KR20010041318A - 6,9-Disubstituted 2-[Trans-(4-Aminocyclohexyl)Amino]Purines - Google Patents

Abstract

The present invention provides novel compounds of Formula 1, pharmaceutically acceptable salts, optical isomers or hydrates thereof.

<Formula 1>

Where

R is selected from the group consisting of R2, R2NH- or R3R4N-R5-;

R 2 is selected from the group consisting of C ₉ -C ₁₂ alkyl, formula 2 and formula 3;

<Formula 2>

<Formula 3>

In Formulas 2 and 3, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer from 0 to 8) X is an integer from 1 to 8, n is an integer from 0 to 8, Z is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, M is hydrogen, C ₁ -C ₄ alkyl, 4 and Formula 5;

<Formula 4>

<Formula 5>

In Formulas 4 and 5, R6 'is each selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m' -phenyl (m' is an integer from 0 to 8) Independently selected, n 'is an integer from 0 to 8, x' is an integer from 1 to 8, Q is hydrogen or C ₁ -C ₄ alkyl, Z 'is phenyl, heterocycle, cycloalkyl and naphthalene Selected from the group consisting of;

Of the substituents,

C ₉ -C ₁₂ alkyl or Z is optionally substituted with 1 to 3 substituents, identical or different, selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9, respectively;

<Formula 6>

<Formula 7>

<Formula 8>

<Formula 9>

In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8 and x" Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11;

<Formula 10>

<Formula 11>

In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes,

The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12;

<Formula 12>

In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 1 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl;

R 3 and R 4 are selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl and (CH ₂ ) _y -phenyl (y is an integer from 0 to 8), wherein R 3 and R 4 are not both hydrogen;

R 5 is C ₁ -C ₈ alkylene;

R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl;

Provided that when R 2 is of formula 3 wherein n is at least 1, R 1 is isopropyl or cyclopentyl, R 6 is hydrogen, C ₁ -C ₄ alkyl or (CH ₂ ) _m -phenyl, Z is phenyl, Heterocycle or cycloalkyl, optionally substituted by 1 to 3 substituents, identical or different, selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9 as defined above.

In addition, the present invention provides a method of inhibiting cell cycle progression. More specifically, the present invention provides methods of inhibiting cyclin dependent kinases, in particular cdk-2.

The present invention also provides a method of inhibiting apoptosis and a method of suppressing the development of neoplasms in nerve cells.

In addition, the present invention provides compositions comprising an analytical amount of the compound of formula 1 in admixture or association with an inert carrier. The present invention also provides pharmaceutical compositions comprising an inhibitory effective amount of a compound of formula 1 in a form mixed or associated with one or more pharmaceutically acceptable carriers or excipients.

Description

6,9-disubstituted 2- [trans- (4-aminocyclohexyl) amino] purine {6,9-Disubstituted 2- [Trans- (4-Aminocyclohexyl) Amino] Purines}

In both normal and neoplastic cells, cell division is an event that is tightly controlled at defined stages. Actively non-dividing stationary cells, such as finally differentiated or temporarily inhibited dividing cells, remain in the G ₀ phase. At the end of the G ₁ phase, called the restriction or R time point, the cell enters the S phase where DNA synthesis is to be made. At the end of S phase, cells enter the second gap (G ₂ ) phase to prepare for division, after which somatic division (M phase) occurs.

Early experiments on the regulation of the cell cycle revealed the presence of a protein called "Maturation Promoting Factor" (MPF) that forms hetero-dimers with kinase active proteins. In later experiments, a group of yeast genes known as cell division control (cdc) genes were identified by comparing the proteins subsequently identified and their underlying genes. In a further experiment, it was found that some cdc genes encode kinases, which were later named cyclin-dependent kinase (cdk). As a result of this reclassification, some cell cycle proteins have two names, for example, cdk1 is also called cdc2. The kinase component of MPF is currently identified as p34 ^cdc2 and the regulatory subunit of MPF is now called ^Cycline B. Cyclin was initially identified as a protein whose concentration changes during the cell cycle and specifically degrades during somatic cell division. Animal cyclins A to I and cdk 1 to 8 have now been identified. The nomenclature was further complicated by the identification of subtypes of cyclins and cdk such as cyclins B1 and B2.

In subsequent studies on cell regulation, it was found that the partial division of cyclin and cyclin-dependent kinases (cdk) resulted in the lateralization of the cell division stage. Cyclin is characterized by the presence of a homologous region of 100 amino acids called the "cyclin box," which in turn regulates cdk and is involved in binding to protein kinase partners. cdk proteins are protein kinases that are very similar in sequence and size (35-40 kDa) and are activated by binding of cyclin regulatory subunits. The cdk protein contains conservatively active sites of about 300 amino acids in size, which are characteristic of eukaryotic protein kinases. Thus, cyclin and cdk proteins appear to be highly conserved protein soldiers.

Isolation of individual cyclins and cdk allowed for further identification of the role and interaction of each component in the cell cycle metastasis. Excess cdk is present at the cell cycle stage. When cyclin is synthesized and binds to the catalytic cdk subunit, cdk is activated, thereby stimulating the activity of cdk serine / threonine kinase. Full activation of cdk requires phosphorylation of conservative threonine residues located in the T-loop by a cyclin-dependent kinase activating kinase (CAK) that activates cyclin-dependent kinase complex consisting of cyclin H and cdk7, It also requires a third protein of about 32 kDa.

Due to the binding of threonine and / or tyrosine phosphorylation or one of myriad intrinsic inhibitory proteins at the ATP-binding site of cdk, the complex of cdk and cyclin can be inactivated.

In the G ₁ group, D-type cyclins bind most commonly to cdk4 and cdk6, although they bind to several different cdk, including cdk2, cdk4, cdk5 and cdk6. Type D cyclins are thought to act as growth factor sensors that advance the cell cycle in response to external signals. Complexes of cyclin E and cdk2 appear after synthesis of complexes of type D cyclin and cdk in the mammalian cell cycle. The synthesis of cyclin E is strictly regulated and appears at the end of the G ₁ group and the beginning of the S group. Complexes of cyclin and cdk are essential for cells to replicate DNA.

Cyclins D and Cycline E, the G ₁ group, transiently produce proteins with a half-life of about 20 minutes. The short half-life is thought to be due to the PEST sequence present in the C-terminal region of the protein, and degradation of the protein seems to be mediated by the ubiquitination pathway.

Ssayikeulrin the ssayikeulrin ssayikeulrin A and B of the group G ₂ is maintained in a stable state during interphase, the specific degradation through the ubiquitin pathway during mitosis. Both cyclin A and cyclin B2 seem to degrade only when complexed with their cdk partners (Cyclin A-cdk2 and Cycline A / B-cdk1 (cdc2)). However, if the somatic cell division is complete at the end of the middle period, the Cyclin B1 is degraded. If spindles are collected incorrectly or chromosomes are incorrectly aligned, degradation of cyclin B1 is inhibited.

The retinoblastoma protein (Rb), a 105 kDa nuclear phosphoprotein, is the substrate for a complex of cyclin and cdk-2, cdk-4, and cdk6 at the G ₁ phase, and the cell cycle through carefully formulated phosphorylation and dephosphorylation. It serves as one of the main checkpoints. In the G ₀ and G ₁ groups, Rb is present in a hypophosphorylated state. As the cells progress to the end of the G ₁ phase, Rb is hyperphosphorylation by the D-type cyclin complex, which inactivates Rb to induce the cells into the S phase, leading to cell cycle progression and cell division. Even in the G ₂ phase, Rb remains superphosphorylated. Rb is dephosphorylated at M phase and returns to a low phosphorylation state. Phosphorylation of Rb protein alters the binding of the protein. In the hypophosphorylated state, Rb binds to a specific transcription factor, such as E2F, to sequester the transcription factor, which inhibits the progression of the cell cycle in the G ₁ phase. Once cdk hyperphosphorylates Rb, a transcription factor is released to activate transcription of genes essential for the progression of the S phase, such as the thymidine kinase gene, myc, myb, the dihydrofolate reductase gene and the DNA polymerase-α gene. Let's do it.

In addition, the location of the complexes of cyclins and CDKs reveals the role of each complex in the cell cycle pathway. Cyclin A and E of the nucleus bind to p107 and p130, presumably because the proteins are present in the nucleus. Cyclin B1 in mammals accumulates in the cytoplasm at G ₂ phase and migrates to the nucleus at the beginning of somatic division. Cycline B is associated with spindle devices, particularly spindle caps, and Cycline B-cdc2 kinase may be involved in the formation of spindles by phosphorylating components of the somatic cell division device. In addition, CyClean B1 is part of a feedback mechanism that accurately collects medium-term somatic cell division devices. Human cyclin B2 is bound to cell membrane compartments and Golgi apparatus. Cycline B2-cdc2 is involved in the dissolution of the Golgi apparatus during somatic division of cells.

cdc2-cycline B kinase is a major somatic dividing factor and is thought to be highly conserved and involved in cell cycle metastasis in eukaryotic cells. Histone H1 is the substrate of cdc2-cycline B and is selectively phosphorylated at specific sites during somatic cell division, which is thought to be an important action for chromatin condensation. In addition, the cdc2-cycline B complex phosphorylates lamin, which is responsible for the degradation of nuclear lamina. Nuclear lamina consists of a polymer of lamin subunits that is superphosphorylated upon somatic cell division, and phosphorylation of lamin is responsible for its dissolution. Lamin is part of the family of intermediate filament proteins, and the cdc2-cycline B complex phosphorylates the phosphorylation sites of the cytoplasmic intermediate filament subunits, vimentin and desmine upon somatic cell division. Thus, the cdc2-cycline B complex is involved in the reconstitution of cell constructs in somatic division.

In addition, cdc2-cycline B is involved in the reconstitution of microfilaments through phosphorylation of non-muscular caldesmon, a 83 kDa protein that binds to actin and calmodulin and inhibits actomyosin ATPase activity. Upon somatic division, the Caldesmone is phosphorylated by cdc2-cycline B, which weakens its affinity for actin, resulting in its separation from the fine filaments.

cdc2-cycline B is involved in the regulation of actomyosin filaments by phosphorylation of myosin in the contractile ring, which divides the cells into two (cytoplasmic division). In the middle, the myosin II regulatory light chain (MLC) is phosphorylated at two major sites present at the N-terminus. Once phosphorylated, myosin cannot interact with actin. Later, both sites are dephosphorylated.

In addition, cdc2-cycline B plays a role in reconstituting cell membrane compartments in somatic cell division. For example, cdc2-cycline B phosphorylates rab1Ap and rab4p. When rab4p is phosphorylated by cdc2-cycline B, rab4p is isolated from the cell membrane compartment.

In somatic division, most transcription is inhibited. In addition, cdc2-cycline B inhibits the transcription mediated by polymerase III through phosphorylation of TFIIIB. Given that transcription mediated by polymerase I, polymerase II and polymerase III share some common factors, such as TATA-binding protein (TBA), cdc2-cycline B is responsible for all forms of transcription during somatic cell division. It may be involved in suppression.

Given the importance of the complex of cyclin and cdk in promoting cell division, the complex should be under tightly regulated mechanisms. Since its initial discovery, cyclins and cdk have been known to interact with other transcription factors and proteins involved in various cellular mechanisms. cdk7 has been found to be a component of the transcription factor IIH (TFIIH) and contains the kinase active site of the C-terminal domain (CTD) of RNA polymerase II. Recently, a cyclocycl C partner cdk8 has also been found to phosphorylate the CTD of RNA polymerase II, but it does not exhibit CAK activity. Thus, it is clear that cdk is involved in various cell functions as well as regulation of the cell cycle. CDK-inhibitory protein (CDI) is a small cyclin-CDK complex, a small protein that binds to and inactivates the monomeric CDK. The inhibitor can be divided into two families based on sequence and functional similarity. TNK4 includes p15 ^INK4B , p16 ^INK4B , p18 and p19 that specifically bind to cdk4 and cdk6. p16 ^INK4B and p15 ^INK4B comprise four ankyrin repeat sequences and share significant homology with each other as well as are encoded by adjacent genes at the 9p12 locus.

Since p16 binds to the Cyclin D-cdk4 complex and the Cyclin D-cdk6 complex, a high intracellular concentration of p16 inactivates cdk4. Because of the rearrangement, deletion or mutation in many tumor cell lines and some primary tumors, p16 ^INK4 (MTS1) is recognized as a potential drug suppressor gene. In the study of hereditary melanoma, about half had germ cell mutations in the p16 ^INK4 gene. Rb was an inhibitor of p16 ^INK4 . Inactivation of cellular Rb by mutant or viral antigens is associated with an increase in the amount of p16 ^INK4 . p16 ^INK4B , p15 ^INK4B and p18 inhibit the binding of cyclin D with cdk4 and cdk6.

The second family of ^CDIs is the Kip / Cip family, which includes p21 ^{Cip1, WAF-1} , p27 ^Kip1 and p57 ^Kip2 . p27 ^Kip1 is found in latent or bound form in proliferating cells. Upon stimulation, p27 ^Kip1 releases its binding and binds to the Cyclin-CDK4 / 6 complex to inhibit CDK. Kip / Cip and protein have high homology to the N-terminus that binds to the Cyclin-cdk complex. Kip / Cip and protein preferentially bind to and inhibit the cyclin-cdk complex associated with the G ₁ and S groups beyond the M phase.

p21 (also known as WAF1, Cip1, and Sdi1) is induced by p53, a proliferating cell nuclear antigen that is a subunit of DNA polymerase δ in several Cyclin-CDK2 complexes including Cyclin A, D1, and E nuclear antigen (PCNA) and form a tertiary complex. Expression of p21 ^WAF-1 in growing cells, inactive cells, and aged cells functions as a negative regulator of entry into the S phase. The mRNA of p21 ^WAF-1 is upregulated when the cell ages or the activity of the cell ceases, and after serum stimulation of the inactive cell, and the mRNA of p21 ^WAF-1 decreases when the cell enters the S phase. p21 inactivates cyclin E-cdk2, cyclin A-cdk2, cyclin D1-cdk4, cyclin D2-cdk4 and cyclin D3-cdk4 complexes.

Genetic analysis of various human tumors has found an unsuitably large number of altered cell cycle proteins, which are thought to be variations that cause abnormal cell cycles. For example, cyclin D1 is a bcl-1 / PRAD1 primitive tumor gene that is overexpressed or uncontrolled in various human tumors. Cyclin D1 / CCND1 gene, located on chromosome 11q13, is amplified in many cancers, mainly breast and non-small cell lung cancer. This is consistent with the observation that overexpression of Cyclin D1 is a common feature that manifests as specific 11q13 amplicons in tumor cells. The genes of p16 are rearranged, deleted or mutated in various tumor cell lines and some primitive tumors. A mutation of cdk4, specifically a mutation of the 24th arginine to cysteine (Arg24Cys), has been identified in two independent genetic melanoma families. The mutation was found in all 11 of 11 melanoma patients, in 2 of 17 non-infected patients, and not in 5 spouses (Zou, L., et al., Nature Genetics 12). 1996: 97-99). This mutation has a specific effect on the p16 ^INK4a binding domain of ^cdk4 , but does not affect the ability to bind ^cyclin D and to form functional kinases. As a result of this mutation, the Cyclin D / cdk4 complex is resistant to normal physiological inhibition by p16 ^INK4a . Other studies have shown that about half of the family-specific melanoma kinase is associated with the chromosome 9q21 region, which contains the p16 ^INK4a gene. Types of p16 ^INK4a mutations identified include nonsense mutations, splice donor mutations, unidentified mutations that inhibit the transcription of p16 ^INK4a , and 3 missense mutations that cannot bind cdk4 or cdk6. Overexpression of cdk4 as a result of gene amplification has been confirmed in the study of 32 glioma cell lines (see He, J., et al., Cancer Res. 54: 5804-5807, 1994). This change was observed in 10 cases with intact p16 gene. Genetic studies of glioma cell lines have revealed that 24 of the 32 glioma cell lines represent one of two alternative genetic changes, each with increased cdk4 kinase activity resulting in glioma tumors. It means to be important. cdk4 is mapped at the long arm of chromosome 12 and is known to be overexpressed in certain tumor cells due to amplification as a component of amplicons including other related genes such as SAS and MDM2. All of the above conditions result in activation of cdk4. In addition, overexpression of Cyclin B1 and E in leukemia cell lines and solid tumor cell lines, as well as altered patterns of Cycline E in breast cancer, have been reported.

In numerous disease states, overproliferation of cells is caused. The most common hyperproliferative disease is a neoplasm, usually named according to the source of the tissue from which the hyperproliferation began. Neoplasm refers to a newly growing animal or plant tissue that is somewhat similar to the tissue in which it originated, but lacks physiological function and is benign, potentially malignant or malignant. Neoplasms occur because of the loss of normal control capacity, making growth control impossible. Neoplastic cells may lack the ability to differentiate and may invade or metastasize to local tissue. Neoplasms can occur in tissues of any organ at any age. The rate of neoplasia and immortality usually increases with age, and some neoplasms develop maximally between 60 and 80 years old (eg, prostate cancer, gastric cancer and colon cancer). However, other neoplasms develop maximally from birth to 10 years of age (eg, acute lymphoblastic leukemia). In addition, exposure to food, carcinogens (especially smoking) and family literacy also affect the development of certain neoplasms.

Neoplastic cells are distinguished from normal cells in important ways, including loss of differentiation capacity, increased invasiveness, and decreased drug sensitivity. Another important difference is the unlimited cells that are thought to be due to the loss of the regulatory mechanisms of normal cells in the cells (inactivating, bypassing or ignoring the mechanisms causing neoplastic cells to proliferate independently of normal regulatory mechanisms). Is multiplication.

The neoplasm is an abnormal mass of tissue, the growth of the neoplasm exceeds the growth of the normal tissue or causes discord and remains in the same excess form as before even after stopping the stimulus causing the change.

Neoplasms are classified as benign or malignant. Benign neoplasms show slow local growth and are usually limited in activity due to encapsulation by fibrous connective tissue capsules. Benign neoplasms do not cause the death of the organism, while untreated malignant neoplasms are very likely to kill the organism. Malignant neoplasms are usually not encapsulated and exhibit much faster growth rates. Malignant neoplasms often invade surrounding tissues and blood vessels and may spread to distant body parts. Malignant neoplasms are collectively referred to as "cancer" or "tumor", of which the term tumor refers to swelling.

Myeloproliferative diseases are a group of diseases characterized by abnormally proliferating by one or more hematopoietic cell lines or connective tissue elements. Four diseases are commonly included in myeloproliferative disorders: true erythrocytosis (primary erythrocytosis, Vaquez 'disease), myelofibrosis (unknown myelodysplastic), chronic myelogenous leukemia, and primary (idiopathic) thrombocytopenia do. Acute leukemia (particularly red leukemia) and paroxysmal nocturnal hemoglobinosis are also classified as myeloproliferative diseases. Each of these diseases is distinguished according to its main characteristics and location of proliferation. Although each disease is the result of proliferation of different cells, the disease is caused by clonal proliferation that occurs at the pluripotent stem cell level, causing abnormal proliferation of erythrocytes, bone marrow, and megakaryocyte precursors of bone marrow to varying degrees. It has been known to be. All myeloproliferative diseases tend to end in acute leukemia.

Leukemia is a malignant neoplasm of hematopoietic tissue. Two or more viruses are involved in causing human leukemia. Epsteinba virus is associated with Burkitt's lymphoma and human T-cell lymphotrophic virus (also called human acute leukemia and lymphoma virus (HTLV-1)) is associated with certain T cell leukemias and lymphomas. Prolonged exposure to chemicals such as benzene and certain neoplastic inhibitors, or exposure to ionizing radiation, genetic literacy (e.g., Down syndrome) and some familial diseases (e.g., FA) You will have a literacy.

The development of leukemia is likely to be induced through a single cell cycle through at least two stages of proliferation and clonal expansion. Leukemia is now classified according to the maturity of the cells. Acute leukemia is primarily an undifferentiated cell population, and chronic leukemia is a more mature cell type. Acute leukemia is additionally a lymphoblastic (ALL, also known as acute lymphocytic leukemia) type and myeloid (also known as AML, acute myeloid leukemia, acute myeloid leukemia, acute myeloid leukemia or acute myeloid leukemia). Classified as They may be further classified by French-US-UK (FAB) classification or by morphological and cytochemical appearance depending on the type and extent of differentiation. Chronic leukemia is classified as either lymphocytic (CLL) or myeloid (CML) leukemia. CLL is characterized by the appearance of mature lymphocytes in the blood, bone marrow and lymphoid organs. CML is characterized by the appearance of granulocyte cells of all differentiation stages, mainly in the blood, bone marrow, liver, spleen and other organs.

Myelodysplastic syndromes (MDS) are characterized by clonal proliferative diseases associated with normal or hypercellular bone marrow anemia and myeloid hematopoietic defects. Hematopoietic cells that can proliferate include erythrocytes, bone marrow and megakaryocyte forms. MDS is a relatively new group of diseases known as pre-leukemia, refractory anemia, Ph chromosome-negative chronic myelogenous leukemia, chronic osteomyeloid leukemia, and unknown myelogenesis. The FAB system can be used to further classify myelofibrosis.

Lymphoma is a heterogeneous group of neoplasms that develop in reticulum endothelial cells and lymphatic system. Major types of lymphoma include Hodgkin's disease and non-Hodgkin's lymphoma, as well as rare Burkitt's lymphoma and mycelial sarcoma. Hodgkin's disease is a chronic disease with unexplained lymphatic reticulum proliferation, which can appear in local or distributed form and can be further classified according to four histopathological profiles. Non-Hodgkin's lymphomas are a heterogeneous group of diseases that usually consist of neoplastic proliferation of lymphocytes, distributed throughout the body. The terms lymph sarcoma and reticulocyte sarcoma are now being translated into terms that reflect the ecology of the cell and the disease of origin. Rappaport classification is a classification based on histopathology, tumor differentiation and growth pattern (whether diffuse or nodular). The Lukes and Collins taxonomy is a taxonomy based on the cell of origin. Specifically, it is a classification method based on whether the disease origin is T cell or B cell, histocyte (or monocyte) origin, or cannot be classified. The International Panel Working Formulation of the National Cancer Institute of the United States classifies non-Hodgkin's lymphomas by the above classification.

Burkitt's lymphoma is a rarely differentiated B-cell lymphoma that tends to be associated with sites other than the lymph nodes and reticuloendothelial system. Unlike other lymphomas, Burkitt's lymphoma has a specific geographic distribution, suggesting the possibility of the presence of unidentified pathogen-borne insects and infectious agents. Evidence is Epicstein's virus, similar to Herpes.

Mycelial sarcoma is an uncommon chronic T cell lymphoma that primarily affects the skin and sometimes the internal organs.

Plasma cell disease (PCD), or monoclonal gamma disease, is characterized by disproportionate proliferation of one clone of cells that normally synthesize immunoglobulin (Ig) and structural and electrophoretic homogeneous IG or polypeptide subunits in serum or urine. It is a disease with existing characteristics. The disease primarily progresses to asymptomatic but obvious neoplasms (eg, multiple myeloma). The disease results from the disproportionate proliferation of one clone producing a particular Ig (IgM, IgA, IgD or IgE).

Multiple myeloma (also known as plasmacytopathy or myeloma) is characterized by the presence of tumors in myeloid plasma cells and intact monoclonal Ig (IgM, IgA, IgD or IgE) or Bence Jones protein (free single single). Clone κ or λ light chain) is an advanced neoplastic disease characterized by overproduction. Extensive osteoporosis or discontinuous osteolytic damage occurs due to the replacement of expandable plasma cell tumors or osteoclast-active factors secreted from malignant plasma cells.

Giant globulinemia, ie primary or Waldestrom's megaglobulinemia, is a plasma cell disease associated with B cells that normally synthesizes and secretes IgM. Megaglobulinemia is distinct from myeloma and other PCDs and is similar to lymphoma disease. Many patients have symptoms such as hyperviscosity, fatigue, weakness, skin bleeding and mucosal bleeding.

Heavy chain disease is a neoplastic plasma cell disease that overproduces homogeneous γ, α, μ and δ Ig heavy chains. The disease produces incomplete monoclonal Ig. The clinical picture is more like lymphoma than multiple myeloma.

Spleen hyperplasia is a syndrome in which circulatory cytopenia is associated with splenomegaly. Patients with splenic hyperactivity do not need to be treated with splenectomy, but require treatment of underlying diseases. Lymphoid proliferative disorders and myeloid proliferative disorders do not cause only splenic hyperactivity, but to some extent cause such disorders. Myeloproliferative disorders that cause splenic hyperplasia include true erythrocytosis, myelofibrosis with myelodysplasia, chronic myelogenous leukemia and idiopathic thrombocytopenia. Chronic lymphocytic leukemia and lymphoma (including Hodgkin's disease) are certain lymphoproliferative disorders that can cause splenic hyperplasia.

Lung tissue is the site where both benign and malignant primary tumors are produced, as well as where cancer spreads to various organs and tissues. More than 90% of men and 70% of women develop lung cancer from smoking. In addition, exposure to occupational drugs such as asbestos, radiation, arsenic, chromate, nickel, chloromethyl ether, poison gas, and emissions from coke kilns can lead to lung cancer. The most common types of lung cancers are squamous cell carcinoma, small cell and large cell carcinoma, and adenocarcinoma.

About 95% of gastric cancers are carcinomas, in addition to lymphomas and leiomyosarcomas. Gastric carcinoma is classified according to gross appearance. That is, they are categorized according to whether they are extruded, penetrating (peak sharp, borderline, can cause ulcers), or spread or mix two different types of properties.

Pancreatic cancer is an exocrine tumor, most of which is adenocarcinoma derived from tubular cells rather than acinar cells, or an endocrine tumor comprising insulinoma. Gastrin-producing pancreatic tumors that are associated with non-β-type cells or develop in the duodenal wall can cause Zolinger-Ellison syndrome, which is manifested by gastrin hyperplasia. Often other endocrine malformations (particularly parathyroid glands, or malformations of the pituitary gland and adrenal glands) cause polysecretory diseases such as multiple endocrine neoplasia (MEN). Non-β islet cell tumors can cause a disease known as VIP species syndrome, characterized by extensive aqueous diarrhea over a long period of time.

Intestinal neoplasias include small intestine tumors, colon tumors, and colon and rectal cancers. Benign small intestine tumors can be derived from ileal and ileal neoplasms, including leiomyomas, lipomas, neurofibromas and fibroids. Malignant small intestine tumors, such as adenocarcinoma, are not common and are usually caused around the plant. Patients with Crohn's disease of the small intestine are more susceptible to adenocarcinoma than those with colon Crohn's disease. In patients with Crohn's disease, tumors tend to appear peripherally in the intestinal bypass loop or inflammatory loop. Typically, carcinoid tumors occur in the small intestine (particularly in the ileum), and in half cases multiple tumors are present. About half of Kaposi's sarcoma, which occurs frequently in transplant recipients and AIDS patients, is associated with the stomach. Damage can occur anywhere in the gastrointestinal tract, but is commonly found in the stomach, small intestine or peripheral colon.

Tumors of the colon include protrusions of the colon and rectum. Protuberance is a mass of tissue formed by the lumen of the intestinal wall protruding into the lumen. Protuberances, based on histology, are classified into coronary adenocarcinoma, coronary adenocarcinoma, chorionic adenocarcinoma, proliferative protuberances, mesothelioma, combustible protrusions, dendritic carcinoma, pseudopolyp, lipoma, leiomyoma and more rare tumors.

Malignant tumors also occur in the rectum. The tumor is an epithelial (squamous cell) carcinoma of the rectum, which accounts for 3 to 5% of rectal and anal cancers.

In Western countries, colon cancer and rectal cancer increase annually, the second most common cancer after lung cancer. In the United States, about 75,000 people died of the cancer in 1989, about 70% of the cancers occurred in the rectal and phase S colons, and 95% were adenocarcinomas.

Hepatic neoplasms include benign and malignant neoplasms that are relatively common but are often undetectable. The most important of benign liver neoplasms is hepatocellular adenocarcinoma. Asymptomatic small hemangiomas occur in about 1-5% of adults. In addition, cholangiocarcinoma and other mesenchymal neoplasms occur, but relatively rarely. Malignant neoplasms of the liver are the most common forms of liver cancer, and the liver is usually the place where metastasis through the blood of lung cancer, breast cancer, colon cancer, pancreatic cancer and gastric primary tumors frequently occurs. In certain parts of Africa and southern Asia, the development of liver cancer is associated with chronic hepatitis B virus. In North America, Europe, and other unknown areas, there is potential cirrhosis in most patients. Fibrolamellar carcinoma is a variant of low-flexibility liver cancer with a unique form (malignant hepatocellular form of fibrous tissue). Typically, lamellar carcinoma occurs in relatively young adults and is free of preexisting cirrhosis, chronic hepatitis B virus, or other known risk factors. Other primary malignant tumors of the liver include cholangiocarcinoma (tumor that develops in biliary epithelial tissue inside the liver), hepatoblastoma (one of the most common cancers in infants), and hemangiosarcoma (associated with industrial exposure to vinyl chloride). . Leukemia and related diseases can be associated with hepatocyte tissue and are thought to develop due to infiltration of abnormal cells.

Multiple endocrine gland (MEN) spondylosis is a genetically distinct familial disease in which adenocarcinoma proliferation and malignant tumors form in various endocrine glands. Type I (MEN-I) is characterized by the formation of tumors in the parathyroid glands, islets and pituitary gland. Type II (MEN-II) is characterized by inducing medullary carcinoma of the thyroid gland, chromogenic affinity tumors and hyperparathyroidism. Type III (MEN-III) is characterized by causing multiple mucosal neuroma, medullary carcinoma of the thyroid gland and chromogenic adenocarcinoma.

Carcinoid syndrome is usually caused by metastatic intestinal carcinoid tumors that secrete excess vascular functional substances, including serotonin, bradykinin, histamine, prostaglandins, and polypeptide hormones. A variety of symptoms are caused by abnormal concentrations of the substance, often with paroxysmal skin redness, cyanosis, abdominal cramps, diarrhea and heart valve disease.

Neoplasms of bones and joints are benign or malignant. Benign tumors of the bone include osteochondroma (osteochondrosis) most common in children aged 10 to 20 years, benign chondromas (located within the bone) most often in children aged 10 to 30 years and young adults, rarely 10 years old Osteo osteomas, giant cell tumors, and fibromatous injuries are the most common among 20 year old children. Primary malignant tumors of bone include the second most common primary bone tumors: osteosarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, cartilage sarcoma, mesenchymal cartilage sarcoma, Ewing's tumor (Ewing's sarcoma), malignant bone Lymphomas, multiple myeloma and malignant giant cell tumors.

Primary cancers of other tissues can metastasize to bone tissue. The most common such cancers are breast cancer, lung cancer, prostate cancer, kidney cancer and thyroid cancer.

Central nervous system (CNS) neoplasms are usually classified according to organ. Primary intracranial neoplasms include (1) skull tumors, (2) meninges tumors, (3) cranial nerve tumors, (4) neuroglial and ventricular tumors, (5) pituitary or pineal gland tumors, and (6) tumors of congenital origin. Subdivided into branches. Cranial neoplasms include osteomas, hemangiomas, granulomas, yellowomas and deformative osteomyelitis. Meningioblasts include meningioma, sarcoma and glioma. Neoplasms of the cranial nerves include glioma of the optic nerve and Schwanoma of the eighth and fifth cranial nerves. Glial neoplasia includes glioma and ventricular cell tumor. Pituitary or pineal neoplasia includes pituitary adenocarcinoma and pineal gland cancer. Neoplasms of congenital origin include craniocytoma, chordoma, germoma, teratoma, dermoid cyst, hemangioma and hematopoietic blastoma.

Spinal neoplasms are disorders that compress the spinal cord or spinal cord roots, which are caused by spinal cord parenchyma, roots, meninges, or spine. Primary spinal cord neoplasia is less common than intracranial tumors. Metastatic disorders often occur and can result from lung cancer, breast cancer, kidney cancer, thyroid cancer or lymphoma.

Urinary genital neoplasms occur regardless of age and sex, but in men, about 30% of cancers and in women, about 4%. Prostate cancer is very metastatic in men over 50. Prostate cancer is thought to be related to hormones, and his pathology is congenital. Adenocarcinoma, a renal sarcoma, accounts for only about 1 to 2% of adult cancers, but the most solid kidney tumors are metastatic. Wilms' tumor, which is an embryonic adenoma of the kidney, develops during fetal periods and may not be diagnosed for many years. Pelvic and ureteral neoplasms are histologically similar. Bladder neoplasms can be induced by known bladder carcinogens such as aniline dyes, the most common being sarcoma of transitional cells and less common is sarcoma of squamous cells. More unusual urogenital neoplasms include urethral and penile cancers. Testicular neoplasms make up the majority of solid metastatic cancers in men under 30 years of age. The most metastatic testicular tumors arise from primitive embryonic cells and are classified according to the type of cell involved.

Breast cancer is the most common cancer in women. In the United States, the cumulative risk of developing breast cancer with age is about 10%, but death with the disease is about 3.6%. However, risk increases with age, family history of breast cancer, radiation exposure, and diet.

Breast cancer is routinely classified into estrogen receptor and progesterone receptor assays. About two thirds of breast tumor patients show an estrogen receptor positive (ER +) response. Progesterone positive breast cancers are thought to have functional estrogen receptors, and the presence of both receptors responds better to endocrine treatment than the presence of only one receptor. Endocrine treatment regimens (usually with tamoxifen) are more preferred for the treatment of estrogen receptor positive tumors. Although estrogens and androgens are effective, they are less desirable than other forms of endocrine treatment because of the side effects caused by large amounts of these hormones. Breast cancer can metastasize to any organ of the body, but the most common metastases are lungs, liver, bones, lymph nodes and skin.

Lobulous carcinoma in situ (LCIS) or lobular neoplasia is the most frequent disease in premenopausal women. Ductal carcinoma in situ (DCIS) occurs in women both before and after menopause. DCIS forms palpable montages. LCIS and DCIS make up about 90% of all breast cancers. The more unusual forms of medulla and tubular breast cancer are readily predictable.

The most common gynecological neoplasm is intrauterine carcinoma, which is the fourth most common cancer in women after breast cancer, colorectal cancer, and lung cancer. In utero carcinoma is characterized by the clinical stage (from stage 0 in its original position to stage IVB with metastases to organs far away). Typically, intrauterine carcinomas produce estrogens and current treatments are approaching surgical methods and progesterone therapy.

Ovarian cancer accounts for about 18% of all gynecological neoplasms. About 80% of metastatic ovarian cancers arise from ovarian epithelium and are classified according to their histological characteristics. Tumors may also arise from embryonic cells or stroma.

Vulvar tumors make up about 3-4% of total gynecological neoplasms. Vulvar tumors usually appear after menopause and about 90% are squamous cell carcinomas. About 4% is basal cell carcinoma, the others include intraepithelial carcinoma, bartholin adenocarcinoma, fibrosarcoma and melanoma.

