d, J = 7.1 Hz, 2H), 4.77 (d, J = 7.0 Hz, 2H), 3.60 (s, 3H), 3.52 - 3.44 (m, 2H), 2.67 (s, 3H), 2.56 (t, J = 10.9 Hz, 2H), 2.46 - 2.25 (m, 8H), 1.95 - 1.89 (m, 2H), 1.81 - 1.76 (m, 2H); 561 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ7.81 (s, 1H), 7.59 - 7.52 (m, 1H), 7.41 (d, J = 5.2 Hz, 2H), 7.24 - 7.16 (m, 2H), 6.95 (dd, J = 8.5, 2.3 Hz, 1H), 6.89 (s, 1H), 6.83 (d, J = 8.5 Hz, 1H), 6.60 (d, J = 1.1 Hz, 1H), 4.84 (d, J = 7.1 Hz, 2H), 4.77 (d, J = 7.0 Hz, 2H), 3.60 (s, 3H), 3.52 - 3.44 (m, 2H), 2.67 (s, 3H), 2.56 (t, J = 10.9 Hz, 2H), 2.46 - 2.25 (m, 8H), 1.95 - 1.89 (m, 2H), 1.81 - 1.76 (m, 2H); 561 [M+H] +
173173 2-(3-((2-((3-메톡시-4-(2-옥사-6-아자스피로[3.3]헵탄-6-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((3-methoxy-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 8.91 (s, 1H), 8.01 (s, 1H), 7.71 (d, J = 8.7 Hz, 1H), 7.55 - 7.48 (m, 1H), 7.31 - 7.16 (m, 3H), 7.11 (d, J = 8.5 Hz, 1H), 6.78 (s, 1H), 6.24 (d, J = 8.5 Hz, 1H), 4.99 (s, 1H), 4.68 (s, 4H), 3.87 (s, 4H), 3.50 (s, 3H), 2.64 (s, 3H), 1.42 (s, 6H); 518 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 8.91 (s, 1H), 8.01 (s, 1H), 7.71 (d, J = 8.7 Hz, 1H), 7.55 - 7.48 (m, 1H), 7.31 - 7.16 (m , 3H), 7.11 (d, J = 8.5 Hz, 1H), 6.78 (s, 1H), 6.24 (d, J = 8.5 Hz, 1H), 4.99 (s, 1H), 4.68 (s, 4H), 3.87 (s, 4H), 3.50 (s, 3H), 2.64 (s, 3H), 1.42 (s, 6H); 518 [M+H] +
174174 2-(6-((2-((3-메톡시-4-(2-옥사-6-아자스피로[3.3]헵탄-6-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((3-methoxy-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)amino)-5-methylthieno[2,3 -d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.17 (s, 1H), 8.29 (br s, 1H), 8.21 (s, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.33 (d, J = 7.5 Hz, 1H), 7.25 (s, 1H), 7.19 (d, J = 8.4 Hz, 1H), 6.88 (s, 1H), 6.35 (d, J = 8.4 Hz, 1H), 5.20 (s, 1H), 4.70 (s, 4H), 3.92 (s, 4H), 3.66 (s, 3H), 2.65 (s, 3H), 1.44 (s, 6H); 519 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.17 (s, 1H), 8.29 (br s, 1H), 8.21 (s, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.33 (d, J = 7.5 Hz, 1H), 7.25 (s, 1H), 7.19 (d, J = 8.4 Hz, 1H), 6.88 (s, 1H), 6.35 (d, J = 8.4 Hz, 1H), 5.20 (s, 1H) , 4.70 (s, 4H), 3.92 (s, 4H), 3.66 (s, 3H), 2.65 (s, 3H), 1.44 (s, 6H); 519 [M+H] +
175175 2-(3-((5-메틸-2-((1-메틸-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)phenyl) propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.04 (s, 1H), 8.12 (br s, 1H), 7.58 - 7.46 (m, 2H), 7.45 - 7.12 (m, 4H), 6.75 (s, 1H), 5.04 (s, 1H), 3.65 (s, 3H), 2.62 (s, 3H), 1.45 (s, 6H); 395 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.04 (s, 1H), 8.12 (br s, 1H), 7.58 - 7.46 (m, 2H), 7.45 - 7.12 (m, 4H), 6.75 (s, 1H), 5.04 (s, 1H), 3.65 (s, 3H), 2.62 (s, 3H), 1.45 (s, 6H); 395 [M+H] +
176176 2-(6-((5-메틸-2-((1-메틸-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridine- 2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.31 (br s, 1H), 8.55 - 8.14 (m, 2H), 7.90 (br s, 1H), 7.79 (t, J = 7.9 Hz, 1H), 7.45 (s, 1H), 7.35 (d, J = 7.6 Hz, 1H), 6.87 (s, 1H), 5.21 (s, 1H), 3.80 (s, 3H), 2.64 (s, 3H), 1.44 (s, 6H); 396 [M+H]+ 1H NMR (400 MHz, DMSO) δ 9.31 (br s, 1H), 8.55 - 8.14 (m, 2H), 7.90 (br s, 1H), 7.79 (t, J = 7.9 Hz, 1H), 7.45 (s , 1H), 7.35 (d, J = 7.6 Hz, 1H), 6.87 (s, 1H), 5.21 (s, 1H), 3.80 (s, 3H), 2.64 (s, 3H), 1.44 (s, 6H) ; 396 [M+H] +
177177 2-(3-((2-((1-(2-옥사스피로[3.3]헵탄-6-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.87 (s, 1H), 8.51 - 8.16 (m, 2H), 7.54 (s, 2H), 7.47 - 7.20 (m, 3H), 6.89 (s, 1H), 5.17 (br s, 1H), 4.53 (br s, 1H), 3.51 (s, 4H), 2.65 (s, 3H), 2.57 - 2.53 (m, 2H), 1.92 (d, J = 9.7 Hz, 2H), 1.44 (s, 6H); 477 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.87 (s, 1H), 8.51 - 8.16 (m, 2H), 7.54 (s, 2H), 7.47 - 7.20 (m, 3H), 6.89 (s, 1H), 5.17 (br s, 1H), 4.53 (br s, 1H), 3.51 (s, 4H), 2.65 (s, 3H), 2.57 - 2.53 (m, 2H), 1.92 (d, J = 9.7 Hz, 2H), 1.44 (s, 6H); 477 [M+H] +
178178 2-(6-((2-((1-(2-옥사스피로[3.3]헵탄-6-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 10.19 (br s, 1H), 8.76 - 8.56 (m, 2H), 8.55 - 8.24 (m, 2H), 7.83 (t, J = 7.9 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.00 (s, 1H), 5.24 (br s, 1H), 4.65 (s, 1H), 3.54 (s, 4H), 2.66 (s, 3H), 2.62 - 2.53 (m, 2H), 2.02 - 1.93 (m, 2H), 1.44 (s, 6H); 478 [M+H]+ 1H NMR (400 MHz, DMSO) δ 10.19 (br s, 1H), 8.76 - 8.56 (m, 2H), 8.55 - 8.24 (m, 2H), 7.83 (t, J = 7.9 Hz, 1H), 7.38 ( d, J = 7.6 Hz, 1H), 7.00 (s, 1H), 5.24 (br s, 1H), 4.65 (s, 1H), 3.54 (s, 4H), 2.66 (s, 3H), 2.62 - 2.53 ( m, 2H), 2.02 - 1.93 (m, 2H), 1.44 (s, 6H); 478 [M+H] +
179179 2-(3-((2-((1-((3S,4R)-3-플루오로피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-((3S,4R)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.07 (s, 1H), 8.16 (br s, 1H), 7.58 - 7.04 (m, 6H), 6.75 (s, 1H), 5.07 (s, 1H), 4.74 - 4.51 (m, 1H), 3.30 - 3.24 (m, 1H), 2.98 - 2.87 (m, 1H), 2.62 (s, 3H), 1.80 (s, 2H), 1.46 (s, 6H); 482 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.07 (s, 1H), 8.16 (br s, 1H), 7.58 - 7.04 (m, 6H), 6.75 (s, 1H), 5.07 (s, 1H), 4.74 - 4.51 (m, 1H), 3.30 - 3.24 (m, 1H), 2.98 - 2.87 (m, 1H), 2.62 (s, 3H), 1.80 (s, 2H), 1.46 (s, 6H); 482 [M+H] +
180180 2-(6-((2-((1-((3S,4R)-3-플루오로피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-((3S,4R)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.33 (br s, 1H), 8.57 - 8.17 (m, 2H), 8.03 (br s, 1H), 7.85 - 7.70 (m, 1H), 7.54 (s, 1H), 7.34 (d, J = 7.6 Hz, 1H), 6.87 (s, 1H), 5.21 (s, 1H), 4.82 - 4.60 (m, 1H), 4.32 (br s, 1H), 3.32 - 3.23 (m, 1H), 2.97 - 2.86 (m, 1H), 2.63 (s, 3H), 1.98 - 1.87 (m, 2H), 1.44 (s, 6H); 483 [M+H]+ 1H NMR (400 MHz, DMSO) δ 9.33 (br s, 1H), 8.57 - 8.17 (m, 2H), 8.03 (br s, 1H), 7.85 - 7.70 (m, 1H), 7.54 (s, 1H) , 7.34 (d, J = 7.6 Hz, 1H), 6.87 (s, 1H), 5.21 (s, 1H), 4.82 - 4.60 (m, 1H), 4.32 (br s, 1H), 3.32 - 3.23 (m, 1H), 2.97 - 2.86 (m, 1H), 2.63 (s, 3H), 1.98 - 1.87 (m, 2H), 1.44 (s, 6H); 483 [M+H] +
181181 메틸 2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)벤조에이트 트리플루오로아테트산Methyl 2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl) amino)-5-methylthieno[2,3-d]pyrimidin-2-yl)amino)benzoate trifluoroacetic acid 1H NMR (400MHz, CDCl3) δ 8.28 (d, J = 8.2 Hz, 1H), 7.96 (s, 1H), 7.83 (d, J = 2.7 Hz, 1H), 7.69 - 7.65 (m, 2H), 73.05 (dd, J = 8.2, 6.9 Hz, 2H), 6.88 (s, 1H), 6.65 (s, 1H), 3.86 (s, 1H), 3.49 (s, 3H), 3.29 - 3.20 (m, 6H), 2.75 - 2.72 (m, 5H), 2.12 - 2.02 (m, 3H), 1.80 (d, J = 11.8 Hz, 2H), 1.47 (s, 6H), 1.31 - 1.25 (m, 2H); 588 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.28 (d, J = 8.2 Hz, 1H), 7.96 (s, 1H), 7.83 (d, J = 2.7 Hz, 1H), 7.69 - 7.65 (m, 2H), 73.05 (dd, J = 8.2, 6.9 Hz, 2H), 6.88 (s, 1H), 6.65 (s, 1H), 3.86 (s, 1H), 3.49 (s, 3H), 3.29 - 3.20 (m, 6H) , 2.75 - 2.72 (m, 5H), 2.12 - 2.02 (m, 3H), 1.80 (d, J = 11.8 Hz, 2H), 1.47 (s, 6H), 1.31 - 1.25 (m, 2H); 588 [M+H] +
182182 메틸 2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)벤조에이트Methyl 2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5 -Methylthieno[2,3-d]pyrimidin-2-yl)amino)benzoate 1H NMR (400MHz, CDCl3) δ 7.74 - 7.65 (m, 3H), 7.55 (s, 1H), 7.33 (dd, J = 7.9, 8.0 Hz, 1H), 7.24 (d, J = 8.3 Hz, 1H), 7.18 (s, 1H), 6.98 (d, J = 8.7 Hz, 1H), 6.88 (s, 1H), 6.59 (s, 1H), 3.83 (s, 3H), 3.24 - 3.20 (m, 6H), 2.72 - 2.67 (m, 5H), 2.12 - 2.04 (m,3H), 1.77 (d, J = 11.4 Hz, 2H), 1.57 (s, 6H), 1.49 - 1.40 (m, 2H); 587 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.74 - 7.65 (m, 3H), 7.55 (s, 1H), 7.33 (dd, J = 7.9, 8.0 Hz, 1H), 7.24 (d, J = 8.3 Hz, 1H) ), 7.18 (s, 1H), 6.98 (d, J = 8.7 Hz, 1H), 6.88 (s, 1H), 6.59 (s, 1H), 3.83 (s, 3H), 3.24 - 3.20 (m, 6H) , 2.72 - 2.67 (m, 5H), 2.12 - 2.04 (m, 3H), 1.77 (d, J = 11.4 Hz, 2H), 1.57 (s, 6H), 1.49 - 1.40 (m, 2H); 587 [M+H] +
183183 2-(6-((5-메틸-2-((1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((5-methyl-2-((1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 8.32 (d, J = 7.5 Hz, 1H), 7.97-7.93 (m, 2H), 7.73 (dd, J = 7.9, 7.9 Hz, 1H), 7.53 (s, 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.64 (s, 2H), 4.71-4.63 (m, 6H), 4.19-4.13 (m, 1H), 3.56-3.52 (m, 1H), 2.89 (d, J = 10.3 Hz, 2H), 2.73 (s, 3H), 2.24-2.01 (m, 6H), 1.55 (s, 6H); 521 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.32 (d, J = 7.5 Hz, 1H), 7.97-7.93 (m, 2H), 7.73 (dd, J = 7.9, 7.9 Hz, 1H), 7.53 (s, 1H) ), 7.06 (d, J = 7.5 Hz, 1H), 6.64 (s, 2H), 4.71–4.63 (m, 6H), 4.19–4.13 (m, 1H), 3.56–3.52 (m, 1H), 2.89 ( d, J = 10.3 Hz, 2H), 2.73 (s, 3H), 2.24–2.01 (m, 6H), 1.55 (s, 6H); 521 [M+H] +
184184 2-(3-((5-메틸-2-((1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((5-methyl-2-((1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400MHz, CDCl3) δ 7.71 (s, 1H), 7.70-7.57 (m, 2H), 7.41-7.36 (m, 3H), 7.12 (s, 1H), 6.66 (s, 1H), 6.57 (s, 1H), 4.71-4.65 (m, 4H), 4.08-4.04 (m, 1H), 3.57-3.48 (m, 2H), 2.86 (d, J = 9.4 Hz, 2H), 2.66 (s, 3H), 2.09 (d, J = 11.1 Hz, 2H), 2.03-1.97 (m, 3H), 1.58 (s, 6H); 520 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.71 (s, 1H), 7.70-7.57 (m, 2H), 7.41-7.36 (m, 3H), 7.12 (s, 1H), 6.66 (s, 1H), 6.57 (s, 1H), 4.71-4.65 (m, 4H), 4.08-4.04 (m, 1H), 3.57-3.48 (m, 2H), 2.86 (d, J = 9.4 Hz, 2H), 2.66 (s, 3H) ), 2.09 (d, J = 11.1 Hz, 2H), 2.03–1.97 (m, 3H), 1.58 (s, 6H); 520 [M+H] +