Vaginal carcinoma accounts for about 1% of gynecologic malignancies, with the highest incidence between about 45 and 65 years old. About 95% of vaginal carcinomas are squamous cell carcinomas. Primary carcinoma of the fallopian tube is rare and usually spreads directly or by lymphatic vessels.

Trophoblast disease or neoplasms of trophoblast cell origin may appear after intrauterine pregnancy or ectopic pregnancy. Degenerative pregnancy results in staphylococcal conditions, with about 80% of the diseases being positive.

Neoplasms can occur in the ear canal and affect hearing. In addition, adenocarcinoma also develops in the ear canal, which appears to be benign in histology but is usually malignant and can be treated by surgical removal. Basal cell and squamous cell carcinoma frequently occurs in the outer ear by regular sunlight, and the carcinoma can also be treated by surgical removal. The middle ear is where squamous cell carcinoma develops. Non-chrome affinity paraganglion may occur in the temporal bone.

The most common malignant tumors in the nose and sinuses are squamous cell carcinomas, less common ones are adenoid cystic and mucosal epithelial carcinomas, malignant mixed tumors, adenocarcinomas, lymphomas, fibromas, osteosarcomas, chondrosarcomas and melanoma.

Squamous cell carcinoma of the nasal pharynx is the most commonly found carcinoma in children and young adults.

The most common malignant tumor in the upper airway is squamous cell carcinoma of the tonsils and larynx. Both of these carcinomas are more common in men, are associated with smoking and alcohol consumption, and 85% of patients with cancer in the head or neck experience smoking and drinking.

About 90% of the head and neck cancers are squamous cell (epidermal) carcinomas. Melanoma, lymphoma and sarcoma are relatively rare carcinomas of the primary cancers of the head and neck. Cancers of the head and neck are classified according to the size and location of primary neoplasia, the number and size of metastases to cervical lymph nodes, and evidence of distant metastasis.

Eye cancer can occur on the surface of the eyelid and can be benign or neoplastic. A typical benign growth is yellow species, which forms an off-white flat lipid plaque subcutaneously. Basal cell carcinoma is the most common and is treated by surgical removal or radiation therapy. Less common malignancies include squamous cell carcinoma, Maybom carcinoma, and other types of melanoma. The most common primary malignant tumor in the eye is the malignant melanoma of the choroid.

In addition, tumors may occur in skin tissue, including malignant tumors, as well as benign tumors such as morphology, lipoma, and the like. About 40-50% of malignant melanomas originate from melanocytes of the state. Malignant skin cancer is a basal cell or squamous cell carcinoma that occurs frequently in skin exposed to the sun. Skin cancer is the most common malignant tumor, and the incidence of the cancer is increasing. Less common malignancies include malignant melanoma, papillary or extramammary Paget's disease, Kaposi's sarcoma (KS), and dermal T cell lymphoma (normal sarcoma). The incidence of KS is increasing due to the increased incidence of AIDS. KS develops in one third of AIDS patients.

Oral cancer accounts for about 5% of cancers in men and about 2% of cancers in women. The most common form of oral cancer is squamous cell carcinoma. The incidence of the cancer increases with age and risk factors (particularly smoking and drinking).

Surgery is the oldest of the methods useful for the treatment of neoplasms. When neoplasms are found early and metastasis has not occurred, surgery is usually successful. Radiation is also an important treatment regimen and is preferred for the treatment of neoplasms such as Hodgkin's disease, early non-Hodgkin's lymphoma and squamous cell carcinoma of the head and neck. Radiation has proven to be very successful as an adjunct to surgical operations and neosuppressive drugs.

Neoplastic inhibitory drugs are also useful for the treatment of neoplasms and are classified according to their mechanism of action. Typically, countless combinations using neoplastic inhibitors with differing mechanisms of action have proven to be particularly effective for treatment if the side effects are minimized at low doses. Primarily neosuppressive drugs target biological basic processes essential for the replication or growth of cells.

Alkylating agents, such as mechlorethamine and cyclophosphamide, alkylate DNA to inhibit DNA replication.

Metabolic inhibitors that interfere with essential cell division pathways include the following:

Folate antagonists bind to dehydrofolate reductase and interfere with the synthesis of pyrimidine. Folate antagonists are specific for the S phase. Methotrexate is a compound that is very commonly used as a neoplastic inhibitor folate antagonist.

Purine antagonists inhibit purine synthesis and are specific for the S phase. 6-mercaptopurine is an example of a purine antagonist.

Pyrimidine antagonists interfere with thymidylate synthesis to reduce the production rate of thymidine and are specific for the S phase. Commonly used pyrimidine antagonists include 5-fluorouracil.

Cytarabine inhibits DNA polymerase and is specific for the S group.

Plant alkyloids include vinca, such as vinblastine and vincristine, and grapephytotoxin, such as etoposide. Plant alkyloids are effective in the mid-term and inhibit somatic cell division by a variety of mechanisms, including changes in microtubule proteins.

Antibiotics include doxorubicin and daunomycin that intercalate between DNA strands to inhibit DNA unwinding, bleomycin to cause incision of DNA strands, and mitomycin that acts as a bifunctional alkylating agent to inhibit DNA synthesis.

Nitrosoureas include carmustine and romustine and alkylate DNA or carbamoylate amino acids in proteins.

Inorganic ions, such as cisplatin, intercalate within or within DNA strands to inhibit DNA loosening.

Although biological response modifiers such as interferon have a proliferative inhibitory effect, their specific role has not yet been identified. Interferons include α (leukocyte) interferon, β (fibroblast) interferon and γ (lymphocyte) interferon.

Enzymes such as asparaginase are also used to alter metabolic pathways that are important for cancer cells. Asparaginase eliminates asparagine inside cells that leukemia cells need.

Hormones such as tamoxifen, flutamide and progesterone and analogs thereof exhibit nonspecific effects, but are useful for the treatment of hormone-associated neoplasms such as breast cancer, ovarian cancer and prostate cancer. Tamoxifen, commonly used in the treatment of breast cancer, puts the cells at a stationary state and binds to estrogen receptors.

Cytokine is a naturally occurring or artificial plant growth regulator. Naturally occurring cytokinins tend to nonspecifically inhibit various protein kinases. The molecular mechanism by which cytokinin regulates cell growth and division is yet unknown. Studies have shown that cytokinin increases the acceptability of DNA templates, activates RNA polymerase, affects polyadenylation and secondary structure of mRNA, and stimulates the formation and activity of polyribosomes. Cytokine is thought to interact with cell cycle proteins and affect cell division. Both cytokinin and cyclin-dependent kinases (cdk) are involved in several similar cell cycle control points (eg, G ₁ and S transitions, G ₂ and M transitions, S and M control points). Works.

Olomoucine, 6- (benzylamino) -2-[(2-hydroxyethyl) amino] -9-methylpurine, is the first herbicide found. Recently, ^olomoucine specifically inhibits some cdk, including p34 ^cdc2 and ^cyclin B kinase, at micromolar concentrations, but has no effect on other major protein kinases such as cAMP- and cGMP-dependent kinases, and protein kinase C. It was found to be an artificial cytokinin. Recently, olomoucine was well selected for CDK-cycline protein kinase, but found to have moderate inhibitory activity (IC ₅₀ is about 7 μM) (Vesely, J., et al., Eur. J. Biochem. , 1994, 224, 771-786). The A2.4A crystal structure of olomosin crystallized with cdk2 results in the purine portion of olomosin binding to the conservative ATP binding pocket, and the benzylamino group being extended to the active site region that is unique to cdk2 kinase. okay.

Roscovitine, 2- (1-ethyl-2-hydroxyethylamino) -6-benzylamino-9-isopropylpurine, is a recently synthesized purine that shows selectivity for some cyclin-dependent kinases and cdk2 And up to 10-fold higher activity than olomosin against cdc2 (see Meijer, L., et al., Eur. J. Biochem., 243: 527-536) and PCT / FR96 / 01905. ). The literature reports that most kinases are not significantly inhibited by roscovitine. However, cdc 2 -cycline B, cdk 2 -cycline A, cdk 2 -cycline E and cdk 5 -p 35 were substantially suppressed so that the values of IC ₅₀ were 0.65, 0.7, 0.7 and 0.2 μM, respectively. In contrast, roscovitine exhibited an IC ₅₀ of over 100 μM in cdk4-cycline D1 and cdk6-cycline D2.

See Havlicek, L., et al., M. Med. Chem. (1997) 40: 408-412 reported that roscovitine and related analogs (substituted at positions 2,6 and / or 9) inhibit p34 ^{cdc2 -cycline} B kinase. The IC ₅₀ value of any analog was no greater than that of Roscovitin's (R) enantiomer (IC ₅₀ = 0.2 μM). (S) was the IC ₅₀ value of the enantiomers is 0.8μM, IC ₅₀ values of the racemic mixture (R and S) was 0.65μM. The authors of this document concluded that the N ⁶ -benzyl substituent of roscovitine is better than the isopentenyl or cyclohexylmethyl substituent.

The National Cancer Society (NCI) is an organization run by the US government to discover and develop new oncology therapeutic products. In 1985, NCI established a new screening strategy for cancer, including human tumor cells, in an in vitro assay for primary cancer screen use. A total of 60 human tumor cell lines derived from cells of seven cancer types (lung cancer, colon cancer, melanoma, kidney cancer, ovarian cancer, brain cancer and leukemia) were selected by the NCI panel (Grever, MR, et al., Seminars in Oncology, 19: 1992: 622-638). In addition, the protocol used for the analysis is reported in the literature. The American Type Culture Collection (ATCC) serves as a depository for these and other tumor cell lines. Useful human tumor cell lines include the following cell lines.

MCF7: human breast adenocarcinoma, hormone-dependent,

MDA-MB-231: human breast adenocarcinoma, hormone-independence,

HT-29: human colon adenocarcinoma, relatively well differentiated into grade II,

HCT-15: human colon adenocarcinoma,

A549: human non-small cell lung carcinoma,

DMS-114: human small cell lung carcinoma,

PC-3: human prostate carcinoma, hormone-independence, and

DU 145: human prostate carcinoma, hormone-independence.

Skehan, P., et al., J. Natl. Cancer Inst. 82: 1107-1112, 1990, describe useful protocols for using such tumor cells to screen for neoplastic inhibitory drugs.

See Meijer, et al., Eur. J. Biochem., 243: 527-536]] shows that roscovitine is an in vitro screen for NCI-disease, i.e., nine tumor types with an average IC ₅₀ value of 16 μM (leukemia, non-small cell lung cancer, colon cancer, central nervous system). Cancer, melanoma, ovarian cancer, kidney cancer, prostate cancer, breast cancer). No results were reported for individual tumor cell lines.

Two unique cdk inhibitors (flavopyridol and olomoucine) inhibit the death of PC12 neurons and sympathetic neurons in two model systems of neuronal survival (Park et al., J. Biol. Chem. 271 (14): 8161-8169, 1996). The concentration of each compound required for survival correlated with the amount required to inhibit proliferation. Neural apoptosis is an important feature necessary for both the development of the nervous system as well as components of nerve damage and disease.

PC12 cell lines were originally derived from adrenal medulla chromogenic affinity tumors in rats. When cultured in a medium containing serum, PC12 cells divide to resemble precursors of adrenal chromaffin cells and sympathetic neurons. When neuronal growth factor (NGF) is added, PC12 cells have the trait properties of sympathetic neurons. Removal of serum or removal of serum and NGF results in apoptosis in native PC12 cells and neurally differentiated PC12 cells, similar to the response of sympathetic neurons.

The role of cell cycle regulation in apoptosis can be demonstrated by the killing of native PC12 cells, resulting in inconsistent cell cycle progression of NGF or serum. The cdk inhibitor did not inhibit the proliferative native PC12 cell death even after removing the nutritional supplement. It was hypothesized that differentiated neurons or sympathetic neurons after somatic division would reenter into an inadequate cell cycle after NGF disappeared leading to cell death. However, apoptosis of these cells was inhibited by exposure to flabopyridol or olomosin, which inhibits cdk.

Changes in the activity of cdk and cyclin were observed during the course of apoptosis of various cell types. In apoptosis of HL60 cells induced by camptothecin or araC, cdc2 activity and cyclin E-related kinase activity were increased. Cytokine D1 expression was increased in apoptosis of camptothecin-induced PKO cells.

Camptothecin causes apoptotic killing of cerebral cortical neurons in rats (see Morris and Geller, J. Cell Biol. 134: 757-770 (1996)). Non-proliferative neuronal differentiation PC12 cells treated with camptothecin died within 6 days after treatment, and cultured rat neurons died within 5 days after treatment, even in the presence of NGF (Park et al., J. Neurosci. 17 ( 4): 1256-1270 (1997). However, with or without camptothecin, about 30% of the cells were killed on day 6 as a result of treatment with olomosin or flabopyridol, or each. Maximal protection of PC12 cells or rat sympathetic neurons from death was observed upon treatment with 1 μM flappyridol and 200 μM olomosin, which concentration completely inhibits DNA synthesis of proliferating PC12 cells. Minimum concentration. Administration of iso-olomocin, an inactivating analog of olomosin, did not inhibit cell death of camptothecin-treated neurons.

In addition, flabopyridol and olomoucine inhibited the killing of cortex nerves induced by camptothecin (see Park et al., J. Neurosci. 17 (4): 1256-1270 (1997)). . IC ₅₀ values of flavopyridol and olomoucine were 0.1 μM and 100 μM, respectively. Administration of iso-olomousin did not inhibit cell death of camptothecin-treated neurons.

The above observations have several implications. It is well known that patients treated with radiation and neoplastic inhibitors experience side effects including the development of new neoplasms or undesirable cellular apoptosis. For example, patients who have been given large amounts of araC to treat refractory leukemia develop cerebellar toxic syndrome, which loses the Purkinje nerve (Winkelman and Hinges, Ann Neurol. 14: 520-527 (1983). ) And Vogel and Horouipian, Cancer 71: 1303-1308 (1993). Patients treated with cis-platinum have been reported to develop peripheral neuropathy (Wallach, et al., J. Fla. Med. Assoc. 79: 821-822 (1992) and Mansfield and Castillo, AJNR Am. J. Neuroradiol. 15: 1178-1180 (1994). In view of the above observations, administration of a compound of the invention together or alone to treat neoplasia reduces or prevents neuronal damage caused by cellular apoptosis, in particular neosuppressive drugs or radiation therapy. Could be.

Cerebrovascular disease is the most common neurological disorder in Western countries. Major types of cerebrovascular diseases include cerebral insufficiency, incomplete flexion fractures, bleeding, and arteriovenous malformations due to transient blood flow obstruction. Stroke usually refers to ischemic injury. Undesirable neuroapoptosis occurs in cerebrovascular disease. Treatment with cdk inhibitors may be an approach to inhibit nerve damage and in this case to inhibit regression.

The present invention relates to the use of 6,9-disubstituted 2- [trans- (4-aminocyclohexyl) amino] purine and tumor suppressor or for the treatment of nerve damage and neurodegeneration.

<Summary of invention>

The present invention provides novel compounds of Formula 1, pharmaceutically acceptable salts, optical isomers or hydrates thereof.

Where

R is selected from the group consisting of R2, R2NH- or R3R4N-R5-;

R 2 is selected from the group consisting of C ₉ -C ₁₂ alkyl, formula 2 and formula 3;

In Formulas 2 and 3, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer from 0 to 8) X is an integer from 1 to 8, n is an integer from 0 to 8, Z is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, M is hydrogen, C ₁ -C ₄ alkyl, 4 and Formula 5;

In Formulas 4 and 5, R6 'is each selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m' -phenyl (m' is an integer from 0 to 8) Independently selected, n 'is an integer from 0 to 8, x' is an integer from 1 to 8, Q is hydrogen or C ₁ -C ₄ alkyl, Z 'is phenyl, heterocycle, cycloalkyl and naphthalene Selected from the group consisting of;

Of the substituents,

C ₉ -C ₁₂ alkyl or Z is optionally substituted with 1 to 3 substituents, identical or different, selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9, respectively;

In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11;

In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes,

The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12;

In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl;

R 3 and R 4 are selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl and (CH ₂ ) _y -phenyl (y is an integer from 0 to 8), wherein R 3 and R 4 are not both hydrogen;

R 5 is C ₁ -C ₈ alkylene;

R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl;

Provided that when R 2 is of formula 3 wherein n is at least 1, R 1 is isopropyl or cyclopentyl, R 6 is hydrogen, C ₁ -C ₄ alkyl or (CH ₂ ) _m -phenyl, Z is phenyl, Heterocycle or haloalkyl, optionally substituted by 1 to 3 substituents, identical or different, selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9 as defined above.

In addition, the present invention provides a method of inhibiting cell cycle progression. More specifically, the present invention provides a method of inhibiting cdk-2.

The present invention also provides a method of inhibiting apoptosis in neurons. Particularly preferred methods of the invention provide methods for inhibiting apoptosis of neurons induced by neoplastic inhibitors or resulting from cerebrovascular disease. Another preferred embodiment of the present invention is a method of inhibiting apoptosis induced by oxygen depletion. In a more preferred embodiment, the present invention provides a method of inhibiting apoptosis induced by cerebrovascular disease. In another preferred embodiment, the present invention provides a method of inhibiting apoptosis induced by stroke or incomplete flex fracture.

The present invention provides a method of inhibiting the development of neoplasms. The present invention also provides a method of treating a patient suffering from a neoplastic condition comprising administering a provided compound of the invention. The dosage is preferably a therapeutically effective amount of the compound of the present invention. Preferred methods of the invention are single administration of a compound of the invention provided. Alternatively, the preferred method of the present invention is to administer a certain amount of a compound of the present invention in combination with another neoplastic inhibitor.

In addition, the present invention provides compositions comprising an analytical amount of the compound of formula 1 in admixture or association with an inert carrier. The present invention also provides pharmaceutical compositions comprising an inhibitory effective amount of a compound of formula 1 in a form mixed or associated with one or more pharmaceutically acceptable carriers or excipients.

<Detailed description of the invention>

The present invention provides novel compounds of Formula 1, pharmaceutically acceptable salts, optical isomers or hydrates thereof.

<Formula 1>

Where

R is selected from the group consisting of R2, R2NH- or R3R4N-R5-;

R 2 is selected from the group consisting of C ₉ -C ₁₂ alkyl, formula 2 and formula 3;

<Formula 2>

<Formula 3>

In Formulas 2 and 3, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer from 0 to 8) X is an integer from 1 to 8, n is an integer from 0 to 8, Z is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, M is hydrogen, C ₁ -C ₄ alkyl, 4 and Formula 5;

<Formula 4>

<Formula 5>

In Formulas 4 and 5, R6 'is each selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m' -phenyl (m' is an integer from 0 to 8) Independently selected, n 'is an integer from 0 to 8, x' is an integer from 1 to 8, Q is hydrogen or C ₁ -C ₄ alkyl, Z 'is phenyl, heterocycle, cycloalkyl and naphthalene Selected from the group consisting of;

Of the substituents,

C ₉ -C ₁₂ alkyl or Z is optionally substituted with 1 to 3 substituents, identical or different, selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9, respectively;

<Formula 6>

<Formula 7>

<Formula 8>

<Formula 9>

In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11;

<Formula 10>

<Formula 11>

In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes,

The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12;

<Formula 12>

In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl;

R3 and R4 are selected from the group consisting of hydrogen, C1-C4 alkyl and (CH2) y-phenyl (y is an integer from 0 to 8), wherein R3 and R4 are not both hydrogen;

R 5 is C 1 -C 8 alkylene;

R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl;

Provided that when R 2 is of formula 3 wherein n is at least 1, R 1 is isopropyl or cyclopentyl, R 6 is hydrogen, C ₁ -C ₄ alkyl or (CH ₂ ) _m -phenyl, Z is phenyl, Heterocycle or haloalkyl, optionally substituted by 1 to 3 substituents, identical or different, selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9 as defined above.

As used herein, the term "heterocycle" means any ring-closed moiety consisting of elements in which one or more atoms of the ring are non-carbon, and include piperidinyl, pyridinyl, isoxazolyl, tetrahydrofuranyl, Pyrrolidinyl, morpholinyl, piperazinyl, benzimidazolyl, thiazolyl, thiophene, furanyl, indolyl, 1,3-benzodioxolyl, tetrahydropyranyl, imidazolyl, tetrahydrothiophene , Pyranyl, dioxanyl, pyrrolyl, pyrimidinyl, parazinyl, thiazinyl, oxazolyl, purinyl, quinolinyl and isoquinolinyl.

As used herein, the term "C ₁ -C ₄ alkyl" refers to a saturated or unsaturated straight or branched chain hydrocarbyl radical having 1 to 4 carbon atoms, which is methyl, ethyl, propyl, isopropyl , 1-propenyl, 2-propenyl, n-butyl, isobutyl, tertiary butyl, sec-butyl, 1-butenyl, 2-butenyl and 3-butenyl, and the like.

As used herein, the term “C ₁ -C ₈ alkyl” refers to a saturated or unsaturated straight or branched chain hydrocarbyl radical having from 1 to 8 carbon atoms, methyl, ethyl, propyl, isopropyl , 1-propenyl, 2-propenyl, n-butyl, isobutyl, tertiary butyl, sec-butyl, 1-butenyl, 2-butenyl, 3-butenyl, pentyl, neopentyl, hexyl, heptyl and Octyl and the like.

As used herein, the term "C ₉ -C ₁₂ alkyl" refers to a saturated or unsaturated straight or branched chain hydrocarbyl radical having 9 to 12 carbon atoms, nonyl, decyl, undecyl and dodec Yarns and the like.

As used herein, the term "C ₁ -C ₈ alkylene" refers to a saturated or unsaturated straight or branched chain hydrocarbylene radical having 1 to 8 carbon atoms, which is methylene, ethylene, propylene, iso Propylene, 1-propylene, 2-propylene, n-butylene, isobutylene, tertiary butylene, sec-butylene, 1-butenylene, 2-butenylene, 3-butenylene, pentylene, neopentylene , Hexylene, heptylene and octylene and the like.

As used herein, the term "cycloalkyl" refers to a saturated or unsaturated alicyclic compound moiety containing from 3 to 8 carbon atoms, wherein cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclo Heptyl and cyclooctyl and the like.

As used herein By sulfur is meant a sulfur atom optionally oxidized to sulfoxide (b = 1) or sulfone (b = 2).

As used herein, the term "Hal" refers to a halogen moiety and includes fluoro, chloro, bromo and iodo moieties.

As used herein, the term "optical isomer" or "optical isomers" refers to any of the various stereoisomeric shapes in which a compound of Formula 1 may be present.

As used herein, the term "hydrate" or "hydrates" refers to the reaction product of one or more water molecules reacted with a compound of Formula 1, in which H-OH bonds are not broken down, as well as multihydrate Monohydrate is also included.

As used herein, the term "pharmaceutically acceptable salts" refers to reaction products in which at least one non-toxic, organic or inorganic acid molecule is reacted with a compound of Formula 1. Examples of inorganic acids that form stable salts include hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid, as well as acid metal salts such as sodium monohydrogen ortho-phosphate and potassium hydrogen sulfate. Examples of organic acids that form stable salts include mono, di and trichloroacetic acid. Examples of the acid include acetic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, benzoic acid, hydroxybenzoic acid, phenylacetic acid , Cinnamic acid, salicylic acid, 2-phenoxybenzoic acid and sulfonic acid (eg, methane sulfonic acid, trifluoromethane sulfonic acid and 2-hydroxyethane sulfonic acid).

Compounds of formula (1) are well known and can be prepared using methods and techniques that are recognized by one of ordinary skill in the art. Conventional synthetic schemes for the preparation of these compounds are described in Scheme A (substituents as defined above), unless otherwise noted.

In Scheme A, by using techniques and methods known to those skilled in the art, 2,6-dichloropurine (1) is reacted with a suitable alcohol of formula (2) to correspond to the 9-substitution of formula (3). Obtain -2,6-dichloropurine compound.

For example, in the presence of triphenylphosphine and diethyl azodicarboxylate, 2,6-dichloropurine (1) is reacted with a suitable alcohol of formula (2) in a suitable anhydrous non-hydrogen solvent such as tetrahydrofuran. Typically, the reaction is stirred at room temperature for 5 hours to 5 days. The resulting 9-substituted-2,6-dichloropurine of formula 3 is recovered by extraction methods known in the art, or more commonly the resulting 9-substituted-2,6-dichloropurine of formula 3 The solvent may be loaded on a silica gel column immediately after removal of the solvent and eluted with methylene chloride or a solvent mixture (for example, a mixture of hexane and ethyl acetate). Subsequently, the 9-substituted-2,6-dichloropurine feed of Structural Formula 3 can be purified by chromatography or used in subsequent steps without a purification step.

In step b, the 9-substituted-6-amino-2-chloropurine compound of formula 5 is reacted by reacting the 6-chloro functional group of 9-substituted-2,6-dichloropurine of formula 3 with a suitable amine of formula 4 To obtain.

For example, 9-substituted-2,6-dichloropurine of formula 3 is reacted with a suitable amine of formula 4 in a suitable anhydrous polar solvent such as ethanol. Typically, the reaction is stirred for 30 minutes to 3 days at reflux. The resulting 9-substituted-6-amino-2-chloropurine of formula 5 is recovered by extraction methods known in the art, or if 9-substituted-6-amino-2-chloropurine of formula 5 is Once precipitated, it is recovered by filtration.

In step c, the 2-chloro functional group of 9-substituted-6-amino-2-chloropurine of formula 5 is reacted with 1,4-cyclohexanediamine (6) to obtain the corresponding compound of formula (1).

For example, a suitable 9-substituted-6-amino-2-chloropurine of formula 5 is reacted with 1,4-cyclohexanediamine (6) in excess molarity. Typically, the reactant is sealed in a pressurized tube and then heated to a temperature of about 80 ° C. to about 150 ° C. for 30 minutes to 3 days. The resulting compound of formula 1 can be recovered by extraction methods known in the art and purified by chromatography.

Starting materials used in the general synthetic methods summarized in Scheme A are readily available to those of ordinary skill in the art. For example, 4-aminopiperidine and 3-aminopyrrolidine of formula 4 can be prepared by the methods described in Schemes B and C below.

4-amino-1-piperidine and 3-amino-1-pyrrolidine derivatives (formula 4 ′), the starting amines of formula 4 used in Scheme A, are represented by Scheme B (unless otherwise noted) As defined).

In Scheme B, the free amino functional group of a suitable 4-carboxamide-1-piperidine or 3-carboxamide-1-pyrrolidine derivative of formula 7 is reacted with a suitable alkyl halide of formula 8 4-carboxamide-1-alkylated-piperidine or 3-carboxamide-1-alkylated-pyrrolidine of 9 is obtained.

For example, in the presence of a suitable base such as cesium carbonate and a catalytically effective amount of a suitable alkylation catalyst (e.g. potassium iodide), a suitable 4-carboxamide of formula 7 in a suitable non-hydrogen organic solvent such as 3-pentanone- 1-piperidine or 3-carboxamide-1-pyrrolidine is reacted with a suitable alkyl halide of formula 8. Typically, the reaction is stirred at reflux for 30 minutes to 12 hours. The resulting 4-carboxamide-1-alkylated-pepyridine or 3-carboxamide-1-alkylated-pyrrolidine of structure 9 is recovered by filtration and solvent evaporation.

In step b, the carboxamide functional group of the suitable 4-carboxamide-1-alkylated-pepyridine or 3-carboxamide-1-alkylated-pyrrolidine of formula 9 is dehydrogenated to correspond to that of 4-amino-1-alkylated-piperidine or 3-amino-1-alkylated-pyrrolidine is obtained.

For example, an excess molar concentration of bis- soluble 4-carboxyamide-1-alkylated-pepyridine or 3-carboxamide-1-alkylated-pyrrolidine of formula 9 in a suitable non-hydrogen polar solvent such as acetonitrile React with (trifluoroacetoxy) -iodobenzene. Typically, the reaction is stirred for 30 minutes to 5 hours at a temperature of about 50 ° C to about 95 ° C. The resulting 4-amino-1-alkylated-piperidine or 3-amino-1-alkylated-pyrrolidine of structure 4 'is recovered by extraction methods known in the art.

Alternatively, 4-amino-1-piperidine and 3-amino-1-pyrrolidine derivatives (formula 4 '), starting amines of formula 4 used in Scheme A, can be represented by Scheme C (unless otherwise noted) All substituents can be prepared as described above).

In step a of Scheme C, the free amino function of a suitable 4-piperidone or 3-pyrrolidone derivative of formula 10 is reacted with a suitable alkyl halide of formula 8 to correspond to the 1-alkylated-4-piperidone of formula Or 1-alkylated-3-pyrrolidone.

For example, in the presence of a suitable base such as cesium carbonate and a catalytically effective amount of a suitable alkylation catalyst (eg, potassium iodide), a suitable 4-piperidone or 3 of formula 10 in a suitable non-hydrogen organic solvent such as 3-pentanone Pyrrolidone is reacted with a suitable alkyl halide of formula 8. Typically, the reaction is stirred at reflux for 30 minutes to 12 hours. The resulting 1-alkylated-4-pepyridone or 1-alkylated-3-pyrrolidone of structure 11 is recovered by filtration and solvent evaporation.

In step b, a suitable 1-alkylated-4-pepyridone or 1-alkylated-3-pyrrolidone ketone functional group of formula 11 is reacted with hydroxylamine hydrochloride (12) to correspond to 1- of formula 13 Alkylated-3-piperidone oxime or 1-alkylated-3-pyrrolidone oxime is obtained.

For example, in the presence of a suitable base such as sodium acetate, hydroxylamine may be substituted with a suitable 1-alkylated-4-pepyridone or 1-alkylated-3-pyrrolidone of formula 11 in a suitable non-hydrogen solvent such as aqueous ethanol. React with hydrochloride (12). Typically, the reaction is stirred at reflux for 30 minutes to 5 hours. The resulting 1-alkylated-40piperidone oxime or 1-alkylated-3-pyrrolidone oxime of formula 13 is recovered by extraction methods known in the art.

In step c, the oxime functionality of the 1-alkylated-40piperidone oxime or 1-alkylated-3-pyrrolidone oxime of formula 13 is reduced to give the corresponding 4-amino-1-alkylated-piperidine or 3-amino Obtain the -1-alkylated-pyrrolidine derivative (formula 4 ').

For example, under an inert atmosphere, a suitable reducing agent, such as lithium aluminum hydride, may be used in a suitable anhydrous solvent such as tetrahydrofuran to form the oxime of 1-alkylated-40piperidone oxime or 1-alkylated-3-pyrrolidone oxime of formula 13. React with Typically, the reaction is stirred at reflux for 30 minutes to 5 hours. The resulting 4-amino-1-alkylated-piperidine or 3-amino-1-alkylated-pyrrolidine derivative (Structure 4 ') is recovered by extraction methods known in the art.

The following examples show conventional synthesis methods as described in Scheme A. The following examples are intended to illustrate the invention, but are not intended to limit the scope of the invention. As used herein, the following terms have the meanings given. "g" means grams, "mmol" means millimoles, "mL" means milliliters, "bp" means boiling points, "° C" means degrees Celsius, "mm Hg" Means millimeters of mercury, "μg" means micrograms, "μM" means micromolar, and "APCI" means Atmospheric Pressure Chemical Ionization. Rf values were used in AQ 4 × 50 columns (YMC) with a linear gradient from 100% C to 100% D for 4 minutes and maintained at 100% D for 2 minutes (C is acetonitrile with 0.1% TFA). Water is a mixture of 5 to 95, and D is a mixture of acetonitrile and water of 5 to 95, comprising 0.085% TFA). Molecular ions were measured using a Finnigan MAT SSQ-7: 10 mass spectrometer.

Example 1

2- [trans- (4-aminocyclohexyl) amino] -6-[(4-trifluorobenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step a: 2,6-dichloro-9-cyclopentylpurine

Cyclopentanol (260 mg, 3.02 mmol), 2.6-dichloropurine (680 mg, 3.60 mmol) and triphenyl phosphine (950 mg, 3.60 mmol) were dissolved in anhydrous THF (20 ml) and cooled to 0 ° C. . Diethyl azodicarboxylate (570 μl, 3.60 mmol) was added dropwise over 15 minutes under nitrogen atmosphere. The resulting solution was stirred for 60 hours at room temperature. The solvent was evaporated in vacuo, directly charged onto a silica gel column and eluted with methylene chloride to afford the title compound as a crude mixture.

Scheme A, step b: 2-chloro-6-[(4-trifluorobenzyl) amino] -9-cyclopentylpurine

2,6-Dichloro-9-cyclopentylpurine (3.00 mmol), 4-trifluorobenzylamine (3.00 mmol) and triethylamine (835 μl, 6.00 mmol) were dissolved in dry ethanol (20 ml). Heat under reflux for 15 hours, cool, and filter the solid to afford the title compound.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(4-trifluorobenzyl) amino] -9-cyclopentylpurine dihydrochloride

2-chloro-6-[(4-trifluorobenzyl) amino] -9-cyclopentylpurine (0.287 mmol) and 1,4-cyclohexanediamine (2.00 g, excess) were mixed in a pressure vessel, sealed and Heated to 140 ° C. for 18 h. The reaction mixture was cooled down, CH ₂ Cl ₂ (40 ml) was added and washed twice with 20 ml of H ₂ O. Dry (MgSO ₄ ), solvent evaporated in vacuo and purified via silica gel chromatography (10: 1: drop of CH ₂ Cl ₂ / MeOH / NH ₄ OH) to afford the title compound. Converted to hydrochloride. CIMS (NH ₃ ) 474 (MH ⁺ ), Rf (min) = 0.58

Example 2

2- [trans- (4-aminocyclohexyl) amino] -6- (2-chlorophenylhydrazino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (2-chlorophenylhydrazino) -9-cyclopentylpurine

Basically 2-chloro-6- (2-chlorophenylhydrazino from 2,6-dichloro-9-cyclopentylpurine, 2-chlorophenylhydrazine and triethylamine as described in Example 1, Scheme A, step b. ) -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (2-chlorophenylhydrazino) -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclohexyl) amino] from 2-chloro-6- (2-chlorophenylhydrazino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -6- (2-chlorophenylhydrazino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 475 (MH ⁺ ), Rf (min) = 3.49

Example 3

2- [trans- (4-aminocyclohexyl) amino] -6- (3,4,5-trimethoxybenzylamino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (3,4,5-trimethoxybenzylamino) -9-cyclopentylpurine

Basically 2-chloro-6- (from 2,6-dichloro-9-cyclopentylpurine, 3,4,5-trimethoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. 3,4,5-trimethoxybenzylamino) -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (3,4,5-trimethoxybenzylamino) -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-amino from 2-chloro-6- (3,4,5-trimethoxybenzylamino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Cyclohexyl) amino] -6- (3,4,5-trimethoxybenzylamino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 496 (MH ⁺ ), Rf (min) = 3.42

Example 4

2- [trans- (4-aminocyclohexyl) amino] -6-[(2,6-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(2,6-dimethoxybenzyl) amino] -9-cyclopentylpurine

Basically, 2-chloro-6-[(2,6) from 2,6-dichloro-9-cyclopentylpurine, 2,6-dimethoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. 6-dimethoxybenzyl) amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(2,6-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclo) from 2-chloro-6-[(2,6-dimethoxybenzyl) amino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Hexyl) amino] -6-[(2,6-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 466 (MH ⁺ ), Rf (min) = 2.29

Example 5

2- [trans- (4-aminocyclohexyl) amino] -6-[(4-trifluoromethoxy) phenylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(4-trifluoromethoxy) phenylamino] -9-cyclopentylpurine

Basically 2-chloro-6-[(4-tri from 2,6-dichloro-9-cyclopentylpurine, 4-trifluoromethoxyaniline and triethylamine as described in Example 1, Scheme A, step b. Fluoromethoxy) phenylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(4-trifluoromethoxy) phenylamino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclo) from 2-chloro-6-[(4-trifluoromethoxy) phenylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Hexyl) amino] -6-[(4-trifluoromethoxy) phenylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 476 (M−H ⁺ ), Rf (minutes) = 4.00

Example 6

2- [trans- (4-aminocyclohexyl) amino] -6- [2- (diethylamino) ethylamino] -9-cyclopentylpurine trihydrochloride

Scheme A, step b: 2-chloro-6- [2- (diethylamino) ethylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [2- (di from 2,6-dichloro-9-cyclopentylpurine, 2-diethylaminoethylamine and triethylamine as described in Example 1, Scheme A, step b. Ethylamino) ethylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [2- (diethylamino) ethylamino] -9-cyclopentylpurine trihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6- [2- (diethylamino) ethylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. ) Amino] -6- [2- (diethylamino) ethylamino] -9-cyclopentylpurine trihydrochloride was prepared. CIMS (NH ₃ ) 415 (M−H ⁺ ), Rf (min) = 3.15

Example 7

2- [trans- (4-aminocyclohexyl) amino] -6-[(1-naphthyl) methylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(1-naphthyl) methylamino] -9-cyclopentylpurine

Basically 2-chloro-6-[(1- from 2,6-dichloro-9-cyclopentylpurine, 1- (aminomethyl) naphthylene and triethylamine as described in Example 1, Scheme A, step b. Naphthyl) methylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(1-naphthyl) methylamino] -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6-[(1-naphthyl) methylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Amino] -6-[(1-naphthyl) methylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 456 (MH ⁺ ), Rf (min) = 3.43

Example 8

2- [trans- (4-aminocyclohexyl) amino] -6-[(4-methoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(4-methoxybenzyl) amino] -9-cyclopentylpurine

Basically 2-chloro-6-[(4-methoxy from 2,6-dichloro-9-cyclopentylpurine, 4-methoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. Benzyl) amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(4-methoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6-[(4-methoxybenzyl) amino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Amino] -6-[(4-methoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 436 (MH ⁺ ), Rf (min) = 2.28

Example 9

2- [trans- (4-aminocyclohexyl) amino] -6-[(3- (5-methoxyindolyl))-2-ethylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(3- (5-methoxyindolyl))-2-ethylamino] -9-cyclopentylpurine

Basically 2-chloro-6-[(3- (5 from 2,6-dichloro-9-cyclopentylpurine, 5-methoxytrytamine and triethylamine as described in Example 1, Scheme A, step b. -Methoxyindolyl))-2-ethylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(3- (5-methoxyindolyl))-2-ethylamino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans from 2-chloro-6-[(3- (5-methoxyindolyl))-2-ethylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -(4-aminocyclohexyl) amino] -6-[(3- (5-methoxyindolyl))-2-ethylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 489 (MH ⁺ ), Rf (min) = 3.44

Example 10

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (hydroxymethyl) cyclohexanemethylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- [4- (hydroxymethyl) cyclohexanemethylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- from 2,6-dichloro-9-cyclopentylpurine, 4- (aminomethyl) cyclohexanemethanol and triethylamine as described in Example 1, Scheme A, step b. (Hydroxymethyl) cyclohexanemethylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (hydroxymethyl) cyclohexanemethylamino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-amino) from 2-chloro-6- [4- (hydroxymethyl) cyclohexanemethylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Cyclohexyl) amino] -6- [4- (hydroxymethyl) cyclohexanemethylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 442 (MH ⁺ ), Rf (min) = 3.34

Example 11

2- [trans- (4-aminocyclohexyl) amino] -6- [2-fluorophenylhydrazino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- [2-fluorophenylhydrazino] -9-cyclopentylpurine

Basically 2-chloro-6- [2-fluorophenyl from 2,6-dichloro-9-cyclopentylpurine, 2-fluorophenylhydrazine and triethylamine as described in Example 1, Scheme A, step b. Hydrazino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [2-fluorophenylhydrazino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclohexyl) amino from 2-chloro-6- [2-fluorophenylhydrazino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. ] -6- [2-fluorophenylhydrazino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 425 (MH ⁺ ), Rf (min) = 3.41

Example 12

2- [trans- (4-aminocyclohexyl) amino] -6-[(2-methoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(2-methoxybenzyl) amino] -9-cyclopentylpurine

Basically 2-chloro-6-[(2-methoxy from 2,6-dichloro-9-cyclopentylpurine, 2-methoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. Benzyl) amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(2-methoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6-[(2-methoxybenzyl) amino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Amino] -6-[(2-methoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 436 (MH ⁺ ), Rf (min) = 2.30

Example 13

2- [trans- (4-aminocyclohexyl) amino] -6-[(2,3-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(2,3-dimethoxybenzyl) amino] -9-cyclopentylpurine

Basically, 2-chloro-6-[(2,2) from 2,6-dichloro-9-cyclopentylpurine, 2,3-dimethoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. 3-dimethoxybenzyl) amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(2,3-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclo) from 2-chloro-6-[(2,3-dimethoxybenzyl) amino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Hexyl) amino] -6-[(2,3-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 466 (MH ⁺ ), Rf (min) = 2.29

Example 14

2- [trans- (4-aminocyclohexyl) amino] -6- [2- (4-methoxyphenyl) ethylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- [2- (4-methoxyphenyl) ethylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [from 2,6-dichloro-9-cyclopentylpurine, 2- (4-methoxyphenyl) ethylamine and triethylamine as described in Example 1, Scheme A, step b. 2- (4-methoxyphenyl) ethylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [2- (4-methoxyphenyl) ethylamino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-amino) from 2-chloro-6- [2- (4-methoxyphenyl) ethylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Cyclohexyl) amino] -6- [2- (4-methoxyphenyl) ethylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 450 (MH ⁺ ), Rf (min) = 3.53

Example 15

2- [trans- (4-aminocyclohexyl) amino] -6- [3- (2-methoxyethoxy) propylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- [3- (2-methoxyethoxy) propylamino] -9-cyclopentylpurine

Basically 2-chloro-6- from 2,6-dichloro-9-cyclopentylpurine, 3- (2-methoxyethoxy) propylamine and triethylamine as described in Example 1, Scheme A, step b. [3- (2-methoxyethoxy) propylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [3- (2-methoxyethoxy) propylamino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4- from 2-chloro-6- [3- (2-methoxyethoxy) propylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Aminocyclohexyl) amino] -6- [3- (2-methoxyethoxy) propylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 432 (MH ⁺ ), Rf (min) = 3.31

Example 16

2- [trans- (4-aminocyclohexyl) amino] -6- (2-methoxyethylamino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (2-methoxyethylamino) -9-cyclopentylpurine

Basically 2-chloro-6- (2-methoxyethyl from 2,6-dichloro-9-cyclopentylpurine, 2-methoxyethylamine and triethylamine as described in Example 1, Scheme A, step b. Amino) -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (2-methoxyethylamino) -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclohexyl) amino] from 2-chloro-6- (2-methoxyethylamino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -6- (2-methoxyethylamino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 374 (MH ⁺ ), Rf (min) = 3.23

Example 17

2- [trans- (4-aminocyclohexyl) amino] -6-[(2,4-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(2,4-dimethoxybenzyl) amino] -9-cyclopentylpurine

Basically, 2-chloro-6-[(2,2) from 2,6-dichloro-9-cyclopentylpurine, 2,4-dimethoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. 4-dimethoxybenzyl) amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(2,4-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclo) from 2-chloro-6-[(2,4-dimethoxybenzyl) amino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Hexyl) amino] -6-[(2,4-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 466 (MH ⁺ ), Rf (min) = 2.29

Example 18

2- [trans- (4-aminocyclohexyl) amino] -6-[(3-diethylamino) propylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(3-diethylamino) propylamino] -9-cyclopentylpurine

Basically 2-chloro-6-[(3-di from 2,6-dichloro-9-cyclopentylpurine, 3-diethylaminopropylamine and triethylamine as described in Example 1, Scheme A, step b. Ethylamino) propylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(3-diethylamino) propylamino] -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6-[(3-diethylamino) propylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. ) Amino] -6-[(3-diethylamino) propylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 429 (MH ⁺ ), Rf (min) = 3.13

Example 19

2- [trans- (4-aminocyclohexyl) amino] -6-[(3,4-dimethoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride

Scheme A, step a: 2,6-dichloro-9- (propyl) purine

2,6-dichloro-9- (propyl) purine was basically purified from 2,6-dichloropurine and isopropanol as described in Example 1, Scheme A, step a, except that isopropanol was used instead of cyclopentanol. Prepared.

Scheme A, step b: 2-chloro-6-[(3,4-dimethoxybenzyl) amino] -9- (2-propyl) purine

Basically 2-chloro-6- [from 2,6-dichloro-9- (2-propyl) purine, 3,4-dimethoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. (3,4-dimethoxybenzyl) amino] -9- (2-propyl) purine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(3,4-dimethoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride

Basically, 2- [trans- (4) from 2-chloro-6-[(3,4-dimethoxybenzyl) amino] -9- (2-propyl) purine as described in Example 1, Scheme A, step c. -Aminocyclohexyl) amino] -6-[(3,4-dimethoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride was prepared. CIMS (NH ₃ ) 440 (MH ⁺ ), Rf (min) = 3.33

Example 20

2- [trans- (4-aminocyclohexyl) amino] -6- [2,6-dichlorophenylhydrazino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- [2,6-dichlorophenylhydrazino] -9-cyclopentylpurine

Basically 2-chloro-6- [2,6- from 2,6-dichloro-9-cyclopentylpurine, 2,6-dichlorophenylhydrazine and triethylamine as described in Example 1, Scheme A, step b. Dichlorophenylhydrazino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [2,6-dichlorophenylhydrazino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclohexyl) from 2-chloro-6- [2,6-dichlorophenylhydrazino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Amino] -6- [2,6-dichlorophenylhydrazino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 475 (M−H ⁺ ), Rf (min) = 3.43

Example 21

2- [trans- (4-aminocyclohexyl) amino] -6- (3-fluorophenylamino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (3-fluorophenylamino) -9-cyclopentylpurine

Basically 2-chloro-6- (3-fluorophenylamino from 2,6-dichloro-9-cyclopentylpurine, 3-fluoroaniline and triethylamine as described in Example 1, Scheme A, step b. ) -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (3-fluorophenylamino) -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclohexyl) amino] from 2-chloro-6- (3-fluorophenylamino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -6- (3-fluorophenylamino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 448 (MH ⁺ ), Rf (min) = 3.44

Example 22

2- [trans- (4-aminocyclohexyl) amino] -6- (3-methoxypropylamino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (3-methoxypropylamino) -9-cyclopentylpurine

Basically 2-chloro-6- (3-methoxypropyl) from 2,6-dichloro-9-cyclopentylpurine, 3-methoxypropylamine and triethylamine as described in Example 1, Scheme A, step b. Amino) -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (3-methoxypropylamino) -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclohexyl) amino] from 2-chloro-6- (3-methoxypropylamino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -6- (3-methoxypropylamino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 388 (MH ⁺ ), Rf (min) = 3.29

Example 23

2- [trans- (4-aminocyclohexyl) amino] -6-[(4-pentyl) phenylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(4-pentyl) phenylamino] -9-cyclopentylpurine

Basically 2-chloro-6-[(4-pentyl) phenyl from 2,6-dichloro-9-cyclopentylpurine, 4-butylphenylamine and triethylamine as described in Example 1, Scheme A, step b. Amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(4-pentyl) phenylamino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclohexyl) amino from 2-chloro-6-[(4-pentyl) phenylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. ] -6-[(4-pentyl) phenylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 462 (MH ⁺ ), Rf (min) = 4.15

Example 24

(+/-)-2- [trans- (4-aminocyclohexyl) amino] -6-[(α-cyclopropyl-4-chlorobenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(α-cyclopropyl-4-chlorobenzyl) amino] -9-cyclopentylpurine

Basically 2-chloro-6-[(2) from 2,6-dichloro-9-cyclopentylpurine, α-cyclopropyl-4-chlorobenzylamine and triethylamine as described in Example 1, Scheme A, step b. α-cyclopropyl-4-chlorobenzyl) amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(α-cyclopropyl-4-chlorobenzyl) amino] -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4- from 2-chloro-6-[(α-cyclopropyl-4-chlorobenzyl) amino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Aminocyclohexyl) amino] -6-[(α-cyclopropyl-4-chlorobenzyl) amino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 480 (MH ⁺ ), Rf (min) = 2.35

Example 25

2- [trans- (4-aminocyclohexyl) amino] -6-[(2-trifluorobenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(2-trifluorobenzyl) amino] -9-cyclopentylpurine

Basically 2-chloro-6-[(2-tri from 2,6-dichloro-9-cyclopentylpurine, 2-trifluorobenzylamine and triethylamine as described in Example 1, Scheme A, step b. Fluorobenzyl) amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(2-trifluorobenzyl) amino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclohexyl) from 2-chloro-6-[(2-trifluorobenzyl) amino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. ) Amino] -6-[(2-trifluorobenzyl) amino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 474 (M−H ⁺ ), Rf (min) = 2.31

Example 26

2- [trans- (4-aminocyclohexyl) amino] -6- (2-hydroxyethoxyethylamino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (2-hydroxyethoxyethylamino) -9-cyclopentylpurine

Basically 2-chloro-6- (2 from 2,6-dichloro-9-cyclopentylpurine, 2- (2-aminoethoxy) ethanol and triethylamine as described in Example 1, Scheme A, step b. -Hydroxyethoxyethylamino) -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (2-hydroxyethoxyethylamino) -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6- (2-hydroxyethoxyethylamino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Amino] -6- (2-hydroxyethoxyethylamino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 404 (MH ⁺ ), Rf (min) = 3.16

Example 27

2- [trans- (4-aminocyclohexyl) amino] -6- [2- (3-methoxyphenyl) ethylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- [2- (3-methoxyphenyl) ethylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [from 2,6-dichloro-9-cyclopentylpurine, 2- (3-methoxyphenyl) ethylamine and triethylamine as described in Example 1, Scheme A, step b. 2- (3-methoxyphenyl) ethylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [2- (3-methoxyphenyl) ethylamino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-amino) from 2-chloro-6- [2- (3-methoxyphenyl) ethylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Cyclohexyl) amino] -6- [2- (3-methoxyphenyl) ethylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 450 (MH ⁺ ), Rf (min) = 3.54

Example 28

2- [trans- (4-aminocyclohexyl) amino] -6-[(3,5-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6-[(3,5-dimethoxybenzyl) amino] -9-cyclopentylpurine

Basically 2-chloro-6-[(3, from 2,6-dichloro-9-cyclopentylpurine, 3,5-dimethoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. 5-dimethoxybenzyl) amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(3,5-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclo) from 2-chloro-6-[(3,5-dimethoxybenzyl) amino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Hexyl) amino] -6-[(3,5-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 466 (MH ⁺ ), Rf (min) = 2.27

Example 29

2- [trans- (4-aminocyclohexyl) amino] -6- (4-methoxybutylamino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (4-methoxybutylamino) -9-cyclopentylpurine

Basically 2-chloro-6- (4-methoxybutyl from 2,6-dichloro-9-cyclopentylpurine, 4-methoxybutylamine and triethylamine as described in Example 1, Scheme A, step b. Amino) -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (4-methoxybutylamino) -9-cyclopentylpurine dihydrochloride

Basically 2- [trans- (4-aminocyclohexyl) amino] from 2-chloro-6- (4-methoxybutylamino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -6- (4-methoxybutylamino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 388 (MH ⁺ ), Rf (min) = 3.29

Example 30

2- [trans- (4-aminocyclohexyl) amino] -6-[(2,3-dimethoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride

Scheme A, step b: 2-chloro-6-[(2,3-dimethoxybenzyl) amino] -9- (2-propyl) purine

Basically 2,6-dichloro-9- (2-propyl) purine (see Example 19 for preparation), 2,3-dimethoxybenzylamine and tree as described in Example 1, Scheme A, step b 2-Chloro-6-[(2,3-dimethoxybenzyl) amino] -9- (2-propyl) purine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(2,3-dimethoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride

Basically, 2- [trans- (4) from 2-chloro-6-[(2,3-dimethoxybenzyl) amino] -9- (2-propyl) purine as described in Example 1, Scheme A, step c. -Aminocyclohexyl) amino] -6-[(2,3-dimethoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride was prepared. CIMS (NH ₃ ) 440 (MH ⁺ ), Rf (min) = 3.39

Example 31

2- [trans- (4-aminocyclohexyl) amino] -6- [2- (phenylamino) ethylamino] -9-cyclopentylpurine trihydrochloride

Scheme A, step b: 2-chloro-6- [2- (phenylamino) ethylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [2- (phenylamino) from 2,6-dichloro-9-cyclopentylpurine, N-phenylethylenediamine and triethylamine as described in Example 1, Scheme A, step b. Ethylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [2- (phenylamino) ethylamino] -9-cyclopentylpurine trihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6- [2- (phenylamino) ethylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Amino] -6- [2- (phenylamino) ethylamino] -9-cyclopentylpurine trihydrochloride was prepared. CIMS (NH ₃ ) 435 (M−H ⁺ ), Rf (min) = 3.34

Example 32

2- [trans- (4-aminocyclohexyl) amino] -6- (phenylamino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (phenylamino) -9-cyclopentylpurine

Basically, 2-chloro-6- (phenylamino) -9-cyclopentylpurine was prepared from 2,6-dichloro-9-cyclopentylpurine, aniline and triethylamine as described in Example 1, Scheme A, step b. Prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (phenylamino) -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) amino] -6- (from 2-chloro-6- (phenylamino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Phenylamino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 392 (MH ⁺ ), Rf (min) = 3.35

Example 33

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-benzyl) piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme A, step b: 2-chloro-6- [4- (1-benzyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4 from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1-benzylpiperidine and triethylamine as described in Example 1, Scheme A, step b. -(1-benzyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-benzyl) piperidinylamino] -9-cyclopentylpurine trihydrochloride

Basically 2- [trans- (4-amino) from 2-chloro-6- [4- (1-benzyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Cyclohexyl) amino] -6- [4- (1-benzyl) piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. CIMS (NH ₃ ) 489 (MH ⁺ ), Rf (min) = 3.29

Example 34

2- [trans- (4-aminocyclohexyl) amino] -6- [3,4-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- [3,4-dimethoxybenzyl) amino] -9-cyclopentylpurine

Basically 2-chloro-6- [3,4 from 2,6-dichloro-9-cyclopentylpurine, 3,4-dimethoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. -Dimethoxybenzyl) amino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [3,4-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6- [3,4-dimethoxybenzyl) amino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. ) Amino] -6- [3,4-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 466 (MH ⁺ ), Rf (min) = 2.25

Example 35

2- [trans- (4-aminocyclohexyl) amino] -6-[(3-iodobenzyl) amino] -9- (2-cyclopentenyl) purine hydrochloride

Scheme A, step a: 2,6-dichloro-9-cyclopentylpurine

2,6-dichloro-9-cyclo from 2,6-dichloropurine and cyclopentenol as described in Example 1, Scheme A, step a, except that cyclopentenol is used instead of cyclopentanol. Pentenylpurine was prepared.

Scheme A, step b: 2-chloro-6-[(3-iodobenzyl) amino] -9-cyclopentenylpurine

Basically 2-chloro-6-[(3-ioo) from 2,6-dichloro-9-cyclopentenylpurine, 3-iodobenzylamine and triethylamine as described in Example 1, Scheme A, step b. Dobenzyl) amino] -9-cyclopentenylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(3-iodobenzyl) amino] -9-cyclopentenylpurine

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6-[(3-iodobenzyl) amino] -9-cyclopentenylpurine as described in Example 1, Scheme A, step c. ) Amino] -6-[(3-iodobenzyl) amino] -9-cyclopentenylpurine hydrochloride was prepared. CIMS (NH ₃ ) 530 (MH ⁺ )

Example 36

2- [trans- (4-aminocyclohexyl) amino] -6- (dodecylamino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (dodecylamino) -9-cyclopentylpurine

Basically 2-chloro-6- (dodecylamino) -9 from 2,6-dichloro-9-cyclopentylpurine, n-dodecylamine and triethylamine as described in Example 1, Scheme A, step b. Cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (dodecylamino) -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) amino] -6- from 2-chloro-6- (dodecylamino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. (Dodecylamino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 484 (MH ⁺ ), Rf (min) = 5.09

Example 37

2- [trans- (4-aminocyclohexyl) amino] -6-[(4-methoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride

Scheme A, step b: 2-chloro-6-[(4-methoxybenzyl) amino] -9- (2-propyl) purine

Basically 2,6-dichloro-9- (2-propyl) purine (see Example 19 for preparation), 4-methoxybenzylamine and triethylamine as described in Example 1, Scheme A, step b. 2-chloro-6-[(4-methoxybenzyl) amino] -9- (2-propyl) purine was prepared from.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6-[(4-methoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride

Basically 2- [trans- (4-amino) from 2-chloro-6-[(4-methoxybenzyl) amino] -9- (2-propyl) purine as described in Example 1, Scheme A, step c. Cyclohexyl) amino] -6-[(4-methoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride was prepared. CIMS (NH ₃ ) 410 (MH ⁺ ), Rf (min) = 3.37

Example 38

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-chlorobenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-chlorobenzyl) piperidine

Isonipecottamide (39 mmol) was dissolved in 3-pentanone (25 ml) and heated to reflux. Cesium carbonate (24 mmol) and catalytic amount of potassium iodide (about 2 spatula tip) were added followed by 4-chlorobenzyl chloride (47 mmol). Stir for 5 hours and reflux. The hot solution was filtered through celite, the filter cake was washed four times with 20 ml of hot acetone, the filtrate and wash were collected, the solvent was evaporated in vacuo and the residue was recrystallized from acetone to give the title compound. .

Scheme B, step b: 4-amino-1- (4-chlorobenzyl) piperidine

Bis (trifluoroacetoxy) iodobenzene (84 mmol) was dissolved in acetonitrile (20 ml) and diluted with water (20 ml). 4-Carboxamide-1- (4-chlorobenzyl) piperidine (7 mmol) was added and heated at 65 ° C. overnight. The mixture was cooled (ice bath), water (60 ml) was added followed by concentrated HCl. Ether) twice. The aqueous layer was concentrated in vacuo and the residue was dissolved in 40 ml of water. Base with aqueous sodium carbonate, extraction into methylene chloride, organic layer dried over Na ₂ S0 ₄ , filtered and solvent evaporated in vacuo to afford the title compound.

Method 2:

Scheme C, step a: 1- (4-chlorobenzyl) -4-piperidone

4-piperidone (17 mmol) was dissolved in 3-pentanone (25 ml) and heated to reflux. Cesium carbonate (19 mmol) and catalytic amount of potassium iodide were added followed by 4-chlorobenzyl chloride (20 mmol). Stir for 4 hours and reflux. The hot suspension is filtered, the residue is washed four times with 20 ml of hot acetone, the filtrate and wash are combined and the solvent is evaporated in vacuo to afford the title compound.

Scheme C, step b: 1- (4-chlorobenzyl) -4-piperidone oxime

1- (4-chlorobenzyl) -4-piperidone (0.0456 mmol), hydroxylamine hydrochloride (0.0456 mmol) and sodium acetate (0.0456 mmol) were dissolved in aqueous ethanol (450 ml). Stir for about 30 minutes to 2 hours while warming. Methylene chloride (450 ml) was added, the organic phase was separated and the aqueous phase was extracted with methylene chloride (100 ml). The organic phases were combined and dried over MgSO ₄ . The solvent was evaporated in vacuo to afford the title compound.

Scheme C, step c: 4-amino-1- (4-chlorobenzyl) piperidine

1- (4-chlorobenzyl) -4-piperidone oxime (1.87 mmol) was added to a lithium aluminum hydride solution (2.5 ml of a 1M solution in tetrahydrofuran) and placed under nitrogen atmosphere. Heated under reflux for 2 hours, cooled and poured into diluted aqueous sodium hydroxide. Extract twice with a mixture of ether and ethyl acetate, wash with aqueous sodium chloride and dry over MgSO ₄ . The solvent was evaporated in vacuo to afford the title compound.

Scheme A, step b: 2-chloro-6- [4- (1- (4-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-chlorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -6- [4- (1- (4-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine

Basically, 2- [trans- from 2-chloro-6- [4- (1- (4-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. (4-aminocyclohexyl) amino] -6- [4- (1- (4-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine was prepared Rf (min) = 2.29, purity 94%, MS (APCI): 523 M ⁺¹

Example 39

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-methoxybenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-methoxybenzyl) piperidine

4-Carboxamide-1- (4-methoxybenzyl) piperidine was prepared basically from isonipecottamide and 4-methoxybenzyl chloride as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1- (4-methoxybenzyl) piperidine

Basically 4-amino-1- (4-methoxybenzyl) piperidine from 4-carboxamide-1- (4-methoxybenzyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (4-methoxybenzyl) -4-piperidone

Basically 1- (4-methoxybenzyl) -4-piperidone was prepared from 4-piperidone and 4-methoxybenzyl chloride as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (4-methoxybenzyl) -4-piperidone oxime

Basically 1- (4-methoxybenzyl) -4-piperidone from 1- (4-methoxybenzyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (4-methoxybenzyl) piperidine

Basically 4-amino-1- (4-methoxybenzyl) piperidine was prepared from 1- (4-methoxybenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (4-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-methoxybenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (4-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine

Basically, 2- [trans from 2-chloro-6- [4- (1- (4-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -(4-aminocyclohexyl) amino] -6- [4- (1- (4-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine was prepared Rf (min) = 2.26, purity 100 %, MS (APCI): 519 M ⁺¹

Example 40

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methylbenzyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-methylbenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-methylbenzyl) piperidine

4-Carboxamide-1- (4-methylbenzyl) piperidine was prepared basically from isonipecottamide and α-chloro-p-xylene as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1- (4-methylbenzyl) piperidine

Basically, 4-amino-1- (4-methylbenzyl) piperidine was prepared from 4-carboxamide-1- (4-methylbenzyl) piperidine as described in Example 38, Scheme B, step b. It was.

Method 2:

Scheme C, step a: 1- (4-methylbenzyl) -4-piperidone

Basically 1- (4-methylbenzyl) -4-piperidone was prepared from 4-piperidone and α-chloro-p-xylene as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (4-methylbenzyl) -4-piperidone oxime

Basically 1- (4-methylbenzyl) -4-piperidone oxime was prepared from 1- (4-methylbenzyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Prepared.

Scheme C, step c: 4-amino-1- (4-methylbenzyl) piperidine

Basically 4-amino-1- (4-methylbenzyl) piperidine was prepared from 1- (4-methylbenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c.

Scheme A, step b: 2-chloro-6- [4- (1- (4-methylbenzyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-methylbenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -6- [4- (1- (4-methylbenzyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methylbenzyl) piperidinylamino] -9-cyclopentylpurine

Basically, 2- [trans- from 2-chloro-6- [4- (1- (4-methylbenzyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. (4-aminocyclohexyl) amino] -6- [4- (1- (4-methylbenzyl) piperidinylamino] -9-cyclopentylpurine was prepared Rf (min) = 2.26, purity 100%, MS (APCI): 503 M ⁺¹

Example 41

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-methoxybenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-methoxybenzyl) piperidine

4-Carboxamide-1- (3-methoxybenzyl) piperidine was prepared essentially from isonipecottamide and 3-methoxybenzyl chloride as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1- (3-methoxybenzyl) piperidine

Basically 4-amino-1- (3-methoxybenzyl) piperidine from 4-carboxamide-1- (3-methoxybenzyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (3-methoxybenzyl) -4-piperidone

Basically 1- (3-methoxybenzyl) -4-piperidone was prepared from 4-piperidone and 3-methoxybenzyl chloride as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-methoxybenzyl) -4-piperidone oxime

Basically 1- (3-methoxybenzyl) -4-piperidone from 1- (3-methoxybenzyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (3-methoxybenzyl) piperidine

Basically 4-amino-1- (3-methoxybenzyl) piperidine was prepared from 1- (3-methoxybenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (3-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-methoxybenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (3-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine

Basically 2- [trans from 2-chloro-6- [4- (1- (3-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -(4-aminocyclohexyl) amino] -6- [4- (1- (3-methoxybenzyl) piperidinylamino] -9-cyclopentylpurine was prepared Rf (min) = 2.27, purity 99 %, MS (APCI): 519 M ⁺¹

Example 42

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-chlorobenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-chlorobenzyl) piperidine

4-Carboxamide-1- (3-chlorobenzyl) piperidine was prepared basically from isonipecottamide and 3-chlorobenzyl chloride as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1- (3-chlorobenzyl) piperidine

Basically, 4-amino-1- (3-chlorobenzyl) piperidine was prepared from 4-carboxamide-1- (3-chlorobenzyl) piperidine as described in Example 38, Scheme B, step b. It was.

Method 2:

Scheme C, step a: 1- (3-chlorobenzyl) -4-piperidone

Basically 1- (3-chlorobenzyl) -4-piperidone was prepared from 4-piperidone and 3-chlorobenzyl chloride as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-chlorobenzyl) -4-piperidone oxime

Basically 1- (3-chlorobenzyl) -4-piperidone oxime was removed from 1- (3-chlorobenzyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Prepared.

Scheme C, step c: 4-amino-1- (3-chlorobenzyl) piperidine

Basically 4-amino-1- (3-chlorobenzyl) piperidine was prepared from 1- (3-chlorobenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c.

Scheme A, step b: 2-chloro-6- [4- (1- (3-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-chlorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -6- [4- (1- (3-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine

Basically, 2- [trans- from 2-chloro-6- [4- (1- (3-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. (4-aminocyclohexyl) amino] -6- [4- (1- (3-chlorobenzyl) piperidinylamino] -9-cyclopentylpurine was prepared Rf (min) = 2.25, purity 95%, MS (APCI): 523 M ⁺¹

Example 43

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-chlorobenzyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-chlorobenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-chlorobenzyl) piperidine

4-Carboxamide-1- (2-chlorobenzyl) piperidine was prepared basically from isonipecottamide and 2-chlorobenzyl chloride as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1- (2-chlorobenzyl) piperidine

Basically, 4-amino-1- (2-chlorobenzyl) piperidine was prepared from 4-carboxamide-1- (2-chlorobenzyl) piperidine as described in Example 38, Scheme B, step b. It was.

Method 2:

Scheme C, step a: 1- (2-chlorobenzyl) -4-piperidone

Basically 1- (2-chlorobenzyl) -4-piperidone was prepared from 4-piperidone and 2-chlorobenzyl chloride as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2-chlorobenzyl) -4-piperidone oxime

Basically 1- (2-chlorobenzyl) -4-piperidone oxime was prepared from 1- (2-chlorobenzyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Prepared.

Scheme C, step c: 4-amino-1- (2-chlorobenzyl) piperidine

Basically 4-amino-1- (2-chlorobenzyl) piperidine was prepared from 1- (2-chlorobenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c.

Scheme A, step b: 2-chloro-6- [4- (1- (2-chlorobenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-chlorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -6- [4- (1- (2-chlorobenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-chlorobenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically, 2- [trans from 2-chloro-6- [4- (1- (2-chlorobenzyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -(4-aminocyclohexyl) amino] -6- [4- (1- (2-chlorobenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared. Rf (min) = 2.25, purity 92%, MS (APCI): 523 M ⁺¹

Example 44

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-methylbenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-methylbenzyl) piperidine

4-Carboxamide-1- (2-methylbenzyl) piperidine was prepared basically from isonipecottamide and α-chloro-o-xylene as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1- (2-methylbenzyl) piperidine

Basically, 4-amino-1- (2-methylbenzyl) piperidine was prepared from 4-carboxamide-1- (2-methylbenzyl) piperidine as described in Example 38, Scheme B, step b. It was.

Method 2:

Scheme C, step a: 1- (2-methylbenzyl) -4-piperidone

Basically 1- (2-methylbenzyl) -4-piperidone was prepared from 4-piperidone and α-chloro-o-xylene as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2-methylbenzyl) -4-piperidone oxime

Basically 1- (2-methylbenzyl) -4-piperidone oxime was prepared from 1- (2-methylbenzyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Prepared.

Scheme C, step c: 4-amino-1- (2-methylbenzyl) piperidine

Basically 4-amino-1- (2-methylbenzyl) piperidine was prepared from 1- (2-methylbenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c.

Scheme A, step b: 2-chloro-6- [4- (1- (2-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-methylbenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -6- [4- (1- (2-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically, 2- [trans from 2-chloro-6- [4- (1- (2-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -(4-aminocyclohexyl) amino] -6- [4- (1- (2-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared. Rf (min) = 2.26, purity 98%, MS (APCI): 503 M ⁺¹

Example 45

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2,6-dichlorobenzyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2,6-dichlorobenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2,6-dichlorobenzyl) piperidine

Basically 4-carboxamide-1- (2,6-dichlorobenzyl) piperidine from isonifecottamide and α, 2,6-trichlorotoluene as described in Example 38, Scheme B, step a Was prepared.

Scheme B, step b: 4-amino-1- (2,6-dichlorobenzyl) piperidine

Basically 4-amino-1- (2,6-dichlorobenzyl) pi from 4-carboxamide-1- (2,6-dichlorobenzyl) piperidine as described in Example 38, Scheme B, step b. Ferridine was prepared.

Method 2:

Scheme C, step a: 1- (2,6-dichlorobenzyl) -4-piperidone

Basically 1- (2,6-dichlorobenzyl) -4-piperidone was prepared from 4-piperidone and α, 2,6-trichlorotoluene as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2,6-dichlorobenzyl) -4-piperidone oxime

Basically 1- (2,6-dichlorobenzyl) -4- from 1- (2,6-dichlorobenzyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2,6-dichlorobenzyl) piperidine

Basically 4-amino-1- (2,6-dichlorobenzyl) piperidine from 1- (2,6-dichlorobenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2,6-dichlorobenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2,6-dichlorobenzyl) piperidine as described in Example 1, Scheme A, step b (method of Example 45 2-chloro-6- [4- (1- (2,6-dichlorobenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared from triethylamine) and triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2,6-dichlorobenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (2,6-dichlorobenzyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. [Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2,6-dichlorobenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared. Rf (min) = 2.28, purity 98%, MS (APCI): 557 M ⁺¹

Example 46

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-trifluoromethylbenzyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-trifluoromethylbenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-trifluoromethylbenzyl) piperidine

Basically 4-carboxamide-1- (4) from isonifecottamide and α′-chloro-α, α, α-trifluoro-p-xylene as described in Example 38, Scheme B, step a Trifluoromethylbenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-trifluoromethylbenzyl) piperidine

Basically 4-amino-1- (4-trifluoromethylbenzyl from 4-carboxamide-1- (4-trifluoromethylbenzyl) piperidine as described in Example 38, Scheme B, step b. Piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4-trifluoromethylbenzyl) -4-piperidone

Basically 1- (4-trifluoromethylbenzyl) from 4-piperidone and α'-chloro-α, α, α-trifluoro-p-xylene as described in Example 38, Scheme C, step a -4-piperidone was prepared.