185185 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.20 Hz, 1H), 7.95 (s, 1H), 7.72 (t, J = 7.92 Hz, 1H), 7.47 (dd, J = 8.52, 2.36 Hz, 1H), 7.43 (d, J = 2.36 Hz, 1H), 7.17 (d, J = 8.12 Hz, 1H), 7.06 (d, J = 7.56 Hz, 1H), 6.97 (s, 1H), 6.64 (d, J = 0.88 Hz, 1H), 4.76 (s, 2H), 3.33 - 3.30 (m, 4H), 3.17 - 3.14 (m, 2H), 2.77 - 2.72 (m, 2H), 2.68 (s, 3H), 2.25 - 2.21 (m, 3H), 1.88 - 1.85 (m, 2H), 1.55 (s, 6H), 1.53 - 1.49 (m, 2H) ; 560 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.32 (d, J = 8.20 Hz, 1H), 7.95 (s, 1H), 7.72 (t, J = 7.92 Hz, 1H), 7.47 (dd, J = 8.52, 2.36 Hz, 1H), 7.43 (d, J = 2.36 Hz, 1H), 7.17 (d, J = 8.12 Hz, 1H), 7.06 (d, J = 7.56 Hz, 1H), 6.97 (s, 1H), 6.64 (d, J = 0.88 Hz, 1H), 4.76 (s, 2H), 3.33 - 3.30 (m, 4H), 3.17 - 3.14 (m, 2H), 2.77 - 2.72 (m, 2H), 2.68 (s, 3H) ), 2.25 - 2.21 (m, 3H), 1.88 - 1.85 (m, 2H), 1.55 (s, 6H), 1.53 - 1.49 (m, 2H); 560 [M+H] +
186186 N4-(3-플루오로페닐)-5-메틸-N2-(1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민N4-(3-fluorophenyl)-5-methyl-N2-(1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)thieno [2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, CDCl3) δ 7.92 (bs, 1H), 7.81 (d, J = 10.64 Hz, 1H), 7.48 (s, 1H), 7.37 - 7.31 (m, 1H), 7.21 - 7.10 (m, 2H), 6.87 (t, J = 6.8 Hz, 1H), 6.81 (s, 1H), 6.62 (s, 1H), 4.73 - 4.51 (m, 4H), 4.16 - 4.12 (m, 1H), 3.58 - 3.51 (m, 1H), 2.90 - 2.78 (m, 2H), 2.53 (s, 3H), 2.17 - 1.90 (m, 6H) ; 480 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.92 (bs, 1H), 7.81 (d, J = 10.64 Hz, 1H), 7.48 (s, 1H), 7.37 - 7.31 (m, 1H), 7.21 - 7.10 ( m, 2H), 6.87 (t, J = 6.8 Hz, 1H), 6.81 (s, 1H), 6.62 (s, 1H), 4.73 - 4.51 (m, 4H), 4.16 - 4.12 (m, 1H), 3.58 - 3.51 (m, 1H), 2.90 - 2.78 (m, 2H), 2.53 (s, 3H), 2.17 - 1.90 (m, 6H); 480 [M+H] +
187187 2-(3-플루오로-5-((5-메틸-2-((1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-fluoro-5-((5-methyl-2-((1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl )amino)thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.78 (bs, 1H), 7.57 (bs,1H), 7.44 (s, 1H), 7.20 - 7.18 (m, 2H), 6.98 (d, J = 8.56 Hz, 1H), 6.85 (s, 1H), 6.59 (s, 1H), 4.70 - 4.67 (m, 4H), 4.15 - 4.09 (m, 1H), 3.55 - 3.53 (m, 1H), 2.87 - 2.85 (m, 2H), 2.66 (s, 3H), 2.13 - 2.11 (m, 2H), 2.04 - 1.99 (m, 4H), 1.57 (s, 6H) ; 538 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.78 (bs, 1H), 7.57 (bs, 1H), 7.44 (s, 1H), 7.20 - 7.18 (m, 2H), 6.98 (d, J = 8.56 Hz, 1H), 6.85 (s, 1H), 6.59 (s, 1H), 4.70 - 4.67 (m, 4H), 4.15 - 4.09 (m, 1H), 3.55 - 3.53 (m, 1H), 2.87 - 2.85 (m, 2H), 2.66 (s, 3H), 2.13 - 2.11 (m, 2H), 2.04 - 1.99 (m, 4H), 1.57 (s, 6H); 538 [M+H] +
188188 2-(6-((2-((1-((3S,4R)-3-플루오로-1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올2-(6-((2-((1-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5 -methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 8.2 Hz, 1H), 8.00 (br s, 1H), 7.92 (s, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.57 (s, 1H), 7.05 (d, J = 7.6 Hz, 1H), 6.70 (s, 1H), 6.62 (s, 1H), 5.03 - 4.82 (m, 1H), 4.72 (s, 1H), 4.18 - 4.04 (m, 1H), 3.34 - 3.26 (m, 1H), 2.98 - 2.89 (m, 1H), 2.72 (s, 3H), 2.40 (s, 3H), 2.31 - 2.14 (m, 4H), 1.55 (s, 6H); 497 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ 8.30 (d, J = 8.2 Hz, 1H), 8.00 (br s, 1H), 7.92 (s, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.57 (s, 1H), 7.05 (d, J = 7.6 Hz, 1H), 6.70 (s, 1H), 6.62 (s, 1H), 5.03 - 4.82 (m, 1H), 4.72 (s, 1H), 4.18 - 4.04 (m, 1H), 3.34 - 3.26 (m, 1H), 2.98 - 2.89 (m, 1H), 2.72 (s, 3H), 2.40 (s, 3H), 2.31 - 2.14 (m, 4H), 1.55 (s, 6H); 497 [M+H] +
189189 2-(3-((2-((1-((3S,4R)-3-플루오로-1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올2-(3-((2-((1-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5 -Methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, CDCl3) δ 7.69 - 7.51 (m, 2H), 7.48 (br zs, 1H), 7.43 - 7.34 (m, 3H), 7.08 (s, 1H), 6.88 (s, 1H), 6.56 (s, 1H), 4.77 - 4.48 (m, 1H), 4.10 - 3.96 (m, 1H), 3.33 - 3.21 (m, 1H), 2.95 - 2.84 (m, 1H), 2.65 (s, 3H), 2.38 (s, 3H), 2.19 - 2.08 (m, 2H), 2.04 - 1.98 (m, 2H), 1.58 (s, 6H); 496 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.69 - 7.51 (m, 2H), 7.48 (br zs, 1H), 7.43 - 7.34 (m, 3H), 7.08 (s, 1H), 6.88 (s, 1H) , 6.56 (s, 1H), 4.77 - 4.48 (m, 1H), 4.10 - 3.96 (m, 1H), 3.33 - 3.21 (m, 1H), 2.95 - 2.84 (m, 1H), 2.65 (s, 3H) , 2.38 (s, 3H), 2.19 - 2.08 (m, 2H), 2.04 - 1.98 (m, 2H), 1.58 (s, 6H); 496 [M+H] +
190190 (2-((2-((1-((3S,4R)-3-플루오로-1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드(2-((2-((1-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methyl Thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphineoxide 1H NMR (400 MHz, CDCl3) δ 9.92 (s, 1H), 8.09 (dd, J = 8.4, 4.2 Hz, 1H), 7.89 (br s, 1H), 7.59 - 7.48 (m, 1H), 7.45 (s, 1H), 7.39 - 7.30 (m, 1H), 7.22 - 7.13 (m, 1H), 6.72 (s, 1H), 6.55 (s, 1H), 4.95 - 4.72 (m, 1H), 4.04 - 3.92 (m, 1H), 3.31 - 3.20 (m, 1H), 2.97 - 2.86 (m, 1H), 2.71 (s, 3H), 2.38 (s, 3H), 2.24 - 2.08 (m, 4H), 1.81 (s, 3H), 1.78 (s, 3H); 514 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 9.92 (s, 1H), 8.09 (dd, J = 8.4, 4.2 Hz, 1H), 7.89 (br s, 1H), 7.59 - 7.48 (m, 1H), 7.45 (s, 1H), 7.39 - 7.30 (m, 1H), 7.22 - 7.13 (m, 1H), 6.72 (s, 1H), 6.55 (s, 1H), 4.95 - 4.72 (m, 1H), 4.04 - 3.92 (m, 1H), 3.31 - 3.20 (m, 1H), 2.97 - 2.86 (m, 1H), 2.71 (s, 3H), 2.38 (s, 3H), 2.24 - 2.08 (m, 4H), 1.81 (s) , 3H), 1.78 (s, 3H); 514 [M+H] +
191191 1-(4-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)피페리딘-1-일)에탄-1-온1-(4-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl )amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one 1H NMR (400 MHz, CDCl3) δ 7.69 (bs, 1H), 7.56 - 7.55 (m, 1H), 7.49 (s, 1H), 7.36 - 7.33 (m, 3H), 7.13 (s, 1H), 6.97 (s, 1H), 6.57 (d, J = 0.84 Hz, 1H), 4.71 - 4.67 (m, 2H), 4.25 - 4.19 (m, 1H), 3.93 - 3.89 (m, 1H), 3.22 - 3.15 (m, 1H), 2.72 - 2.66 (m, 4H), 2.16 (s, 3H), 2.02 - 1.99 (m, 2H), 1.81 - 1.79 (m, 2H), 1.59 (s, 3H), 1.58 (s, 3H) ; 506 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 7.69 (bs, 1H), 7.56 - 7.55 (m, 1H), 7.49 (s, 1H), 7.36 - 7.33 (m, 3H), 7.13 (s, 1H), 6.97 (s, 1H), 6.57 (d, J =0.84 Hz, 1H), 4.71 - 4.67 (m, 2H), 4.25 - 4.19 (m, 1H), 3.93 - 3.89 (m, 1H), 3.22 - 3.15 m, 1H), 2.72 - 2.66 (m, 4H), 2.16 (s, 3H), 2.02 - 1.99 (m, 2H), 1.81 - 1.79 (m, 2H), 1.59 (s, 3H), 1.58 (s, 3H); 506 [M+H] +
192192 1-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)시클로부탄-1-올1-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d] pyrimidin-4-yl) amino) pyridin-2-yl) cyclobutan-1-ol 1H NMR (400MHz, CDCl3) δ 8.34 (d, J = 8.2 Hz, 1H), 7.92 (s, 1H), 7.71 (dd, J = 7.9, 8.0 Hz, 1H), 7.28-7.23 (m, 2H), 7.06 (dd, J = 8.5, 2.3 Hz, 1H), 6.93 (d, J = 8.5 Hz, 1H), 6.87 (s, 1H), 6.31 (d, J = 1.0 Hz, 1H), 4.91 (s, 1H), 3.83 (s, 3H), 3.49-3.39 (m, 2H), 3.26-3.22 (m, 4H), 2.72 (s, 3H), 2.66-2.46 (m, 6H), 2.16-2.01 (m, 4H), 1.92-1.87 (m, 3H), 1.85-1.82 (m, 2H); 572 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.34 (d, J = 8.2 Hz, 1H), 7.92 (s, 1H), 7.71 (dd, J = 7.9, 8.0 Hz, 1H), 7.28-7.23 (m, 2H) ), 7.06 (dd, J = 8.5, 2.3 Hz, 1H), 6.93 (d, J = 8.5 Hz, 1H), 6.87 (s, 1H), 6.31 (d, J = 1.0 Hz, 1H), 4.91 (s , 1H), 3.83 (s, 3H), 3.49-3.39 (m, 2H), 3.26-3.22 (m, 4H), 2.72 (s, 3H), 2.66-2.46 (m, 6H), 2.16-2.01 (m , 4H), 1.92-1.87 (m, 3H), 1.85-1.82 (m, 2H); 572 [M+H] +
193193 (2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드(2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)phenyl)dimethylphosphineoxide 1H NMR (400MHz, CDCl3) δ 9.98 (s, 1H), 8.12 (dd, J = 4.2, 8.1 Hz, 1H), 7.49 (dd, J = 8.3, 7.4 Hz, 1H), 7.35-7.29 (m, 2H), 7.23 (s, 1H), 7.17-7.13 (m, 1H), 7.02 (dd, J= 2.4, 8.5 Hz, 1H), 6.80 (d, J = 8.5 Hz, 1H), 6.77 (s, 1H), 6.55 (d, J = 1.2 Hz, 1H), 3.83 (q, J = 7.0 Hz, 2H), 4.92-4.90 (m, 2H), 3.23-3.19 (m, 4H), 2.72-2.55 (m, 2H), 2.10-2.04 (m, 3H), 1.82-7.1.62 (m, 8H), 1.47-1.43 (m, 2H), 1.36 (t, J = 7.0 Hz, 3H); 591 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 9.98 (s, 1H), 8.12 (dd, J = 4.2, 8.1 Hz, 1H), 7.49 (dd, J = 8.3, 7.4 Hz, 1H), 7.35-7.29 (m , 2H), 7.23 (s, 1H), 7.17–7.13 (m, 1H), 7.02 (dd, J = 2.4, 8.5 Hz, 1H), 6.80 (d, J = 8.5 Hz, 1H), 6.77 (s, 1H), 6.55 (d, J = 1.2 Hz, 1H), 3.83 (q, J = 7.0 Hz, 2H), 4.92–4.90 (m, 2H), 3.23–3.19 (m, 4H), 2.72–2.55 (m , 2H), 2.10–2.04 (m, 3H), 1.82–7.1.62 (m, 8H), 1.47–1.43 (m, 2H), 1.36 (t, J = 7.0 Hz, 3H); 591 [M+H] +
194194 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)-1,1,1-트리플루오로프로판-2-올2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)-1,1,1-trifluoropropan-2-ol 1H NMR (400 MHz, CDCl3) δ7.73 - 7.67 (m, 2H), 7.44 - 7.32 (m, 3H), 7.18 (s, 1H), 6.99 - 6.95 (m, 1H), 6.88 - 6.81 (m, 2H), 6.60 (s, 1H), 3.65 (s, 3H), 3.53 - 3.45 (m, 2H), 2.68 (s, 3H), 2.59 - 2.51 (m, 2H), 2.42 (s, 6H), 1.98 - 1.92 (m, 2H), 1.83 - 1.78 (m, 2H), 1.71 (s, 3H); 601 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.73 - 7.67 (m, 2H), 7.44 - 7.32 (m, 3H), 7.18 (s, 1H), 6.99 - 6.95 (m, 1H), 6.88 - 6.81 ( m, 2H), 6.60 (s, 1H), 3.65 (s, 3H), 3.53 - 3.45 (m, 2H), 2.68 (s, 3H), 2.59 - 2.51 (m, 2H), 2.42 (s, 6H) , 1.98 - 1.92 (m, 2H), 1.83 - 1.78 (m, 2H), 1.71 (s, 3H); 601 [M+H] +
195195 1,1,1-트리플루오로-2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올1,1,1-trifluoro-2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino )thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ9.05 (s, 1H), 8.31 - 8.16 (m, 1H), 7.61 (s, 1H), 7.46 - 7.37 (m, 2H), 7.31 - 7.19 (m, 1H), 6.75 (s, 2H), 2.87 - 2.79 (m, 2H), 2.60 (s, 3H), 2.20 (s, 3H), 2.06 - 1.97 (m, 2H), 1.85 - 1.63 (m, 7H); 532 [M+H]+ 1H NMR (400 MHz, DMSO) δ9.05 (s, 1H), 8.31 - 8.16 (m, 1H), 7.61 (s, 1H), 7.46 - 7.37 (m, 2H), 7.31 - 7.19 (m, 1H) ), 6.75 (s, 2H), 2.87 - 2.79 (m, 2H), 2.60 (s, 3H), 2.20 (s, 3H), 2.06 - 1.97 (m, 2H), 1.85 - 1.63 (m, 7H); 532 [M+H] +
196196 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)-1,1,1-트리플루오로프로판-2-올2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)-1,1,1-trifluoropropan-2-ol 1H NMR (400 MHz, DMSO) δ9.00 (s, 1H), 8.15 (s, 1H), 7.83 (d, J = 7.1 Hz, 1H), 7.63 (s, 1H), 7.37 - 7.28 (m, 2H), 7.24 - 7.20 (m, 1H), 7.14 (d, J = 8.2 Hz, 1H), 6.81 (d, J = 1.2 Hz, 1H), 6.73 - 6.66 (m, 2H), 3.68 (s, 3H), 3.33 - 3.28 (m, 4H), 3.20 - 3.14 (m, 2H), 2.62 (s, 3H), 2.46 - 2.41 (m, 2H), 2.04 - 1.96 (m, 2H), 1.75 - 1.68 (m, 2H), 1.66 (s, 3H), 1.33 - 1.24 (m, 2H); 613 [M+H]+ 1H NMR (400 MHz, DMSO) δ9.00 (s, 1H), 8.15 (s, 1H), 7.83 (d, J = 7.1 Hz, 1H), 7.63 (s, 1H), 7.37 - 7.28 (m, 2H), 7.24 - 7.20 (m, 1H), 7.14 (d, J = 8.2 Hz, 1H), 6.81 (d, J = 1.2 Hz, 1H), 6.73 - 6.66 (m, 2H), 3.68 (s, 3H) ), 3.33 - 3.28 (m, 4H), 3.20 - 3.14 (m, 2H), 2.62 (s, 3H), 2.46 - 2.41 (m, 2H), 2.04 - 1.96 (m, 2H), 1.75 - 1.68 (m , 2H), 1.66 (s, 3H), 1.33 - 1.24 (m, 2H); 613 [M+H] +
197197 1-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)-2-메틸프로판-2-올1-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine-2- yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol 1H NMR (400 MHz, CDCl3) δ8.32 (d, J = 8.0 Hz, 1H), 7.94 (s, 2H), 7.72 (t, J = 7.9 Hz, 1H), 7.59 (s, 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.72 - 6.61 (m, 2H), 4.73 (s, 1H), 4.06 (s, 2H), 4.02 (s, 1H), 2.73 (s, 3H), 1.55 (s, 6H), 1.21 (s, 6H); 454 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ8.32 (d, J = 8.0 Hz, 1H), 7.94 (s, 2H), 7.72 (t, J = 7.9 Hz, 1H), 7.59 (s, 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.72 - 6.61 (m, 2H), 4.73 (s, 1H), 4.06 (s, 2H), 4.02 (s, 1H), 2.73 (s, 3H), 1.55 (s, 6H), 1.21 (s, 6H); 454 [M+H] +
198198 1-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)-2-메틸프로판-2-올1-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl)amino) -1H-pyrazol-1-yl)-2-methylpropan-2-ol 1H NMR (400 MHz, CDCl3) δ7.61 (s, 1H), 7.58 - 7.50 (m, 1H), 7.46 (s, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.32 - 7.26 (m, 1H), 7.15 (s, 1H), 6.83 (s, 1H), 6.58 (d, J = 1.1 Hz, 1H), 3.94 (s, 2H), 3.82 (br s, 1H), 2.66 (s, 3H), 2.29 (br s, 1H), 1.60 (s, 6H), 1.15 (s, 6H); 453 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ7.61 (s, 1H), 7.58 - 7.50 (m, 1H), 7.46 (s, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.32 - 7.26 (m, 1H), 7.15 (s, 1H), 6.83 (s, 1H), 6.58 (d, J = 1.1 Hz, 1H), 3.94 (s, 2H), 3.82 (br s, 1H), 2.66 (s , 3H), 2.29 (br s, 1H), 1.60 (s, 6H), 1.15 (s, 6H); 453 [M+H] +
199199 (2-((2-((1-(2-하이드록시-2-메틸프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드(2-((2-((1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine- 4-yl) amino) phenyl) dimethylphosphine oxide 1H NMR (400 MHz, CDCl3) δ9.97 (s, 1H), 8.11 - 8.04 (m, 1H), 7.83 (br s, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.46 (s, 1H), 7.39 - 7.31 (m, 1H), 7.23 - 7.15 (m, 1H), 6.73 (br s, 1H), 6.56 (d, J = 1.2 Hz, 1H), 3.95 (s, 3H), 2.78 - 2.64 (m, 3H), 1.81 (s, 3H), 1.78 (s, 3H), 1.15 (s, 6H); 471 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ9.97 (s, 1H), 8.11 - 8.04 (m, 1H), 7.83 (br s, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.46 ( s, 1H), 7.39 - 7.31 (m, 1H), 7.23 - 7.15 (m, 1H), 6.73 (br s, 1H), 6.56 (d, J = 1.2 Hz, 1H), 3.95 (s, 3H), 2.78 - 2.64 (m, 3H), 1.81 (s, 3H), 1.78 (s, 3H), 1.15 (s, 6H); 471 [M+H] +
200200 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)-1,1,1-트리플루오로프로판-2-올2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d] pyrimidin-4-yl) amino) pyridin-2-yl) -1,1,1-trifluoropropan-2-ol 1H NMR (400 MHz, CDCl3) δ8.49 (d, J = 8.3 Hz, 1H), 7.95 (s, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.24 - 7.15 (m, 2H), 7.06 (dd, J = 8.4, 2.3 Hz, 1H), 6.95 - 6.89 (m, 1H), 6.88 (s, 1H), 6.66 (d, J = 1.1 Hz, 1H), 5.80 (s, 1H), 4.39 (s, 3H), 3.81 (s, 3H), 3.50 - 3.28 (m, 5H), 2.73 (s, 3H), 2.63 (t, J = 11.4 Hz, 2H), 2.35 - 2.24 (m, 1H), 2.23 - 2.11 (m, 2H), 1.89 - 1.81 (m, 2H), 1.73 (s, 3H); 614 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ8.49 (d, J = 8.3 Hz, 1H), 7.95 (s, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.24 - 7.15 (m, 2H) ), 7.06 (dd, J = 8.4, 2.3 Hz, 1H), 6.95 - 6.89 (m, 1H), 6.88 (s, 1H), 6.66 (d, J = 1.1 Hz, 1H), 5.80 (s, 1H) , 4.39 (s, 3H), 3.81 (s, 3H), 3.50 - 3.28 (m, 5H), 2.73 (s, 3H), 2.63 (t, J = 11.4 Hz, 2H), 2.35 - 2.24 (m, 1H) ), 2.23 - 2.11 (m, 2H), 1.89 - 1.81 (m, 2H), 1.73 (s, 3H); 614 [M+H] +
201201 1,1,1-트리플루오로-2-(6-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올1,1,1-trifluoro-2-(6-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino ) thieno [2,3-d] pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol 1H NMR (400 MHz, CDCl3) δ8.49 (d, J = 8.1 Hz, 1H), 7.94 (s, 2H), 7.80 (t, J = 7.9 Hz, 1H), 7.53 (s, 1H), 7.19 (d, J = 7.5 Hz, 1H), 6.72 - 6.58 (m, 2H), 5.80 (br s, 1H), 4.19 - 4.08 (m, 1H), 3.01 (d, J = 9.3 Hz, 2H), 2.72 (s, 3H), 2.36 (s, 3H), 2.25 - 1.98 (m, 6H), 1.73 (s, 3H); 533 [M+H]+ 1H NMR (400 MHz, CDCl 3 ) δ8.49 (d, J = 8.1 Hz, 1H), 7.94 (s, 2H), 7.80 (t, J = 7.9 Hz, 1H), 7.53 (s, 1H), 7.19 (d, J = 7.5 Hz, 1H), 6.72 - 6.58 (m, 2H), 5.80 (br s, 1H), 4.19 - 4.08 (m, 1H), 3.01 (d, J = 9.3 Hz, 2H), 2.72 (s, 3H), 2.36 (s, 3H), 2.25 - 1.98 (m, 6H), 1.73 (s, 3H); 533 [M+H] +
202202 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol 1H NMR (400 MHz, DMSO) δ 9.21 (s, 1H), 8.15 (s, 1H), 7.83 (d, J = 11.2 Hz, 1H), 7.63 (dd, J = 8.6, 2.6 Hz, 1H), 7.53 (s, 1H), 7.31 (s, 1H), 7.00 - 6.89 (m, 2H), 6.83 (s, 1H), 5.15 (s, 1H), 5.05 (t, J = 5.5 Hz, 1H), 4.48 (d, J = 4.9 Hz, 2H), 3.14 - 3.02 (m, 4H), 2.97 - 2.87 (m, 2H), 2.65 (s, 3H), 2.59 - 2.54 (m, 2H), 2.10 - 2.01 (m, 1H), 1.92 (p, J = 6.8 Hz, 2H), 1.75 - 1.65 (m, 2H), 1.43 (s, 6H), 1.32 - 1.25 (m, 2H); 577 [M+H]+ 1H NMR (400 MHz, DMSO) δ 9.21 (s, 1H), 8.15 (s, 1H), 7.83 (d, J = 11.2 Hz, 1H), 7.63 (dd, J = 8.6, 2.6 Hz, 1H), 7.53 (s, 1H), 7.31 (s, 1H), 7.00 - 6.89 (m, 2H), 6.83 (s, 1H), 5.15 (s, 1H), 5.05 (t, J = 5.5 Hz, 1H), 4.48 (d, J = 4.9 Hz, 2H), 3.14 - 3.02 (m, 4H), 2.97 - 2.87 (m, 2H), 2.65 (s, 3H), 2.59 - 2.54 (m, 2H), 2.10 - 2.01 (m , 1H), 1.92 (p, J = 6.8 Hz, 2H), 1.75 - 1.65 (m, 2H), 1.43 (s, 6H), 1.32 - 1.25 (m, 2H); 577 [M+H] +
203203 (2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3,5-디플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)페닐)메탄올(2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3,5-difluorophenyl)amino)-5-methylthieno[2 ,3-d] pyrimidin-2-yl) amino) phenyl) methanol 1H NMR (400 MHz, DMSO) δ 9.35 (s, 1H), 8.26 (s, 1H), 7.67 - 7.50 (m, 4H), 6.96 (d, J = 8.6 Hz, 1H), 6.93 - 6.83 (m, 2H), 5.06 (t, J = 5.4 Hz, 1H), 4.50 (d, J = 5.0 Hz, 2H), 3.08 (t, J = 6.8 Hz, 4H), 2.96 - 2.90 (m, 2H), 2.64 (s, 3H), 2.58 - 2.53 (m, 2H), 2.11 - 2.02 (m, 1H), 1.92 (h, J = 6.1, 5.4 Hz, 2H), 1.74 - 1.66 (m, 2H), 1.33 - 1.25 (m, 2H); 537 [M+H]+ 1H NMR (400 MHz, DMSO) δ 9.35 (s, 1H), 8.26 (s, 1H), 7.67 - 7.50 (m, 4H), 6.96 (d, J = 8.6 Hz, 1H), 6.93 - 6.83 (m , 2H), 5.06 (t, J = 5.4 Hz, 1H), 4.50 (d, J = 5.0 Hz, 2H), 3.08 (t, J = 6.8 Hz, 4H), 2.96 - 2.90 (m, 2H), 2.64 (s, 3H), 2.58 - 2.53 (m, 2H), 2.11 - 2.02 (m, 1H), 1.92 (h, J = 6.1, 5.4 Hz, 2H), 1.74 - 1.66 (m, 2H), 1.33 - 1.25 (m, 2H); 537 [M+H] +
204204 N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3,5-디플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3,5-difluorophenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine 1H NMR (400 MHz, DMSO) δ 9.27 (s, 1H), 8.29 (s, 1H), 7.59 - 7.52 (m, 2H), 7.25 (d, J = 9.6 Hz, 2H), 6.92 - 6.85 (m, 2H), 6.79 (d, J = 8.3 Hz, 1H), 3.68 (s, 3H), 3.20 - 3.14 (m, 2H), 3.09 (t, J = 6.8 Hz, 4H), 2.63 (s, 3H), 2.56 - 2.53 (m, 2H), 2.08 - 2.02 (m, 1H), 1.93 (q, J = 6.7 Hz, 2H), 1.72 - 1.65 (m, 2H), 1.31 - 1.25 (m, 2H); 537 [M+H]+ 1 H NMR (400 MHz, DMSO) δ 9.27 (s, 1H), 8.29 (s, 1H), 7.59 - 7.52 (m, 2H), 7.25 (d, J = 9.6 Hz, 2H), 6.92 - 6.85 (m , 2H), 6.79 (d, J = 8.3 Hz, 1H), 3.68 (s, 3H), 3.20 - 3.14 (m, 2H), 3.09 (t, J = 6.8 Hz, 4H), 2.63 (s, 3H) , 2.56 - 2.53 (m, 2H), 2.08 - 2.02 (m, 1H), 1.93 (q, J = 6.7 Hz, 2H), 1.72 - 1.65 (m, 2H), 1.31 - 1.25 (m, 2H); 537 [M+H] +
205205 N4-(3,5-디플루오로페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민N4-(3,5-difluorophenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[2,3 -d] pyrimidine-2,4-diamine 1H NMR (400 MHz, MeOD) δ 7.92 (br s, 1H), 7.53 (s, 1H), 7.47 - 7.37 (m, 2H), 6.70 (s, 1H), 6.69 - 6.60 (m, 1H), 4.65 (br s, 2H), 4.16 - 4.02 (m, 1H), 3.05 - 2.94 (m, 2H), 2.65 (s, 3H), 2.28 - 2.19 (m, 2H), 2.13 - 2.07 (m, 2H); 456 [M+H]+ 1 H NMR (400 MHz, MeOD) δ 7.92 (br s, 1H), 7.53 (s, 1H), 7.47 - 7.37 (m, 2H), 6.70 (s, 1H), 6.69 - 6.60 (m, 1H), 4.65 (br s, 2H), 4.16 - 4.02 (m, 1H), 3.05 - 2.94 (m, 2H), 2.65 (s, 3H), 2.28 - 2.19 (m, 2H), 2.13 - 2.07 (m, 2H) ; 456 [M+H] +
206206 (2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드(2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5-methylthieno[2 ,3-d] pyrimidin-4-yl) amino) phenyl) dimethylphosphine oxide 1H NMR (400MHz, CDCl3) δ 8.11 (dd, J = 4.5, 8.5 Hz, 1H), 7.54 (dd, J = 7.3, 8.0 Hz, 1H), 7.41 - 7.32 (m, 3H), 7.22 - 7.20 (m, 1H), 7.12 (d, J = 9.2 Hz, 1H), 6.87 (s, 1H), 6.58 (d, J = 1.2 Hz, 1H), 4.63 (s, 2H), 3.22 (t, J = 7.0 Hz, 4H), 3.12 - 3.08 (m, 2H), 2.75 - 2.69 (m, 5H), 2.18 - 2.06 (m, 4H), 1.85 - 1.79 (m, 8H), 1.51 - 1.48 (m, 2H); 577 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 8.11 (dd, J = 4.5, 8.5 Hz, 1H), 7.54 (dd, J = 7.3, 8.0 Hz, 1H), 7.41 - 7.32 (m, 3H), 7.22 - 7.20 (m, 1H), 7.12 (d, J = 9.2 Hz, 1H), 6.87 (s, 1H), 6.58 (d, J = 1.2 Hz, 1H), 4.63 (s, 2H), 3.22 (t, J = 7.0 Hz, 4H), 3.12 - 3.08 (m, 2H), 2.75 - 2.69 (m, 5H), 2.18 - 2.06 (m, 4H), 1.85 - 1.79 (m, 8H), 1.51 - 1.48 (m, 2H) ; 577 [M+H] +