Scheme C, step b: 1- (4-trifluoromethylbenzyl) -4-piperidone oxime

Basically 1- (4-trifluoromethylbenzyl)-from 1- (4-trifluoromethylbenzyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4-trifluoromethylbenzyl) piperidine

Basically 4-amino-1- (4-trifluoromethylbenzyl) piperi from 1- (4-trifluoromethylbenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Dean was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4-trifluoromethylbenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-trifluoromethylbenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- (1- (4-trifluoromethylbenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-trifluoromethylbenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (4-trifluoromethylbenzyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-trifluoromethylbenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared. Rf (min) = 2.38, purity 100%, MS (APCI): 557 M ⁺¹

Example 47

(+/-)-2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (α-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of (R, S) -4-amino-1- (α-methylbenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (α-methylbenzyl) piperidine

4-Carboxamide-1- (α-methylbenzyl) piperidine was prepared essentially from isonipecottamide and α-methylbenzyl bromide as described in Example 38, Scheme B, step a.

Scheme B, step b: (R, S) -4-amino-1- (α-methylbenzyl) piperidine

Basically (R, S) -4-amino-1- (α-methylbenzyl) from 4-carboxamide-1- (α-methylbenzyl) piperidine as described in Example 38, Scheme B, step b. Piperidine was prepared.

Method 2:

Scheme C, step a: 1- (α-methylbenzyl) -4-piperidone

Basically 1- (α-methylbenzyl) -4-piperidone was prepared from 4-piperidone and α-methylbenzyl bromide as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (α-methylbenzyl) -4-piperidone oxime

Basically 1- (α-methylbenzyl) -4-piperidone oxime was prepared from 1- (α-methylbenzyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Prepared.

Scheme C, step c: (R, S) -4-amino-1- (α-methylbenzyl) piperidine

Basically (R, S) -4-amino-1- (α-methylbenzyl) piperi from 1- (α-methylbenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Dean was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (α-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, (R, S) -4-amino-1- (α-methylbenzyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (α-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (α-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2- [trans from 2-chloro-6- [4- (1- (α-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -(4-aminocyclohexyl) amino] -6- [4- (1- (α-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 48

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-phenoxypropyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-phenoxypropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-phenoxypropyl) piperidine

Basically 4-carboxamide-1- (3-phenoxypropyl) piperidine was obtained from isonifecottamide and 1-chloro-3-phenoxypropane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (3-phenoxypropyl) piperidine

Basically 4-amino-1- (3-phenoxypropyl) piperidine from 4-carboxamide-1- (3-phenoxypropyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (3-phenoxypropyl) -4-piperidone

Basically 1- (3-phenoxypropyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-3-phenoxypropane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-phenoxypropyl) -4-piperidone oxime

Basically 1- (3-phenoxypropyl) -4-piperidone from 1- (3-phenoxypropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (3-phenoxypropyl) piperidine

Basically 4-amino-1- (3-phenoxypropyl) piperidine was prepared from 1- (3-phenoxypropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (3-phenoxypropyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-phenoxypropyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (3-phenoxypropyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-phenoxypropyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (3-phenoxypropyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-phenoxypropyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 49

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenoxyethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-phenoxyethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-phenoxyethyl) piperidine

Basically 4-carboxamide-1- (2-phenoxyethyl) piperidine was obtained from isonifecottamide and 1-chloro-2-phenoxytane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (2-phenoxyethyl) piperidine

Basically 4-amino-1- (2-phenoxyethyl) piperidine from 4-carboxamide-1- (2-phenoxyethyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (2-phenoxyethyl) -4-piperidone

Basically 1- (2-phenoxyethyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-2-phenoxyethane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2-phenoxyethyl) -4-piperidone oxime

Basically 1- (2-phenoxyethyl) -4-piperidone from 1- (2-phenoxyethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (2-phenoxyethyl) piperidine

Basically 4-amino-1- (2-phenoxyethyl) piperidine was prepared from 1- (2-phenoxyethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (2-phenoxyethyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-phenoxyethyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (2-phenoxyethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenoxyethyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (2-phenoxyethyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenoxyethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 50

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenylethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-phenylethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-phenylethyl) piperidine

4-Carboxamide-1- (2-phenylethyl) piperidine was prepared basically from isonipecottamide and (2-chloroethyl) benzene as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1- (2-phenylethyl) piperidine

Basically, 4-amino-1- (2-phenylethyl) piperidine was prepared from 4-carboxamide-1- (2-phenylethyl) piperidine as described in Example 38, Scheme B, step b. It was.

Method 2:

Scheme C, step a: 1- (2-phenylethyl) -4-piperidone

Basically 1- (2-phenylethyl) -4-piperidone was prepared from 4-piperidone and (2-chloroethyl) benzene as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2-phenylethyl) -4-piperidone oxime

Basically 1- (2-phenylethyl) -4-piperidone oxime was removed from 1- (2-phenylethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Prepared.

Scheme C, step c: 4-amino-1- (2-phenylethyl) piperidine

Basically 4-amino-1- (2-phenylethyl) piperidine was prepared from 1- (2-phenylethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c.

Scheme A, step b: 2-chloro-6- [4- (1- (2-phenylethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-phenylethyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -6- [4- (1- (2-phenylethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenylethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2- [trans from 2-chloro-6- [4- (1- (2-phenylethyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -(4-aminocyclohexyl) amino] -6- [4- (1- (2-phenylethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 51

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1-propylpiperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1-propylpiperidine

4-Carboxamide-1-propylpiperidine was prepared basically from isonipecottamide and 1-chloropropane as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1-propylpiperidine

Basically 4-amino-1-propylpiperidine was prepared from 4-carboxamide-1-propylpiperidine as described in Example 38, Scheme B, step b.

Method 2:

Scheme C, step a: 1-propyl-4-piperidone

Basically 1-propyl-4-piperidone was prepared from 4-piperidone and 1-chloropropane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1-propyl-4-piperidone oxime

Basically 1-propyl-4-piperidone oxime was prepared from 1-propyl-4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b.

Scheme C, step c: 4-amino-1-propylpiperidine

4-Amino-1-propylpiperidine was prepared basically from 1-propyl-4-piperidone oxime as described in Example 38, Scheme C, step c.

Scheme A, step b: 2-chloro-6- [4- (1-propyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4 from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1-propylpiperidine and triethylamine as described in Example 1, Scheme A, step b. -(1-propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-propyl) piperidinylamino] -9-cyclopentylpurine

Basically 2- [trans- (4-amino) from 2-chloro-6- [4- (1-propyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Cyclohexyl) amino] -6- [4- (1-propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 52

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-cyclopropylmethyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1-cyclopropylmethylpiperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1-cyclopropylmethylpiperidine

4-Carboxamide-1-cyclopropylmethylpiperidine was prepared essentially from isonipecottamide and (chloromethyl) cyclopropane as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1-cyclopropylmethylpiperidine

Basically 4-amino-1-cyclopropylmethylpiperidine was prepared from 4-carboxamide-1-cyclopropylmethylpiperidine as described in Example 38, Scheme B, step b.

Method 2:

Scheme C, step a: 1- (cyclopropylmethyl) -4-piperidone

Basically 1- (cyclopropylmethyl) -4-piperidone was prepared from 4-piperidone and (chloromethyl) cyclopropane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (cyclopropylmethyl) -4-piperidone oxime

Basically 1- (cyclopropylmethyl) -4-piperidone oxime was prepared from 1- (cyclopropylmethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. .

Scheme C, step c: 4-amino-1-cyclopropylmethylpiperidine

Basically 4-amino-1-cyclopropylmethylpiperidine was prepared from 1- (cyclopropylmethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c.

Scheme A, step b: 2-chloro-6- [4- (1-cyclopropylmethyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1-cyclopropylmethylpiperidine and triethylamine as described in Example 1, Scheme A, step b. [4- (1-cyclopropylmethyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-cyclopropylmethyl) piperidinylamino] -9-cyclopentylpurine

Basically 2- [trans- (4) from 2-chloro-6- [4- (1-cyclopropylmethyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -Aminocyclohexyl) amino] -6- [4- (1-cyclopropylmethyl) piperidinylamino] -9-cyclopentylpurine was prepared. Rf (min) = 2.19, purity 100%, MS (APCI): 454 M ⁺¹

Example 53

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-pyridinylmethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-pyridinylmethyl) piperidine

Basically 4-carboxamide-1- (2-pyridinylmethyl) piperidine was prepared from isonipecottamide and 2-picolinyl chloride hydrochloride as described in Example 38, Scheme B, step a. .

Scheme B, step b: 4-amino-1- (2-pyridinylmethyl) piperidine

Basically 4-amino-1- (2-pyridinylmethyl) piperidine from 4-carboxamide-1- (2-pyridinylmethyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (2-pyridinylmethyl) -4-piperidone

Basically 1- (2-pyridinylmethyl) -4-piperidone was prepared from 4-piperidone and 2-picolyl chloride hydrochloride as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2-pyridinylmethyl) -4-piperidone oxime

Basically 1- (2-pyridinylmethyl) -4-piperidone from 1- (2-pyridinylmethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (2-pyridinylmethyl) piperidine

Basically 4-amino-1- (2-pyridinylmethyl) piperidine was prepared from 1- (2-pyridinylmethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (2-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-pyridinylmethyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (2-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (2-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 54

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-pyridinylmethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-pyridinylmethyl) piperidine

4-Carboxamide-1- (3-pyridinylmethyl) piperidine was prepared essentially from isonipecottamide and 3-picolinyl chloride hydrochloride as described in Example 38, Scheme B, step a. .

Scheme B, step b: 4-amino-1- (3-pyridinylmethyl) piperidine

Basically 4-amino-1- (3-pyridinylmethyl) piperidine from 4-carboxamide-1- (3-pyridinylmethyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (3-pyridinylmethyl) -4-piperidone

Basically 1- (3-pyridinylmethyl) -4-piperidone was prepared from 4-piperidone and 3-picolyl chloride hydrochloride as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-pyridinylmethyl) -4-piperidone oxime

Basically 1- (3-pyridinylmethyl) -4-piperidone from 1- (3-pyridinylmethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (3-pyridinylmethyl) piperidine

Basically 4-amino-1- (3-pyridinylmethyl) piperidine was prepared from 1- (3-pyridinylmethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (3-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-pyridinylmethyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (3-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (3-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 55

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-pyridinylmethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-pyridinylmethyl) piperidine

4-Carboxamide-1- (4-pyridinylmethyl) piperidine was prepared essentially from isonipecottamide and 4-picolinyl chloride hydrochloride as described in Example 38, Scheme B, step a. .

Scheme B, step b: 4-amino-1- (4-pyridinylmethyl) piperidine

Basically 4-amino-1- (4-pyridinylmethyl) piperidine from 4-carboxamide-1- (4-pyridinylmethyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (4-pyridinylmethyl) -4-piperidone

Basically 1- (4-pyridinylmethyl) -4-piperidone was prepared from 4-piperidone and 4-picolinyl chloride hydrochloride as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (4-pyridinylmethyl) -4-piperidone oxime

Basically 1- (4-pyridinylmethyl) -4-piperidone from 1- (4-pyridinylmethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (4-pyridinylmethyl) piperidine

Basically 4-amino-1- (4-pyridinylmethyl) piperidine was prepared from 1- (4-pyridinylmethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (4-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-pyridinylmethyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (4-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (4-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 56

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (2,4-dimethylisoxazolyl)) methyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3- (2,4-dimethylisoxazolyl) methylpiperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3- (2,4-dimethylisoxazolyl) methyl) piperidine

Basically 4-carboxamide-1- (3- (2,4) from isonifecottamide and 2,4-dimethyl-3-chloromethyl-isoxazole as described in Example 38, Scheme B, step a -Dimethylisoxazolyl) methyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3- (2,4-dimethylisoxazolyl) methylpiperidine

Basically 4-amino-1- (3 from 4-carboxamide-1- (3- (2,4-dimethylisoxazolyl) methyl) piperidine as described in Example 38, Scheme B, step b. -(2,4-dimethylisoxazolyl) methylpiperidine was prepared.

Method 2:

Scheme C, step a: 1- (3- (2,4-dimethylisoxazolyl) methyl) -4-piperidone

Basically 1- (3- (2,4-dimethylisoxazolyl) methyl from 4-piperidone and 2,4-dimethyl-3-chloromethyl-isoxazole as described in Example 38, Scheme C, step a ) -4-piperidone was prepared.

Scheme C, step b: 1- (3- (2,4-dimethylisoxazolyl) methyl) -4-piperidone oxime

Basically from 1- (3- (2,4-dimethylisoxazolyl) methyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 2,4-dimethylisoxazolyl) methyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3- (2,4-dimethylisoxazolyl) methylpiperidine

Basically 4-amino-1- (3- (2 from 1- (3- (2,4-dimethylisoxazolyl) methyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. , 4-dimethylisoxazolyl) methylpiperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3- (2,4-dimethylisoxazolyl)) methyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3- (2,4-dimethylisoxazolyl) methylpiperidine as described in Example 1, Scheme A, step b. And 2-chloro-6- [4- (1- (3- (2,4-dimethylisoxazolyl)) methyl) piperidinylamino] -9-cyclopentylpurine from triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (2,4-dimethylisoxazolyl)) methyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3- (2,4-dimethylisoxazolyl)) methyl) piperidinylamino] -9 as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (2,4-dimethylisoxazolyl)) methyl) piperidinylamino]-from cyclopentylpurine 9-cyclopentylpurine was prepared.

Example 57

(R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-benzyl-3-methyl) piperidinylamino] -9-cyclopentylpurine

Preparation of (R, S) -4-amino-1-benzyl-3-methylpiperidine:

Method 1:

Scheme B, step a: (R, S) -4-carboxamide-1-benzyl-3-methylpiperidine

Basically (R, S) -4-carboxamide-1 from (R, S) -4-carboxamide-3-methylpiperidine and benzyl chloride as described in Example 38, Scheme B, step a. -Benzyl-3-methylpiperidine was prepared.

Scheme B, step b: (R, S) -4-amino-1-benzyl-3-methylpiperidine

Basically (R, S) -4-amino-1- from (R, S) -4-carboxamide-1-benzyl-3-methylpiperidine as described in Example 38, Scheme B, step b. Benzyl-3-methylpiperidine was prepared.

Method 2:

Scheme C, step a: (R, S) -1-benzyl-3-methyl-4-piperidone

Except for using (R, S) -3-methyl-4-piperidone instead of 4-piperidone, basically (R, S) -3- as described in Example 38, Scheme C, step a (R, S) -1-benzyl-3-methyl-4-piperidone was prepared from methyl-4-piperidone and benzyl chloride.

Scheme C, step b: (R, S) -1-benzyl-3-methyl-4-piperidone oxime

(R, S) -1-benzyl- from (R, S) -1-benzyl-3-methyl-4-piperidone and hydroxylamine hydrochloride, essentially as described in Example 38, Scheme C, step b. 3-Methyl-4-piperidone oxime was prepared.

Scheme C, step c: (R, S) -4-amino-1-benzyl-3-methylpiperidine

Basically (R, S) -4-amino-1-benzyl-3 from (R, S) -1-benzyl-3-methyl-4-piperidone oxime as described in Example 38, Scheme C, step c. -Methylpiperidine was prepared.

Scheme A, step b: (R, S) -2-chloro-6- [4- (1-benzyl-3-methyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, (R, S) -4-amino-1-benzyl-3-methylpiperidine and triethyl as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- (1-benzyl-3-methyl) piperidinylamino] -9-cyclopentylpurine was prepared from the amine.

Scheme A, step c: (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-benzyl-3-methyl) piperidinylamino] -9-cyclo Pentylpurine

Basically (R, S) -2-chloro-6- [4- (1-benzyl-3-methyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-benzyl-3-methyl) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 58a

(R) -2- [trans- (4-aminocyclohexyl) amino] -6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine

Scheme A, step b: (R) -2-chloro-6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine

(R) from 2,6-dichloro-9-cyclopentylpurine, (R) -4-amino-1-benzyl-pyrrolidine and triethylamine, basically as described in Example 1, Scheme A, step b. -2-Chloro-6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: (R) -2- [trans- (4-aminocyclohexyl) amino] -6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine

(R) -2 from (R) -2-chloro-6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine basically as described in Example 1, Scheme A, step c. -[Trans- (4-aminocyclohexyl) amino] -6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine was prepared.

Example 58b

(S) -2- [trans- (4-aminocyclohexyl) amino] -6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine

Scheme A, step b: (S) -2-chloro-6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine

(S) from 2,6-dichloro-9-cyclopentylpurine, (S) -4-amino-1-benzyl-pyrrolidine and triethylamine, basically as described in Example 1, Scheme A, step b. -2-Chloro-6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: (S) -2- [trans- (4-aminocyclohexyl) amino] -6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine

Basically (S) -2 from (S) -2-chloro-6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -[Trans- (4-aminocyclohexyl) amino] -6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine was prepared.

Example 59

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1-butylpiperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1-butylpiperidine

4-Carboxamide-1-butylpiperidine was prepared basically from isonipecottamide and 1-chlorobutane as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1-butylpiperidine

Basically 4-amino-1-butylpiperidine was prepared from 4-carboxamide-1-butylpiperidine as described in Example 38, Scheme B, step b.

Method 2:

Scheme C, step a: 1-butyl-4-piperidone

Basically 1-butyl-4-piperidone was prepared from 4-piperidone and 1-chlorobutane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1-butyl-4-piperidone oxime

Basically 1-butyl-4-piperidone oxime was prepared from 1-butyl-4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b.

Scheme C, step c: 4-amino-1-butylpiperidine

Basically 4-amino-1-butylpiperidine was prepared from 1-butyl-4-piperidone oxime as described in Example 38, Scheme C, step c.

Scheme A, step b: 2-chloro-6- [4- (1-butyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4 from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1-butylpiperidine and triethylamine as described in Example 1, Scheme A, step b. -(1-butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-butyl) piperidinylamino] -9-cyclopentylpurine

Basically 2- [trans- (4-amino) from 2-chloro-6- [4- (1-butyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Cyclohexyl) amino] -6- [4- (1-butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 60

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-thiomethoxyethyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-thiomethoxyethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-thiomethoxyethyl) piperidine

Basically 4-carboxamide-1- (2-thiomethoxyethyl) piperi from isonifecottamide and 1-chloro-2-thiomethoxyethane as described in Example 38, Scheme B, step a Dean was prepared.

Scheme B, step b: 4-amino-1- (2-thiomethoxyethyl) piperidine

Basically 4-amino-1- (2-thiomethoxyethyl) pi from 4-carboxamide-1- (2-thiomethoxyethyl) piperidine as described in Example 38, Scheme B, step b. Ferridine was prepared.

Method 2:

Scheme C, step a: 1- (2-thiomethoxyethyl) -4-piperidone

Basically 1- (2-thiomethoxyethyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-2-thiomethoxyethane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2-thiomethoxyethyl) -4-piperidone oxime

Basically 1- (2-thiomethoxyethyl) -4- from 1- (2-thiomethoxyethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-thiomethoxyethyl) piperidine

Basically 4-amino-1- (2-thiomethoxyethyl) piperidine was obtained from 1- (2-thiomethoxyethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-thiomethoxyethyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-thiomethoxyethyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -Chloro-6- [4- (1- (2-thiomethoxyethyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-thiomethoxyethyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (2-thiomethoxyethyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-thiomethoxyethyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 61

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenylsulfinyl) ethyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-phenylsulfinylethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-phenylsulfinylethyl) piperidine

Basically 4-carboxamide-1- (2-phenylsulfinylethyl) piperi from isonifecottamide and 1-chloro-2-phenylsulfinylethane as described in Example 38, Scheme B, step a Dean was prepared.

Scheme B, step b: 4-amino-1- (2-phenylsulfinylethyl) piperidine

Basically 4-amino-1- (2-phenylsulfinylethyl) pi from 4-carboxamide-1- (2-phenylsulfinylethyl) piperidine as described in Example 38, Scheme B, step b. Ferridine was prepared.

Method 2:

Scheme C, step a: 1- (2-phenylsulfinylethyl) -4-piperidone

Basically 1- (2-phenylsulfinylethyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-2-phenylsulfinylethane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2-phenylsulfinylethyl) -4-piperidone oxime

Basically 1- (2-phenylsulfinylethyl) -4- from 1- (2-phenylsulfinylethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-phenylsulfinylethyl) piperidine

Basically 4-amino-1- (2-phenylsulfinylethyl) piperidine from 1- (2-phenylsulfinylethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c Prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-phenylsulfinyl) ethyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-phenylsulfinylethyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -Chloro-6- [4- (1- (2-phenylsulfinyl) ethyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenylsulfinyl) ethyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (2-phenylsulfinyl) ethyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. [Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenylsulfinyl) ethyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 62

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-hydroxy) propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-hydroxypropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-hydroxypropyl) piperidine

4-Carboxamide-1- (3-hydroxypropyl) piperidine was prepared basically from isonifecottamide and 3-chloro-1-propanol as described in Example 38, Scheme B, step a. .

Scheme B, step b: 4-amino-1- (3-hydroxypropyl) piperidine

Basically 4-amino-1- (3-hydroxypropyl) piperidine from 4-carboxamide-1- (3-hydroxypropyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (3-hydroxypropyl) -4-piperidone

Basically 1- (3-hydroxypropyl) -4-piperidone was prepared from 4-piperidone and 3-chloro-1-propanol as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-hydroxypropyl) -4-piperidone oxime

Basically 1- (3-hydroxypropyl) -4-piperidone from 1- (3-hydroxypropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (3-hydroxypropyl) piperidine

Basically 4-amino-1- (3-hydroxypropyl) piperidine was prepared from 1- (3-hydroxypropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (3-hydroxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-hydroxypropyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (3-hydroxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-hydroxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (3-hydroxy) propyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-hydroxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 63

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-methoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-methoxypropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-methoxypropyl) piperidine

Basically 4-carboxamide-1- (3-methoxypropyl) piperidine was obtained from isonifecottamide and 1-chloro-3-methoxypropane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (3-methoxypropyl) piperidine

Basically 4-amino-1- (3-methoxypropyl) piperidine from 4-carboxamide-1- (3-methoxypropyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (3-methoxypropyl) -4-piperidone

Basically 1- (3-methoxypropyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-3-methoxypropane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-methoxypropyl) -4-piperidone oxime

Basically 1- (3-methoxypropyl) -4-piperidone from 1- (3-methoxypropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (3-methoxypropyl) piperidine

Basically 4-amino-1- (3-methoxypropyl) piperidine was prepared from 1- (3-methoxypropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (3-methoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-methoxypropyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (3-methoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-methoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (3-methoxy) propyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-methoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 64

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-ethoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-ethoxypropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-ethoxypropyl) piperidine

Basically 4-carboxamide-1- (3-ethoxypropyl) piperidine was obtained from isonifecottamide and 1-chloro-3-ethoxypropane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (3-ethoxypropyl) piperidine

Basically 4-amino-1- (3-ethoxypropyl) piperidine from 4-carboxamide-1- (3-ethoxypropyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (3-ethoxypropyl) -4-piperidone

Basically 1- (3-ethoxypropyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-3-ethoxypropane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-ethoxypropyl) -4-piperidone oxime

Basically 1- (3-ethoxypropyl) -4-piperidone from 1- (3-ethoxypropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (3-ethoxypropyl) piperidine

Basically 4-amino-1- (3-ethoxypropyl) piperidine was prepared from 1- (3-ethoxypropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (3-ethoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-ethoxypropyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (3-ethoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-ethoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (3-ethoxy) propyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-ethoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 65

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-propoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-propoxypropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-propoxypropyl) piperidine

Basically 4-carboxamide-1- (3-propoxypropyl) piperidine was obtained from isonipecottamide and 1-chloro-3-propoxypropane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (3-propoxypropyl) piperidine

Basically 4-amino-1- (3-propoxypropyl) piperidine from 4-carboxamide-1- (3-propoxypropyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (3-propoxypropyl) -4-piperidone

Basically 1- (3-propoxypropyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-3-propoxypropane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-propoxypropyl) -4-piperidone oxime

Basically 1- (3-propoxypropyl) -4-piperidone from 1- (3-propoxypropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (3-propoxypropyl) piperidine

Basically 4-amino-1- (3-propoxypropyl) piperidine was prepared from 1- (3-propoxypropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (3-propoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-propoxypropyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (3-propoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-propoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (3-propoxy) propyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-propoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 66

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-butoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-butoxypropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-butoxypropyl) piperidine

Basically 4-carboxamide-1- (3-butoxypropyl) piperidine was obtained from isonifecottamide and 1-chloro-3-butoxypropane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (3-butoxypropyl) piperidine

Basically 4-amino-1- (3-butoxypropyl) piperidine from 4-carboxamide-1- (3-butoxypropyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (3-butoxypropyl) -4-piperidone

Basically 1- (3-butoxypropyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-3-butoxypropane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-butoxypropyl) -4-piperidone oxime

Basically 1- (3-butoxypropyl) -4-piperidone from 1- (3-butoxypropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (3-butoxypropyl) piperidine

Basically 4-amino-1- (3-butoxypropyl) piperidine was prepared from 1- (3-butoxypropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (3-butoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-butoxypropyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (3-butoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-butoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (3-butoxy) propyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-butoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 67

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-benzyloxy) propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-benzyloxypropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-benzyloxypropyl) piperidine

Basically 4-carboxamide-1- (3-benzyloxypropyl) piperidine was obtained from isonifecottamide and 1-chloro-3-benzyloxypropane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (3-benzyloxypropyl) piperidine

Basically 4-amino-1- (3-benzyloxypropyl) piperidine from 4-carboxamide-1- (3-benzyloxypropyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (3-benzyloxypropyl) -4-piperidone

Basically 1- (3-benzyloxypropyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-3-benzyloxypropane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-benzyloxypropyl) -4-piperidone oxime

Basically 1- (3-benzyloxypropyl) -4-piperidone from 1- (3-benzyloxypropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (3-benzyloxypropyl) piperidine

Basically 4-amino-1- (3-benzyloxypropyl) piperidine was prepared from 1- (3-benzyloxypropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (3-benzyloxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-benzyloxypropyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (3-benzyloxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-benzyloxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (3-benzyloxy) propyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-benzyloxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 68

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (2-phenylethyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3- (2-phenylethyleneoxy) propyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3- (2-phenylethyleneoxy) propyl) piperidine

Basically 4-carboxamide-1- (3- (2-) from isonifecottamide and 1-chloro-3- (2-phenylethyleneoxy) propane as described in Example 38, Scheme B, step a. Phenylethyleneoxy) propyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3- (2-phenylethyleneoxy) propyl) piperidine

Basically 4-amino-1- (3- (2) from 4-carboxamide-1- (3- (2-phenylethyleneoxy) propyl) piperidine as described in Example 38, Scheme B, step b. -Phenylethyleneoxy) propyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3- (2-phenylethyleneoxy) -4-piperidone

Basically 1- (3- (2-phenylethyleneoxy) -4- from 4-piperidone and 1-chloro-3- (2-phenylethyleneoxy) propane as described in Example 38, Scheme C, step a. Piperidone was prepared.

Scheme C, step b: 1- (3- (2-phenylethyleneoxy) -4-piperidone oxime

Basically 1- (3- (2-phenylethyleneoxy) from 1- (3- (2-phenylethyleneoxy) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. ) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3- (2-phenylethyleneoxy) propyl) piperidine

Basically 4-amino-1- (3- (2-phenylethyleneoxy) from 1- (3- (2-phenylethyleneoxy) -4-piperidone oxime as described in Example 38, Scheme C, step c. Propyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3- (2-phenylethyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3- (2-phenylethyleneoxy) propyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (3- (2-phenylethyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (2-phenylethyleneoxy) propyl) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (3- (2-phenylethyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (2-phenylethyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 69

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (3-phenylpropyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3- (3-phenylpropyleneoxy) propyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3- (3-phenylpropyleneoxy) propyl) piperidine

Basically 4-carboxamide-1- (3- (3-) from isonifecottamide and 1-chloro-3- (3-phenylpropyleneoxy) propane as described in Example 38, Scheme B, step a. Phenylpropyleneoxy) propyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3- (3-phenylpropyleneoxy) propyl) piperidine

Basically 4-amino-1- (3- (3) from 4-carboxamide-1- (3- (3-phenylpropyleneoxy) propyl) piperidine as described in Example 38, Scheme B, step b. -Phenylpropyleneoxy) propyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3- (3-phenylpropyleneoxy) propyl) -4-piperidone

Basically 1- (3- (3-phenylpropyleneoxy) propyl)-from 4-piperidone and 1-chloro-3- (3-phenylpropyleneoxy) propane as described in Example 38, Scheme C, step a. 4-piperidone was prepared.

Scheme C, step b: 1- (3- (3-phenylpropyleneoxy) propyl) -4-piperidone oxime

Basically 1- (3- (3-phenyl) from 1- (3- (3-phenylpropyleneoxy) propyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Propyleneoxy) propyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3- (3-phenylpropyleneoxy) propyl) piperidine

Basically 4-amino-1- (3- (3-phenylpropylene) from 1- (3- (3-phenylpropyleneoxy) propyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Oxy) propyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3- (3-phenylpropyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3- (3-phenylpropyleneoxy) propyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (3- (3-phenylpropyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (3-phenylpropyleneoxy) propyl) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (3- (3-phenylpropyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (3-phenylpropyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 70

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (4-phenylbutyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3- (4-phenylbutyleneoxy) propyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3- (4-phenylbutyleneoxy) propyl) piperidine

Basically 4-carboxamide-1- (3- (4) from isonifecottamide and 1-chloro-3- (4-phenylbutyleneoxy) propane as described in Example 38, Scheme B, step a. -Phenylbutyleneoxy) propyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3- (4-phenylbutyleneoxy) propyl) piperidine

Basically 4-amino-1- (3- (from 4-carboxamide-1- (3- (4-phenylbutyleneoxy) propyl) piperidine as described in Example 38, Scheme B, step b. 4-phenylbutyleneoxy) propyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3- (4-phenylbutyleneoxy) propyl) -4-piperidone

Basically 1- (3- (4-phenylbutyleneoxy) propyl from 4-piperidone and 1-chloro-3- (4-phenylbutyleneoxy) propane as described in Example 38, Scheme C, step a ) -4-piperidone was prepared.

Scheme C, step b: 1- (3- (4-phenylbutyleneoxy) propyl) -4-piperidone oxime

Basically 1- (3- (4-) from 1- (3- (4-phenylbutyleneoxy) propyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Phenylbutyleneoxy) propyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3- (4-phenylbutyleneoxy) propyl) piperidine

Basically 4-amino-1- (3- (4-phenyl) from 1- (3- (4-phenylbutyleneoxy) propyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Butyleneoxy) propyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3- (4-phenylbutyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3- (4-phenylbutyleneoxy) propyl) piperidine as described in Example 1, Scheme A, step b and 2-Chloro-6- [4- (1- (3- (4-phenylbutyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine was prepared from triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (4-phenylbutyleneoxy) propyl) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3- (4-phenylbutyleneoxy) propyl) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From Purine 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (4-phenylbutyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 71

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-hydroxy) butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-hydroxybutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-hydroxybutyl) piperidine

4-Carboxamide-1- (4-hydroxybutyl) piperidine was prepared basically from isonipecottamide and 4-chloro-1-butanol as described in Example 38, Scheme B, step a. .