207207 (2-((2-((1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드,2,2,2-트리플루오로아세트산(2-((2-((1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl) amino) phenyl) dimethylphosphine oxide, 2,2,2-trifluoroacetic acid 1H NMR (400MHz, DMSO) δ10.19 (s, 1H), 9.26 - 9.16 (m, 2H), 8.03 (s, 1H), 7.61 - 7.59 (m, 2H), 7.47 (s, 1H), 7.26 (s, 1H), 6.81 (s, 1H), 3.39 - 3.35 (m, 2H), 3.16 - 3.02 (m, 4H), 2.60 (s, 3H), 2.15 - 2.08 (m, 4H), 1.76 (s, 3H), 1.72 (s, 3H), 1.24 (t, J = 7.3 Hz, 3H); 510 [M+H]+ 1H NMR (400MHz, DMSO) δ10.19 (s, 1H), 9.26 - 9.16 (m, 2H), 8.03 (s, 1H), 7.61 - 7.59 (m, 2H), 7.47 (s, 1H), 7.26 (s, 1H), 6.81 (s, 1H), 3.39 - 3.35 (m, 2H), 3.16 - 3.02 (m, 4H), 2.60 (s, 3H), 2.15 - 2.08 (m, 4H), 1.76 (s , 3H), 1.72 (s, 3H), 1.24 (t, J = 7.3 Hz, 3H); 510 [M+H] +
208208 1-(4-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)피페리딘-1-일)에탄-1-온1-(4-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine -2-yl) amino) -1H-pyrazol-1-yl) piperidin-1-yl) ethan-1-one 1H NMR (400MHz, CDCl3) δ 8.30 (d, J = 7.8 Hz, 1H), 7.95 - 7.93 (m, 2H), 7.71 (t, J = 7.9, 7.9 Hz, 1H), 7.53 (s, 1H), 7.07 (d, J = 7.3 Hz, 1H), 6.70 (s, 1H), 6.64 (d, J = 1.0 Hz, 1H), 4.75 (d, J = 13.8 Hz, 1H), 4.37 - 4.29 (m, 1H), 3.97 (d, J = 14.2 Hz, 1H), 3.28 - 3.21 (m, 1H), 2.81 - 2.73 (m, 4H), 2.25 - 2.15 (m, 4H), 2.05 - 1.89 (m, 3H); 507 [M+H]+ 1H NMR (400MHz, CDCl 3 ) δ 8.30 (d, J = 7.8 Hz, 1H), 7.95 - 7.93 (m, 2H), 7.71 (t, J = 7.9, 7.9 Hz, 1H), 7.53 (s, 1H) ), 7.07 (d, J = 7.3 Hz, 1H), 6.70 (s, 1H), 6.64 (d, J = 1.0 Hz, 1H), 4.75 (d, J = 13.8 Hz, 1H), 4.37 - 4.29 (m , 1H), 3.97 (d, J = 14.2 Hz, 1H), 3.28 - 3.21 (m, 1H), 2.81 - 2.73 (m, 4H), 2.25 - 2.15 (m, 4H), 2.05 - 1.89 (m, 3H) ); 507 [M+H] +
209209 1-(4-(4-((4-((2-(디메틸포스포릴)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)피페리딘-1-일)에탄-1-온1-(4-(4-((4-((2-(dimethylphosphoryl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl)amino)-1H- pyrazol-1-yl)piperidin-1-yl)ethan-1-one 1H NMR (400MHz, CDCl3) δ 9.97 (s, 1H), 8.08 (dd, J = 4.0, 8.0 Hz, 1H), 7.86 (s, 1H), 7.52 (dd, J = 7.8, 7.9 Hz, 1H), 7.40 - 7.32 (m, 2H), 7.18 (ddd, J = 1.3, 7.5, 7.4 Hz, 1H), 6.62 (s, 1H), 6.56 (d, J = 1.3 Hz, 1H), 4.70 (d, J = 13.8 Hz, 1H), 4.28 - 4.21 (m, 1H), 3.93 (d, J = 14.0 Hz, 1H), 3.25 - 3.18 (m, 1H), 2.78 - 2.71 (m, 4H), 2.20 - 2.15 (m, 4H), 2.08 - 2.05 (m, 1H), 1.92 - 1.79 (m, 8H); 524 [M+H]+ 1 H NMR (400 MHz, CDCl 3 ) δ 9.97 (s, 1H), 8.08 (dd, J = 4.0, 8.0 Hz, 1H), 7.86 (s, 1H), 7.52 (dd, J = 7.8, 7.9 Hz, 1H) ), 7.40 - 7.32 (m, 2H), 7.18 (ddd, J = 1.3, 7.5, 7.4 Hz, 1H), 6.62 (s, 1H), 6.56 (d, J = 1.3 Hz, 1H), 4.70 (d, J = 13.8 Hz, 1H), 4.28 - 4.21 (m, 1H), 3.93 (d, J = 14.0 Hz, 1H), 3.25 - 3.18 (m, 1H), 2.78 - 2.71 (m, 4H), 2.20 - 2.15 (m, 4H), 2.08 - 2.05 (m, 1H), 1.92 - 1.79 (m, 8H); 524 [M+H] +
<< 실험예Experimental example 1> 본 발명에 따른 화학식 1로 표시되는 화합물의 1> of the compound represented by Formula 1 according to the present invention IRAK4IRAK4 억제 control
본 발명에 따른 화합물의 IRAK4 키나아제 억제 활성을 평가하기 위하여 하기와 같은 실험을 수행하였다.In order to evaluate the IRAK4 kinase inhibitory activity of the compound according to the present invention, the following experiment was performed.
구체적으로, white 384- 웰 플레이트에 5배수로 연속 희석된 12가지 농도의 화합물 (DMSO 대조군 포함)을 첨가하고, 각각 웰 당 0.1 μg/μl 농도의 MBP 기질 및 10 μM 농도의 ATP를 첨가하여 최종 화합물 농도 0.000005 ~ 50 μM이 되도록 한 뒤 25°C 배양기에서 1시간 동안 배양하였다. 1시간 후, ADP-Glo (Promega) 5 μl를 처리하고 25°C 배양기에서 40분 동안 배양한 후, Detection Reagent (Promega) 10 μl를 처리하고 25°C 배양기에서 30분 동안 배양하였다. 그 후, 마이크로플레이트 판독기로 Luminescence 값을 통해 키나아제 활성 정도를 측정하였다. 측정값은 GraphPad Prism 7.0 (GraphPad Software Inc.)을 이용하여 IC50 값을 산출하였다.Specifically, in a white 384-well plate, 12 concentrations of compounds (including DMSO control) serially diluted in 5-fold were added, and MBP substrate at a concentration of 0.1 μg/μl and ATP at a concentration of 10 μM were added per well, respectively, to obtain the final compound. After making the concentration 0.000005 ~ 50 μM, it was incubated for 1 hour in a 25°C incubator. After 1 hour, 5 μl of ADP-Glo (Promega) was treated and incubated in a 25°C incubator for 40 minutes, followed by 10 μl of Detection Reagent (Promega) and incubated in a 25°C incubator for 30 minutes. Then, the degree of kinase activity was measured through the luminescence value with a microplate reader. IC50 values were calculated using GraphPad Prism 7.0 (GraphPad Software Inc.).
측정된 키나아제의 IC50값을 100nM 미만인 경우 A, 100nM ~ 1μM인 경우 B, 1μM 초과인 경우 C로 분류하여 하기 표 7에 정리하여 나타내었다.The measured IC50 values of kinases were classified as A when less than 100 nM, B when 100 nM to 1 μM, and C when greater than 1 μM, and are summarized in Table 7 below.
하기 표를 통해서 확인할 수 있듯이 본 발명의 화합물들은 IRAK4를 효과적으로 억제하여 암 또는 자가면역질환의 치료에 유용할 수 있음을 확인하였다.As can be seen from the table below, it was confirmed that the compounds of the present invention can effectively inhibit IRAK4 and thus be useful for the treatment of cancer or autoimmune diseases.
실시예Example IRAK4 IC50 IRAK4 IC 50 실시예Example IRAK4 IC50 IRAK4 IC 50
1One BB 106106 AA
22 AA 107107 AA
33 AA 108108 AA
44 BB 109109 BB
55 BB 110110 AA
66 BB 111111 BB
77 BB 112112 BB
88 CC 113113 AA
99 BB 114114 AA
1010 AA 115115 AA
1111 CC 116116 BB
1212 BB 117117 AA
1313 CC 118118 CC
1414 AA 119119 CC
1515 BB 120120 AA
1616 BB 121121 AA
1717 AA 122122 AA
1818 AA 123123 BB
1919 CC 124124 AA
2020 CC 125125 BB
2121 BB 126126 BB
2222 BB 127127 BB
2323 CC 128128 AA
2424 BB 129129 AA
2525 CC 130130 AA
2626 BB 131131 CC
2727 BB 132132 CC
2828 BB 133133 BB
2929 CC 134134 BB
3030 AA 135135 BB
3131 AA 136136 AA
3232 BB 137137 BB
3333 AA 138138 BB
3434 BB 139139 BB
3535 BB 140140 BB
3636 BB 141141 AA
3737 CC 142142 CC
3838 BB 143143 CC
3939 BB 144144 CC
4040 AA 145145 BB
4141 AA 146146 BB
4242 AA 147147 CC
4343 AA 148148 AA
4444 AA 149149 BB
4545 AA 150150 CC
4646 AA 151151 CC
4747 BB 152152 CC
4848 CC 153153 AA
4949 CC 154154 AA
5050 BB 155155 CC
5151 BB 156156 CC
5252 BB 157157 CC
5353 CC 158158 AA
5454 CC 159159 BB
5555 CC 160160 BB
5656 CC 161161 CC
5757 CC 162162 AA
5858 BB 163163 AA
5959 BB 164164 AA
6060 AA 165165 AA
6161 CC 166166 AA
6262 BB 167167 AA
6363 BB 168168 AA
6464 AA 169169 AA
6565 AA 170170 CC
6666 AA 171171 AA
6767 BB 172172 AA
6868 BB 173173 BB
6969 AA 174174 BB
7070 CC 175175 BB
7171 CC 176176 BB
7272 BB 177177 CC
7373 AA 178178 CC
7474 AA 179179 AA
7575 CC 180180 AA
7676 BB 181181 AA
7777 CC 182182 AA
7878 AA 183183 AA
7979 AA 184184 AA
8080 AA 185185 AA
8181 AA 186186 AA
8282 AA 187187 BB
8383 CC 188188 BB
8484 CC 189189 AA
8585 BB 190190 AA
8686 AA 191191 AA
8787 AA 192192 AA
8888 AA 193193 AA
8989 AA 194194 AA
9090 BB 195195 BB
9191 BB 196196 AA
9292 BB 197197 BB
9393 BB 198198 BB
9494 BB 199199 BB
9595 BB 200200 BB
9696 AA 201201 AA
9797 BB 202202 AA
9898 BB 203203 AA
9999 AA 204204 AA
100100 AA 205205 AA
101101 AA 206206 AA
102102 AA 207207 BB
103103 BB 208208 AA
104104 AA 209209 AA
105105 AA
<< 실험예Experimental example 2> 본 발명에 따른 화학식 1로 표시되는 화합물의 2> of the compound represented by Formula 1 according to the present invention TNFTNF -α, IL-6 발현 억제-α, inhibition of IL-6 expression
본 발명에 따른 화합물의 TNF-α, IL-6 발현 억제능을 평가하기 위하여 하기와 같은 실험을 수행하였다.In order to evaluate the ability of the compound according to the present invention to inhibit expression of TNF-α and IL-6, the following experiment was performed.
구체적으로, 동결되어 있는 human Peripheral Blood Mononuclear Cell (hPBMC)를 녹여서 PBS로 2번 wash 한 후, 48- 웰 세포 배양용 플레이트에 well 당 2.7 x 105/200 μl가 되게 seeding하였다. 화합물을 duplicate로 well 당 1 μM 농도로 처리 후 37 °C, 5 % CO2 배양기에서 30분간 배양하였다. 그 후, Lipoteichoic acid (LTA)를 well 당 1 μg/ml 농도로 처리한 후 배양기에서 24시간 배양하였다. 24시간 후 각 well의 배지를 2000 g, 10분간 원심분리하여 세포를 제외한 배지만을 얻었다. ELISA용 96- 웰 플레이트에 배지를 50 μl씩 넣고, TNF-α 또는 IL-6 ELISA용 antibody 혼합액을 well 당 50 μl씩 넣은 후 상온에서 1시간 반응시켰다. 그 후 wash buffer로 3번 wash 후 TMB 발색용액을 well 당 100 μl씩 넣고 micro plate reader에서 450 nm 파장으로 O.D 값을 측정하였다. 측정값은 GraphPad Prism 7.0 (GraphPad Software Inc.)을 이용하여 DMSO 처리 값 대비 억제능 백분율 값을 산출하였다.Specifically, frozen human Peripheral Blood Mononuclear Cells (hPBMC) were thawed, washed twice with PBS, and then seeded in a 48-well cell culture plate at 2.7 x 105/200 μl per well. The compound was treated in duplicate at a concentration of 1 μM per well and then incubated for 30 minutes in a 37 °C, 5% CO 2 incubator. Then, after treatment with Lipoteichoic acid (LTA) at a concentration of 1 μg/ml per well, the cells were incubated for 24 hours in an incubator. After 24 hours, the medium of each well was centrifuged at 2000 g for 10 minutes to obtain only the medium excluding the cells. 50 μl of medium was added to a 96-well plate for ELISA, and 50 μl of antibody mixture for TNF-α or IL-6 ELISA was added per well, followed by reaction at room temperature for 1 hour. Then, after washing three times with wash buffer, 100 μl of TMB coloring solution was added per well, and the OD value was measured using a micro plate reader at a wavelength of 450 nm. The measured value was calculated as a percentage value of inhibition compared to the DMSO treatment value using GraphPad Prism 7.0 (GraphPad Software Inc.).
측정된 백분율 값이 50% 초과인 경우 A등급, 50%~10%인 경우 B등급, 10% 미만인 경우 C등급으로 분류하여 하기 표 8에 정리하여 나타내었다.If the measured percentage value is more than 50%, it is classified as A grade, 50% to 10% as B grade, and less than 10% as C grade, and summarized in Table 8 below.
하기 표를 통해서 확인할 수 있듯이, 본 발명의 화합물들은 자가면역질환과 관련된 염증인자로서 사이토카인인 TNF-α 및 IL-6의 발현을 효과적으로 억제하는바, 자가면역질환의 치료에 효과적임을 확인할 수 있었다.As can be seen from the table below, the compounds of the present invention effectively inhibit the expression of TNF-α and IL-6, which are cytokines as inflammatory factors related to autoimmune diseases, and it was confirmed that they are effective in treating autoimmune diseases. .
실시예Example TNF-αTNF-α IL-6IL-6 실시예Example TNF-αTNF-α IL-6IL-6
22 CC CC 122122 BB AA
33 BB BB 124124 BB BB
3030 BB BB 128128 CC BB
3131 BB BB 130130 BB BB
3333 BB CC 136136 CC CC
4141 CC CC 154154 BB BB
4242 CC CC 158158 BB BB
4343 CC CC 162162 BB BB
4444 CC CC 163163 AA BB
4545 BB CC 164164 AA AA
4646 BB CC 165165 BB BB
6060 BB BB 166166 AA AA
6464 BB BB 169169 CC BB
6969 BB BB 171171 BB BB
8787 BB BB 181181 BB BB
8888 BB BB 182182 BB BB
8989 AA BB 185185 AA BB
100100 BB BB 186186 BB BB
101101 CC BB 192192 BB BB
104104 BB BB 193193 AA AA
105105 CC CC 201201 CC CC
107107 BB BB 202202 AA AA
108108 BB BB 203203 BB BB
110110 CC CC 204204 BB BB
113113 CC CC 206206 AA AA
114114 BB CC
115115 BB BB
117117 BB CC
120120 AA BB
121121 AA BB

Claims (18)

  1. 하기 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염:A compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof:
    [화학식 1][Formula 1]
    Figure PCTKR2022016628-appb-img-000061
    Figure PCTKR2022016628-appb-img-000061
    상기 화학식 1에서,In Formula 1,
    R1은 수소 또는 C1-10알킬이고, R 1 is hydrogen or C 1-10 alkyl;
    R2는 비치환 또는 치환된 C6- 10아릴, 비치환 또는 치환된 5-10원자헤테로아릴이거나, 또는R 2 is unsubstituted or substituted C 6-10 aryl, unsubstituted or substituted 5-10 membered heteroaryl, or
    R1와 R2는 이들이 결합된 질소원자와 함께 비치환 또는 치환된 5-10원자헤테로아릴을 형성하고,R 1 and R 2 together with the nitrogen atom to which they are bonded form an unsubstituted or substituted 5-10 membered heteroaryl;
    여기서, 상기 치환된 C6- 10아릴 및 치환된 5-10원자헤테로아릴은 각각 독립적으로 비치환 또는 치환된 C1- 10알킬, 비치환 또는 치환된 C3- 10시클로알킬, 할로겐, 하이드록시, C1- 10알콕시, -SO2R2a, -C(=O)NR2aR2b, -SO2NR2aR2b, 비치환 또는 치환된 3-10원자헤테로시클로알킬, -C(=O)OR2a, -P(=O)R2aR2b 로 하나 이상 치환되고, 이때 치환된 C1- 10알킬, 치환된 C3- 10시클로알킬 및 치환된 3-10원자헤테로시클로알킬은 독립적으로 하이드록시, C1- 10알콕시, 할로겐 및 CN로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환되고,Here, the substituted C 6-10 aryl and the substituted 5-10-membered heteroaryl are each independently selected from unsubstituted or substituted C 1-10 alkyl , unsubstituted or substituted C 3-10 cycloalkyl, halogen, hydroxy , C 1-10 alkoxy, -SO 2 R 2a , -C(=O)NR 2a R 2b , -SO 2 NR 2a R 2b , unsubstituted or substituted 3-10 membered heterocycloalkyl, -C( = O )OR 2a , -P(=O)R 2a R 2b , wherein the substituted C 1-10 alkyl, substituted C 3-10 cycloalkyl and substituted 3-10 membered heterocycloalkyl are independently substituted with one or more substituents selected from the group consisting of hydroxy, C 1-10 alkoxy, halogen and CN;
    여기서, R2a 및 R2b는 독립적으로 수소 또는 C1-10알킬이고;wherein R 2a and R 2b are independently hydrogen or C 1-10 alkyl;
    R3는 치환된 C3- 10시클로알킬, 치환된 C6- 10아릴 또는 치환된 5-10원자헤테로아릴이고, R 3 is substituted C 3-10 cycloalkyl, substituted C 6-10 aryl or substituted 5-10 membered heteroaryl ;
    여기서, 치환된 C3- 10시클로알킬, 치환된 C6- 10아릴 및 치환된 5-10원자 헤테로아릴은 각각 독립적으로 하이드록시, C1- 10알콕시, 할로겐, C1- 10알콕시카보닐, -NR3aR3b, 비치환 또는 치환된 C1- 10알킬, 또는 링커 L을 통해 연결되는 비치환 또는 치환된 3-10원자헤테로시클로알킬로 치환되고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, Here, substituted C 3-10 cycloalkyl, substituted C 6-10 aryl , and substituted 5-10 membered heteroaryl are each independently hydroxy , C 1-10 alkoxy, halogen, C 1-10 alkoxycarbonyl, -NR 3a R 3b , unsubstituted or substituted C 1-10 alkyl, or unsubstituted or substituted 3-10 membered heterocycloalkyl linked through a linker L, wherein the linker L is a single bond, -C( =O)- or -C(=O)NH-,
    여기서, 치환된 C1- 10알킬은 할로겐, C1- 10알콕시, 디C1 - 10알킬아미노, 하이드록시 또는 -C(=O)NH2 로 치환되고, wherein the substituted C 1-10 alkyl is substituted with halogen, C 1-10 alkoxy, diC 1-10 alkylamino, hydroxy or -C(=O)NH 2 ;
    여기서, 치환된 3-10원자헤테로시클로알킬은 C1- 10알킬, C3- 10시클로알킬, 3-10원자헤테로시클로알킬 또는 -NR3aR3b로 치환되고,wherein the substituted 3-10 membered heterocycloalkyl is substituted with C 1-10 alkyl , C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl or -NR 3a R 3b ;
    여기서 R3a 및 R3b는 각각 독립적으로 수소, 비치환 또는 N(C1- 10알킬)2로 치환된C1 -10알킬, 또는 C1-10알콕시카보닐이고; wherein R 3a and R 3b are each independently hydrogen, C 1-10 alkyl unsubstituted or substituted with N(C 1-10 alkyl) 2 , or C 1-10 alkoxycarbonyl ;
    R4는 수소 또는 C1-10알킬이고; R 4 is hydrogen or C 1-10 alkyl;
    R5 및 R6는 각각 독립적으로 수소, 비치환 또는 하나 이상의 할로겐으로 치환된 C1- 10알킬, -C(=O)NR5aR5b 또는 -C(=O)OR5a이고, 이때 R5a 및 R5b는 수소 또는 C1- 10알킬이다.R 5 and R 6 are each independently hydrogen, C 1-10 alkyl unsubstituted or substituted with one or more halogens, -C(=O)NR 5a R 5b or -C( = O)OR 5a , wherein R 5a and R 5b is hydrogen or C 1-10 alkyl .
  2. 제1항에 있어서,According to claim 1,
    R1은 수소 또는 C1-6알킬이고, R 1 is hydrogen or C 1-6 alkyl;
    R2는 비치환 또는 치환된 페닐 비치환 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 5-10원자헤테로아릴이거나, 또는R 2 is unsubstituted or substituted phenyl unsubstituted or substituted 5-10 membered heteroaryl containing at least one heteroatom selected from the group consisting of N and O, or
    R1와 R2는 이들이 결합된 질소원자와 함께 비치환 또는 치환된 N원자를 1 이상 포함하는 5-10원자헤테로아릴을 형성하고,R 1 and R 2 together with the nitrogen atom to which they are bonded form a 5- to 10-membered heteroaryl containing one or more unsubstituted or substituted N atoms;
    여기서, 상기 치환된 페닐 및 치환된 5-10원자헤테로아릴은 각각 독립적으로 비치환 또는 치환된 C1- 6알킬, 비치환 또는 치환된 C3- 7시클로알킬, 할로겐, 하이드록시, C1- 6알콕시, -SO2R2a, -C(=O)NR2aR2b, -SO2NR2aR2b, 비치환 또는 치환된 3-7원자헤테로시클로알킬, -C(=O)OR2a, -P(=O)R2aR2b 로 하나 이상 치환되고, 이때 치환된 C1- 6알킬, 치환된 C3- 7시클로알킬 및 치환된 3-7원자헤테로시클로알킬은 독립적으로 하이드록시, C1- 6알콕시, 할로겐 또는 CN로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환되고,Here, the substituted phenyl and substituted 5-10-membered heteroaryl are each independently selected from unsubstituted or substituted C 1-6 alkyl , unsubstituted or substituted C 3-7 cycloalkyl , halogen, hydroxy, C 1- 6 alkoxy, -SO 2 R 2a , -C(=O)NR 2a R 2b , -SO 2 NR 2a R 2b , unsubstituted or substituted 3-7 membered heterocycloalkyl, -C(=O)OR 2a , -P(=O) R 2a is substituted with one or more R 2b , wherein the substituted C 1-6 alkyl, substituted C 3-7 cycloalkyl and substituted 3-7 membered heterocycloalkyl are independently hydroxy, C 1-6 is substituted with one or more substituents selected from the group consisting of alkoxy, halogen or CN;
    여기서, R2a 및 R2b는 독립적으로 수소 또는 C1-6알킬이고;wherein R 2a and R 2b are independently hydrogen or C 1-6 alkyl;
    R3는 치환된 C4- 8시클로알킬, 치환된 페닐 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 5-8원자헤테로아릴이고,R 3 is a 5-8 membered heteroaryl containing at least one heteroatom selected from the group consisting of substituted C 4-8 cycloalkyl, substituted phenyl or substituted N and O;
    여기서, 치환된 C4- 8시클로알킬, 치환된 페닐 및 치환된 5-8원자 헤테로아릴은 각각 독립적으로 하이드록시, C1- 6알콕시, 할로겐, C1- 6알콕시카보닐, -NR3aR3b, 비치환 또는 치환된 C1- 6알킬, 또는 링커 L을 통해 연결되는 비치환 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 3-10원자헤테로시클로알킬로 치환되고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, Wherein, substituted C 4-8 cycloalkyl, substituted phenyl and substituted 5-8 membered heteroaryl are each independently hydroxy, C 1-6 alkoxy, halogen, C 1-6 alkoxycarbonyl , -NR 3a R 3b , unsubstituted or substituted C 1-6 alkyl, or 3-10 membered heterocycloalkyl containing at least one heteroatom selected from the group consisting of unsubstituted or substituted N and O linked through a linker L. substituted, wherein the linker L is a single bond, -C(=O)- or -C(=O)NH-,
    여기서, 상기 3-10원자헤테로시클로알킬은 3-7원자 단일고리 헤테로시클로알킬 또는 7-10원자 스피로이중고리 헤테로시클로알킬이고,Here, the 3-10 membered heterocycloalkyl is a 3-7 membered monocyclic heterocycloalkyl or a 7-10 membered spiro bicyclic heterocycloalkyl,
    여기서, 치환된 C1- 6알킬은 할로겐, C1- 6알콕시, 디C1 - 6알킬아미노, 하이드록시 또는 -C(=O)NH2로 치환되고,wherein the substituted C 1-6 alkyl is substituted with halogen, C 1-6 alkoxy, diC 1-6 alkylamino, hydroxy or -C(=O ) NH 2 ;
    여기서, 치환된 3-10원자헤테로시클로알킬은 C1- 6알킬, C3- 8시클로알킬, N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 3-8원자헤테로시클로알킬 또는 -NR3aR3b로 치환되고,Here, the substituted 3-10 membered heterocycloalkyl is C 1-6 alkyl, C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl containing at least one heteroatom selected from the group consisting of N and O, or -NR 3a R 3b is substituted;
    여기서 R3a 및 R3b는 각각 독립적으로 수소, 비치환 또는 N(C1- 6알킬)2로 치환된C1 -6알킬, 또는 C1-6알콕시카보닐이고; wherein R 3a and R 3b are each independently hydrogen , C 1-6 alkyl unsubstituted or substituted with N(C 1-6 alkyl) 2 , or C 1-6 alkoxycarbonyl ;
    R4는 수소 또는 C1-6알킬이고; R 4 is hydrogen or C 1-6 alkyl;
    R5 및 R6는 각각 독립적으로 수소, 비치환 또는 하나 이상의 할로겐으로 치환된 C1- 6알킬, -C(=O)NR5aR5b 또는 -C(=O)OR5a이고, 이때 R5a 및 R5b는 수소 또는 C1- 6알킬인,R 5 and R 6 are each independently hydrogen, C 1-6 alkyl unsubstituted or substituted with one or more halogens, -C(=O)NR 5a R 5b or -C(=O) OR 5a , wherein R 5a and R 5b is hydrogen or C 1-6 alkyl;
    화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
  3. 제1항에 있어서,According to claim 1,
    R1은 수소 또는 C1- 4알킬이고, R 1 is hydrogen or C 1-4 alkyl;
    R2는 비치환 또는 치환된 페닐, 비치환 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 5-6원자 헤테로아릴, 또는 비치환 또는 치환된 N 원자를 1 이상 포함하는 융합된 9-10원자헤테로아릴이거나, 또는R 2 is an unsubstituted or substituted phenyl, an unsubstituted or substituted 5-6 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N and O, or one or more unsubstituted or substituted N atoms is a fused 9-10 membered heteroaryl comprising
    R1와 R2는 이들이 결합된 질소원자와 함께 비치환 또는 치환된 N원자를 1 이상 포함하는 5-원자헤테로아릴을 형성하고,R 1 and R 2 together with the nitrogen atom to which they are bonded form a 5-membered heteroaryl containing one or more unsubstituted or substituted N atoms;