Scheme B, step b: 4-amino-1- (4-hydroxybutyl) piperidine

Basically 4-amino-1- (4-hydroxybutyl) piperidine from 4-carboxamide-1- (4-hydroxybutyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (4-hydroxybutyl) -4-piperidone

Basically 1- (4-hydroxybutyl) -4-piperidone was prepared from 4-piperidone and 4-chloro-1-butanol as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (4-hydroxybutyl) -4-piperidone oxime

Basically 1- (4-hydroxybutyl) -4-piperidone from 1- (4-hydroxybutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (4-hydroxybutyl) piperidine

Basically 4-amino-1- (4-hydroxybutyl) piperidine was prepared from 1- (4-hydroxybutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (4-hydroxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-hydroxybutyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (4-hydroxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-hydroxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (4-hydroxy) butyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-hydroxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 72

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-methoxybutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-methoxybutyl) piperidine

Basically 4-carboxamide-1- (4-methoxybutyl) piperidine was obtained from isonifecottamide and 1-chloro-4-methoxybutane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (4-methoxybutyl) piperidine

Basically 4-amino-1- (4-methoxybutyl) piperidine from 4-carboxamide-1- (4-methoxybutyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (4-methoxybutyl) -4-piperidone

Basically 1- (4-methoxybutyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-4-methoxybutane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (4-methoxybutyl) -4-piperidone oxime

Basically 1- (4-methoxybutyl) -4-piperidone from 1- (4-methoxybutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (4-methoxybutyl) piperidine

Basically 4-amino-1- (4-methoxybutyl) piperidine was prepared from 1- (4-methoxybutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (4-methoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-methoxybutyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (4-methoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (4-methoxy) butyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 73

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-ethoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-ethoxybutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-ethoxybutyl) piperidine

Basically 4-carboxamide-1- (4-ethoxybutyl) piperidine was obtained from isonifecottamide and 1-chloro-4-ethoxybutane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (4-ethoxybutyl) piperidine

Basically 4-amino-1- (4-ethoxybutyl) piperidine from 4-carboxamide-1- (4-ethoxybutyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (4-ethoxybutyl) -4-piperidone

Basically 1- (4-ethoxybutyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-4-ethoxybutane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (4-ethoxybutyl) -4-piperidone oxime

Basically 1- (4-ethoxybutyl) -4-piperidone from 1- (4-ethoxybutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (4-ethoxybutyl) piperidine

Basically 4-amino-1- (4-ethoxybutyl) piperidine was prepared from 1- (4-ethoxybutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (4-ethoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-ethoxybutyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (4-ethoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-ethoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (4-ethoxy) butyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-ethoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 74

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-propoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-propoxybutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-propoxybutyl) piperidine

Basically 4-carboxamide-1- (4-propoxybutyl) piperidine was obtained from isonifecottamide and 1-chloro-4-propoxybutane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (4-propoxybutyl) piperidine

Basically 4-amino-1- (4-propoxybutyl) piperidine from 4-carboxamide-1- (4-propoxybutyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (4-propoxybutyl) -4-piperidone

Basically 1- (4-propoxybutyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-4-propoxybutane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (4-propoxybutyl) -4-piperidone oxime

Basically 1- (4-propoxybutyl) -4-piperidone from 1- (4-propoxybutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (4-propoxybutyl) piperidine

Basically 4-amino-1- (4-propoxybutyl) piperidine was prepared from 1- (4-propoxybutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (4-propoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-propoxybutyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (4-propoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-propoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (4-propoxy) butyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-propoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 75

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-butoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-butoxybutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-butoxybutyl) piperidine

Basically 4-carboxamide-1- (4-butoxybutyl) piperidine was obtained from isonifecottamide and 1-chloro-4-butoxybutane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (4-butoxybutyl) piperidine

Basically 4-amino-1- (4-butoxybutyl) piperidine from 4-carboxamide-1- (4-butoxybutyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (4-butoxybutyl) -4-piperidone

Basically 1- (4-butoxybutyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-4-butoxybutane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (4-butoxybutyl) -4-piperidone oxime

Basically 1- (4-butoxybutyl) -4-piperidone from 1- (4-butoxybutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (4-butoxybutyl) piperidine

Basically 4-amino-1- (4-butoxybutyl) piperidine was prepared from 1- (4-butoxybutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (4-butoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-butoxybutyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (4-butoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-butoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (4-butoxy) butyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-butoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 76

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-benzyloxy) butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-benzyloxybutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-benzyloxybutyl) piperidine

Basically 4-carboxamide-1- (4-benzyloxybutyl) piperidine was obtained from isonifecottamide and 1-chloro-4-benzyloxybutane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (4-benzyloxybutyl) piperidine

Basically 4-amino-1- (4-benzyloxybutyl) piperidine from 4-carboxamide-1- (4-benzyloxybutyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (4-benzyloxybutyl) -4-piperidone

Basically 1- (4-benzyloxybutyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-4-benzyloxybutane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (4-benzyloxybutyl) -4-piperidone oxime

Basically 1- (4-benzyloxybutyl) -4-piperidone from 1- (4-benzyloxybutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (4-benzyloxybutyl) piperidine

Basically 4-amino-1- (4-benzyloxybutyl) piperidine was prepared from 1- (4-benzyloxybutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (4-benzyloxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-benzyloxybutyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (4-benzyloxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-benzyloxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (4-benzyloxy) butyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-benzyloxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 77

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (2-phenylethyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4- (2-phenylethyleneoxy) butyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4- (2-phenylethyleneoxy) butyl) piperidine

Basically 4-carboxamide-1- (4- (2-) from isonifecottamide and 1-chloro-4- (2-phenylethyleneoxy) butane as described in Example 38, Scheme B, step a. Phenylethyleneoxy) butyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4- (2-phenylethyleneoxy) butyl) piperidine

Basically 4-amino-1- (4- (2) from 4-carboxamide-1- (4- (2-phenylethyleneoxy) butyl) piperidine as described in Example 38, Scheme B, step b. -Phenylethyleneoxy) butyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4- (2-phenylethyleneoxy) butyl) -4-piperidone

Basically 1- (4- (2-phenylethyleneoxy) butyl)-from 4-piperidone and 1-chloro-4- (2-phenylethyleneoxy) butane as described in Example 38, Scheme C, step a 4-piperidone was prepared.

Scheme C, step b: 1- (4- (2-phenylethyleneoxy) butyl) -4-piperidone oxime

Basically 1- (4- (2-phenyl) from 1- (4- (2-phenylethyleneoxy) butyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Ethyleneoxy) butyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4- (2-phenylethyleneoxy) butyl) piperidine

Basically 4-amino-1- (4- (2-phenylethylene) from 1- (4- (2-phenylethyleneoxy) butyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Oxy) butyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4- (2-phenylethyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4- (2-phenylethyleneoxy) butyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (4- (2-phenylethyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (2-phenylethyleneoxy) butyl) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (4- (2-phenylethyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (2-phenylethyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 78

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (3-phenylpropyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4- (3-phenylpropyleneoxy) butyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4- (3-phenylpropyleneoxy) butyl) piperidine

Basically 4-carboxamide-1- (4- (3-) from isonifecottamide and 1-chloro-4- (3-phenylpropyleneoxy) butane as described in Example 38, Scheme B, step a. Phenylpropyleneoxy) butyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4- (3-phenylpropyleneoxy) butyl) piperidine

Basically 4-amino-1- (4- (3) from 4-carboxamide-1- (4- (3-phenylpropyleneoxy) butyl) piperidine as described in Example 38, Scheme B, step b. -Phenylpropyleneoxy) butyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4- (3-phenylpropyleneoxy) butyl) -4-piperidone

Basically 1- (4- (3-phenylpropyleneoxy) butyl)-from 4-piperidone and 1-chloro-4- (3-phenylpropyleneoxy) butane as described in Example 38, Scheme C, step a 4-piperidone was prepared.

Scheme C, step b: 1- (4- (3-phenylpropyleneoxy) butyl) -4-piperidone oxime

Basically 1- (4- (3-phenyl) from 1- (4- (3-phenylpropyleneoxy) butyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Propyleneoxy) butyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4- (3-phenylpropyleneoxy) butyl) piperidine

Basically 4-amino-1- (4- (3-phenylpropylene) from 1- (4- (3-phenylpropyleneoxy) butyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Oxy) butyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4- (3-phenylpropyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4- (3-phenylpropyleneoxy) butyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (4- (3-phenylpropyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (3-phenylpropyleneoxy) butyl) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (4- (3-phenylpropyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (3-phenylpropyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 79

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (4-phenylbutyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4- (4-phenylbutyleneoxy) butyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4- (4-phenylbutyleneoxy) butyl) piperidine

Basically 4-carboxamide-1- (4- (4) from isonifecottamide and 1-chloro-4- (4-phenylbutyleneoxy) butane as described in Example 38, Scheme B, step a -Phenylbutyleneoxy) butyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4- (4-phenylbutyleneoxy) butyl) piperidine

Basically 4-amino-1- (4- () from 4-carboxamide-1- (4- (4-phenylbutyleneoxy) butyl) piperidine as described in Example 38, Scheme B, step b. 4-phenylbutyleneoxy) butyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4- (4-phenylbutyleneoxy) butyl) -4-piperidone

Basically 1- (4- (4-phenylbutyleneoxy) butyl from 4-piperidone and 1-chloro-4- (4-phenylbutyleneoxy) butane as described in Example 38, Scheme C, step a ) -4-piperidone was prepared.

Scheme C, step b: 1- (4- (4-phenylbutyleneoxy) butyl) -4-piperidone oxime

Basically 1- (4- (4-) from 1- (4- (4-phenylbutyleneoxy) butyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Phenylbutyleneoxy) butyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4- (4-phenylbutyleneoxy) butyl) piperidine

Basically 4-amino-1- (4- (4-phenyl) from 1- (4- (4-phenylbutyleneoxy) butyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Butyleneoxy) butyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4- (4-phenylbutyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4- (4-phenylbutyleneoxy) butyl) piperidine as described in Example 1, Scheme A, step b and 2-Chloro-6- [4- (1- (4- (4-phenylbutyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine was prepared from triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (4-phenylbutyleneoxy) butyl) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (4- (4-phenylbutyleneoxy) butyl) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (4-phenylbutyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 80

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-hydroxypentyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-hydroxypentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-hydroxypentyl) piperidine

Basically 4-carboxamide-1- (5-hydroxypentyl) piperidine was obtained from isonifecottamide and 1-chloro-5-hydroxypentane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (5-hydroxypentyl) piperidine

Basically 4-amino-1- (5-hydroxypentyl) piperidine from 4-carboxamide-1- (5-hydroxypentyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (5-hydroxypentyl) -4-piperidone

Basically 1- (5-hydroxypentyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-5-hydroxypentane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (5-hydroxypentyl) -4-piperidone oxime

Basically 1- (5-hydroxypentyl) -4-piperidone from 1- (5-hydroxypentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (5-hydroxypentyl) piperidine

Basically 4-amino-1- (5-hydroxypentyl) piperidine was prepared from 1- (5-hydroxypentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (5-hydroxypentyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-hydroxypentyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (5-hydroxypentyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-hydroxypentyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (5-hydroxypentyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-hydroxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 81

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-methoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-methoxypentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-methoxypentyl) piperidine

Basically 4-carboxamide-1- (5-methoxypentyl) piperidine was obtained from isonifecottamide and 1-chloro-5-methoxypentane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (5-methoxypentyl) piperidine

Basically 4-amino-1- (5-methoxypentyl) piperidine from 4-carboxamide-1- (5-methoxypentyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (5-methoxypentyl) -4-piperidone

Basically 1- (5-methoxypentyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-5-methoxypentane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (5-methoxypentyl) -4-piperidone oxime

Basically 1- (5-methoxypentyl) -4-piperidone from 1- (5-methoxypentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (5-methoxypentyl) piperidine

Basically 4-amino-1- (5-methoxypentyl) piperidine was prepared from 1- (5-methoxypentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (5-methoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-methoxypentyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (5-methoxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-methoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (5-methoxypentyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-methoxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 82

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-ethoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-ethoxypentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-ethoxypentyl) piperidine

Basically 4-carboxamide-1- (5-ethoxypentyl) piperidine was obtained from isonifecottamide and 1-chloro-5-ethoxypentane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (5-ethoxypentyl) piperidine

Basically 4-amino-1- (5-ethoxypentyl) piperidine from 4-carboxamide-1- (5-ethoxypentyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (5-ethoxypentyl) -4-piperidone

Basically 1- (5-ethoxypentyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-5-ethoxypentane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (5-ethoxypentyl) -4-piperidone oxime

Basically 1- (5-ethoxypentyl) -4-piperidone from 1- (5-ethoxypentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (5-ethoxypentyl) piperidine

Basically 4-amino-1- (5-ethoxypentyl) piperidine was prepared from 1- (5-ethoxypentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (5-ethoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-ethoxypentyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (5-ethoxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-ethoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (5-ethoxypentyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-ethoxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 83

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-propoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-propoxypentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-propoxypentyl) piperidine

Basically 4-carboxamide-1- (5-propoxypentyl) piperidine was obtained from isonifecottamide and 1-chloro-5-propoxypentane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (5-propoxypentyl) piperidine

Basically 4-amino-1- (5-propoxypentyl) piperidine from 4-carboxamide-1- (5-propoxypentyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (5-propoxypentyl) -4-piperidone

Basically 1- (5-propoxypentyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-5-propoxypentane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (5-propoxypentyl) -4-piperidone oxime

Basically 1- (5-propoxypentyl) -4-piperidone from 1- (5-propoxypentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (5-propoxypentyl) piperidine

Basically 4-amino-1- (5-propoxypentyl) piperidine was prepared from 1- (5-propoxypentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (5-propoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-propoxypentyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (5-propoxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-propoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (5-propoxypentyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-propoxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 84

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-butoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-butoxypentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-butoxypentyl) piperidine

Basically 4-carboxamide-1- (5-butoxypentyl) piperidine was obtained from isonipecottamide and 1-chloro-5-butoxypentane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (5-butoxypentyl) piperidine

Basically 4-amino-1- (5-butoxypentyl) piperidine from 4-carboxamide-1- (5-butoxypentyl) piperidine as described in Example 38, Scheme B, step b Was prepared.

Method 2:

Scheme C, step a: 1- (5-butoxypentyl) -4-piperidone

Basically 1- (5-butoxypentyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-5-butoxypentane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (5-butoxypentyl) -4-piperidone oxime

Basically 1- (5-butoxypentyl) -4-piperidone from 1- (5-butoxypentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (5-butoxypentyl) piperidine

Basically 4-amino-1- (5-butoxypentyl) piperidine was prepared from 1- (5-butoxypentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (5-butoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-butoxypentyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (5-butoxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-butoxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (5-butoxypentyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-butoxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 85

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-benzyloxypentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-benzyloxypentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-benzyloxypentyl) piperidine

Basically 4-carboxamide-1- (5-benzyloxypentyl) piperidine was obtained from isonifecottamide and 1-chloro-5-benzyloxypentane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (5-benzyloxypentyl) piperidine

Basically 4-amino-1- (5-benzyloxypentyl) piperidine from 4-carboxamide-1- (5-benzyloxypentyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (5-benzyloxypentyl) -4-piperidone

Basically 1- (5-benzyloxypentyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-5-benzyloxypentane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (5-benzyloxypentyl) -4-piperidone oxime

Basically 1- (5-benzyloxypentyl) -4-piperidone from 1- (5-benzyloxypentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (5-benzyloxypentyl) piperidine

Basically 4-amino-1- (5-benzyloxypentyl) piperidine was prepared from 1- (5-benzyloxypentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (5-benzyloxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-benzyloxypentyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (5-benzyloxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-benzyloxypentyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (5-benzyloxypentyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-benzyloxypentyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 86

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (2-phenylethyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5- (2-phenylethyleneoxy) pentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5- (2-phenylethyleneoxy) pentyl) piperidine

Basically 4-carboxamide-1- (5- (2-) from isonifecottamide and 1-chloro-5- (2-phenylethyleneoxy) pentane as described in Example 38, Scheme B, step a. Phenylethyleneoxy) pentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5- (2-phenylethyleneoxy) pentyl) piperidine

Basically 4-amino-1- (5- (2) from 4-carboxamide-1- (5- (2-phenylethyleneoxy) pentyl) piperidine as described in Example 38, Scheme B, step b. -Phenylethyleneoxy) pentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5- (2-phenylethyleneoxy) pentyl) -4-piperidone

Basically 1- (5- (2-phenylethyleneoxy) pentyl)-from 4-piperidone and 1-chloro-5- (2-phenylethyleneoxy) pentane as described in Example 38, Scheme C, step a 4-piperidone was prepared.

Scheme C, step b: 1- (5- (2-phenylethyleneoxy) pentyl) -4-piperidone oxime

Basically 1- (5- (2-phenyl) from 1- (5- (2-phenylethyleneoxy) pentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Ethyleneoxy) pentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5- (2-phenylethyleneoxy) pentyl) piperidine

Basically 4-amino-1- (5- (2-phenylethylene) from 1- (5- (2-phenylethyleneoxy) pentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c Oxy) pentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5- (2-phenylethyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5- (2-phenylethyleneoxy) pentyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (5- (2-phenylethyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (2-phenylethyleneoxy) pentyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5- (2-phenylethyleneoxy) pentyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (2-phenylethyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 87

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (3-phenylpropyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5- (3-phenylpropyleneoxy) pentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5- (3-phenylpropyleneoxy) pentyl) piperidine

Basically 4-carboxamide-1- (5- (3-) from isonifecottamide and 1-chloro-5- (3-phenylpropyleneoxy) pentane as described in Example 38, Scheme B, step a. Phenylpropyleneoxy) pentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5- (3-phenylpropyleneoxy) pentyl) piperidine

Basically 4-amino-1- (5- (3) from 4-carboxamide-1- (5- (3-phenylpropyleneoxy) pentyl) piperidine as described in Example 38, Scheme B, step b. -Phenylpropyleneoxy) pentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5- (3-phenylpropyleneoxy) pentyl) -4-piperidone

Basically 1- (5- (3-phenylpropyleneoxy) pentyl)-from 4-piperidone and 1-chloro-5- (3-phenylpropyleneoxy) pentane as described in Example 38, Scheme C, step a 4-piperidone was prepared.

Scheme C, step b: 1- (5- (3-phenylpropyleneoxy) pentyl) -4-piperidone oxime

Basically 1- (5- (3-phenyl) from 1- (5- (3-phenylpropyleneoxy) pentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Propyleneoxy) pentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5- (3-phenylpropyleneoxy) pentyl) piperidine

Basically 4-amino-1- (5- (3-phenylpropylene) from 1- (5- (3-phenylpropyleneoxy) pentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Oxy) pentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5- (3-phenylpropyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5- (3-phenylpropyleneoxy) pentyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (5- (3-phenylpropyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (3-phenylpropyleneoxy) pentyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5- (3-phenylpropyleneoxy) pentyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (3-phenylpropyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 88

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (4-phenylbutyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5- (4-phenylbutyleneoxy) pentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5- (4-phenylbutyleneoxy) pentyl) piperidine

Basically 4-carboxamide-1- (5- (4) from isonifecottamide and 1-chloro-5- (4-phenylbutyleneoxy) pentane as described in Example 38, Scheme B, step a -Phenylbutyleneoxy) pentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5- (4-phenylbutyleneoxy) pentyl) piperidine

Basically 4-amino-1- (5- () from 4-carboxamide-1- (5- (4-phenylbutyleneoxy) pentyl) piperidine as described in Example 38, Scheme B, step b. 4-phenylbutyleneoxy) pentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5- (4-phenylbutyleneoxy) pentyl) -4-piperidone

Basically 1- (5- (4-phenylbutyleneoxy) pentyl from 4-piperidone and 1-chloro-5- (4-phenylbutyleneoxy) pentane as described in Example 38, Scheme C, step a ) -4-piperidone was prepared.

Scheme C, step b: 1- (5- (4-phenylbutyleneoxy) pentyl) -4-piperidone oxime

Basically 1- (5- (4-) from 1- (5- (4-phenylbutyleneoxy) pentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Phenylbutyleneoxy) pentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5- (4-phenylbutyleneoxy) pentyl) piperidine

Basically 4-amino-1- (5- (4-phenyl) from 1- (5- (4-phenylbutyleneoxy) pentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Butyleneoxy) pentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5- (4-phenylbutyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5- (4-phenylbutyleneoxy) pentyl) piperidine as described in Example 1, Scheme A, step b and 2-Chloro-6- [4- (1- (5- (4-phenylbutyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine was prepared from triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (4-phenylbutyleneoxy) pentyl)) piperidinylamino] -9 Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5- (4-phenylbutyleneoxy) pentyl)) piperidinylamino] -9-cyclo as described in Example 1, Scheme A, step c 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (4-phenylbutyleneoxy) pentyl)) piperidinylamino] -9-cyclopentyl from pentylpurine Purine was prepared.

Example 89

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-hydroxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (6-hydroxyhexyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (6-hydroxyhexyl) piperidine

Basically, 4-carboxamide-1- (6-hydroxyhexyl) piperidine was prepared from isonifecottamide and 6-chloro-1-hexanol as described in Example 38, Scheme B, step a. It was.

Scheme B, step b: 4-amino-1- (6-hydroxyhexyl) piperidine

Basically 4-amino-1- (6-hydroxyhexyl) piperidine from 4-carboxamide-1- (6-hydroxyhexyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (6-hydroxyhexyl) -4-piperidone

Basically 1- (6-hydroxyhexyl) -4-piperidone was prepared from 4-piperidone and 6-chloro-1-hexanol as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (6-hydroxyhexyl) -4-piperidone oxime

Basically 1- (6-hydroxyhexyl) -4-piperidone from 1- (6-hydroxyhexyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (6-hydroxyhexyl) piperidine

Basically 4-amino-1- (6-hydroxyhexyl) piperidine was prepared from 1- (6-hydroxyhexyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (6-hydroxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (6-hydroxyhexyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (6-hydroxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-hydroxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (6-hydroxy) hexyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-hydroxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 90

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-methoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (6-methoxyhexyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (6-methoxyhexyl) piperidine

Basically 4-carboxamide-1- (6-methoxyhexyl) piperidine was obtained from isonipecottamide and 1-chloro-6-methoxyhexane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (6-methoxyhexyl) piperidine

Basically 4-amino-1- (6-methoxyhexyl) piperidine from 4-carboxamide-1- (6-methoxyhexyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (6-methoxyhexyl) -4-piperidone

Basically 1- (6-methoxyhexyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-6-methoxyhexane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (6-methoxyhexyl) -4-piperidone oxime

Basically 1- (6-methoxyhexyl) -4-piperidone from 1- (6-methoxyhexyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (6-methoxyhexyl) piperidine

Basically 4-amino-1- (6-methoxyhexyl) piperidine was prepared from 1- (6-methoxyhexyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (6-methoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (6-methoxyhexyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (6-methoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-methoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (6-methoxy) hexyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-methoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 91

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-ethoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (6-ethoxyhexyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (6-ethoxyhexyl) piperidine

Basically 4-carboxamide-1- (6-ethoxyhexyl) piperidine was obtained from isonipecottamide and 1-chloro-6-ethoxyhexane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (6-ethoxyhexyl) piperidine

Basically 4-amino-1- (6-ethoxyhexyl) piperidine from 4-carboxamide-1- (6-ethoxyhexyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (6-ethoxyhexyl) -4-piperidone

Basically 1- (6-ethoxyhexyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-6-ethoxyhexane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (6-ethoxyhexyl) -4-piperidone oxime

Basically 1- (6-ethoxyhexyl) -4-piperidone from 1- (6-ethoxyhexyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (6-ethoxyhexyl) piperidine

Basically 4-amino-1- (6-ethoxyhexyl) piperidine was prepared from 1- (6-ethoxyhexyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (6-ethoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (6-ethoxyhexyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (6-ethoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-ethoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (6-ethoxy) hexyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-ethoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 92

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-propoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (6-propoxyhexyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (6-propoxyhexyl) piperidine

Basically 4-carboxamide-1- (6-propoxyhexyl) piperidine was obtained from isonipecottamide and 1-chloro-6-propoxyhexane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (6-propoxyhexyl) piperidine

Basically 4-amino-1- (6-propoxyhexyl) piperidine from 4-carboxamide-1- (6-propoxyhexyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (6-propoxyhexyl) -4-piperidone

Basically 1- (6-propoxyhexyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-6-propoxyhexane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (6-propoxyhexyl) -4-piperidone oxime

Basically 1- (6-propoxyhexyl) -4-piperidone from 1- (6-propoxyhexyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (6-propoxyhexyl) piperidine

Basically 4-amino-1- (6-propoxyhexyl) piperidine was prepared from 1- (6-propoxyhexyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (6-propoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (6-propoxyhexyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (6-propoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-propoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (6-propoxy) hexyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-propoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 93

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-butoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (6-butoxyhexyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (6-butoxyhexyl) piperidine

Basically 4-carboxamide-1- (6-butoxyhexyl) piperidine was obtained from isonipecottamide and 1-chloro-6-butoxyhexane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (6-butoxyhexyl) piperidine

Basically 4-amino-1- (6-butoxyhexyl) piperidine from 4-carboxamide-1- (6-butoxyhexyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (6-butoxyhexyl) -4-piperidone

Basically 1- (6-butoxyhexyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-6-butoxyhexane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (6-butoxyhexyl) -4-piperidone oxime

Basically 1- (6-butoxyhexyl) -4-piperidone from 1- (6-butoxyhexyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (6-butoxyhexyl) piperidine

Basically 4-amino-1- (6-butoxyhexyl) piperidine was prepared from 1- (6-butoxyhexyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (6-butoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (6-butoxyhexyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (6-butoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-butoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (6-butoxy) hexyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-butoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 94

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-benzyloxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (6-benzyloxyhexyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (6-benzyloxyhexyl) piperidine

Basically 4-carboxamide-1- (6-benzyloxyhexyl) piperidine was obtained from isonipecottamide and 1-chloro-6-benzyloxyhexane as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (6-benzyloxyhexyl) piperidine

Basically 4-amino-1- (6-benzyloxyhexyl) piperidine from 4-carboxamide-1- (6-benzyloxyhexyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Method 2:

Scheme C, step a: 1- (6-benzyloxyhexyl) -4-piperidone

Basically 1- (6-benzyloxyhexyl) -4-piperidone was prepared from 4-piperidone and 1-chloro-6-benzyloxyhexane as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (6-benzyloxyhexyl) -4-piperidone oxime

Basically 1- (6-benzyloxyhexyl) -4-piperidone from 1- (6-benzyloxyhexyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. An oxime was prepared.

Scheme C, step c: 4-amino-1- (6-benzyloxyhexyl) piperidine

Basically 4-amino-1- (6-benzyloxyhexyl) piperidine was prepared from 1- (6-benzyloxyhexyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. .

Scheme A, step b: 2-chloro-6- [4- (1- (6-benzyloxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (6-benzyloxyhexyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (6-benzyloxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-benzyloxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (6-benzyloxy) hexyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-benzyloxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 95

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (2-phenylethyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (6- (2-phenylethyleneoxy) hexyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (6- (2-phenylethyleneoxy) hexyl) piperidine

Basically 4-carboxamide-1- (6- (2-) from isonifecottamide and 1-chloro-6- (2-phenylethyleneoxy) hexane as described in Example 38, Scheme B, step a. Phenylethyleneoxy) hexyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (6- (2-phenylethyleneoxy) hexyl) piperidine

Basically 4-amino-1- (6- (2) from 4-carboxamide-1- (6- (2-phenylethyleneoxy) hexyl) piperidine as described in Example 38, Scheme B, step b. -Phenylethyleneoxy) hexyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (6- (2-phenylethyleneoxy) hexyl) -4-piperidone

Basically 1- (6- (2-phenylethyleneoxy) hexyl)-from 4-piperidone and 1-chloro-6- (2-phenylethyleneoxy) hexane as described in Example 38, Scheme C, step a 4-piperidone was prepared.

Scheme C, step b: 1- (6- (2-phenylethyleneoxy) hexyl) -4-piperidone oxime

Basically 1- (6- (2-phenyl) from 1- (6- (2-phenylethyleneoxy) hexyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Ethyleneoxy) hexyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (6- (2-phenylethyleneoxy) hexyl) piperidine

Basically 4-amino-1- (6- (2-phenylethylene) from 1- (6- (2-phenylethyleneoxy) hexyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Oxy) hexyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (6- (2-phenylethyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (6- (2-phenylethyleneoxy) hexyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (6- (2-phenylethyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (2-phenylethyleneoxy) hexyl) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (6- (2-phenylethyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (2-phenylethyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 96

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (3-phenylpropyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (6- (3-phenylpropyleneoxy) hexyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (6- (3-phenylpropyleneoxy) hexyl) piperidine

Basically 4-carboxamide-1- (6- (3-) from isonifecottamide and 1-chloro-6- (3-phenylpropyleneoxy) hexane as described in Example 38, Scheme B, step a. Phenylpropyleneoxy) hexyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (6- (3-phenylpropyleneoxy) hexyl) piperidine

Basically 4-amino-1- (6- (3) from 4-carboxamide-1- (6- (3-phenylpropyleneoxy) hexyl) piperidine as described in Example 38, Scheme B, step b. -Phenylpropyleneoxy) hexyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (6- (3-phenylpropyleneoxy) hexyl) -4-piperidone

Basically 1- (6- (3-phenylpropyleneoxy) hexyl)-from 4-piperidone and 1-chloro-6- (3-phenylpropyleneoxy) hexane as described in Example 38, Scheme C, step a. 4-piperidone was prepared.

Scheme C, step b: 1- (6- (3-phenylpropyleneoxy) hexyl) -4-piperidone oxime

Basically 1- (6- (3-phenyl) from 1- (6- (3-phenylpropyleneoxy) hexyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Propyleneoxy) hexyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (6- (3-phenylpropyleneoxy) hexyl) piperidine

Basically 4-amino-1- (6- (3-phenylpropylene) from 1- (6- (3-phenylpropyleneoxy) hexyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Oxy) hexyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (6- (3-phenylpropyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (6- (3-phenylpropyleneoxy) hexyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (6- (3-phenylpropyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (3-phenylpropyleneoxy) hexyl) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (6- (3-phenylpropyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (3-phenylpropyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 97

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (4-phenylbutyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (6- (4-phenylbutyleneoxy) hexyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (6- (4-phenylbutyleneoxy) hexyl) piperidine

Basically 4-carboxamide-1- (6- (4) from isonifecottamide and 1-chloro-6- (4-phenylbutyleneoxy) hexane as described in Example 38, Scheme B, step a. -Phenylbutyleneoxy) hexyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (6- (4-phenylbutyleneoxy) hexyl) piperidine

Basically 4-amino-1- (6- (from 4-carboxamide-1- (6- (4-phenylbutyleneoxy) hexyl) piperidine as described in Example 38, Scheme B, step b. 4-phenylbutyleneoxy) hexyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (6- (4-phenylbutyleneoxy) hexyl) -4-piperidone

Basically 1- (6- (4-phenylbutyleneoxy) hexyl from 4-piperidone and 1-chloro-6- (4-phenylbutyleneoxy) hexane as described in Example 38, Scheme C, step a ) -4-piperidone was prepared.

Scheme C, step b: 1- (6- (4-phenylbutyleneoxy) hexyl) -4-piperidone oxime

Basically 1- (6- (4-) from 1- (6- (4-phenylbutyleneoxy) hexyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Phenylbutyleneoxy) hexyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (6- (4-phenylbutyleneoxy) hexyl) piperidine

Basically 4-amino-1- (6- (4-phenyl) from 1- (6- (4-phenylbutyleneoxy) hexyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Butyleneoxy) hexyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (6- (4-phenylbutyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (6- (4-phenylbutyleneoxy) hexyl) piperidine as described in Example 1, Scheme A, step b and 2-Chloro-6- [4- (1- (6- (4-phenylbutyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine was prepared from triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (4-phenylbutyleneoxy) hexyl) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (6- (4-phenylbutyleneoxy) hexyl) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (4-phenylbutyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine from purine Prepared.

Example 98

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (allyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (allyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (allyl) piperidine

4-Carboxamide-1- (allyl) piperidine was prepared essentially from isonipecottamide and allyl chloride as described in Example 38, Scheme B, step a.

Scheme B, step b: 4-amino-1- (allyl) piperidine

Basically 4-amino-1- (allyl) piperidine was prepared from 4-carboxamide-1- (allyl) piperidine as described in Example 38, Scheme B, step b.

Method 2:

Scheme C, step a: 1- (allyl) -4-piperidone

Basically 1- (allyl) -4-piperidone was prepared from 4-piperidone and allyl chloride as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (allyl) -4-piperidone oxime

Basically 1- (allyl) -4-piperidone oxime was prepared from 1- (allyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b.

Scheme C, step c: 4-amino-1- (allyl) piperidine

Basically 4-amino-1- (allyl) piperidine was prepared from 1- (allyl) -4-piperidone oxime as described in Example 38, Scheme C, step c.

Scheme A, step b: 2-chloro-6- [4- (1- (allyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (allyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. [4- (1- (allyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (allyl) piperidinylamino] -9-cyclopentylpurine

Basically 2- [trans- (4- from 2-chloro-6- [4- (1- (allyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Aminocyclohexyl) amino] -6- [4- (1- (allyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 99

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (2-hydroxyethyleneoxy) ethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2- (2-hydroxyethyleneoxy) ethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2- (2-hydroxyethyleneoxy) ethyl) piperidine

Basically 4-carboxamide-1- (2- (2-hydroxyethyleneoxy) from isonifecottamide and 2- (2-chloroethoxy) ethanol as described in Example 38, Scheme B, step a Ethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2- (2-hydroxyethyleneoxy) ethyl) piperidine

Basically 4-amino-1- (2- () from 4-carboxamide-1- (2- (2-hydroxyethyleneoxy) ethyl) piperidine as described in Example 38, Scheme B, step b. 2-hydroxyethyleneoxy) ethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2- (2-hydroxyethyleneoxy) ethyl) -4-piperidone

Basically 1- (2- (2-hydroxyethyleneoxy) ethyl) -4-pi from 4-piperidone and 2- (2-chloroethoxy) ethanol as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (2- (2-hydroxyethyleneoxy) ethyl) -4-piperidone oxime

Basically 1- (2- (2-) from 1- (2- (2-hydroxyethyleneoxy) ethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Hydroxyethyleneoxy) ethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2- (2-hydroxyethyleneoxy) ethyl) piperidine

Basically 4-amino-1- (2- (2-hydride) from 1- (2- (2-hydroxyethyleneoxy) ethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Oxyethyleneoxy) ethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2- (2-hydroxyethyleneoxy) ethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2- (2-hydroxyethyleneoxy) ethyl) piperidine as described in Example 1, Scheme A, step b and 2-Chloro-6- [4- (1- (2- (2-hydroxyethyleneoxy) ethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (2-hydroxyethyleneoxy) ethyl)) piperidinylamino] -9 Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2- (2-hydroxyethyleneoxy) ethyl)) piperidinylamino] -9-cyclo as described in Example 1, Scheme A, step c 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (2-hydroxyethyleneoxy) ethyl)) piperidinylamino] -9-cyclopentyl from pentylpurine Purine was prepared.

Example 100

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dimethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-N, N-dimethylaminoethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-N, N-dimethylaminoethyl) piperidine

Basically 4-carboxamide-1- (2-N, N-dimethylaminoethyl from isonipecottamide and 2-N, N-dimethylaminoethyl chloride as described in Example 38, Scheme B, step a Piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-N, N-dimethylaminoethyl) piperidine

Basically 4-amino-1- (2-N, N from 4-carboxamide-1- (2-N, N-dimethylaminoethyl) piperidine as described in Example 38, Scheme B, step b. -Dimethylaminoethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2-N, N-dimethylaminoethyl) -4-piperidone

Basically 1- (2-N, N-dimethylaminoethyl) -4-piperidone was obtained from 4-piperidone and 2-N, N-dimethylaminoethyl chloride as described in Example 38, Scheme C, step a. Prepared.

Scheme C, step b: 1- (2-N, N-dimethylaminoethyl) -4-piperidone oxime

Basically 1- (2-N, N-dimethyl from 1- (2-N, N-dimethylaminoethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Aminoethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-N, N-dimethylaminoethyl) piperidine

Basically 4-amino-1- (2-N, N-dimethylamino from 1- (2-N, N-dimethylaminoethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Ethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-N, N-dimethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-N, N-dimethylaminoethyl) piperidine and triethyl as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- (1- (2-N, N-dimethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from the amine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dimethylaminoethyl)) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (2-N, N-dimethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dimethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 101

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dimethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-N, N-dimethylaminopropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-N, N-dimethylaminopropyl) piperidine

Basically 4-carboxamide-1- (3-N, N-dimethylaminopropyl) from isonipecottamide and 3-N, N-dimethylaminopropyl chloride as described in Example 38, Scheme B, step a. Piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-N, N-dimethylaminopropyl) piperidine

Basically 4-amino-1- (3-N, N from 4-carboxamide-1- (3-N, N-dimethylaminopropyl) piperidine as described in Example 38, Scheme B, step b. -Dimethylaminopropyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3-N, N-dimethylaminopropyl) -4-piperidone

Basically 1- (3-N, N-dimethylaminopropyl) -4-piperidone was obtained from 4-piperidone and 3-N, N-dimethylaminopropyl chloride as described in Example 38, Scheme C, step a. Prepared.