    여기서, 상기 치환된 페닐, 치환된 5-6원자 헤테로아릴, 치환된 9-10원자 헤테로아릴 및 치환된 5원자헤테로아릴은 각각 독립적으로 비치환 또는 치환된 C1- 4알킬, 비치환 또는 치환된 C3- 6시클로알킬, 할로겐, 하이드록시, C1- 4알콕시, -SO2R2a, -C(=O)NR2aR2b, -SO2NR2aR2b, 비치환 또는 치환된 3-6원자헤테로시클로알킬, -C(=O)OR2a, -P(=O)R2aR2b 로 하나 이상 치환되고, 이때 치환된 C1- 4알킬, 치환된 C3- 6시클로알킬 및 치환된 3-6원자헤테로시클로알킬은 독립적으로 하이드록시, C1- 4알콕시, 할로겐 및 CN로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환되고,Here, the substituted phenyl, substituted 5-6 membered heteroaryl, substituted 9-10 membered heteroaryl and substituted 5-membered heteroaryl are each independently unsubstituted or substituted C 1-4 alkyl , unsubstituted or substituted C 3-6 cycloalkyl, halogen, hydroxy, C 1-4 alkoxy, -SO 2 R 2a , -C(=O ) NR 2a R 2b , -SO 2 NR 2a R 2b , unsubstituted or substituted 3 one or more substituted with -6-membered heterocycloalkyl, -C(=O)OR 2a , -P(=O)R 2a R 2b , wherein substituted C 1-4 alkyl, substituted C 3-6 cycloalkyl and the substituted 3-6 membered heterocycloalkyls are independently substituted with one or more substituents selected from the group consisting of hydroxy, C 1-4 alkoxy, halogen and CN;
    여기서, R2a 및 R2b는 독립적으로 수소 또는 C1-4알킬이고;wherein R 2a and R 2b are independently hydrogen or C 1-4 alkyl;
    R3는 치환된 C5- 6시클로알킬, 치환된 페닐 또는 하나 이상의 N원자를 포함하는 치환된 5-6원자헤테로아릴이고,R 3 is substituted C 5-6 cycloalkyl, substituted phenyl or substituted 5-6 membered heteroaryl containing one or more N atoms;
    여기서, 치환된 C5- 6시클로알킬, 치환된 페닐 및 치환된 5-6원자 헤테로아릴은 각각 독립적으로 하이드록시, C1- 4알콕시, 할로겐, C1- 4알콕시카보닐, -NR3aR3b, 비치환 또는 치환된 C1- 4알킬, 또는 링커 L을 통해 연결되는 비치환 또는 치환된 N 및 O로 이루어지는 군으로부터 선택되는 1종 이상의 헤테로원자를 포함하는 4-10원자헤테로시클로알킬로 치환되고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, Wherein, substituted C 5-6 cycloalkyl, substituted phenyl and substituted 5-6 membered heteroaryl are each independently hydroxy, C 1-4 alkoxy, halogen , C 1-4 alkoxycarbonyl, -NR 3a R 3b , unsubstituted or substituted C 1-4 alkyl, or 4-10 membered heterocycloalkyl containing at least one heteroatom selected from the group consisting of unsubstituted or substituted N and O linked through a linker L. substituted, wherein the linker L is a single bond, -C(=O)- or -C(=O)NH-,
    여기서, 치환된 C1- 4알킬은 할로겐, C1- 4알콕시, 디C1 - 4알킬아미노, 하이드록시 또는 NH2CO-로 치환되고, wherein the substituted C 1-4 alkyl is substituted with halogen, C 1-4 alkoxy, diC 1-4 alkylamino, hydroxy or NH 2 CO— ;
    여기서, 치환된 4-10원자헤테로시클로알킬은 C1- 4알킬, C3- 6시클로알킬, 3-7원자헤테로시클로알킬 또는 -NR3aR3b로 치환되고,wherein the substituted 4-10 membered heterocycloalkyl is substituted with C 1-4 alkyl , C 3-6 cycloalkyl, 3-7 membered heterocycloalkyl or -NR 3a R 3b ;
    여기서 R3a 및 R3b는 각각 독립적으로 수소, 비치환 또는 N(C1- 4알킬)2로 치환된 C1-4알킬, 또는 C1-4알콕시카보닐이고; wherein R 3a and R 3b are each independently hydrogen , C 1-4 alkyl unsubstituted or substituted with N(C 1-4 alkyl) 2 , or C 1-4 alkoxycarbonyl;
    R4는 수소 또는 C1-4알킬이고; R 4 is hydrogen or C 1-4 alkyl;
    R5 및 R6는 각각 독립적으로 수소, 비치환 또는 하나 이상의 할로겐으로 치환된 C1-4알킬, -C(=O)NR5aR5b 또는 -C(=O)OR5a이고, 이때 R5a 및 R5b는 수소 또는 C1- 4알킬인,R 5 and R 6 are each independently hydrogen, C 1-4 alkyl unsubstituted or substituted with one or more halogens, -C(=O)NR 5a R 5b or -C(=O)OR 5a , wherein R 5a and R 5b is hydrogen or C 1-4 alkyl;
    화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
  4. 제1항에 있어서,According to claim 1,
    R1은 수소이고, R 1 is hydrogen;
    R2는 비치환 또는 치환된 페닐, 비치환 또는 치환된 헤테로아릴이되, 이 때 헤테로아릴은 피리딜, 피라졸릴, 옥사졸릴, 인다졸릴 또는 퀴놀리닐이거나, 또는R 2 is unsubstituted or substituted phenyl, unsubstituted or substituted heteroaryl, wherein heteroaryl is pyridyl, pyrazolyl, oxazolyl, indazolyl or quinolinyl; or
    R1와 R2는 이들이 결합된 질소원자와 함께 치환된 이미다졸릴을 형성하고,R 1 and R 2 together with the nitrogen atom to which they are attached form a substituted imidazolyl,
    여기서, 상기 치환된 페닐, 치환된 헤테로아릴 및 치환된 이미다졸릴은 각각 독립적으로 비치환 또는 치환된 C1- 4알킬, 할로겐, C1- 4알콕시, 하이드록시, C1- 4알킬설포닐, 디(C1-4알킬)아미노설포닐, C1- 4알콕시카보닐, 디(C1-4알킬)포스피닐, 카르복실, 하이드록시 치환된 옥세타닐, 하이드록시 치환된 시클로부틸 및 CONH2 로 이루어지는 군에서 선택되는 1 이상으로 치환되고, 이때 치환된 C1- 4알킬은 하이드록시, C1-4알콕시, 할로겐 또는 CN로 치환되고;Here, the substituted phenyl, substituted heteroaryl, and substituted imidazolyl are each independently selected from unsubstituted or substituted C 1-4 alkyl, halogen, C 1-4 alkoxy, hydroxy, C 1-4 alkylsulfonyl , di(C 1-4 alkyl )aminosulfonyl, C 1-4 alkoxycarbonyl, di(C 1-4 alkyl ) phosphinyl, carboxyl, hydroxy substituted oxetanyl, hydroxy substituted cyclobutyl, and substituted with one or more selected from the group consisting of CONH 2 , wherein the substituted C 1-4 alkyl is substituted with hydroxy, C 1-4 alkoxy, halogen or CN;
    R3는 치환된 시클로펜틸, 시클로헥실, 페닐 또는 치환된 피라졸릴이고,R 3 is substituted cyclopentyl, cyclohexyl, phenyl or substituted pyrazolyl;
    여기서, 치환된 시클로펜틸, 시클로헥실, 페닐 또는 피라졸릴은 각각 독립적으로 하이드록시, C1- 3알콕시, 할로겐, 메톡시카보닐, 디메틸아미노에틸(메틸)아미노, 비치환되거나 하나 이상의 할로겐, 메톡시, 디메틸아미노, -C(=O)NH2 또는 하이드록시로 치환된 C1- 4알킬, 또는 링커 L을 통해 연결되는 비치환 또는 치환된 비치환 또는 치환된 3-10원자헤테로시클로알킬로 치환되고, 여기서 3-10원자헤테로시클로알킬은 옥세타닐, 테트라하이드로퓨라닐, 테트라하이드로피라닐, 피롤리디닐, 피페리디닐, 피페라지닐, 아제파닐, 몰포리닐, 1,4-디옥사-8-아자스피로[4.5]데카닐, 2,6-디아자스피로[3.3]헵타닐, 2-옥사-6-아자스피로[3.3]헵타닐, 및 2-옥사스피로[3.3]헵타닐로부터 선택되고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, wherein each substituted cyclopentyl, cyclohexyl, phenyl or pyrazolyl is independently hydroxy, C 1-3 alkoxy, halogen, methoxycarbonyl, dimethylaminoethyl ( methyl)amino, unsubstituted or one or more halogen, methyl C 1-4 alkyl substituted with oxy, dimethylamino, -C(=0)NH 2 or hydroxy, or unsubstituted or substituted 3-10 membered heterocycloalkyl connected through a linker L; substituted, wherein the 3-10 membered heterocycloalkyl is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, morpholinyl, 1,4-di from oxa-8-azaspiro[4.5]decanyl, 2,6-diazaspiro[3.3]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 2-oxaspiro[3.3]heptanyl selected, wherein the linker L is a single bond, -C(=O)- or -C(=O)NH-,
    여기서, 치환된 3-10원자헤테로시클로알킬의 치환기는 C1- 2알킬, C3- 4시클로알킬, 아지리디닐, 아제티디닐, 피롤리디닐, 메틸피페라지닐, 옥세타닐, NMe2, NEt2, NHMe, NHCO2t-Bu, 메톡시, NH2 또는 아세틸이고; Here, the substituent of the substituted 3-10 membered heterocycloalkyl is C 1-2 alkyl, C 3-4 cycloalkyl, aziridinyl, azetidinyl, pyrrolidinyl, methylpiperazinyl, oxetanyl, NMe 2 , NEt 2 , NHMe, NHCO 2 t-Bu, methoxy, NH 2 or acetyl;
    R4는 수소이고; R 4 is hydrogen;
    R5 및 R6는 각각 독립적으로 수소, 비치환 또는 1 내지 3의 할로겐으로 치환된 C1- 4알킬, -C(=O)NR5aR5b 또는 -C(=O)OR5a이고, 이때 R5a 및 R5b는 수소 또는 C1- 4알킬인,R 5 and R 6 are each independently hydrogen, unsubstituted or 1 to 3 halogen-substituted C 1-4 alkyl, -C(=O)NR 5a R 5b or -C(=O)OR 5a , wherein R 5a and R 5b are hydrogen or C 1-4 alkyl;
    화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
  5. 제1항에 있어서,According to claim 1,
    상기 R3는 하기에서 선택되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염:R 3 is a compound selected from the following, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof:
    Figure PCTKR2022016628-appb-img-000062
    Figure PCTKR2022016628-appb-img-000062
    여기서,here,
    R7 및 R8은 독립적으로 비치환 또는 치환된 C1- 10알킬, -NR3aR3b 또는 링커 L을 통해 연결되는 비치환 또는 치환된 3-10원자헤테로시클로알킬이고, 이때 링커 L은 단일결합, -C(=O)- 또는 -C(=O)NH-이고, R 7 and R 8 are independently unsubstituted or substituted C 1-10 alkyl, -NR 3a R 3b or unsubstituted or substituted 3-10 membered heterocycloalkyl linked through a linker L, wherein the linker L is a single a bond, -C(=O)- or -C(=O)NH-;
    여기서, 치환된 C1- 10알킬은 C1- 10알콕시, 디C1 - 10알킬아미노, 하이드록시 또는 NH2CO-로 치환되고, wherein the substituted C 1-10 alkyl is substituted with C 1-10 alkoxy, diC 1-10 alkylamino, hydroxy or NH 2 CO— ;
    여기서, 치환된 3-10원자헤테로시클로알킬은 C1- 10알킬, C3- 10시클로알킬, 3-10원자헤테로시클로알킬 또는 -NR3aR3b로 치환되고,wherein the substituted 3-10 membered heterocycloalkyl is substituted with C 1-10 alkyl, C 3-10 cycloalkyl , 3-10 membered heterocycloalkyl or -NR 3a R 3b ;
    여기서 R3a 및 R3b는 각각 독립적으로 수소, 또는 비치환 또는 N(C1- 10알킬)2로 치환된C1-10알킬이고,Wherein R 3a and R 3b are each independently hydrogen or C 1-10 alkyl unsubstituted or substituted with N(C 1-10 alkyl ) 2 ;
    R7a, R8a 및 R8b는 각각 독립적으로, 수소, 비치환 또는 하이드록시 또는 할로겐으로 치환된 C1-10알킬, C1-10알콕시, 할로겐, 또는 C1-10알콕시카보닐이고,R 7a , R 8a and R 8b are each independently hydrogen, unsubstituted or hydroxy- or halogen-substituted C 1-10 alkyl, C 1-10 alkoxy, halogen, or C 1-10 alkoxycarbonyl;
    R9는 하이드록시로 치환된 C1-10알킬 또는 3-10원자헤테로시클로알킬이고,R 9 is C 1-10 alkyl substituted with hydroxy or 3-10 membered heterocycloalkyl;
    R9a 및 R9b는 수소 또는 하이드록시이고,R 9a and R 9b are hydrogen or hydroxy;
    n은 1 또는 2인,n is 1 or 2;
    화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
  6. 제1항에 있어서,According to claim 1,
    R1은 수소이고;R 1 is hydrogen;
    R2는 다음 중에서 선택되거나,R 2 is selected from;
    Figure PCTKR2022016628-appb-img-000063
    Figure PCTKR2022016628-appb-img-000063
    Figure PCTKR2022016628-appb-img-000064
    Figure PCTKR2022016628-appb-img-000064
    또는 R1와 R2는 서로 결합하여
    Figure PCTKR2022016628-appb-img-000065
    를 형성하는,    Or R 1 and R 2 are bonded to each other
    Figure PCTKR2022016628-appb-img-000065
    to form,
    화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
  7. 제1항에 있어서, R3는 다음 중에서 선택되고,The method of claim 1, wherein R 3 is selected from
    Figure PCTKR2022016628-appb-img-000066
    Figure PCTKR2022016628-appb-img-000066
    Figure PCTKR2022016628-appb-img-000067
    Figure PCTKR2022016628-appb-img-000067
    Figure PCTKR2022016628-appb-img-000068
    Figure PCTKR2022016628-appb-img-000069
    ;
    Figure PCTKR2022016628-appb-img-000068
    Figure PCTKR2022016628-appb-img-000069
    ;
    R4는 수소인,R 4 is hydrogen;
    화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
  8. 제1항에 있어서, According to claim 1,
    R5는 수소 또는 메틸이고;R 5 is hydrogen or methyl;
    R6는 수소, 메틸, CF3, 이소프로필,-C(=O)NH2, ,에틸옥시카보닐, 또는 1-메틸프로필옥시인, 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.R 6 is hydrogen, methyl, CF 3 , isopropyl, -C(=O)NH 2 , ethyloxycarbonyl, or 1-methylpropyloxy, a compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or A pharmaceutically acceptable salt.
  9. 제1항에 있어서,According to claim 1,
    상기 화학식 1로 표시되는 화합물은 하기 화합물 군으로부터 선택되는 어느 하나인 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염:The compound represented by Formula 1 is any one compound selected from the following compound group, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof:
    <1> 2-(6-((2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<1> 2-(6-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridine -2-yl)propan-2-ol;
    <2> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<2> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)thieno[2,3-d]pyridine midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <3> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<3> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <4> 2-(6-((5-메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<4> 2-(6-((5-methyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl )amino)pyridin-2-yl)propan-2-ol;
    <5> 2-(6-((5,6-디메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<5> 2-(6-((5,6-dimethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol;
    <6> 2-(6-((5,6-디메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<6> 2-(6-((5,6-dimethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol;
    <7> 2-(6-((5,6-디메틸-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<7> 2-(6-((5,6-dimethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol;
    <8> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-2-메톡시페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<8> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)thieno[2,3-d]pyridine midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <9> 2-(6-((2-((3-메톡시-4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<9> 2-(6-((2-((3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4- yl)amino)pyridin-2-yl)propan-2-ol;
    <10> 2-(6-((2-((1-(테트라하이드로-2H-피란-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<10> 2-(6-((2-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <11> 2-(6-((2-((4-(4-(4-메틸피페라진-1-일)피페리딘-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<11> 2-(6-((2-((4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)thieno[2,3-d ]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <12> 2-(6-((2-((4-((2-(디메틸아미노)에틸)(메틸)아미노)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<12> 2-(6-((2-((4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl )amino)pyridin-2-yl)propan-2-ol;
    <13> 2-(6-((2-((4-(4-에틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<13> 2-(6-((2-((4-(4-ethylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridine -2-yl)propan-2-ol;
    <14> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-이소프로필티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<14> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-isopropylthieno[2, 3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <15> 2-(6-((5-이소프로필-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<15> 2-(6-((5-isopropyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[2,3-d]pyrimidine-4- yl)amino)pyridin-2-yl)propan-2-ol;
    <16> 2-(6-((2-((3-메톡시-4-(4-메틸피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<16> 2-(6-((2-((3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <17> 2-(6-((5-메틸-2-((1-(테트라하이드로-2H-피란-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<17> 2-(6-((5-methyl-2-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <18> 2-(6-((2-((3-메톡시-4-(피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<18> 2-(6-((2-((3-methoxy-4-(piperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine-4 -yl)amino)pyridin-2-yl)propan-2-ol;
    <19> sec-부틸 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트;<19> sec-butyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropane- 2-yl)pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxylate;
    <20> sec-부틸 4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-5-카복실레이트;<20> sec-butyl 4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-2-((4-(4-methylpiperazin-1-yl)phenyl )amino)thieno[2,3-d]pyrimidine-5-carboxylate;
    <21> 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카르복사미드;<21> 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2-yl )pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxamide;
    <22> 4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-2-((4-(4-메틸피페라진-1-일)페닐)아미노)티에노[2,3-d]피리미딘-5-카르복사미드;<22> 4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-2-((4-(4-methylpiperazin-1-yl)phenyl)amino) thieno[2,3-d]pyrimidine-5-carboxamide;
    <23> (1R,4R)-4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)시클로헥산-1-올;<23> (1R,4R)-4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d ]pyrimidin-2-yl)amino)cyclohexan-1-ol;
    <24> 에틸 2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)티에노[2,3-d]피리미딘-5-카복실레이트;<24> Ethyl 2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-4-((6-(2-hydroxypropan-2- yl)pyridin-2-yl)amino)thieno[2,3-d]pyrimidine-5-carboxylate;
    <25> 2-(6-((5-메틸-2-(((1R,4R)-4-모르폴리노시클로헥실)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<25> 2-(6-((5-methyl-2-(((1R,4R)-4-morpholinocyclohexyl)amino)thieno[2,3-d]pyrimidin-4-yl) amino) pyridin-2-yl) propan-2-ol;
    <26> 2-(6-((5-메틸-2-(((1R,4R)-4-(피페리딘-1-일)시클로헥실)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<26> 2-(6-((5-methyl-2-(((1R,4R)-4-(piperidin-1-yl)cyclohexyl)amino)thieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <27> (1S,2R,3R,5R)-3-(하이드록시메틸)-5-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)시클펜탄-1,2-디올;<27> (1S,2R,3R,5R)-3-(hydroxymethyl)-5-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino) -5-methylthieno[2,3-d]pyrimidin-2-yl)amino)cyclopentane-1,2-diol;
    <28> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-(트리플루오로메틸)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<28> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-(trifluoromethyl)thie no[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <29> 2-(6-((2-((4-(4-메틸피페라진-1-일)페닐)아미노)-5-(트리플루오로메틸)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<29> 2-(6-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)thieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <30> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(피리딘-2-일)티에노[2,3-d]피리미딘-2,4-디아민;<30> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(pyridin-2-yl)thieno[2,3 -d] pyrimidine-2,4-diamine;
    <31> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-페닐티에노[2,3-d]피리미딘-2,4-디아민;<31> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-phenylthieno[2,3-d]pyrimidine- 2,4-diamine;
    <32> 2-(6-((5-메틸-2-((1-(옥세탄-3-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<32> 2-(6-((5-methyl-2-((1-(oxetan-3-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <33> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<33> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <34> N4-(6-(터트-부틸)피리딘-2-일)-N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<34> N4-(6-(tert-butyl)pyridin-2-yl)-N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5- methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <35> 2-(6-((5-메틸-2-((1-(테트라하이드로퓨란-3-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<35> 2-(6-((5-methyl-2-((1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <36> 2-(6-((2-((3-플루오로-4-(4-메틸피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<36> 2-(6-((2-((3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methylthieno[2,3-d]pyryl midin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <37> 2-(6-((5-메틸-2-((4-(4-메틸피페라진-1-일)-3-(트리플루오로메틸)페닐)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<37> 2-(6-((5-methyl-2-((4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <38> 4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시-N-(1-메틸피페리딘-4-일)벤즈아미드;<38> 4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine-2- yl)amino)-2-methoxy-N-(1-methylpiperidin-4-yl)benzamide;
    <39> 메틸 5-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-(4-메틸피페라진-1-일)벤조에이트;<39> Methyl 5-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine-2 -yl)amino)-2-(4-methylpiperazin-1-yl)benzoate;
    <40> 2-(6-((2-((3-(하이드록시메틸)-4-(4-메틸피페라진-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<40> 2-(6-((2-((3-(hydroxymethyl)-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <41> 2-(6-((2-((1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<41> 2-(6-((2-((1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <42> 2-(6-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<42> 2-(6-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <43> 2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<43> 2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <44> 2-(3-((2-((1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<44> 2-(3-((2-((1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <45> 5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)-N4-페닐티에노[2,3-d]피리미딘-2,4-디아민;<45> 5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-N4-phenylthieno[2,3-d]pyrimidine- 2,4-diamine;
    <46> N2-(1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)-5-메틸-N4-페닐티에노[2,3-d]피리미딘-2,4-디아민;<46> N2-(1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-methyl-N4-phenylthieno[2,3-d]pyrimidine- 2,4-diamine;
    <47> 2-(6-((2-((4-(4-(디에틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<47> 2-(6-((2-((4-(4-(diethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <48> 2-(6-((2-((3-메톡시-4-(1,4-디옥사-8-아자스피로[4.5]데칸-8-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<48> 2-(6-((2-((3-methoxy-4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)phenyl)amino)-5-methyl thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <49> (4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)(4-메틸피페라진-1-일)메타논;<49> (4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine-2 -yl)amino)-2-methoxyphenyl)(4-methylpiperazin-1-yl)methanone;
    <50> 2-메틸-2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판니트릴;<50> 2-methyl-2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propanenitrile;
    <51> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)-2-메틸프로판니트릴;<51> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)-2-methylpropanenitrile;
    <52> 5-메틸-N4-(1-메틸-1H-피라졸-4-일)-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<52> 5-methyl-N4-(1-methyl-1H-pyrazol-4-yl)-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d ]pyrimidine-2,4-diamine;
    <53> N4-(5-(터트-부틸)이속사졸-3-일)-5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<53> N4-(5-(tert-butyl)isoxazol-3-yl)-5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3- d] pyrimidine-2,4-diamine;
    <54> N4-(1H-인다졸-6-일)-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<54> N4-(1H-indazol-6-yl)-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyrimidine-2,4- diamine;
    <55> 5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)-N4-(퀴놀린-7-일)티에노[2,3-d]피리미딘-2,4-디아민;<55> 5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)-N4-(quinolin-7-yl)thieno[2,3-d]pyrimidine-2,4 -diamine;
    <56> N4-(1H-인다졸-6-일)-5-메틸-N2-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<56> N4-(1H-indazol-6-yl)-5-methyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)thieno[2,3-d]pyrimidine- 2,4-diamine;
    <57> 5-메틸-4-(4-메틸-1H-이미다졸-1-일)-N-(4-(4-메틸피페라진-1-일)페닐)티에노[2,3-d]피리미딘-2-아민;<57> 5-methyl-4- (4-methyl-1H-imidazol-1-yl) -N- (4- (4-methylpiperazin-1-yl) phenyl) thieno [2,3-d ]pyrimidin-2-amine;
    <58> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-1-메틸-1H-피라졸-5-일)프로판-2-올;<58> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)-1-methyl-1H-pyrazol-5-yl)propan-2-ol;
    <59> 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤즈아마이드;<59> 3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)benzamide;
    <60>2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<60> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <61> 2-(6-((2-((4-(3-(디메틸아미노)피롤리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<61> 2-(6-((2-((4-(3-(dimethylamino)pyrrolidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <62> 2-(3-((2-((4-(3-(디메틸아미노)피롤리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<62> 2-(3-((2-((4-(3-(dimethylamino)pyrrolidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <63> 2-(6-((2-((3-메톡시-4-(4-(피롤리딘-1-일)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<63> 2-(6-((2-((3-methoxy-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <64> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<64> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <65> 2-(3-((2-((3-메톡시-4-(4-(피롤리딘-1-일)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<65> 2-(3-((2-((3-methoxy-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <66> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-메톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<66> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-methoxypropan-2-yl)pyridin-2 -yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <67> 2-(3-((2-((4-(4-(디메틸아미노)아제판-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<67> 2-(3-((2-((4-(4-(dimethylamino)azepan-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <68> 2-(6-((2-((4-(4-(디메틸아미노)아제판-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<68> 2-(6-((2-((4-(4-(dimethylamino)azepan-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3- d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <69> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-메톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<69> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-methoxypropan-2-yl) )pyridin-2-yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <70> 터트-부틸(1-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)피페리딘-4-일)카바메이트;<70> tert-butyl(1-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3- d]pyrimidin-2-yl)amino)-2-methoxyphenyl)piperidin-4-yl)carbamate;
    <71> 터트-부틸(1-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-2-메톡시페닐)피페리딘-4-일)카바메이트;<71> tert-butyl(1-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine -2-yl)amino)-2-methoxyphenyl)piperidin-4-yl)carbamate;
    <72> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-에톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<72> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-ethoxypropan-2-yl)pyridin-2 -yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <73> 2-(4-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<73> 2-(4-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <74> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-에톡시프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<74> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-ethoxypropan-2-yl) )pyridin-2-yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <75> 2-(2-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-4-일)프로판-2-올;<75> 2-(2-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-4-yl)propan-2-ol;
    <76> 2-(3-((2-((4-(4-(아지리딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<76> 2-(3-((2-((4-(4-(aziridin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <77> 2-(2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-4-일)프로판-2-올;<77> 2-(2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-4-yl)propan-2-ol;
    <78> 1-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)시클로부탄-1-올;<78> 1-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)cyclobutan-1-ol;
    <79> 2-(6-((2-((4-(4-(아지리딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<79> 2-(6-((2-((4-(4-(aziridin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <80> 2-(6-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)-2-메틸프로판니트릴;<80> 2-(6-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)-2-methylpropanenitrile;
    <81> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)-2-메틸프로판니트릴;<81> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)-2-methylpropanenitrile;
    <82> 2-(6-((2-((3-메톡시-4-(4-(메틸아미노)피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<82> 2-(6-((2-((3-methoxy-4-(4-(methylamino)piperidin-1-yl)phenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <83> 2-(6-((2-((3-메톡시-4-(4-메톡시피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<83> 2-(6-((2-((3-methoxy-4-(4-methoxypiperidin-1-yl)phenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <84> 2-(3-((2-((3-메톡시-4-(4-메톡시피페리딘-1-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<84> 2-(3-((2-((3-methoxy-4-(4-methoxypiperidin-1-yl)phenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <85> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(3-(2-메톡시프로판-2-일)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<85> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-(2-methoxypropan-2-yl)phenyl)- 5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <86> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3-(2-메톡시프로판-2-일)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<86> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-(2-methoxypropan-2-yl) )phenyl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <87> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<87> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno[2,3 -d] pyrimidine-2,4-diamine;
    <88> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<88> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
    <89> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(3-(트리플루오로메틸)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<89> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(3-(trifluoromethyl) phenyl)thieno[2,3-d]pyrimidine-2,4-diamine;
    <90> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(3-(트리플루오로메틸)페닐)티에노[2,3-d]피리미딘-2,4-디아민;<90> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(3-(trifluoromethyl)phenyl)thieno [2,3-d]pyrimidine-2,4-diamine;
    <91> 2-(6-((2-((1-(3-(디메틸아미노)프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<91> 2-(6-((2-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <92> 2-(6-((2-((1-(2-(디메틸아미노)에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<92> 2-(6-((2-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <93> 2-(3-((2-((1-(2-(디메틸아미노)에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<93> 2-(3-((2-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <94> 2-(6-((2-((1-(2-메톡시에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<94> 2-(6-((2-((1-(2-methoxyethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl)amino)pyridin-2-yl)propan-2-ol;
    <95> 2-(3-((2-((1-(2-메톡시에틸)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<95> 2-(3-((2-((1-(2-methoxyethyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl)amino)phenyl)propan-2-ol;
    <96> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-플루오로피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<96> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-fluoropyridin-2-yl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
    <97> 2-(3-((2-((1-(3-(디메틸아미노)프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<97> 2-(3-((2-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <98> 2-(6-((2-((4-(4-아미노피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<98> 2-(6-((2-((4-(4-aminopiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <99> 2-(3-((2-((4-(4-아미노피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<99> 2-(3-((2-((4-(4-aminopiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <100> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(3-메톡시페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<100> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-methoxyphenyl)-5-methylthieno[2,3 -d] pyrimidine-2,4-diamine;
    <101> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3-메톡시페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<101> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3-methoxyphenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
    <102> 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페놀;<102> 3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)phenol;
    <103> 3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페놀;<103> 3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenol;
    <104> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(2-(이소프로필설포닐)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<104> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(2-(isopropylsulfonyl)phenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
    <105> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(2-(이소프로필설포닐)페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<105> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(2-(isopropylsulfonyl)phenyl)-5 -Methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <106> N4-(2-(이소프로필설포닐)페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<106> N4-(2-(isopropylsulfonyl)phenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno [2,3-d]pyrimidine-2,4-diamine;
    <107> 2-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-N,N-디메틸벤젠설폰아미드;<107> 2-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide;
    <108> 2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-N,N-디메틸벤젠설폰아미드;<108> 2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide;
    <109> N,N-디메틸-2-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤젠설폰아미드;<109> N,N-dimethyl-2-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[ 2,3-d]pyrimidin-4-yl)amino)benzenesulfonamide;
    <110> N4-(3-메톡시페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<110> N4-(3-methoxyphenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[2,3 -d] pyrimidine-2,4-diamine;
    <111> 메틸 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트;<111> methyl 3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)benzoate;
    <112> 메틸 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트;<112> methyl 3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d ]pyrimidin-4-yl)amino)benzoate;
    <113> 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페놀;<113> 3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] pyrimidin-4-yl)amino)phenol;
    <114> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올;<114> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol;
    <115> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올;<115> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol;
    <116> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-(트리플루오로메틸)페닐)프로판-2-올;<116> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)-5-(trifluoromethyl)phenyl)propan-2-ol;
    <117> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-(트리플루오로메틸)페닐)프로판-2-올;<117> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)-5-(trifluoromethyl)phenyl)propan-2-ol;
    <118> 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-3,5-디메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<118> 2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-3,5-dimethyl-1H-pyrazol-4-yl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <119> 2-(6-((2-((1-(1-시클로프로필피페리딘-4-일)-3,5-디메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<119> 2-(6-((2-((1-(1-cyclopropylpiperidin-4-yl)-3,5-dimethyl-1H-pyrazol-4-yl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <120> (2-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<120> (2-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide;