Scheme C, step b: 1- (3-N, N-dimethylaminopropyl) -4-piperidone oxime

Basically 1- (3-N, N-dimethyl from 1- (3-N, N-dimethylaminopropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Aminopropyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3-N, N-dimethylaminopropyl) piperidine

Basically 4-amino-1- (3-N, N-dimethylamino from 1- (3-N, N-dimethylaminopropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Propyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3-N, N-dimethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-N, N-dimethylaminopropyl) piperidine and triethyl as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- (1- (3-N, N-dimethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine was prepared from amines.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dimethylaminopropyl)) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (3-N, N-dimethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dimethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 102

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dimethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-N, N-dimethylaminobutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-N, N-dimethylaminobutyl) piperidine

Basically 4-carboxamide-1- (4-N, N-dimethylaminobutyl) from isonipecottamide and 3-N, N-dimethylaminobutyl chloride as described in Example 38, Scheme B, step a Piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-N, N-dimethylaminobutyl) piperidine

Basically 4-amino-1- (4-N, N from 4-carboxamide-1- (4-N, N-dimethylaminobutyl) piperidine as described in Example 38, Scheme B, step b. -Dimethylaminobutyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4-N, N-dimethylaminobutyl) -4-piperidone

Basically 1- (4-N, N-dimethylaminobutyl) -4-piperidone was obtained from 4-piperidone and 3-N, N-dimethylaminobutyl chloride as described in Example 38, Scheme C, step a. Prepared.

Scheme C, step b: 1- (4-N, N-dimethylaminobutyl) -4-piperidone oxime

Basically 1- (4-N, N-dimethyl from 1- (4-N, N-dimethylaminobutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Aminobutyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4-N, N-dimethylaminobutyl) piperidine

Basically 4-amino-1- (4-N, N-dimethylamino from 1- (4-N, N-dimethylaminobutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Butyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4-N, N-dimethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-N, N-dimethylaminobutyl) piperidine and triethyl as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- (1- (4-N, N-dimethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine was prepared from the amine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dimethylaminobutyl)) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (4-N, N-dimethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dimethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 103

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dimethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-N, N-dimethylaminopentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-N, N-dimethylaminopentyl) piperidine

Basically 4-carboxamide-1- (5-N, N-dimethylaminopentyl from isonifecottamide and 5-N, N-dimethylaminopentyl chloride as described in Example 38, Scheme B, step a Piperidine was prepared.

Scheme B, step b: 4-amino-1- (5-N, N-dimethylaminopentyl) piperidine

Basically 4-amino-1- (5-N, N from 4-carboxamide-1- (5-N, N-dimethylaminopentyl) piperidine as described in Example 38, Scheme B, step b. -Dimethylaminopentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5-N, N-dimethylaminopentyl) -4-piperidone

Basically 1- (5-N, N-dimethylaminopentyl) -4-piperidone was prepared from 4-piperidone and 5-N, N-dimethylaminopentyl chloride as described in Example 38, Scheme C, step a. Prepared.

Scheme C, step b: 1- (5-N, N-dimethylaminopentyl) -4-piperidone oxime

Basically 1- (5-N, N-dimethyl from 1- (5-N, N-dimethylaminopentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Aminopentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5-N, N-dimethylaminopentyl) piperidine

Basically 4-amino-1- (5-N, N-dimethylaminophen from 1- (5-N, N-dimethylaminopentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Til) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5-N, N-dimethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-N, N-dimethylaminopentyl) piperidine and triethyl as described in Example 1, Scheme A, step b. 2-chloro-6- [4- (1- (5-N, N-dimethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine was prepared from amines.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dimethylaminopentyl)) piperidinylamino] -9-cyclo Pentylpurine

Basically 2-chloro-6- [4- (1- (5-N, N-dimethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dimethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine was prepared from .

Example 104

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-diethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-N, N-diethylaminoethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-N, N-diethylaminoethyl) piperidine

Basically 4-carboxamide-1- (2-N, N-diethyl from isonipecottamide and 2-N, N-diethylaminoethyl chloride as described in Example 38, Scheme B, step a Aminoethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-N, N-diethylaminoethyl) piperidine

Basically 4-amino-1- (2-N, from 4-carboxamide-1- (2-N, N-diethylaminoethyl) piperidine as described in Example 38, Scheme B, step b. N-diethylaminoethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2-N, N-diethylaminoethyl) -4-piperidone

Basically 1- (2-N, N-diethylaminoethyl) -4-pi from 4-piperidone and 2-N, N-diethylaminoethyl chloride as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (2-N, N-diethylaminoethyl) -4-piperidone oxime

Basically 1- (2-N, N- from 1- (2-N, N-diethylaminoethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Diethylaminoethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-N, N-diethylaminoethyl) piperidine

Basically 4-amino-1- (2-N, N-di from 1- (2-N, N-diethylaminoethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Ethylaminoethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-N, N-diethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-N, N-diethylaminoethyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (2-N, N-diethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-diethylaminoethyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2-N, N-diethylaminoethyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From Purine 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-diethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 105

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-diethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-N, N-diethylaminopropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-N, N-diethylaminopropyl) piperidine

Basically 4-carboxamide-1- (3-N, N-diethyl from isonipecottamide and 3-N, N-diethylaminopropyl chloride as described in Example 38, Scheme B, step a Aminopropyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-N, N-diethylaminopropyl) piperidine

Basically 4-amino-1- (3-N, from 4-carboxamide-1- (3-N, N-diethylaminopropyl) piperidine as described in Example 38, Scheme B, step b. N-diethylaminopropyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3-N, N-diethylaminopropyl) -4-piperidone

Basically 1- (3-N, N-diethylaminopropyl) -4-pi from 4-piperidone and 3-N, N-diethylaminopropyl chloride as described in Example 38, Scheme C, step a. Peridone was prepared.

Scheme C, step b: 1- (3-N, N-diethylaminopropyl) -4-piperidone oxime

Basically 1- (3-N, N- from 1- (3-N, N-diethylaminopropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Diethylaminopropyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3-N, N-diethylaminopropyl) piperidine

Basically 4-amino-1- (3-N, N-di from 1- (3-N, N-diethylaminopropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Ethylaminopropyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3-N, N-diethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-N, N-diethylaminopropyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (3-N, N-diethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-diethylaminopropyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3-N, N-diethylaminopropyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-diethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 106

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-diethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-N, N-diethylaminobutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-N, N-diethylaminobutyl) piperidine

Basically 4-carboxamide-1- (4-N, N-diethyl from isonipecottamide and 4-N, N-diethylaminobutyl chloride as described in Example 38, Scheme B, step a Aminobutyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-N, N-diethylaminobutyl) piperidine

Basically 4-amino-1- (4-N, from 4-carboxamide-1- (4-N, N-diethylaminobutyl) piperidine as described in Example 38, Scheme B, step b. N-diethylaminobutyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4-N, N-diethylaminobutyl) -4-piperidone

Basically 1- (4-N, N-diethylaminobutyl) -4-pi from 4-piperidone and 4-N, N-diethylaminobutyl chloride as described in Example 38, Scheme C, step a. Peridone was prepared.

Scheme C, step b: 1- (4-N, N-diethylaminobutyl) -4-piperidone oxime

Basically 1- (4-N, N- from 1- (4-N, N-diethylaminobutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Diethylaminobutyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4-N, N-diethylaminobutyl) piperidine

Basically 4-amino-1- (4-N, N-di from 1- (4-N, N-diethylaminobutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Ethylaminobutyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4-N, N-diethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-N, N-diethylaminobutyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (4-N, N-diethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-diethylaminobutyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (4-N, N-diethylaminobutyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From Purine 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-diethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 107

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-diethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-N, N-diethylaminopentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-N, N-diethylaminopentyl) piperidine

Basically 4-carboxamide-1- (5-N, N-diethyl from isonifecottamide and 5-N, N-diethylaminopentyl chloride as described in Example 38, Scheme B, step a) Aminopentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5-N, N-diethylaminopentyl) piperidine

Basically 4-amino-1- (5-N, from 4-carboxamide-1- (5-N, N-diethylaminopentyl) piperidine as described in Example 38, Scheme B, step b. N-diethylaminopentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5-N, N-diethylaminopentyl) -4-piperidone

Basically 1- (5-N, N-diethylaminopentyl) -4-pi from 4-piperidone and 5-N, N-diethylaminopentyl chloride as described in Example 38, Scheme C, step a. Peridone was prepared.

Scheme C, step b: 1- (5-N, N-diethylaminopentyl) -4-piperidone oxime

Basically 1- (5-N, N- from 1- (5-N, N-diethylaminopentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Diethylaminopentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5-N, N-diethylaminopentyl) piperidine

Basically 4-amino-1- (5-N, N-di from 1- (5-N, N-diethylaminopentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Ethylaminopentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5-N, N-diethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-N, N-diethylaminopentyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (5-N, N-diethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-diethylaminopentyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5-N, N-diethylaminopentyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-diethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 108

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dipropylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-N, N-dipropylaminoethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-N, N-dipropylaminoethyl) piperidine

Basically 4-carboxamide-1- (2-N, N-dipropyl from isonifecottamide and 2-N, N-dipropylaminoethyl chloride as described in Example 38, Scheme B, step a Aminoethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-N, N-dipropylaminoethyl) piperidine

Basically 4-amino-1- (2-N, from 4-carboxamide-1- (2-N, N-dipropylaminoethyl) piperidine as described in Example 38, Scheme B, step b. N-dipropylaminoethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2-N, N-dipropylaminoethyl) -4-piperidone

Basically 1- (2-N, N-dipropylaminoethyl) -4-pi from 4-piperidone and 2-N, N-dipropylaminoethyl chloride as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (2-N, N-dipropylaminoethyl) -4-piperidone oxime

Basically 1- (2-N, N- from 1- (2-N, N-dipropylaminoethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dipropylaminoethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-N, N-dipropylaminoethyl) piperidine

Basically 4-amino-1- (2-N, N-di from 1- (2-N, N-dipropylaminoethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Propylaminoethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-N, N-dipropylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-N, N-dipropylaminoethyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (2-N, N-dipropylaminoethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dipropylaminoethyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2-N, N-dipropylaminoethyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dipropylaminoethyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 109

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dipropylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-N, N-dipropylaminopropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-N, N-dipropylaminopropyl) piperidine

Basically 4-carboxamide-1- (3-N, N-dipropyl from isonipecottamide and 3-N, N-dipropylaminopropyl chloride as described in Example 38, Scheme B, step a Aminopropyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-N, N-dipropylaminopropyl) piperidine

Basically 4-amino-1- (3-N, from 4-carboxamide-1- (3-N, N-dipropylaminopropyl) piperidine as described in Example 38, Scheme B, step b. N-dipropylaminopropyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3-N, N-dipropylaminopropyl) -4-piperidone

Basically 1- (3-N, N-dipropylaminopropyl) -4-pi from 4-piperidone and 3-N, N-dipropylaminopropyl chloride as described in Example 38, Scheme C, step a. Peridone was prepared.

Scheme C, step b: 1- (3-N, N-dipropylaminopropyl) -4-piperidone oxime

Basically 1- (3-N, N- from 1- (3-N, N-dipropylaminopropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dipropylaminopropyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3-N, N-dipropylaminopropyl) piperidine

Basically 4-amino-1- (3-N, N-di from 1- (3-N, N-dipropylaminopropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Propylaminopropyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3-N, N-dipropylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-N, N-dipropylaminopropyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (3-N, N-dipropylaminopropyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dipropylaminopropyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3-N, N-dipropylaminopropyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dipropylaminopropyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 110

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dipropylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-N, N-dipropylaminobutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-N, N-dipropylaminobutyl) piperidine

Basically 4-carboxamide-1- (4-N, N-dipropyl from isonifecottamide and 4-N, N-dipropylaminobutyl chloride as described in Example 38, Scheme B, step a Aminobutyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-N, N-dipropylaminobutyl) piperidine

Basically 4-amino-1- (4-N, from 4-carboxamide-1- (4-N, N-dipropylaminobutyl) piperidine as described in Example 38, Scheme B, step b. N-dipropylaminobutyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4-N, N-dipropylaminobutyl) -4-piperidone

Basically 1- (4-N, N-dipropylaminobutyl) -4-pi from 4-piperidone and 4-N, N-dipropylaminobutyl chloride as described in Example 38, Scheme C, step a. Peridone was prepared.

Scheme C, step b: 1- (4-N, N-dipropylaminobutyl) -4-piperidone oxime

Basically 1- (4-N, N- from 1- (4-N, N-dipropylaminobutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dipropylaminobutyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4-N, N-dipropylaminobutyl) piperidine

Basically 4-amino-1- (4-N, N-di from 1- (4-N, N-dipropylaminobutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Propylaminobutyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4-N, N-dipropylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-N, N-dipropylaminobutyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (4-N, N-dipropylaminobutyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dipropylaminobutyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (4-N, N-dipropylaminobutyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From Purine 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dipropylaminobutyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 111

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dipropylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-N, N-dipropylaminopentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-N, N-dipropylaminopentyl) piperidine

Basically 4-carboxamide-1- (5-N, N-dipropyl from isonifecottamide and 5-N, N-dipropylaminopentyl chloride as described in Example 38, Scheme B, step a Aminopentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5-N, N-dipropylaminopentyl) piperidine

Basically 4-amino-1- (5-N, from 4-carboxamide-1- (5-N, N-dipropylaminopentyl) piperidine as described in Example 38, Scheme B, step b. N-dipropylaminopentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5-N, N-dipropylaminopentyl) -4-piperidone

Basically 1- (5-N, N-dipropylaminopentyl) -4-pi from 4-piperidone and 5-N, N-dipropylaminopentyl chloride as described in Example 38, Scheme C, step a. Peridone was prepared.

Scheme C, step b: 1- (5-N, N-dipropylaminopentyl) -4-piperidone oxime

Basically 1- (5-N, N- from 1- (5-N, N-dipropylaminopentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dipropylaminopentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5-N, N-dipropylaminopentyl) piperidine

Basically 4-amino-1- (5-N, N-di from 1- (5-N, N-dipropylaminopentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Propylaminopentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5-N, N-dipropylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-N, N-dipropylaminopentyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (5-N, N-dipropylaminopentyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dipropylaminopentyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5-N, N-dipropylaminopentyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dipropylaminopentyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 112

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dibutylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-N, N-dibutylaminoethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-N, N-dibutylaminoethyl) piperidine

Basically 4-carboxamide-1- (2-N, N-dibutyl from isonipecottamide and 2-N, N-dibutylaminoethyl chloride as described in Example 38, Scheme B, step a Aminoethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-N, N-dibutylaminoethyl) piperidine

Basically 4-amino-1- (2-N, from 4-carboxamide-1- (2-N, N-dibutylaminoethyl) piperidine as described in Example 38, Scheme B, step b. N-dibutylaminoethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2-N, N-dibutylaminoethyl) -4-piperidone

Basically 1- (2-N, N-dibutylaminoethyl) -4-pi from 4-piperidone and 2-N, N-dibutylaminoethyl chloride as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (2-N, N-dibutylaminoethyl) -4-piperidone oxime

Basically 1- (2-N, N- from 1- (2-N, N-dibutylaminoethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dibutylaminoethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-N, N-dibutylaminoethyl) piperidine

Basically 4-amino-1- (2-N, N-di from 1- (2-N, N-dibutylaminoethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Butylaminoethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-N, N-dibutylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-N, N-dibutylaminoethyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (2-N, N-dibutylaminoethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dibutylaminoethyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2-N, N-dibutylaminoethyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From Purine 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dibutylaminoethyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 113

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dibutylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-N, N-dibutylaminopropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-N, N-dibutylaminopropyl) piperidine

Basically 4-carboxamide-1- (3-N, N-dibutyl from isonipecottamide and 3-N, N-dibutylaminopropyl chloride as described in Example 38, Scheme B, step a Aminopropyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-N, N-dibutylaminopropyl) piperidine

Basically 4-amino-1- (3-N, from 4-carboxamide-1- (3-N, N-dibutylaminopropyl) piperidine as described in Example 38, Scheme B, step b. N-dibutylaminopropyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3-N, N-dibutylaminopropyl) -4-piperidone

Basically 1- (3-N, N-dibutylaminopropyl) -4-pi from 4-piperidone and 3-N, N-dibutylaminopropyl chloride as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (3-N, N-dibutylaminopropyl) -4-piperidone oxime

Basically 1- (3-N, N- from 1- (3-N, N-dibutylaminopropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dibutylaminopropyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3-N, N-dibutylaminopropyl) piperidine

Basically 4-amino-1- (3-N, N-di from 1- (3-N, N-dibutylaminopropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Butylaminopropyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3-N, N-dibutylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-N, N-dibutylaminopropyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (3-N, N-dibutylaminopropyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dibutylaminopropyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3-N, N-dibutylaminopropyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dibutylaminopropyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 114

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dibutylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-N, N-dibutylaminobutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-N, N-dibutylaminobutyl) piperidine

Basically 4-carboxamide-1- (4-N, N-dibutyl from isonipecottamide and 4-N, N-dibutylaminobutyl chloride as described in Example 38, Scheme B, step a Aminobutyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-N, N-dibutylaminobutyl) piperidine

Basically 4-amino-1- (4-N, from 4-carboxamide-1- (4-N, N-dibutylaminobutyl) piperidine as described in Example 38, Scheme B, step b. N-dibutylaminobutyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4-N, N-dibutylaminobutyl) -4-piperidone

Basically 1- (4-N, N-dibutylaminobutyl) -4-pi from 4-piperidone and 4-N, N-dibutylaminobutyl chloride as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (4-N, N-dibutylaminobutyl) -4-piperidone oxime

Basically 1- (4-N, N- from 1- (4-N, N-dibutylaminobutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dibutylaminobutyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4-N, N-dibutylaminobutyl) piperidine

Basically 4-amino-1- (4-N, N-di from 1- (4-N, N-dibutylaminobutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Butylaminobutyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4-N, N-dibutylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-N, N-dibutylaminobutyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (4-N, N-dibutylaminobutyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dibutylaminobutyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (4-N, N-dibutylaminobutyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dibutylaminobutyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 115

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dibutylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-N, N-dibutylaminopentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-N, N-dibutylaminopentyl) piperidine

Basically 4-carboxamide-1- (5-N, N-dibutyl) from isonifecottamide and 5-N, N-dibutylaminopentyl chloride as described in Example 38, Scheme B, step a Aminopentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5-N, N-dibutylaminopentyl) piperidine

Basically 4-amino-1- (5-N, from 4-carboxamide-1- (5-N, N-dibutylaminopentyl) piperidine as described in Example 38, Scheme B, step b. N-dibutylaminopentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5-N, N-dibutylaminopentyl) -4-piperidone

Basically 1- (5-N, N-dibutylaminopentyl) -4-pi from 4-piperidone and 5-N, N-dibutylaminopentyl chloride as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (5-N, N-dibutylaminopentyl) -4-piperidone oxime

Basically 1- (5-N, N- from 1- (5-N, N-dibutylaminopentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dibutylaminopentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5-N, N-dibutylaminopentyl) piperidine

Basically 4-amino-1- (5-N, N-di from 1- (5-N, N-dibutylaminopentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Butylaminopentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5-N, N-dibutylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-N, N-dibutylaminopentyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (5-N, N-dibutylaminopentyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dibutylaminopentyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5-N, N-dibutylaminopentyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dibutylaminopentyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 116

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dibenzylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-N, N-dibenzylaminoethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-N, N-dibenzylaminoethyl) piperidine

Basically 4-carboxamide-1- (2-N, N-dibenzyl) from isonipecottamide and 2-N, N-dibenzylaminoethyl chloride as described in Example 38, Scheme B, step a Aminoethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-N, N-dibenzylaminoethyl) piperidine

Basically 4-amino-1- (2-N, from 4-carboxamide-1- (2-N, N-dibenzylaminoethyl) piperidine as described in Example 38, Scheme B, step b. N-dibenzylaminoethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2-N, N-dibenzylaminoethyl) -4-piperidone

Basically 1- (2-N, N-dibenzylaminoethyl) -4-pi from 4-piperidone and 2-N, N-dibenzylaminoethyl chloride as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (2-N, N-dibenzylaminoethyl) -4-piperidone oxime

Basically 1- (2-N, N- from 1- (2-N, N-dibenzylaminoethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dibenzylaminoethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-N, N-dibenzylaminoethyl) piperidine

Basically 4-amino-1- (2-N, N-di from 1- (2-N, N-dibenzylaminoethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Benzylaminoethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-N, N-dibenzylaminoethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-N, N-dibenzylaminoethyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (2-N, N-dibenzylaminoethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dibenzylaminoethyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2-N, N-dibenzylaminoethyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From Purine 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dibenzylaminoethyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 117

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dibenzylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-N, N-dibenzylaminopropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-N, N-dibenzylaminopropyl) piperidine

Basically 4-carboxamide-1- (3-N, N-dibenzyl) from isonifecottamide and 3-N, N-dibenzylaminopropyl chloride as described in Example 38, Scheme B, step a Aminopropyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-N, N-dibenzylaminopropyl) piperidine

Basically 4-amino-1- (3-N, from 4-carboxamide-1- (3-N, N-dibenzylaminopropyl) piperidine as described in Example 38, Scheme B, step b. N-dibenzylaminopropyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3-N, N-dibenzylaminopropyl) -4-piperidone

Basically 1- (3-N, N-dibenzylaminopropyl) -4-pi from 4-piperidone and 3-N, N-dibenzylaminopropyl chloride as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (3-N, N-dibenzylaminopropyl) -4-piperidone oxime

Basically 1- (3-N, N- from 1- (3-N, N-dibenzylaminopropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dibenzylaminopropyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3-N, N-dibenzylaminopropyl) piperidine

Basically 4-amino-1- (3-N, N-di from 1- (3-N, N-dibenzylaminopropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Benzylaminopropyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3-N, N-dibenzylaminopropyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-N, N-dibenzylaminopropyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (3-N, N-dibenzylaminopropyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dibenzylaminopropyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3-N, N-dibenzylaminopropyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From Purine 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dibenzylaminopropyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 118

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dibenzylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4-N, N-dibenzylaminobutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-N, N-dibenzylaminobutyl) piperidine

Basically 4-carboxamide-1- (4-N, N-dibenzyl) from isonifecottamide and 4-N, N-dibenzylaminobutyl chloride as described in Example 38, Scheme B, step a Aminobutyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-N, N-dibenzylaminobutyl) piperidine

Basically 4-amino-1- (4-N, from 4-carboxamide-1- (4-N, N-dibenzylaminobutyl) piperidine as described in Example 38, Scheme B, step b. N-dibenzylaminobutyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4-N, N-dibenzylaminobutyl) -4-piperidone

Basically 1- (4-N, N-dibenzylaminobutyl) -4-pi from 4-piperidone and 4-N, N-dibenzylaminobutyl chloride as described in Example 38, Scheme C, step a. Peridone was prepared.

Scheme C, step b: 1- (4-N, N-dibenzylaminobutyl) -4-piperidone oxime

Basically 1- (4-N, N- from 1- (4-N, N-dibenzylaminobutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dibenzylaminobutyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4-N, N-dibenzylaminobutyl) piperidine

Basically 4-amino-1- (4-N, N-di from 1- (4-N, N-dibenzylaminobutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Benzylaminobutyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4-N, N-dibenzylaminobutyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-N, N-dibenzylaminobutyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (4-N, N-dibenzylaminobutyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dibenzylaminobutyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (4-N, N-dibenzylaminobutyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dibenzylaminobutyl)) piperidinylamino] -9-cyclopentylpurine from purine Prepared.

Example 119

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dibenzylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (5-N, N-dibenzylaminopentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-N, N-dibenzylaminopentyl) piperidine

Basically 4-carboxamide-1- (5-N, N-dibenzyl) from isonifecottamide and 5-N, N-dibenzylaminopentyl chloride as described in Example 38, Scheme B, step a Aminopentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5-N, N-dibenzylaminopentyl) piperidine

Basically 4-amino-1- (5-N, from 4-carboxamide-1- (5-N, N-dibenzylaminopentyl) piperidine as described in Example 38, Scheme B, step b. N-dibenzylaminopentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5-N, N-dibenzylaminopentyl) -4-piperidone

Basically 1- (5-N, N-dibenzylaminopentyl) -4-pi from 4-piperidone and 5-N, N-dibenzylaminopentyl chloride as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (5-N, N-dibenzylaminopentyl) -4-piperidone oxime

Basically 1- (5-N, N- from 1- (5-N, N-dibenzylaminopentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Dibenzylaminopentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5-N, N-dibenzylaminopentyl) piperidine

Basically 4-amino-1- (5-N, N-di from 1- (5-N, N-dibenzylaminopentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Benzylaminopentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5-N, N-dibenzylaminopentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-N, N-dibenzylaminopentyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (5-N, N-dibenzylaminopentyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dibenzylaminopentyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5-N, N-dibenzylaminopentyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dibenzylaminopentyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 120

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di- (2-phenylethylene) aminoethyl)) piperidinylamino] -9- Cyclopentylpurine

Preparation of 4-amino-1- (2-N, N-di- (2-phenylethylene) aminoethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-N, N-di- (2-phenylethylene) aminoethyl) piperidine

Basically 4-carboxamide-1- (2- from isonifecottamide and 2-N, N-di- (2-phenylethyleneamino) ethyl chloride as described in Example 38, Scheme B, step a N, N-di- (2-phenylethylene) aminoethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-N, N-di- (2-phenylethylene) aminoethyl) piperidine

Basically 4-amino-1 from 4-carboxamide-1- (2-N, N-di- (2-phenylethylene) aminoethyl) piperidine as described in Example 38, Scheme B, step b. -(2-N, N-di- (2-phenylethylene) aminoethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2-N, N-di- (2-phenylethylene) aminoethyl) -4-piperidone

Basically 1- (2-N, N-di- () from 4-piperidone and 2-N, N-di- (2-phenylethylene) aminoethyl chloride as described in Example 38, Scheme C, step a. 2-phenylethylene) aminoethyl) -4-piperidone was prepared.

Scheme C, step b: 1- (2-N, N-di- (2-phenylethylene) aminoethyl) -4-piperidone oxime

Basically 1- (from 1- (2-N, N-di- (2-phenylethylene) aminoethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 2-N, N-di- (2-phenylethylene) aminoethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-N, N-di- (2-phenylethylene) aminoethyl) piperidine

Basically 4-amino-1- (2 from 1- (2-N, N-di- (2-phenylethylene) aminoethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. -N, N-di- (2-phenylethylene) aminoethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-N, N-di- (2-phenylethylene) aminoethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-N, N-di- (2-phenylethylene) aminoethyl as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (2-N, N-di- (2-phenylethylene) aminoethyl)) piperidinylamino] -9-cyclopentyl from piperidine and triethylamine Purine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di- (2-phenylethylene) aminoethyl)) piperidi Nylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2-N, N-di- (2-phenylethylene) aminoethyl)) piperidinylamino as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di- (2-phenylethylene) aminoethyl) from] -9-cyclopentylpurine) Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 121

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-di- (2-phenylethylene) aminopropyl)) piperidinylamino] -9- Cyclopentylpurine

Preparation of 4-amino-1- (3-N, N-di- (2-phenylethylene) aminopropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-N, N-di- (2-phenylethylene) aminopropyl) piperidine

Basically 4-carboxamide-1- (3- from isonipecottamide and 3-N, N-di- (2-phenylethyleneamino) propyl chloride as described in Example 38, Scheme B, step a. N, N-di- (2-phenylethylene) aminopropyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-N, N-di- (2-phenylethylene) aminopropyl) piperidine

Basically 4-amino-1 from 4-carboxamide-1- (3-N, N-di- (2-phenylethylene) aminopropyl) piperidine as described in Example 38, Scheme B, step b. -(3-N, N-di- (2-phenylethylene) aminopropyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3-N, N-di- (2-phenylethylene) aminopropyl) -4-piperidone

Basically 1- (3-N, N-di- () from 4-piperidone and 3-N, N-di- (2-phenylethyleneamino) propyl chloride as described in Example 38, Scheme C, step a. 2-phenylethylene) aminopropyl) -4-piperidone was prepared.

Scheme C, step b: 1- (3-N, N-di- (2-phenylethylene) aminopropyl) -4-piperidone oxime

Basically 1- (from 1- (3-N, N-di- (2-phenylethylene) aminopropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 3-N, N-di- (2-phenylethylene) aminopropyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3-N, N-di- (2-phenylethylene) aminopropyl) piperidine

Basically 4-amino-1- (3 from 1- (3-N, N-di- (2-phenylethylene) aminopropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. -N, N-di- (2-phenylethylene) aminopropyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3-N, N-di- (2-phenylethylene) aminopropyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-N, N-di- (2-phenylethylene) aminopropyl as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (3-N, N-di- (2-phenylethylene) aminopropyl)) piperidinylamino] -9-cyclopentyl from piperidine and triethylamine Purine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-di- (2-phenylethylene) aminopropyl)) piperidi Nylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3-N, N-di- (2-phenylethylene) aminopropyl)) piperidinylamino as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-di- (2-phenylethylene) aminopropyl)) from] -9-cyclopentylpurine Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 122

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (2-phenylethylene) aminobutyl)) piperidinylamino] -9- Cyclopentylpurine

Preparation of 4-amino-1- (4-N, N-di- (2-phenylethylene) aminobutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-N, N-di- (2-phenylethylene) aminobutyl) piperidine

Basically 4-carboxamide-1- (4- from isonipecottamide and 4-N, N-di- (2-phenylethyleneamino) butyl chloride as described in Example 38, Scheme B, step a. N, N-di- (2-phenylethylene) aminobutyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-N, N-di- (2-phenylethylene) aminobutyl) piperidine

Basically 4-amino-1 from 4-carboxamide-1- (4-N, N-di- (2-phenylethylene) aminobutyl) piperidine as described in Example 38, Scheme B, step b. -(4-N, N-di- (2-phenylethylene) aminobutyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4-N, N-di- (2-phenylethylene) aminobutyl) -4-piperidone

Basically 1- (4-N, N-di- () from 4-piperidone and 4-N, N-di- (2-phenylethyleneamino) butyl chloride as described in Example 38, Scheme C, step a. 2-phenylethylene) aminobutyl) -4-piperidone was prepared.

Scheme C, step b: 1- (4-N, N-di- (2-phenylethylene) aminobutyl) -4-piperidone oxime

Basically 1- (from 1- (4-N, N-di- (2-phenylethylene) aminobutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 4-N, N-di- (2-phenylethylene) aminobutyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4-N, N-di- (2-phenylethylene) aminobutyl) piperidine

Basically 4-amino-1- (4 from 1- (4-N, N-di- (2-phenylethylene) aminobutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. -N, N-di- (2-phenylethylene) aminobutyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4-N, N-di- (2-phenylethylene) aminobutyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-N, N-di- (2-phenylethylene) aminobutyl as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (4-N, N-di- (2-phenylethylene) aminobutyl)) piperidinylamino] -9-cyclopentyl from piperidine and triethylamine Purine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (2-phenylethylene) aminobutyl)) piperidi Nylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (4-N, N-di- (2-phenylethylene) aminobutyl)) piperidinylamino as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (2-phenylethylene) aminobutyl)) from] -9-cyclopentylpurine Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 123

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (2-phenylethylene) aminopentyl)) piperidinylamino] -9- Cyclopentylpurine

Preparation of 4-amino-1- (5-N, N-di- (2-phenylethylene) aminopentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-N, N-di- (2-phenylethylene) aminopentyl) piperidine

Basically 4-carboxamide-1- (5- from isonipecottamide and 5-N, N-di- (2-phenylethyleneamino) pentyl chloride as described in Example 38, Scheme B, step a. N, N-di- (2-phenylethylene) aminopentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5-N, N-di- (2-phenylethylene) aminopentyl) piperidine

Basically 4-amino-1 from 4-carboxamide-1- (5-N, N-di- (2-phenylethylene) aminopentyl) piperidine as described in Example 38, Scheme B, step b. -(5-N, N-di- (2-phenylethylene) aminopentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5-N, N-di- (2-phenylethylene) aminopentyl) -4-piperidone

Basically 1- (5-N, N-di- () from 4-piperidone and 5-N, N-di- (2-phenylethylene) aminopentyl chloride as described in Example 38, Scheme C, step a 2-phenylethylene) aminopentyl) -4-piperidone was prepared.

Scheme C, step b: 1- (5-N, N-di- (2-phenylethylene) aminopentyl) -4-piperidone oxime

Basically 1- (from 1- (5-N, N-di- (2-phenylethylene) aminopentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 5-N, N-di- (2-phenylethylene) aminopentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5-N, N-di- (2-phenylethylene) aminopentyl) piperidine

Basically 4-amino-1- (5 from 1- (5-N, N-di- (2-phenylethylene) aminopentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. -N, N-di- (2-phenylethylene) aminopentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5-N, N-di- (2-phenylethylene) aminopentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-N, N-di- (2-phenylethylene) aminopentyl as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (5-N, N-di- (2-phenylethylene) aminopentyl)) piperidinylamino] -9-cyclopentyl from piperidine and triethylamine Purine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (2-phenylethylene) aminopentyl)) piperidi Nylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5-N, N-di- (2-phenylethylene) aminopentyl)) piperidinylamino as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (2-phenylethylene) aminopentyl)) from] -9-cyclopentylpurine) Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 124

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di- (3-phenylpropylene) aminoethyl)) piperidinylamino] -9- Cyclopentylpurine

Preparation of 4-amino-1- (2-N, N-di- (3-phenylpropylene) aminoethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-N, N-di- (3-phenylpropylene) aminoethyl) piperidine

Basically 4-carboxamide-1- (2- from isonipecottamide and 2-N, N-di- (3-phenylpropyleneamino) ethyl chloride as described in Example 38, Scheme B, step a. N, N-di- (3-phenylpropylene) aminoethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-N, N-di- (3-phenylpropylene) aminoethyl) piperidine

Basically 4-amino-1 from 4-carboxamide-1- (2-N, N-di- (3-phenylpropylene) aminoethyl) piperidine as described in Example 38, Scheme B, step b. -(2-N, N-di- (3-phenylpropylene) aminoethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2-N, N-di- (3-phenylpropylene) aminoethyl) -4-piperidone

Basically 1- (2-N, N-di- () from 4-piperidone and 2-N, N-di- (3-phenylpropyleneamino) ethyl chloride as described in Example 38, Scheme C, step a. 3-phenylpropylene) aminoethyl) -4-piperidone was prepared.