    <121> (2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<121> (2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide;
    <122> 디메틸(2-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)포스핀옥사이드<122> Dimethyl(2-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3- d] pyrimidin-4-yl) amino) phenyl) phosphine oxide
    <123> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(6-(트리플루오로메틸)피리딘-2-일)티에노[2,3-d]피리미딘-2,4-디아민<123> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(6-(trifluoromethyl)pyridine-2- yl)thieno[2,3-d]pyrimidine-2,4-diamine
    <124> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(6-플루오로피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<124> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-fluoropyridin-2-yl)-5 -Methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <125> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-5-메틸-N4-(6-(트리플루오로메틸)피리딘-2-일)티에노[2,3-d]피리미딘-2,4-디아민;<125> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-5-methyl-N4-(6-(trifluoromethyl) pyridin-2-yl)thieno[2,3-d]pyrimidine-2,4-diamine;
    <126> 2-(6-((2-((1-(3-메톡시프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<126> 2-(6-((2-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl)amino)pyridin-2-yl)propan-2-ol;
    <127> 2-(3-((2-((1-(3-메톡시프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<127> 2-(3-((2-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidine -4-yl)amino)phenyl)propan-2-ol;
    <128> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<128> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-fluorophenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <129> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<129> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-fluorophenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <130> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-플루오로페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<130> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-fluorophenyl)-N4-(3-fluorophenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
    <131> N2-(3,5-디메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<131> N2-(3,5-dimethyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-N4-(3-fluorophenyl)-5-methyl thieno[2,3-d]pyrimidine-2,4-diamine;
    <132> 2-(3-((2-((3,5-디메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<132> 2-(3-((2-((3,5-dimethyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methyl thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <133> 2-(6-((5-메틸-2-((3-메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<133> 2-(6-((5-methyl-2-((3-methyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <134> 3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)벤조산;<134> 3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3-d] pyrimidin-4-yl)amino)benzoic acid;
    <135> 3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조산;<135> 3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)benzoic acid;
    <136> N4-(3-플루오로페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<136> N4-(3-fluorophenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[2,3 -d] pyrimidine-2,4-diamine;
    <137> N2-(1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<137> N2-(1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)-N4-(3-fluorophenyl)-5-methylthieno[2, 3-d] pyrimidine-2,4-diamine;
    <138> 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올;<138> 2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol;
    <139> 2-(3-플루오로-5-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<139> 2-(3-fluoro-5-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thie no[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <140> 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<140> 2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <141> 2-(6-((2-((1-(1-시클로프로필피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<141> 2-(6-((2-((1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2, 3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <142> 2-(6-((2-((1-(1-시클로프로필피페리딘-4-일)-3-메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<142> 2-(6-((2-((1-(1-cyclopropylpiperidin-4-yl)-3-methyl-1H-pyrazol-4-yl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <143> 2-(3-((2-((5-클로로-1-((3S,4S)-3-플루오로-1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<143> 2-(3-((2-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl) -1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <144> 2-(3-((2-((5-클로로-1-((3S,4S)-3-플루오로-1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<144> 2-(3-((2-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl) -1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <145> 2-(3-((2-((3-메톡시-4-(2,6-디아자스피로[3.3]헵탄-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<145> 2-(3-((2-((3-methoxy-4-(2,6-diazaspiro[3.3]heptan-2-yl)phenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <146> 2-(6-((2-((3-메톡시-4-(2,6-디아자스피로[3.3]헵탄-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<146> 2-(6-((2-((3-methoxy-4-(2,6-diazaspiro[3.3]heptan-2-yl)phenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <147> 2-(3-((2-((1-(1-시클로프로필피페리딘-4-일)-3-메틸-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<147> 2-(3-((2-((1-(1-cyclopropylpiperidin-4-yl)-3-methyl-1H-pyrazol-4-yl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <148> 메틸 3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조에이트;<148> Methyl 3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)benzoate;
    <149> 3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)벤조산;<149> 3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl)amino)benzoic acid;
    <150> 2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)-5-(트리플루오로메틸)페닐)프로판-2-올;<150> 2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno[2,3 -d]pyrimidin-4-yl)amino)-5-(trifluoromethyl)phenyl)propan-2-ol;
    <151> 2-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-3-메틸-1H-피라졸-1-일)-2-메틸프로판아미드;<151> 2-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine -2-yl)amino)-3-methyl-1H-pyrazol-1-yl)-2-methylpropanamide;
    <152> 2-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-3-메틸-1H-피라졸-1-일)-2-메틸프로판아미드;<152> 2-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl )amino)-3-methyl-1H-pyrazol-1-yl)-2-methylpropanamide;
    <153> 1-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)시클로부탄-1-올;<153> 1-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)cyclobutan-1-ol;
    <154> 1-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)시클로부탄-1-올;<154> 1-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)cyclobutan-1-ol;
    <155> 2-(3-((5-메틸-2-((3-메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<155> 2-(3-((5-methyl-2-((3-methyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)thieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <156> 2-(6-((2-((4-(4-시클로프로필피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<156> 2-(6-((2-((4-(4-cyclopropylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <157> 2-(3-((2-((4-(4-시클로프로필피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<157> 2-(3-((2-((4-(4-cyclopropylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <158> 메틸 2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)벤조에이트;<158> Methyl 2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3-fluorophenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-2-yl)amino)benzoate;
    <159> N2-(4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)-N4-(6-(2-플루오로프로판-2-일)피리딘-2-일)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<159> N2-(4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)-N4-(6-(2-fluoropropan-2-yl)pyridin-2 -yl)-5-methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <160> 2-(6-((2-((4-(4-시클로부틸피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<160> 2-(6-((2-((4-(4-cyclobutylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <161> 2-(3-((2-((4-(4-시클로부틸피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<161> 2-(3-((2-((4-(4-cyclobutylpiperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <162> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<162> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <163> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<163> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <164> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<164> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)-N4-(3-fluorophenyl)-5-methylthieno [2,3-d]pyrimidine-2,4-diamine;
    <165> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<165> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <166> (2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3-플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)페닐)메탄올;<166> (2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3-fluorophenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-2-yl)amino)phenyl)methanol;
    <167> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-이소프로폭시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<167> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropoxyphenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <168> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-이소프로폭시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<168> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropoxyphenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <169> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-이소프로폭시페닐)-N4-(3-플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<169> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropoxyphenyl)-N4-(3-fluorophenyl)-5-methylthier no[2,3-d]pyrimidine-2,4-diamine;
    <170> 2-(6-((2-((3,5-디메틸-1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<170> 2-(6-((2-((3,5-dimethyl-1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methyl thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <171> 3-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)옥세탄-3-올;<171> 3-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)oxetan-3-ol;
    <172> 3-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)옥세탄-3-올;<172> 3-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)oxetan-3-ol;
    <173> 2-(3-((2-((3-메톡시-4-(2-옥사-6-아자스피로[3.3]헵탄-6-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<173> 2-(3-((2-((3-methoxy-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)amino)-5-methylthieno[ 2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <174> 2-(6-((2-((3-메톡시-4-(2-옥사-6-아자스피로[3.3]헵탄-6-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<174> 2-(6-((2-((3-methoxy-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)amino)-5-methylthieno[ 2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <175> 2-(3-((5-메틸-2-((1-메틸-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<175> 2-(3-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino )phenyl)propan-2-ol;
    <176> 2-(6-((5-메틸-2-((1-메틸-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<176> 2-(6-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino )pyridin-2-yl)propan-2-ol;
    <177> 2-(3-((2-((1-(2-옥사스피로[3.3]헵탄-6-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<177> 2-(3-((2-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <178> 2-(6-((2-((1-(2-옥사스피로[3.3]헵탄-6-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<178> 2-(6-((2-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <179> 2-(3-((2-((1-((3S,4R)-3-플루오로피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<179> 2-(3-((2-((1-((3S,4R)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <180> 2-(6-((2-((1-((3S,4R)-3-플루오로피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<180> 2-(6-((2-((1-((3S,4R)-3-fluoropiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <181> 메틸 2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)벤조에이트;<181> Methyl 2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((6-(2-hydroxypropan-2-yl)pyridin-2 -yl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl)amino)benzoate;
    <182> 메틸 2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)벤조에이트;<182> methyl 2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino )-5-methylthieno[2,3-d]pyrimidin-2-yl)amino)benzoate;
    <183> 2-(6-((5-메틸-2-((1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<183> 2-(6-((5-methyl-2-((1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino )thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <184> 2-(3-((5-메틸-2-((1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<184> 2-(3-((5-methyl-2-((1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino )thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <185> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<185> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <186> N4-(3-플루오로페닐)-5-메틸-N2-(1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<186> N4-(3-fluorophenyl)-5-methyl-N2-(1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl ) thieno[2,3-d]pyrimidine-2,4-diamine;
    <187> 2-(3-플루오로-5-((5-메틸-2-((1-(1-(옥세탄-3-일)피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<187> 2-(3-fluoro-5-((5-methyl-2-((1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol- 4-yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <188> 2-(6-((2-((1-((3S, 4R)-3-플루오로-1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<188> 2-(6-((2-((1-((3S, 4R)-3-fluoro-1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino )-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <189> 2-(3-((2-((1-((3S,4R)-3-플루오로-1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<189> 2-(3-((2-((1-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino )-5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <190> (2-((2-((1-((3S,4R)-3-플루오로-1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<190> (2-((2-((1-((3S,4R)-3-fluoro-1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)- 5-methylthieno[2,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphineoxide;
    <191> 1-(4-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)피페리딘-1-일)에탄-1-온;<191> 1-(4-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine- 2-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;
    <192> 1-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)시클로부탄-1-올;<192> 1-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)cyclobutan-1-ol;
    <193> (2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-에톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<193> (2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-ethoxyphenyl)amino)-5-methylthieno[2 ,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide;
    <194> 2-(3-((2-((4-(4-(디메틸아미노)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)-1,1,1-트리플루오로프로판-2-올;<194> 2-(3-((2-((4-(4-(dimethylamino)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno[2,3 -d]pyrimidin-4-yl)amino)phenyl)-1,1,1-trifluoropropan-2-ol;
    <195> 1,1,1-트리플루오로-2-(3-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)페닐)프로판-2-올;<195> 1,1,1-trifluoro-2-(3-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4- yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)propan-2-ol;
    <196> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)-1,1,1-트리플루오로프로판-2-올;<196> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)phenyl)-1,1,1-trifluoropropan-2-ol;
    <197> 1-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)-2-메틸프로판-2-올;<197> 1-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d]pyrimidine -2-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol;
    <198> 1-(4-((4-((3-(2-하이드록시프로판-2-일)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)-2-메틸프로판-2-올;<198> 1-(4-((4-((3-(2-hydroxypropan-2-yl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl )amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol;
    <199> (2-((2-((1-(2-하이드록시-2-메틸프로필)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<199> (2-((2-((1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d] pyrimidin-4-yl) amino) phenyl) dimethylphosphine oxide;
    <200> 2-(6-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)-1,1,1-트리플루오로프로판-2-올;<200> 2-(6-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-5-methylthieno [2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)-1,1,1-trifluoropropan-2-ol;
    <201> 1,1,1-트리플루오로-2-(6-((5-메틸-2-((1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)아미노)티에노[2,3-d]피리미딘-4-일)아미노)피리딘-2-일)프로판-2-올;<201> 1,1,1-trifluoro-2-(6-((5-methyl-2-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4- yl)amino)thieno[2,3-d]pyrimidin-4-yl)amino)pyridin-2-yl)propan-2-ol;
    <202> 2-(3-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)-5-플루오로페닐)프로판-2-올;<202> 2-(3-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5- methylthieno[2,3-d]pyrimidin-4-yl)amino)-5-fluorophenyl)propan-2-ol;
    <203> (2-(4-(아제티딘-1-일)피페리딘-1-일)-5-((4-((3,5-디플루오로페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)페닐)메탄올;<203> (2-(4-(azetidin-1-yl)piperidin-1-yl)-5-((4-((3,5-difluorophenyl)amino)-5-methylthier no[2,3-d]pyrimidin-2-yl)amino)phenyl)methanol;
    <204> N2-(4-(4-(아제티딘-1-일)피페리딘-1-일)-3-메톡시페닐)-N4-(3,5-디플루오로페닐)-5-메틸티에노[2,3-d]피리미딘-2,4-디아민;<204> N2-(4-(4-(azetidin-1-yl)piperidin-1-yl)-3-methoxyphenyl)-N4-(3,5-difluorophenyl)-5- methylthieno[2,3-d]pyrimidine-2,4-diamine;
    <205> N4-(3,5-디플루오로페닐)-5-메틸-N2-(1-(1-메틸피페리딘-4-일)-1H-피라졸-4-일)티에노[2,3-d]피리미딘-2,4-디아민;<205> N4-(3,5-difluorophenyl)-5-methyl-N2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)thieno[ 2,3-d] pyrimidine-2,4-diamine;
    <206> (2-((2-((4-(4-(아제티딘-1-일)피페리딘-1-일)-3-(하이드록시메틸)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<206> (2-((2-((4-(4-(azetidin-1-yl)piperidin-1-yl)-3-(hydroxymethyl)phenyl)amino)-5-methylthier no[2,3-d]pyrimidin-4-yl)amino)phenyl)dimethylphosphineoxide;
    <207> (2-((2-((1-(1-에틸피페리딘-4-일)-1H-피라졸-4-일)아미노)-5-메틸티에노[2,3-d]피리미딘-4-일)아미노)페닐)디메틸포스핀옥사이드;<207> (2-((2-((1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylthieno[2,3-d ]pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide;
    <208> 1-(4-(4-((4-((6-(2-하이드록시프로판-2-일)피리딘-2-일)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)피페리딘-1-일)에탄-1-온;<208> 1-(4-(4-((4-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)amino)-5-methylthieno[2,3-d ]pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;
    <209> 1-(4-(4-((4-((2-(디메틸포스포릴)페닐)아미노)-5-메틸티에노[2,3-d]피리미딘-2-일)아미노)-1H-피라졸-1-일)피페리딘-1-일)에탄-1-온.<209> 1-(4-(4-((4-((2-(dimethylphosphoryl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidin-2-yl)amino) -1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one.
  10. 하기 반응식 1에 나타낸 바와 같이,As shown in Scheme 1 below,
    화학식 2로 표시되는 화합물과 화학식 3으로 표시되는 화합물을 반응시켜 화학식 1로 표시되는 화합물을 제조하는 단계를 포함하는 화학식 1로 표시되는 화합물의 제조방법:A method for producing a compound represented by Formula 1 comprising the step of preparing a compound represented by Formula 1 by reacting a compound represented by Formula 2 with a compound represented by Formula 3:
    [반응식 1][Scheme 1]
    상기 반응식 1에서,In Scheme 1 above,
    R1, R2, R3, R4, R5 및 R6는 제1항의 화학식 1에서 정의한 바와 같다.R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in Formula 1 of claim 1.
  11. 제1항의 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는,Containing the compound represented by Formula 1 of claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient,
    암 또는 자가면역질환의 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating cancer or autoimmune diseases.
  12. 제1항의 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는,Containing the compound represented by Formula 1 of claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient,
    IRAK4의 과활성화로 인한 질환의 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating diseases caused by overactivation of IRAK4.
  13. 제11항에 있어서,According to claim 11,
    상기 암은 백혈병, 림프종, 다발성 골수종, 방광암, 유방암, 결장암, 신장암, 간암, 폐암, 소세포폐암, 식도암, 담낭암, 난소암, 췌장암, 위암, 자궁 경부암, 갑상선암, 전립선암, 또는 피부암인 것을 특징으로 하는 약학적 조성물.The cancer is leukemia, lymphoma, multiple myeloma, bladder cancer, breast cancer, colon cancer, kidney cancer, liver cancer, lung cancer, small cell lung cancer, esophageal cancer, gallbladder cancer, ovarian cancer, pancreatic cancer, stomach cancer, cervical cancer, thyroid cancer, prostate cancer, or skin cancer. A pharmaceutical composition to be.
  14. 제11항에 있어서, According to claim 11,
    상기 자가면역질환은 건선, 류마티스성 관절염, 혈관염, 염증성 장 질환, 피부염, 골관절염, 천식, 염증성 근육 질환, 알러지성 질환, 질염, 간질 방광염, 경피증, 골다공증, 습진, 동종이계 또는 이종발생성 이식 거부, 이식편대숙주질환(GVHD), 홍반성 낭창, 염증성 질환, I형 당뇨병, 폐 섬유증, 피부근염, 쇼그렌 증후군, 갑상선염, 중증 근무력증, 자가면역 용혈성 빈혈, 다발성 경화증, 낭포성 섬유증, 만성적 재발성 간염, 원발성 담도성 간경변증, 알러지성 결막염 또는 아토피 피부염인 것을 특징으로 하는 약학적 조성물.The autoimmune disease is psoriasis, rheumatoid arthritis, vasculitis, inflammatory bowel disease, dermatitis, osteoarthritis, asthma, inflammatory muscle disease, allergic disease, vaginitis, interstitial cystitis, scleroderma, osteoporosis, eczema, allogeneic or xenogeneic transplant rejection , Graft-versus-host disease (GVHD), lupus erythematosus, inflammatory disease, type I diabetes, pulmonary fibrosis, dermatomyositis, Sjogren's syndrome, thyroiditis, myasthenia gravis, autoimmune hemolytic anemia, multiple sclerosis, cystic fibrosis, chronic recurrent hepatitis , Primary biliary cirrhosis, allergic conjunctivitis or atopic dermatitis, characterized in that the pharmaceutical composition.
  15. 제1항의 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 암 또는 자가면역질환의 예방 또는 개선용 건강기능식품 조성물.A health functional food composition for preventing or improving cancer or autoimmune diseases, containing the compound represented by Formula 1 of claim 1, its stereoisomer, its solvate, its hydrate, or its pharmaceutically acceptable salt as an active ingredient.
  16. 암 또는 자가면역질환의 예방 또는 치료에 사용하기 위한 제1항의 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.A compound represented by formula 1 of claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof, for use in the prevention or treatment of cancer or autoimmune disease.
  17. 제1항의 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염을 투여하는 단계를 포함하는, 암 또는 자가면역질환의 치료 방법.A method for treating cancer or autoimmune disease, comprising administering the compound represented by Formula 1 of claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
  18. 제1항의 화학식 1로 표시되는 화합물, 이의 입체이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염의 암 또는 자가면역질환 치료용 약제의 제조에의 사용.Use of the compound represented by Formula 1 of claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof for the preparation of a drug for treating cancer or autoimmune disease.
PCT/KR2022/016628 2021-10-28 2022-10-28 Novel thieno[2,3-d]pyrimidine derivative, method for preparing same, and pharmaceutical composition for prevention or treatment of cancer or autoimmune disease comprising same as active ingredient WO2023075479A1 (en)

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