Scheme C, step b: 1- (2-N, N-di- (3-phenylpropylene) aminoethyl) -4-piperidone oxime

Basically 1- (from 1- (2-N, N-di- (3-phenylpropylene) aminoethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 2-N, N-di- (3-phenylpropylene) aminoethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-N, N-di- (3-phenylpropylene) aminoethyl) piperidine

Basically 4-amino-1- (2 from 1- (2-N, N-di- (3-phenylpropylene) aminoethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. -N, N-di- (3-phenylpropylene) aminoethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-N, N-di- (3-phenylpropylene) aminoethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-N, N-di- (3-phenylpropylene) aminoethyl as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (2-N, N-di- (3-phenylpropylene) aminoethyl)) piperidinylamino] -9-cyclopentyl from piperidine and triethylamine Purine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di- (3-phenylpropylene) aminoethyl)) piperidi Nylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2-N, N-di- (3-phenylpropylene) aminoethyl)) piperidinylamino as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di- (3-phenylpropylene) aminoethyl) from] -9-cyclopentylpurine) Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 125

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-di- (3-phenylpropylene) aminopropyl)) piperidinylamino] -9- Cyclopentylpurine

Preparation of 4-amino-1- (3-N, N-di- (3-phenylpropylene) aminopropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-N, N-di- (3-phenylpropylene) aminopropyl) piperidine

Basically 4-carboxamide-1- (3- from isonipecottamide and 3-N, N-di- (3-phenylpropyleneamino) propyl chloride as described in Example 38, Scheme B, step a. N, N-di- (3-phenylpropylene) aminopropyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-N, N-di- (3-phenylpropylene) aminopropyl) piperidine

Basically 4-amino-1 from 4-carboxamide-1- (3-N, N-di- (3-phenylpropylene) aminopropyl) piperidine as described in Example 38, Scheme B, step b. -(3-N, N-di- (3-phenylpropylene) aminopropyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3-N, N-di- (3-phenylpropylene) aminopropyl) -4-piperidone

Basically 1- (3-N, N-di- () from 4-piperidone and 3-N, N-di- (3-phenylpropyleneamino) propyl chloride as described in Example 38, Scheme C, step a. 3-phenylpropylene) aminopropyl) -4-piperidone was prepared.

Scheme C, step b: 1- (3-N, N-di- (3-phenylpropylene) aminopropyl) -4-piperidone oxime

Basically 1- (from 1- (3-N, N-di- (3-phenylpropylene) aminopropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 3-N, N-di- (3-phenylpropylene) aminopropyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3-N, N-di- (3-phenylpropylene) aminopropyl) piperidine

Basically 4-amino-1- (3 from 1- (3-N, N-di- (3-phenylpropylene) aminopropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. -N, N-di- (3-phenylpropylene) aminopropyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3-N, N-di- (3-phenylpropylene) aminopropyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-N, N-di- (3-phenylpropylene) aminopropyl as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (3-N, N-di- (3-phenylpropylene) aminopropyl)) piperidinylamino] -9-cyclopentyl from piperidine and triethylamine Purine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-di- (3-phenylpropylene) aminopropyl)) piperidi Nylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3-N, N-di- (3-phenylpropylene) aminopropyl)) piperidinylamino as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-di- (3-phenylpropylene) aminopropyl)) from] -9-cyclopentylpurine Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 126

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (3-phenylpropylene) aminobutyl)) piperidinylamino] -9- Cyclopentylpurine

Preparation of 4-amino-1- (4-N, N-di- (3-phenylpropylene) aminobutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-N, N-di- (3-phenylpropylene) aminobutyl) piperidine

Basically 4-carboxamide-1- (4- from isonipecottamide and 4-N, N-di- (3-phenylpropyleneamino) butyl chloride as described in Example 38, Scheme B, step a. N, N-di- (3-phenylpropylene) aminobutyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-N, N-di- (3-phenylpropylene) aminobutyl) piperidine

Basically 4-amino-1 from 4-carboxamide-1- (4-N, N-di- (3-phenylpropylene) aminobutyl) piperidine as described in Example 38, Scheme B, step b. -(4-N, N-di- (3-phenylpropylene) aminobutyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4-N, N-di- (3-phenylpropylene) aminobutyl) -4-piperidone

Basically 1- (4-N, N-di- () from 4-piperidone and 4-N, N-di- (3-phenylpropyleneamino) butyl chloride as described in Example 38, Scheme C, step a. 3-phenylpropylene) aminobutyl) -4-piperidone was prepared.

Scheme C, step b: 1- (4-N, N-di- (3-phenylpropylene) aminobutyl) -4-piperidone oxime

Basically 1- (from 1- (4-N, N-di- (3-phenylpropylene) aminobutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 4-N, N-di- (3-phenylpropylene) aminobutyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4-N, N-di- (3-phenylpropylene) aminobutyl) piperidine

Basically 4-amino-1- (4 from 1- (4-N, N-di- (3-phenylpropylene) aminobutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. -N, N-di- (3-phenylpropylene) aminobutyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4-N, N-di- (3-phenylpropylene) aminobutyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-N, N-di- (3-phenylpropylene) aminobutyl as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (4-N, N-di- (3-phenylpropylene) aminobutyl)) piperidinylamino] -9-cyclopentyl from piperidine and triethylamine Purine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (3-phenylpropylene) aminobutyl)) piperidi Nylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (4-N, N-di- (3-phenylpropylene) aminobutyl)) piperidinylamino as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (3-phenylpropylene) aminobutyl)) from] -9-cyclopentylpurine) Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 127

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (3-phenylpropylene) aminopentyl)) piperidinylamino] -9- Cyclopentylpurine

Preparation of 4-amino-1- (5-N, N-di- (3-phenylpropylene) aminopentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-N, N-di- (3-phenylpropylene) aminopentyl) piperidine

Basically 4-carboxamide-1- (5- from isonifecottamide and 5-N, N-di- (3-phenylpropyleneamino) pentyl chloride as described in Example 38, Scheme B, step a N, N-di- (3-phenylpropylene) aminopentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5-N, N-di- (3-phenylpropylene) aminopentyl) piperidine

Basically 4-amino-1 from 4-carboxamide-1- (5-N, N-di- (3-phenylpropylene) aminopentyl) piperidine as described in Example 38, Scheme B, step b. -(5-N, N-di- (3-phenylpropylene) aminopentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5-N, N-di- (3-phenylpropylene) aminopentyl) -4-piperidone

Basically 1- (5-N, N-di- () from 4-piperidone and 5-N, N-di- (3-phenylpropyleneamino) pentyl chloride as described in Example 38, Scheme C, step a. 3-phenylpropylene) aminopentyl) -4-piperidone was prepared.

Scheme C, step b: 1- (5-N, N-di- (3-phenylpropylene) aminopentyl) -4-piperidone oxime

Basically, 1- (from 1- (5-N, N-di- (3-phenylpropylene) aminopentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 5-N, N-di- (3-phenylpropylene) aminopentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5-N, N-di- (3-phenylpropylene) aminopentyl) piperidine

Basically 4-amino-1- (5 from 1- (5-N, N-di- (3-phenylpropylene) aminopentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. -N, N-di- (3-phenylpropylene) aminopentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5-N, N-di- (3-phenylpropylene) aminopentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-N, N-di- (3-phenylpropylene) aminopentyl as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (5-N, N-di- (3-phenylpropylene) aminopentyl)) piperidinylamino] -9-cyclopentyl from piperidine and triethylamine Purine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (3-phenylpropylene) aminopentyl)) piperidi Nylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5-N, N-di- (3-phenylpropylene) aminopentyl)) piperidinylamino as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (3-phenylpropylene) aminopentyl)) from] -9-cyclopentylpurine) Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 128

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di- (4-phenylbutylene) aminoethyl)) piperidinylamino] -9 Cyclopentylpurine

Preparation of 4-amino-1- (2-N, N-di- (4-phenylbutylene) aminoethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-N, N-di- (4-phenylbutylene) aminoethyl) piperidine

Basically 4-carboxamide-1- (2 from isonifecottamide and 2-N, N-di- (4-phenylbutyleneamino) ethyl chloride as described in Example 38, Scheme B, step a -N, N-di- (4-phenylbutylene) aminoethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-N, N-di- (4-phenylbutylene) aminoethyl) piperidine

Basically 4-amino- from 4-carboxamide-1- (2-N, N-di- (4-phenylbutylene) aminoethyl) piperidine as described in Example 38, Scheme B, step b. 1- (2-N, N-di- (4-phenylbutylene) aminoethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2-N, N-di- (4-phenylbutylene) aminoethyl) -4-piperidone

Basically 1- (2-N, N-di- from 4-piperidone and 2-N, N-di- (4-phenylbutyleneamino) ethyl chloride as described in Example 38, Scheme C, step a (4-phenylbutylene) aminoethyl) -4-piperidone was prepared.

Scheme C, step b: 1- (2-N, N-di- (4-phenylbutylene) aminoethyl) -4-piperidone oxime

Basically 1- from 1- (2-N, N-di- (4-phenylbutylene) aminoethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. (2-N, N-di- (4-phenylbutylene) aminoethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-N, N-di- (4-phenylbutylene) aminoethyl) piperidine

Basically 4-amino-1- (from 1- (2-N, N-di- (4-phenylbutylene) aminoethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. 2-N, N-di- (4-phenylbutylene) aminoethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-N, N-di- (4-phenylbutylene) aminoethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-N, N-di- (4-phenylbutylene) amino as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (2-N, N-di- (4-phenylbutylene) aminoethyl)) piperidinylamino] -9- from ethyl) piperidine and triethylamine Cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di- (4-phenylbutylene) aminoethyl)) pipepe Ridinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2-N, N-di- (4-phenylbutylene) aminoethyl)) piperidinyl as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di- (4-phenylbutylene) aminoethyl from amino] -9-cyclopentylpurine )) Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 129

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-di- (4-phenylbutylene) aminopropyl)) piperidinylamino] -9 Cyclopentylpurine

Preparation of 4-amino-1- (3-N, N-di- (4-phenylbutylene) aminopropyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-N, N-di- (4-phenylbutylene) aminopropyl) piperidine

Basically 4-carboxamide-1- (3 from isonifecottamide and 3-N, N-di- (4-phenylbutyleneamino) propyl chloride as described in Example 38, Scheme B, step a. -N, N-di- (4-phenylbutylene) aminopropyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-N, N-di- (4-phenylbutylene) aminopropyl) piperidine

Basically 4-amino- from 4-carboxamide-1- (3-N, N-di- (4-phenylbutylene) aminopropyl) piperidine as described in Example 38, Scheme B, step b. 1- (3-N, N-di- (4-phenylbutylene) aminopropyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3-N, N-di- (4-phenylbutylene) aminopropyl) -4-piperidone

Basically 1- (3-N, N-di- from 4-piperidone and 3-N, N-di- (4-phenylbutyleneamino) propyl chloride as described in Example 38, Scheme C, step a (4-phenylbutylene) aminopropyl) -4-piperidone was prepared.

Scheme C, step b: 1- (3-N, N-di- (4-phenylbutylene) aminopropyl) -4-piperidone oxime

Basically 1- from 1- (3-N, N-di- (4-phenylbutylene) aminopropyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. (3-N, N-di- (4-phenylbutylene) aminopropyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3-N, N-di- (4-phenylbutylene) aminopropyl) piperidine

Basically 4-amino-1- (from 1- (3-N, N-di- (4-phenylbutylene) aminopropyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. 3-N, N-di- (4-phenylbutylene) aminopropyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3-N, N-di- (4-phenylbutylene) aminopropyl)) piperidinylamino] -9-cyclopentylpurine

Basically, as described in Example 1, Scheme A, step b, 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-N, N-di- (4-phenylbutylene) amino Propyl) piperidine and triethylamine from 2-chloro-6- [4- (1- (3-N, N-di- (4-phenylbutylene) aminopropyl)) piperidinylamino] -9- Cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-di- (4-phenylbutylene) aminopropyl)) pipepe Ridinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3-N, N-di- (4-phenylbutylene) aminopropyl)) piperidinyl as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-di- (4-phenylbutylene) aminopropyl from amino] -9-cyclopentylpurine )) Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 130

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (4-phenylbutylene) aminobutyl)) piperidinylamino] -9 Cyclopentylpurine

Preparation of 4-amino-1- (4-N, N-di- (4-phenylbutylene) aminobutyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4-N, N-di- (4-phenylbutylene) aminobutyl) piperidine

Basically 4-carboxamide-1- (4 from isonifecottamide and 4-N, N-di- (4-phenylbutyleneamino) butyl chloride as described in Example 38, Scheme B, step a -N, N-di- (4-phenylbutylene) aminobutyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-N, N-di- (4-phenylbutylene) aminobutyl) piperidine

Basically 4-amino- from 4-carboxamide-1- (4-N, N-di- (4-phenylbutylene) aminobutyl) piperidine as described in Example 38, Scheme B, step b. 1- (4-N, N-di- (4-phenylbutylene) aminobutyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4-N, N-di- (4-phenylbutylene) aminobutyl) -4-piperidone

Basically 1- (4-N, N-di- from 4-piperidone and 4-N, N-di- (4-phenylbutyleneamino) butyl chloride as described in Example 38, Scheme C, step a (4-phenylbutylene) aminobutyl) -4-piperidone was prepared.

Scheme C, step b: 1- (4-N, N-di- (4-phenylbutylene) aminobutyl) -4-piperidone oxime

Basically from 1- (4-N, N-di- (4-phenylbutylene) aminobutyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. (4-N, N-di- (4-phenylbutylene) aminobutyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4-N, N-di- (4-phenylbutylene) aminobutyl) piperidine

Basically 4-amino-1- (from 1- (4-N, N-di- (4-phenylbutylene) aminobutyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. 4-N, N-di- (4-phenylbutylene) aminobutyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4-N, N-di- (4-phenylbutylene) aminobutyl)) piperidinylamino] -9-cyclopentylpurine

Basically, as described in Example 1, Scheme A, step b, 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-N, N-di- (4-phenylbutylene) amino 2-chloro-6- [4- (1- (4-N, N-di- (4-phenylbutylene) aminobutyl)) piperidinylamino] -9- from butyl) piperidine and triethylamine Cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (4-phenylbutylene) aminobutyl)) pipepe Ridinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (4-N, N-di- (4-phenylbutylene) aminobutyl)) piperidinyl as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (4-phenylbutylene) aminobutyl from amino] -9-cyclopentylpurine )) Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 131

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (4-phenylbutylene) aminopentyl)) piperidinylamino] -9 Cyclopentylpurine

Preparation of 4-amino-1- (5-N, N-di- (4-phenylbutylene) aminopentyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (5-N, N-di- (4-phenylbutylene) aminopentyl) piperidine

Basically 4-carboxamide-1- (5) from isonifecottamide and 5-N, N-di- (4-phenylbutyleneamino) pentyl chloride as described in Example 38, Scheme B, step a. -N, N-di- (4-phenylbutylene) aminopentyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (5-N, N-di- (4-phenylbutylene) aminopentyl) piperidine

Basically 4-amino- from 4-carboxamide-1- (5-N, N-di- (4-phenylbutylene) aminopentyl) piperidine as described in Example 38, Scheme B, step b. 1- (5-N, N-di- (4-phenylbutylene) aminopentyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (5-N, N-di- (4-phenylbutylene) aminopentyl) -4-piperidone

Basically 1- (5-N, N-di- from 4-piperidone and 5-N, N-di- (4-phenylbutyleneamino) pentyl chloride as described in Example 38, Scheme C, step a (4-phenylbutylene) aminopentyl) -4-piperidone was prepared.

Scheme C, step b: 1- (5-N, N-di- (4-phenylbutylene) aminopentyl) -4-piperidone oxime

Basically 1- from 1- (5-N, N-di- (4-phenylbutylene) aminopentyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. (5-N, N-di- (4-phenylbutylene) aminopentyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (5-N, N-di- (4-phenylbutylene) aminopentyl) piperidine

Basically 4-amino-1- (from 1- (5-N, N-di- (4-phenylbutylene) aminopentyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. 5-N, N-di- (4-phenylbutylene) aminopentyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (5-N, N-di- (4-phenylbutylene) aminopentyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (5-N, N-di- (4-phenylbutylene) aminophen as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (5-N, N-di- (4-phenylbutylene) aminopentyl)) piperidinylamino] -9- from yl) piperidine and triethylamine Cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (4-phenylbutylene) aminopentyl)) pipepe Ridinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (5-N, N-di- (4-phenylbutylene) aminopentyl)) piperidinyl as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (4-phenylbutylene) aminopentyl from amino] -9-cyclopentylpurine )) Piperidinylamino] -9-cyclopentylpurine was prepared.

Example 132

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-tetrahydrofuranyl) methyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3-tetrahydrofuranylmethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3-tetrahydrofuranylmethyl) piperidine

4-Carboxamide-1- (3-tetrahydrofuranylmethyl) piperidine was prepared basically from isonipecottamide and tetrahydrofurfuryl chloride as described in Example 38, Scheme B, step a. .

Scheme B, step b: 4-amino-1- (3-tetrahydrofuranylmethyl) piperidine

Basically 4-amino-1- (3-tetrahydrofuranylmethyl from 4-carboxamide-1- (3-tetrahydrofuranylmethyl) piperidine as described in Example 38, Scheme B, step b. Piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3-tetrahydrofuranylmethyl) -4-piperidone

Basically 1- (3-tetrahydrofuranylmethyl) -4-piperidone was prepared from 4-piperidone and tetrahydrofurfuryl chloride as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (3-tetrahydrofuranylmethyl) -4-piperidone oxime

Basically 1- (3-tetrahydrofuranylmethyl)-from 1- (3-tetrahydrofuranylmethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3-tetrahydrofuranylmethyl) piperidine

Basically 4-amino-1- (3-tetrahydrofuranylmethyl) piperi from 1- (3-tetrahydrofuranylmethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Dean was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3-tetrahydrofuranyl) methyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-tetrahydrofuranylmethyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- (1- (3-tetrahydrofuranyl) methyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-tetrahydrofuranyl) methyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (3-tetrahydrofuranyl) methyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-tetrahydrofuranyl) methyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 133

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1-pyrrolidinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2- (1-pyrrolidinyl) ethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2- (1-pyrrolidinyl) ethyl) piperidine

Basically 4-carboxamide-1- (2- (1-pyrrolidinyl) from isonipecottamide and 1- (2-chloroethyl) pyrrolidine as described in Example 38, Scheme B, step a Ethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2- (1-pyrrolidinyl) ethyl) piperidine

Basically 4-amino-1- (2- (1) from 4-carboxamide-1- (2- (1-pyrrolidinyl) ethyl) piperidine as described in Example 38, Scheme B, step b. Pyrrolidinyl) ethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2- (1-pyrrolidinyl) ethyl) -4-piperidone

Basically 1- (2- (1-pyrrolidinyl) ethyl) -4-pi from 4-piperidone and 1- (2-chloroethyl) pyrrolidine as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (2- (1-pyrrolidinyl) ethyl) -4-piperidone oxime

Basically 1- (2- (1-P) from 1- (2- (1-pyrrolidinyl) ethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Lolidinyl) ethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2- (1-pyrrolidinyl) ethyl) piperidine

Basically 4-amino-1- (2- (1-pyrroli) from 1- (2- (1-pyrrolidinyl) ethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Diny) ethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2- (1-pyrrolidinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2- (1-pyrrolidinyl) ethyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (2- (1-pyrrolidinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1-pyrrolidinyl) ethyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2- (1-pyrrolidinyl) ethyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From Purine 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1-pyrrolidinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 134

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1-piperidinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2- (1-piperidinyl) ethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2- (1-piperidinyl) ethyl) piperidine

Basically 4-carboxamide-1- (2- (1-piperidinyl) from isonipecottamide and 1- (2-chloroethyl) piperidine as described in Example 38, Scheme B, step a Ethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2- (1-piperidinyl) ethyl) piperidine

Basically 4-amino-1- (2- (1) from 4-carboxamide-1- (2- (1-piperidinyl) ethyl) piperidine as described in Example 38, Scheme B, step b. -Piperidinyl) ethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2- (1-piperidinyl) ethyl) -4-piperidone

Basically 1- (2- (1-piperidinyl) ethyl) -4-pi from 4-piperidone and 1- (2-chloroethyl) piperidine as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (2- (1-piperidinyl) ethyl) -4-piperidone oxime

Basically 1- (2- (1-pipe) from 1- (2- (1-piperidinyl) ethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Ridinyl) ethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2- (1-piperidinyl) ethyl) piperidine

Basically 4-amino-1- (2- (1-piperididi) from 1- (2- (1-piperidinyl) ethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Nil) ethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2- (1-piperidinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2- (1-piperidinyl) ethyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (2- (1-piperidinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1-piperidinyl) ethyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2- (1-piperidinyl) ethyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1-piperidinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 135

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (4-morpholinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2- (4-morpholinyl) ethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2- (4-morpholinyl) ethyl) piperidine

Basically 4-carboxamide-1- (2- (4-morpholinyl) from isonipecottamide and 1- (2-chloroethyl) morpholine as described in Example 38, Scheme B, step a Ethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2- (4-morpholinyl) ethyl) piperidine

Basically 4-amino-1- (2- (4) from 4-carboxamide-1- (2- (4-morpholinyl) ethyl) piperidine as described in Example 38, Scheme B, step b. -Morpholinyl) ethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2- (4-morpholinyl) ethyl) -4-piperidone

Basically 1- (2- (4-morpholinyl) ethyl) -4-piperidone from 4-piperidone and 1- (2-chloroethyl) morpholine as described in Example 38, Scheme C, step a Was prepared.

Scheme C, step b: 1- (2- (4-morpholinyl) ethyl) -4-piperidone oxime

Basically 1- (2- (4-morph) from 1- (2- (4-morpholinyl) ethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Polyyl) ethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2- (4-morpholinyl) ethyl) piperidine

Basically 4-amino-1- (2- (4-morpholi) from 1- (2- (4-morpholinyl) ethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Nil) ethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2- (4-morpholinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2- (4-morpholinyl) ethyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (2- (4-morpholinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (4-morpholinyl) ethyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2- (4-morpholinyl) ethyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From Purine 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (4-morpholinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 136

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (1-piperidinyl) propyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (3- (1-piperidinyl) propyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3- (1-piperidinyl) propyl) piperidine

Basically 4-carboxamide-1- (3- (1-piperidinyl) from isonipecottamide and 1- (3-chloropropyl) piperidine as described in Example 38, Scheme B, step a ) Propyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3- (1-piperidinyl) propyl) piperidine

Basically 4-amino-1- (3- (1) from 4-carboxamide-1- (3- (1-piperidinyl) propyl) piperidine as described in Example 38, Scheme B, step b. -Piperidinyl) propyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3- (1-piperidinyl) propyl) -4-piperidone

Basically 1- (3- (1-piperidinyl) propyl) -4-pi from 4-piperidone and 1- (3-chloropropyl) piperidine as described in Example 38, Scheme C, step a Peridone was prepared.

Scheme C, step b: 1- (3- (1-piperidinyl) propyl) -4-piperidone oxime

Basically 1- (3- (1-pipe) from 1- (3- (1-piperidinyl) propyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Ridinyl) propyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (3- (1-piperidinyl) propyl) piperidine

Basically 4-amino-1- (3- (1-piperididi) from 1- (3- (1-piperidinyl) propyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Nil) propyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3- (1-piperidinyl) propyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3- (1-piperidinyl) propyl) piperidine and tri as described in Example 1, Scheme A, step b 2-Chloro-6- [4- (1- (3- (1-piperidinyl) propyl)) piperidinylamino] -9-cyclopentylpurine was prepared from ethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (1-piperidinyl) propyl)) piperidinylamino] -9- Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (3- (1-piperidinyl) propyl)) piperidinylamino] -9-cyclopentyl as described in Example 1, Scheme A, step c. From furin 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (1-piperidinyl) propyl)) piperidinylamino] -9-cyclopentylpurine Prepared.

Example 137

(R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (1-methyl) piperidinyl) methyl)) piperidinylamino]- 9-cyclopentylpurine

Preparation of (R, S) -4-amino-1- (3- (1-methylpiperidinyl) methyl) piperidine:

Method 1:

Scheme B, step a: (R, S) -4-carboxamide-1- (3- (1-methylpiperidinyl) methyl) piperidine

Basically (R, S) -4-carboxamide from isonipecottamide and (R, S) -3-chloromethyl-1-methylpiperidine as described in Example 38, Scheme B, step a -1- (3- (1-methylpiperidinyl) methyl) piperidine was prepared.

Scheme B, step b: (R, S) -4-amino-1- (3- (1-methylpiperidinyl) methyl) piperidine

Basically from (R, S) -4-carboxamide-1- (3- (1-methylpiperidinyl) methyl) piperidine (R, S) as described in Example 38, Scheme B, step b. ) -4-amino-1- (3- (1-methylpiperidinyl) methyl) piperidine was prepared.

Method 2:

Scheme C, step a: (R, S) -1- (3- (1-methylpiperidinyl) methyl) -4-piperidone

Basically, as described in Example 38, Scheme C, step a, 4-R piperidon and (R, S) -3-chloromethyl-1-methylpiperidine were selected from (R, S) -1- (3- ( 1-methylpiperidinyl) methyl) -4-piperidone was prepared.

Scheme C, step b: (R, S) -1- (3- (1-methylpiperidinyl) methyl) -4-piperidone oxime

Basically from (R, S) -1- (3- (1-methylpiperidinyl) methyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. , S) -1- (3- (1-methylpiperidinyl) methyl) -4-piperidone oxime was prepared.

Scheme C, step c: (R, S) -4-amino-1- (3- (1-methylpiperidinyl) methyl) piperidine

Basically (R, S) -4 from (R, S) -1- (3- (1-methylpiperidinyl) methyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Amino-1- (3- (1-methylpiperidinyl) methyl) piperidine was prepared.

Scheme A, step b: (R, S) -2-chloro-6- [4- (1- (3- (1-methyl) piperidinyl) methyl)) piperidinylamino] -9-cyclopentylpurine

Basically, as described in Example 1, Scheme A, step b, 2,6-dichloro-9-cyclopentylpurine, (R, S) -4-amino-1- (3- (1-methylpiperidinyl) (R, S) -2-chloro-6- [4- (1- (3- (1-methyl) piperidinyl) methyl)) piperidinylamino] -9 from methyl) piperidine and triethylamine Cyclopentylpurine was prepared.

Scheme A, step c: (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (1-methyl) piperidinyl) methyl)) Piperidinylamino] -9-cyclopentylpurine

Basically (R, S) -2-chloro-6- [4- (1- (3- (1-methyl) piperidinyl) methyl)) piperidi as described in Example 1, Scheme A, step c. (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (1-methyl) piperidinyl from Nylamino] -9-cyclopentylpurine ) Methyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 138

(R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (3- (1-methyl) pyrrolidinyl) ethyl)) piperidinyl Amino] -9-cyclopentylpurine

Preparation of (R, S) -4-amino-1- (2- (3- (1-methylpyrrolidinyl)) ethyl) piperidine:

Method 1:

Scheme B, step a: (R, S) -4-carboxamide-1- (2- (3- (1-methylpyrrolidinyl)) ethyl) piperidine

Basically, (R, S) -4 from isonipecottamide and (R, S) -3- (2-chloroethyl) -1-methylpyrrolidine as described in Example 38, Scheme B, step a. -Carboxamide-1- (2- (3- (1-methylpyrrolidinyl)) ethyl) piperidine was prepared.

Scheme B, step b: (R, S) -4-amino-1- (2- (3- (1-methylpyrrolidinyl)) ethyl) piperidine

Basically from (R, S) -4-carboxamide-1- (2- (3- (1-methylpyrrolidinyl)) ethyl) piperidine as described in Example 38, Scheme B, step b (R, S) -4-amino-1- (2- (3- (1-methylpyrrolidinyl)) ethyl) piperidine was prepared.

Method 2:

Scheme C, step a: (R, S) -1- (2- (3- (1-methylpyrrolidinyl)) ethyl) -4-piperidone

Basically (R, S) -1- from 4-piperidone and (R, S) -3- (2-chloroethyl) -1-methylpyrrolidine as described in Example 38, Scheme C, step a (2- (3- (1-methylpyrrolidinyl)) ethyl) -4-piperidone was prepared.

Scheme C, step b: (R, S) -1- (2- (3- (1-methylpyrrolidinyl)) ethyl) -4-piperidone oxime

Basically, as described in Example 38, Scheme C, step b, (R, S) -1- (2- (3- (1-methylpyrrolidinyl)) ethyl) -4-piperidone and hydroxylamine hydro (R, S) -1- (2- (3- (1-methylpyrrolidinyl)) ethyl) -4-piperidone oxime was prepared from chloride.

Scheme C, step c: (R, S) -4-amino-1- (2- (3- (1-methylpyrrolidinyl)) ethyl) piperidine

Basically from (R, S) -1- (2- (3- (1-methylpyrrolidinyl)) ethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. S) -4-amino-1- (2- (3- (1-methylpyrrolidinyl)) ethyl) piperidine was prepared.

Scheme A, step b: (R, S) -2-chloro-6- [4- (1- (2- (3- (1-methyl) pyrrolidinyl) ethyl)) piperidinylamino] -9- Cyclopentylpurine

Basically, as described in Example 1, Scheme A, step b, 2,6-dichloro-9-cyclopentylpurine, (R, S) -4-amino-1- (2- (3- (1-methylpy) (R, S) -2-chloro-6- [4- (1- (2- (3- (1-methyl) pyrrolidinyl) ethyl)) from ralidinyl)) ethyl) piperidine and triethylamine Piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (3- (1-methyl) pyrrolidinyl) Ethyl)) piperidinylamino] -9-cyclopentylpurine

Basically, as described in Example 1, Scheme A, Step c, (R, S) -2-chloro-6- [4- (1- (2- (3- (1-methyl) pyrrolidinyl) ethyl) (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (3- (1)) from piperidinylamino] -9-cyclopentylpurine -Methyl) pyrrolidinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 139

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1- (4-methyl) piperazinyl) ethyl)) piperidinylamino] -9-cyclo Pentylpurine

Preparation of 4-amino-1- (2- (1- (4-methylpiperazinyl)) ethyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2- (1- (4-methylpiperazinyl)) ethyl) piperidine

Basically 4-carboxamide-1- (2- (1- (1- (1- (1- (1- (1- (1- (1)))) from isonifecottamide and 1- (2-chloroethyl) -4-methylpiperazine as described in Example 38, Scheme B, step a. (4-methylpiperazinyl)) ethyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2- (1- (4-methylpiperazinyl)) ethyl) piperidine

Basically 4-amino-1-from 4-carboxamide-1- (2- (1- (4-methylpiperazinyl)) ethyl) piperidine as described in Example 38, Scheme B, step b. (2- (1- (4-methylpiperazinyl)) ethyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (2- (1- (4-methylpiperazinyl)) ethyl) -4-piperidone

Basically 1- (2- (1- (4-methylpiperazinyl) from 4-piperidone and 1- (2-chloroethyl) -4-methylpiperazin as described in Example 38, Scheme C, step a. )) Ethyl) -4-piperidone was prepared.

Scheme C, step b: 1- (2- (1- (4-methylpiperazinyl)) ethyl) -4-piperidone oxime

Basically 1- (2 from 1- (2- (1- (4-methylpiperazinyl)) ethyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. -(1- (4-methylpiperazinyl)) ethyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2- (1- (4-methylpiperazinyl)) ethyl) piperidine

Basically 4-amino-1- (2- from 1- (2- (1- (4-methylpiperazinyl)) ethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. (1- (4-methylpiperazinyl)) ethyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2- (1- (4-methyl) piperazinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2- (1- (4-methylpiperazinyl)) ethyl) as described in Example 1, Scheme A, step b 2-chloro-6- [4- (1- (2- (1- (4-methyl) piperazinyl) ethyl)) piperidinylamino] -9-cyclopentylpurine from piperidine and triethylamine Prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1- (4-methyl) piperazinyl) ethyl)) piperidinyl Amino] -9-cyclopentylpurine

Basically 2-chloro-6- [4- (1- (2- (1- (4-methyl) piperazinyl) ethyl)) piperidinylamino] as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1- (4-methyl) piperazinyl) ethyl)) piperidi from -9-cyclopentylpurine Nylamino] -9-cyclopentylpurine was prepared.

Example 140

(R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenyl-2-hydroxyethyl)) piperidinylamino] -9-cyclo Pentylpurine

Preparation of (R, S) -4-amino-1- (2-phenyl-2-hydroxyethyl) piperidine:

Method 1:

Scheme B, step a: (R, S) -4-carboxamide-1- (2-phenyl-2-hydroxyethyl) piperidine

(R, S) -4-carboxamide- basically from isonipecottamide and (R, S) -1-hydroxy-2-chloroethylbenzene as described in Example 38, Scheme B, step a. 1- (2-phenyl-2-hydroxyethyl) piperidine was prepared.

Scheme B, step b: (R, S) -4-amino-1- (2-phenyl-2-hydroxyethyl) piperidine

Basically from (R, S) -4-carboxamide-1- (2-phenyl-2-hydroxyethyl) piperidine (R, S)-as described in Example 38, Scheme B, step b. 4-amino-1- (2-phenyl-2-hydroxyethyl) piperidine was prepared.

Method 2:

Scheme C, step a: (R, S) -1- (2-phenyl-2-hydroxyethyl) -4-piperidone

(R, S) -1- (2-phenyl- from 4-piperidone and (R, S) -1-hydroxy-2-chloroethylbenzene, essentially as described in Example 38, Scheme C, step a. 2-hydroxyethyl) -4-piperidone was prepared.

Scheme C, step b: (R, S) -1- (2-phenyl-2-hydroxyethyl) -4-piperidone oxime

Basically from (R, S) -1- (2-phenyl-2-hydroxyethyl) -4-piperidone and hydroxylamine hydrochloride (R, S) as described in Example 38, Scheme C, step b. ) -1- (2-phenyl-2-hydroxyethyl) -4-piperidone oxime was prepared.

Scheme C, step c: (R, S) -4-amino-1- (2-phenyl-2-hydroxyethyl) piperidine

Basically (R, S) -4-amino from (R, S) -1- (2-phenyl-2-hydroxyethyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. -1- (2-phenyl-2-hydroxyethyl) piperidine was prepared.

Scheme A, step b: (R, S) -2-chloro-6- [4- (1- (2-phenyl-2-hydroxyethyl)) piperidinylamino] -9-cyclopentylpurine

Basically, as described in Example 1, Scheme A, step b, 2,6-dichloro-9-cyclopentylpurine, (R, S) -4-amino-1- (2-phenyl-2-hydroxyethyl) (R, S) -2-chloro-6- [4- (1- (2-phenyl-2-hydroxyethyl)) piperidinylamino] -9-cyclopentylpurine from piperidine and triethylamine Prepared.

Scheme A, step c: (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenyl-2-hydroxyethyl)) piperidinyl Amino] -9-cyclopentylpurine

Basically, as described in Example 1, Scheme A, Step c, (R, S) -2-chloro-6- [4- (1- (2-phenyl-2-hydroxyethyl)) piperidinylamino] (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenyl-2-hydroxyethyl)) piperidi from -9-cyclopentylpurine Nylamino] -9-cyclopentylpurine was prepared.

Example 141

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3,4-methylenedioxybenzyl)) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino- (3,4-methylenedioxybenzyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (3,4-methylenedioxybenzyl) piperidine

Basically 4-carboxamide-1- (2- (1- (3) from isonifecottamide and 5-chloromethyl-1,3-benzodioxol as described in Example 38, Scheme B, step a , 4-methylenedioxybenzyl) piperidine was prepared.

Scheme B, step b: 4-amino- (3,4-methylenedioxybenzyl) piperidine

Basically 4-amino- (3,4-methylenedioxybenzyl from 4-carboxamide-1- (3,4-methylenedioxybenzyl) piperidine as described in Example 38, Scheme B, step b. Piperidine was prepared.

Method 2:

Scheme C, step a: 1- (3,4-methylenedioxy) benzyl-4-piperidone

Basically 1- (3,4-methylenedioxy) benzyl-4-piperidone from 4-piperidone and 5-chloromethyl-1,3-benzodioxol as described in Example 38, Scheme C, step a Was prepared.

Scheme C, step b: 1- (3,4-methylenedioxy) benzyl-4-piperidone oxime

Basically 1- (3,4-methylenedioxy) from 1- (3,4-methylenedioxy) benzyl-4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Benzyl-4-piperidone oxime was prepared.

Scheme C, step c: 4-amino- (3,4-methylenedioxybenzyl) piperidine

Basically 4-amino- (3,4-methylenedioxybenzyl) piperi from 1- (3,4-methylenedioxybenzyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Dean was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (3,4-methylenedioxybenzyl)) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino- (3,4-methylenedioxybenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -Chloro-6- [4- (1- (3,4-methylenedioxybenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3,4-methylenedioxybenzyl)) piperidinylamino] -9-cyclopentyl Purine

Basically from 2-chloro-6- [4- (1- (3,4-methylenedioxybenzyl)) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3,4-methylenedioxybenzyl)) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 142

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-benzimidazolinyl) methyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-benzimidazolinyl) methylpiperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-benzimidazolinyl) methylpiperidine

Basically 4-carboxamide-1- (2-benzimidazolinyl) methylpi from isonifecottamide and 2- (chloromethyl) benzimidazole as described in Example 38, Scheme B, step a Ferridine was prepared.

Scheme B, step b: 4-amino-1- (2-benzimidazolinyl) methylpiperidine

Basically 4-amino-1- (2-benzimidazoli from 4-carboxamide-1- (2-benzimidazolinyl) methylpiperidine as described in Example 38, Scheme B, step b. Nil) methylpiperidine was prepared.

Method 2:

Scheme C, step a: 1- (2-benzimidazolyl) methyl-4-piperidone

Basically 1- (2-benzimidazolyl) methyl-4-piperidone was prepared from 4-piperidone and 2- (chloromethyl) benzimidazole as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2-benzimidazolyl) methyl-4-piperidone oxime

Basically 1- (2-benzimidazolyl) methyl- from 1- (2-benzimidazolyl) methyl-4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. 4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-benzimidazolinyl) methylpiperidine

Basically 4-amino-1- (2-benzimidazolinyl) methylpi from 1- (2-benzimidazolyl) methyl-4-piperidone oxime as described in Example 38, Scheme C, step c. Ferridine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-benzimidazolinyl) methyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-benzimidazolinyl) methylpiperidine and triethylamine as described in Example 1, Scheme A, step b. 2-chloro-6- [4- (1- (2-benzimidazolinyl) methyl) piperidinylamino] -9-cyclopentylpurine was prepared from.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-benzimidazolinyl) methyl) piperidinylamino] -9-cyclopentyl Purine

Basically from 2-chloro-6- [4- (1- (2-benzimidazolinyl) methyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-benzimidazolinyl) methyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 143

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (2-methyl) thiazolinyl) methyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (4- (2-methylthiazolinyl) methyl) piperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (4- (2-methylthiazolinyl)) methylpiperidine

Basically 4-carboxamide-1- (4- (2-methylthiazine) from isonifecottamide and 2-methyl-5- (chloromethyl) thiazole as described in Example 38, Scheme B, step a Zolinyl)) methylpiperidine was prepared.

Scheme B, step b: 4-amino-1- (4- (2-methylthiazolinyl) methyl) piperidine

Basically 4-amino-1- (4- (from 4-carboxamide-1- (4- (2-methylthiazolinyl)) methylpiperidine as described in Example 38, Scheme B, step b. 2-methylthiazolinyl) methyl) piperidine was prepared.

Method 2:

Scheme C, step a: 1- (4- (2-methylthiazolinyl) methyl) -4-piperidone

Basically 1- (4- (2-methylthiazolinyl) methyl) -4 from 4-piperidone and 2-methyl-5- (chloromethyl) thiazole as described in Example 38, Scheme C, step a Piperidone was prepared.

Scheme C, step b: 1- (4- (2-methylthiazolinyl) methyl) -4-piperidone oxime

Basically 1- (4- (2- from 1- (4- (2-methylthiazolinyl) methyl) -4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Methylthiazolinyl) methyl) -4-piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (4- (2-methylthiazolinyl) methyl) piperidine

Basically 4-amino-1- (4- (2-methyl) from 1- (4- (2-methylthiazolinyl) methyl) -4-piperidone oxime as described in Example 38, Scheme C, step c. Thiazolinyl) methyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (4- (2-methyl) thiazolinyl) methyl) piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4- (2-methylthiazolinyl) methyl) piperidine and as described in Example 1, Scheme A, step b and 2-Chloro-6- [4- (1- (4- (2-methyl) thiazolinyl) methyl) piperidinylamino] -9-cyclopentylpurine was prepared from triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (2-methyl) thiazolinyl) methyl) piperidinylamino] -9 Cyclopentylpurine

Basically 2-chloro-6- [4- (1- (4- (2-methyl) thiazolinyl) methyl) piperidinylamino] -9-cyclo as described in Example 1, Scheme A, step c 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (2-methyl) thiazolinyl) methyl) piperidinylamino] -9-cyclopentyl from pentylpurine Purine was prepared.

Example 144

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-thiophenyl) methyl) piperidinylamino] -9-cyclopentylpurine

Preparation of 4-amino-1- (2-thiophenyl) methylpiperidine:

Method 1:

Scheme B, step a: 4-carboxamide-1- (2-thiophenyl) methylpiperidine

Basically 4-carboxamide-1- (2-thiophenyl) methylpiperidine was obtained from isonifecottamide and 2- (chloromethyl) thiophene as described in Example 38, Scheme B, step a. Prepared.

Scheme B, step b: 4-amino-1- (2-thiophenyl) methylpiperidine

Basically 4-amino-1- (2-thiophenyl) methylpi from 4-carboxamide-1- (2-thiophenyl) methylpiperidine as described in Example 38, Scheme B, step b. Ferridine was prepared.

Method 2:

Scheme C, step a: 1- (2-thiophenyl) methyl-4-piperidone

Basically 1- (2-thiophenyl) methyl-4-piperidone was prepared from 4-piperidone and 2- (chloromethyl) thiophene as described in Example 38, Scheme C, step a.

Scheme C, step b: 1- (2-thiophenyl) methyl-4-piperidone oxime

Basically 1- (2-thiophenyl) methyl-4- from 1- (2-thiophenyl) methyl-4-piperidone and hydroxylamine hydrochloride as described in Example 38, Scheme C, step b. Piperidone oxime was prepared.

Scheme C, step c: 4-amino-1- (2-thiophenyl) methylpiperidine

Basically, 4-amino-1- (2-thiophenyl) methylpiperidine was extracted from 1- (2-thiophenyl) methyl-4-piperidone oxime as described in Example 38, Scheme C, step c. Prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (2-thiophenyl) methyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-thiophenyl) methylpiperidine and triethylamine as described in Example 1, Scheme A, step b. -Chloro-6- [4- (1- (2-thiophenyl) methyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-thiophenyl) methyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2-chloro-6- [4- (1- (2-thiophenyl) methyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. [Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-thiophenyl) methyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Example 145a

Trans-2- [trans- (4-aminocyclohexyl) amino] -6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: trans-2-chloro-6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine

Essentially trans-2-chloro-6- from 2,6-dichloro-9-cyclopentylpurine, trans-4- (amino) cyclohexanol and triethylamine as described in Example 1, Scheme A, step b. [(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: trans-2- [trans- (4-aminocyclohexyl) amino] -6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine dihydrochloride

Basically, trans-2- [trans- (4) from trans-2-chloro-6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -Aminocyclohexyl) amino] -6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 414 (M−H ⁺ ), Rf (min) = 3.25

Example 145b

Cis-2- [trans- (4-aminocyclohexyl) amino] -6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: cis-2-chloro-6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine

Basically cis-2-chloro-6- from 2,6-dichloro-9-cyclopentylpurine, cis-4- (amino) cyclohexanol and triethylamine as described in Example 1, Scheme A, step b. [(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: cis-2- [trans- (4-aminocyclohexyl) amino] -6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine dihydrochloride

Basically cis-2- [trans- (4) from cis-2-chloro-6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -Aminocyclohexyl) amino] -6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 414 (M−H ⁺ ), Rf (min) = 3.25

Example 146

(R, S) -2- [trans- (4-aminocyclohexyl) amino] -6-[(1-hydroxymethyl) cyclopentylamino] -9-cyclopentylpurine dihydrochloride

Scheme A, step b: (R, S) -2-chloro-6-[(1-hydroxymethyl) cyclopentylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, (R, S) -2-hydroxymethyl-1-aminocyclopentane and triethylamine as described in Example 1, Scheme A, step b ( R, S) -2-chloro-6-[(1-hydroxymethyl) cyclopentylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6-[(1-hydroxymethyl) cyclopentylamino] -9-cyclopentylpurine dihydrochloride

Basically from (R, S) -2-chloro-6-[(1-hydroxymethyl) cyclopentylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c ) -2- [trans- (4-aminocyclohexyl) amino] -6-[(1-hydroxymethyl) cyclopentylamino] -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 414 (M−H ⁺ ), Rf (min) = 3.27

Example 147

2- [trans- (4-aminocyclohexyl) amino] -6- (2,4-dichlorophenylhydrazino) -9-cyclopentylpurine dihydrochloride

Scheme A, step b: 2-chloro-6- (2,4-dichlorophenylhydrazino) -9-cyclopentylpurine

Basically 2-chloro-6- (2,4- from 2,6-dichloro-9-cyclopentylpurine, 2,4-dichlorophenylhydrazine and triethylamine as described in Example 1, Scheme A, step b. Dichlorophenylhydrazino) -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- (2,4-dichlorophenylhydrazino) -9-cyclopentylpurine dihydrochloride

Basically, 2- [trans- (4-aminocyclohexyl) from 2-chloro-6- (2,4-dichlorophenylhydrazino) -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Amino] -6- (2,4-dichlorophenylhydrazino) -9-cyclopentylpurine dihydrochloride was prepared. CIMS (NH ₃ ) 475 (MH ⁺ ), Rf (min) = 3.49

Example 147-a

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (1-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (1-naphthyl) methylpiperidine

Basically 4-carboxamide-1- (1-naphthyl) from isonifecottamide and 1- (chloromethyl) naphthalene (available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Methylpiperidine was prepared.

Scheme B, step b: 4-amino-1- (1-naphthyl) methylpiperidine

Basically 4-amino-1- (1-naphthyl) methylpiperidine from 4-carboxamide-1- (1-naphthyl) methylpiperidine as described in Example 38, Scheme B, step b. Was prepared.

Scheme A, step b: 2-chloro-6- [4- (1- (1-naphthyl) methyl) piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (1-naphthyl) methylpiperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- (1- (1-naphthyl) methyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (1-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine trihydro Chloride

Basically from 2-chloro-6- [4- [1- (1-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (1-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 539 (M ⁺¹ ), R _f (minutes) = 2.33

Example 147-b

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2-trifluoromethylbenzyl) piperidine

Basically 4-carboxamide-1- (2- from isonipecottamide and 2- (trifluoromethyl) benzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Trifluoromethylbenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-trifluoromethylbenzyl) piperidine

Basically 4-amino-1- (2-trifluoromethylbenzyl from 4-carboxamide-1- (2-trifluoromethylbenzyl) piperidine as described in Example 38, Scheme B, step b. Piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-trifluoromethylbenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- [1- (2-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (2-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -[Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 557 (M ⁺¹ ), R _f (minutes) = 2.29

Example 147-c

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-dimethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3,5-dimethoxybenzyl) piperidine

4-Carboxamide-1- (2-trifluorine) from isonipecottamide and 3,5-dimethoxybenzyl chloride (commercially available from Aldrich Chemical Company) as basically described in Example 38, Scheme B, step a Romethylbenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3,5-dimethoxybenzyl) piperidine

Basically 4-amino-1- (3,5-dimethoxybenzyl from 4-carboxamide-1- (3,5-dimethoxybenzyl) piperidine as described in Example 38, Scheme B, step b. Piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3,5-dimethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3,5-dimethoxybenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- [1- (3,5-dimethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-dimethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (3,5-dimethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -[Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-dimethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 549 (M ⁺¹ ), R _f (minutes) = 2.27

Example 147-d

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- [3,5-bis (trifluoromethyl) benzyl]] piperidinylamino] -9-cyclopentylpurine tree Hydrochloride

Scheme B, step a: 4-carboxamide-1- (3,5-bis-trifluoromethylbenzyl) piperidine

4-Carboxamide-1- basically from Isonipecotamide and bis (3,5-trifluoromethyl) benzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a. (3,5-bis-trifluoromethylbenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3,5-bis-trifluoromethylbenzyl) piperidine

Basically 4-amino-1- (3,5 from 4-carboxamide-1- (3,5-bis-trifluoromethylbenzyl) piperidine as described in Example 38, Scheme B, step b. -Bis-trifluoromethylbenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3,5-bis-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3,5-bis-trifluoromethylbenzyl) piperidine as described in Example 1, Scheme A, step b and 2-Chloro-6- [4- [1- (3,5-bis-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-bis-trifluoromethylbenzyl)] piperidinylamino] -9 Cyclopentylpurine trihydrochloride

Basically 2-chloro-6- [4- [1- [bis (3,5-trifluoromethyl) benzyl]] piperidinylamino] -9- as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- [3,5-bis (trifluoromethyl) benzyl]] piperidinylamino] -9- from cyclopentylpurine Cyclopentylpurine trihydrochloride was prepared. APCI: 625 (M ⁺¹ ), R _f (minutes) = 2.37

Example 147-e

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,3-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2,3-difluorobenzyl) piperidine

4-Carboxamide-1- (2,3 from Basics isonipecotamide and 2,3-difluorobenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a -Difluorobenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2,3-difluorobenzyl) piperidine

Basically 4-amino-1- (2,3-difluoro from 4-carboxamide-1- (2,3-difluorobenzyl) piperidine as described in Example 38, Scheme B, step b. Robbenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2,3-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2,3-difluorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-chloro-6- [4- [1- (2,3-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,3-difluorobenzyl)] piperidinylamino] -9-cyclopentyl Purine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (2,3-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Prepare 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,3-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride It was. APCI: 525 (M ⁺¹ ), R _f (minutes) = 2.26

Example 147-f

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2,5-difluorobenzyl) piperidine

Basically 4-carboxamide-1- (2,5 from isonipecotamide and 2,5-difluorobenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a -Difluorobenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2,5-difluorobenzyl) piperidine

Basically 4-amino-1- (2,5-difluoro from 4-carboxamide-1- (2,5-difluorobenzyl) piperidine as described in Example 38, Scheme B, step b. Robbenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2,5-difluorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-chloro-6- [4- [1- (2,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,5-difluorobenzyl)] piperidinylamino] -9-cyclopentyl Purine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (2,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Prepare 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride It was. APCI: 525 (M ⁺¹ ), R _f (minutes) = 2.26

Example 147-g

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3,5-difluorobenzyl) piperidine

Basically 4-carboxamide-1- (3,5 from isonipecotamide and 3,5-difluorobenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a -Difluorobenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3,5-difluorobenzyl) piperidine

Basically 4-amino-1- (3,5-difluoro from 4-carboxamide-1- (3,5-difluorobenzyl) piperidine as described in Example 38, Scheme B, step b. Robbenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3,5-difluorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-chloro-6- [4- [1- (3,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-difluorobenzyl)] piperidinylamino] -9-cyclopentyl Purine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (3,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Prepare 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride It was. APCI: 525 (M ⁺¹ ), R _f (minutes) = 2.25

Example 147-h

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2,4-difluorobenzyl) piperidine

Basically 4-carboxamide-1- (2,4 from isonifecottamide and 2,4-difluorobenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a -Difluorobenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2,4-difluorobenzyl) piperidine

Basically 4-amino-1- (2,4-difluoro from 4-carboxamide-1- (2,4-difluorobenzyl) piperidine as described in Example 38, Scheme B, step b. Robbenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2,4-difluorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-chloro-6- [4- [1- (2,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-difluorobenzyl)] piperidinylamino] -9-cyclopentyl Purine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (2,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Prepare 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride It was. APCI: 525 (M ⁺¹ ), R _f (minutes) = 2.25

Example 147-i

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3-methylbenzyl) piperidine

Basically 4-carboxamide-1- (3-methylbenzyl) piperi from isonifecottamide and 3-methylbenzyl bromide (available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Dean was prepared.

Scheme B, step b: 4-amino-1- (3-methylbenzyl) piperidine

Basically 4-amino-1- (3-methylbenzyl) piperidine was prepared from 4-carboxamide-1- (3-methylbenzyl) piperidine as described in Example 38, Scheme B, step b. It was.

Scheme A, step b: 2-chloro-6- [4- [1- (3-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-methylbenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -6- [4- [1- (3-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Basically 2- [trans from 2-chloro-6- [4- [1- (3-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -(4-aminocyclohexyl) amino] -6- [4- [1- (3-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 503 (M ⁺¹ ), R _f (minutes) = 2.24

Example 147-j

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3-fluorobenzyl) piperidine

Basically 4-carboxamide-1- (3-fluorobenzyl) from isonifecottamide and 3-fluorobenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-fluorobenzyl) piperidine

Basically 4-amino-1- (3-fluorobenzyl) piperidine from 4-carboxamide-1- (3-fluorobenzyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-fluorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- [1- (3-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydro Chloride

Basically from 2-chloro-6- [4- [1- (3-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 507 (M ⁺¹ ), R _f (minutes) = 2.25

Example 147-k

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2-fluorobenzyl) piperidine

Basically 4-carboxamide-1- (2-fluorobenzyl) from isonifecottamide and 2-fluorobenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-fluorobenzyl) piperidine

Basically 4-amino-1- (2-fluorobenzyl) piperidine from 4-carboxamide-1- (2-fluorobenzyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-fluorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- [1- (2-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydro Chloride

Basically from 2-chloro-6- [4- [1- (2-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 507 (M ⁺¹ ), R _f (minutes) = 2.22

Example 147-l

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (4-fluorobenzyl) piperidine

Basically 4-carboxamide-1- (4-fluorobenzyl) from isonifecottamide and 4-fluorobenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-fluorobenzyl) piperidine

Basically 4-amino-1- (4-fluorobenzyl) piperidine from 4-carboxamide-1- (4-fluorobenzyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2-, from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-fluorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- [1- (4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydro Chloride

Basically from 2-chloro-6- [4- [1- (4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 507 (M ⁺¹ ), R _f (minutes) = 2.23

Example 147-m

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3-trifluoromethylbenzyl) piperidine

4-Carboxamide-1- (3- basically from isonipecotamide and 3- (trifluoromethyl) benzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Trifluoromethylbenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-trifluoromethylbenzyl) piperidine

Basically 4-amino-1- (3-trifluoromethylbenzyl from 4-carboxamide-1- (3-trifluoromethylbenzyl) piperidine as described in Example 38, Scheme B, step b. Piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-trifluoromethylbenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- [1- (3-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (3-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -[Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 557 (M ⁺¹ ), R _f (minutes) = 2.31

Example 147-n

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-chloro-6-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2-chloro-6-fluorobenzyl) piperidine

Basically 4-carboxamide-1- (2- from isonifecottamide and 2-chloro-6-fluorobenzyl chloride (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a. Chloro-6-fluorobenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-chloro-6-fluorobenzyl) piperidine

Basically 4-amino-1- (2-chloro-6 from 4-carboxamide-1- (2-chloro-6-fluorobenzyl) piperidine as described in Example 38, Scheme B, step b. -Fluorobenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2-chloro-6-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-chloro-6-fluorobenzyl) piperidine and triethyl as described in Example 1, Scheme A, step b. 2-chloro-6- [4- [1- (2-chloro-6-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from the amine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-chloro-6-fluorobenzyl)] piperidinylamino] -9-cyclo Pentylpurine trihydrochloride

Basically 2-chloro-6- [4- [1- (2-chloro-6-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-chloro-6-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride from Was prepared. APCI: 541 (M ⁺¹ ), R _f (minutes) = 2.22

Example 147-o

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3,4-dichlorobenzyl) piperidine

Basically 4-carboxamide-1- (3,4-dichloro from isonifecottamide and 3,4-dichlorobenzyl chloride (available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Benzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3,4-dichlorobenzyl) piperidine

Basically 4-amino-1- (3,4-dichlorobenzyl) pi from 4-carboxamide-1- (3,4-dichlorobenzyl) piperidine as described in Example 38, Scheme B, step b. Ferridine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3,4-dichlorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -Chloro-6- [4- [1- (3,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine tree Hydrochloride

Basically from 2-chloro-6- [4- [1- (3,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. [Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 557 (M ⁺¹ ), R _f (minutes) = 2.33

Example 147-p

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2-naphthyl) methylpiperidine

Basically 4-carboxamide-1- (2-naphthyl) from isonifecottamide and 2- (chloromethyl) naphthalene (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Methylpiperidine was prepared.

Scheme B, step b: 4-amino-1- (2-naphthyl) methylpiperidine

Basically 4-amino-1- (2-naphthyl) methylpiperidine from 4-carboxamide-1- (2-naphthyl) methylpiperidine as described in Example 38, Scheme B, step b. Was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-naphthyl) methylpiperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- [1- (2-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine trihydro Chloride

Basically from 2-chloro-6- [4- [1- (2-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 539 (M ⁺¹ ), R _f (minutes) = 2.30

Example 147-q

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-methoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2-methoxybenzyl) piperidine

Basically 4-carboxamide-1- (2-methoxybenzyl) from isonifecottamide and 2-methoxybenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-methoxybenzyl) piperidine

Basically 4-amino-1- (2-methoxybenzyl) piperidine from 4-carboxamide-1- (2-methoxybenzyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2-methoxybenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-methoxybenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- [1- (2-methoxybenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-methoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydro Chloride

Basically from 2-chloro-6- [4- [1- (2-methoxybenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-methoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 519 (M ⁺¹ ), R _f (minutes) = 2.19

Example 147-r

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2,5-dichlorobenzyl) piperidine

Basically 4-carboxamide-1- (2,5-dichloro from isonipecottamide and 2,5-dichlorobenzyl chloride (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Benzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2,5-dichlorobenzyl) piperidine

Basically 4-amino-1- (2,5-dichlorobenzyl) pi from 4-carboxamide-1- (2,5-dichlorobenzyl) piperidine as described in Example 38, Scheme B, step b. Ferridine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2,5-dichlorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -Chloro-6- [4- [1- (2,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine tree Hydrochloride

Basically from 2-chloro-6- [4- [1- (2,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. [Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 557 (M ⁺¹ ), R _f (minutes) = 2.22

Example 147-s

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-cyclohexylmethyl) piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1-cyclohexylmethylpiperidine

4-Carboxamide-1-cyclohexylmethylpiperidine was prepared basically from isonipecottamide and cyclohexylmethyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a. .

Scheme B, step b: 4-amino-1-cyclohexylmethylpiperidine

Basically 4-amino-1-cyclohexylmethylpiperidine was prepared from 4-carboxamide-1-cyclohexylmethylpiperidine as described in Example 38, Scheme B, step b.

Scheme A, step b: 2-chloro-6- [4- (1-cyclohexylmethyl) piperidinylamino] -9-cyclopentylpurine

Basically 2-chloro-6- from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1-cyclohexylmethylpiperidine and triethylamine as described in Example 1, Scheme A, step b. [4- (1-cyclohexylmethyl) piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-cyclohexylmethyl) piperidinylamino] -9-cyclopentylpurine trihydrochloride

Basically 2- (trans- (4) from 2-chloro-6- [4- (1-cyclohexylmethyl) piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -Aminocyclohexyl) amino] -6- [4- (1-cyclohexylmethyl) piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 495 (M ⁺¹ ), R _f (minutes) = 2.25

Example 147-t

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-chloro-4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2-chloro-4-fluorobenzyl) piperidine

Basically 4-carboxamide-1- (2- from isonipecottamide and 2-chloro-4-fluorobenzyl chloride (commercially available from Lancaster or Acros) as described in Example 38, Scheme B, step a. Chloro-4-fluorobenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-chloro-4-fluorobenzyl) piperidine

Basically 4-amino-1- (2-chloro-4 from 4-carboxamide-1- (2-chloro-4-fluorobenzyl) piperidine as described in Example 38, Scheme B, step b. -Fluorobenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2-chloro-4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-chloro-4-fluorobenzyl) piperidine and triethyl as described in Example 1, Scheme A, step b. 2-chloro-6- [4- [1- (2-chloro-4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from amines.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-chloro-4-fluorobenzyl)] piperidinylamino] -9-cyclo Pentylpurine trihydrochloride

Basically 2-chloro-6- [4- [1- (2-chloro-4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. From 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-chloro-4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride Was prepared. APCI: 541 (M ⁺¹ ), R _f (minutes) = 2.28

Example 147-u

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3,4-difluorobenzyl) piperidine

Basically 4-carboxamide-1- (3,4 from isonifecottamide and 3,4-difluorobenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a -Difluorobenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3,4-difluorobenzyl) piperidine

Basically 4-amino-1- (3,4-difluoro from 4-carboxamide-1- (3,4-difluorobenzyl) piperidine as described in Example 38, Scheme B, step b. Robbenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3,4-difluorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-chloro-6- [4- [1- (3,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-difluorobenzyl)] piperidinylamino] -9-cyclopentyl Purine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (3,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Prepare 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride It was. APCI: 525 (M ⁺¹ ), R _f (minutes) = 2.29

Example 147-v

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,6-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2,6-difluorobenzyl) piperidine

4-Carboxamide-1- (2,6) from basically Isonipecotamide and 2,6-difluorobenzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a -Difluorobenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2,6-difluorobenzyl) piperidine

Basically 4-amino-1- (2,6-difluoro from 4-carboxamide-1- (2,6-difluorobenzyl) piperidine as described in Example 38, Scheme B, step b. Robbenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2,6-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2,6-difluorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-chloro-6- [4- [1- (2,6-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,6-difluorobenzyl)] piperidinylamino] -9-cyclopentyl Purine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (2,6-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Prepare 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,6-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride It was. APCI: 525 (M ⁺¹ ), R _f (minutes) = 2.26

Example 147-w

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3,5-dichlorobenzyl) piperidine

Basically 4-carboxamide-1- (3 from isonifecottamide and 3,5-dichlorobenzyl chloride (commercially available from Trans World Chemicals or Fluorochem Ltd.) as described in Example 38, Scheme B, step a. , 5-dichlorobenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3,5-dichlorobenzyl) piperidine

Basically 4-amino-1- (3,5-dichlorobenzyl) pi from 4-carboxamide-1- (3,5-dichlorobenzyl) piperidine as described in Example 38, Scheme B, step b. Ferridine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3,5-dichlorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -Chloro-6- [4- [1- (3,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine tree Hydrochloride

Basically from 2-chloro-6- [4- [1- (3,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. [Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,5-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 557 (M ⁺¹ ), R _f (minutes) = 2.31

Example 147-x

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2,4-dichlorobenzyl) piperidine

Basically 4-carboxamide-1- (2,4-dichloro from isonipecottamide and 2,4-dichlorobenzyl chloride (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a Benzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2,4-dichlorobenzyl) piperidine

Basically 4-amino-1- (2,4-dichlorobenzyl) pi from 4-carboxamide-1- (2,4-dichlorobenzyl) piperidine as described in Example 38, Scheme B, step b. Ferridine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2,4-dichlorobenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. -Chloro-6- [4- [1- (2,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine tree Hydrochloride

Basically from 2-chloro-6- [4- [1- (2,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. [Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-dichlorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 557 (M ⁺¹ ), R _f (minutes) = 2.31

Example 147-y

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-chloro-4-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3-chloro-4-methylbenzyl) piperidine

Basically 4-carboxamide-1- (3-chloro from isonifecottamide and 3-chloro-4-methylbenzyl chloride (commercially available from Pfaltz-Bauer) as described in Example 38, Scheme B, step a 4-Methylbenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (3-chloro-4-methylbenzyl) piperidine

Basically 4-amino-1- (3-chloro-4- from 4-carboxamide-1- (3-chloro-4-methylbenzyl) piperidine as described in Example 38, Scheme B, step b. Methylbenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3-chloro-4-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-chloro-4-methylbenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-chloro-6- [4- [1- (3-chloro-4-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-chloro-4-methylbenzyl)] piperidinylamino] -9-cyclopentyl Purine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (3-chloro-4-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Prepare 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-chloro-4-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride It was. APCI: 537 (M ⁺¹ ), R _f (minutes) = 2.25

Example 147-z

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (4-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (4-trifluoromethoxybenzyl) piperidine

Basically 4-carboxamide-1- (4- Trifluoromethoxybenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (4-trifluoromethoxybenzyl) piperidine

Basically 4-amino-1- (4-trifluoromethoxybenzyl from 4-carboxamide-1- (4-trifluoromethoxybenzyl) piperidine as described in Example 38, Scheme B, step b. Piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (4-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (4-trifluoromethoxybenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- [1- (4-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (4-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (4-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -[Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (4-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 573 (M ⁺¹ ), R _f (minutes) = 2.23

Example 147-aa

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-bis-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydro Chloride

Scheme B, step a: 4-carboxamide-1- (2,4-bis-trifluoromethylbenzyl) piperidine

4-Carboxamide-1- basically from Isonipecottamide and bis (2,4-trifluoromethyl) benzyl bromide (commercially available from Aldrich Chemical Company) as described in Example 38, Scheme B, step a. (2,4-bis-trifluoromethylbenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2,4-bis-trifluoromethylbenzyl) piperidine

Basically 4-amino-1- (2,4 from 4-carboxamide-1- (2,4-bis-trifluoromethylbenzyl) piperidine as described in Example 38, Scheme B, step b. -Bis-trifluoromethylbenzyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2,4-bis-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2,4-bis-trifluoromethylbenzyl) piperidine as described in Example 1, Scheme A, step b and 2-Chloro-6- [4- [1- (2,4-bis-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared from triethylamine.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-bis-trifluoromethylbenzyl)] piperidinylamino] -9 Cyclopentylpurine trihydrochloride

Basically 2-chloro-6- [4- [1- (2,4-bis-trifluoromethylbenzyl)] piperidinylamino] -9-cyclo as described in Example 1, Scheme A, step c 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-bis-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentyl from pentylpurine Purine trihydrochloride was prepared. APCI: 625 (M ⁺¹ ), R _f (min) = 1.44

Example 147-ab

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (2-trifluoromethoxybenzyl) piperidine

Basically 4-carboxamide-1- (2- Trifluoromethoxybenzyl) piperidine was prepared.

Scheme B, step b: 4-amino-1- (2-trifluoromethoxybenzyl) piperidine

Basically 4-amino-1- (2-trifluoromethoxybenzyl from 4-carboxamide-1- (2-trifluoromethoxybenzyl) piperidine as described in Example 38, Scheme B, step b. Piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (2-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (2-trifluoromethoxybenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. 2-Chloro-6- [4- [1- (2-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine Trihydrochloride

Basically from 2-chloro-6- [4- [1- (2-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. -[Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-trifluoromethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 573 (M ⁺¹ ), R _f (minutes) = 2.26

Example 147-ac

2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-benzyl) piperidinylmethylamino] -9-cyclopentylpurine trihydrochloride

N-benzyl-4- (aminomethyl) piperidine

N-benzyl-4- (amino from 4- (aminomethyl) piperidine (commercially available from Aldrich Chemical Company) as described in LGHumber, J. Med. Chem., 9, 441-443 (1966) Methyl) piperidine was prepared.

Scheme A, step b: 2-chloro-6- [4- (1-benzyl) piperidinylmethylamino] -9-cyclopentylpurine

Basically 2-chloro-6- [from 2,6-dichloro-9-cyclopentylpurine, N-benzyl-4-aminomethylpiperidine and triethylamine as described in Example 1, Scheme A, step b. 4- (1-benzyl) piperidinylmethylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-benzyl) piperidinylmethylamino] -9-cyclopentylpurine trihydrochloride

Basically 2- (trans- (4-) from 2-chloro-6- [4- (1-benzyl) piperidinylmethylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Aminocyclohexyl) amino] -6- [4- (1-benzyl) piperidinylmethylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 503 (M ⁺¹ ), R _f (minutes) = 2.24

Example 147-ad

2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-phenoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride

Scheme B, step a: 4-carboxamide-1- (3-phenoxybenzyl) piperidine

Basically 4-carboxamide-1- (3-phenoxybenzyl) piperi from isonifecottamide and 3-phenoxybenzyl chloride (commercially available from Lancaster) as described in Example 38, Scheme B, step a Dean was prepared.

Scheme B, step b: 4-amino-1- (3-phenoxybenzyl) piperidine

Basically 4-amino-1- (3-phenoxybenzyl) piperidine from 4-carboxamide-1- (3-phenoxybenzyl) piperidine as described in Example 38, Scheme B, step b. Was prepared.

Scheme A, step b: 2-chloro-6- [4- [1- (3-phenoxybenzyl)] piperidinylamino] -9-cyclopentylpurine

Basically from 2,6-dichloro-9-cyclopentylpurine, 4-amino-1- (3-phenoxybenzyl) piperidine and triethylamine as described in Example 1, Scheme A, step b. Chloro-6- [4- [1- (3-phenoxybenzyl)] piperidinylamino] -9-cyclopentylpurine was prepared.

Scheme A, step c: 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-phenoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydro Chloride

Basically from 2-chloro-6- [4- [1- (3-phenoxybenzyl)] piperidinylamino] -9-cyclopentylpurine as described in Example 1, Scheme A, step c. Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-phenoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride was prepared. APCI: 581 (M ⁺¹ ), R _f (minutes) = 2.35

The term "neoplastic disease state" as used herein refers to an abnormal condition or condition characterized by uncontrolled proliferation. Neoplastic disease states include leukemia, carcinoma and adenocarcinoma, sarcoma, melanoma, and mixed types of neoplasms.

Leukemias include but are not limited to acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia and chronic myeloid leukemia.

Carcinomas and adenocarcinomas include, but are not limited to, cervical cancer, breast cancer, prostate cancer, esophageal cancer, gastric cancer, small intestine cancer, colon cancer, ovarian cancer and lung cancer.

Sarcomas include but are not limited to osteosarcoma, osteogenic sarcoma, lipoma, liposarcoma, hemangioma and angiosarcoma.

Melanoma includes but is not limited to melanin deficient melanoma and melanogenic melanoma.

Mixed types of neoplasms include, but are not limited to, carcinosarcoma disease, lymphoid tissue type disease, follicular reticulum disease, cell sarcoma disease, and Hodgkin's disease.

The term "therapeutically effective amount" of a compound of Formula 1 refers to an amount effective to control the growth or metastasis of neoplasms or to inhibit apoptosis when administered to a patient in single or multiple doses. The therapeutically effective amount of a compound of the present invention will vary depending on age, weight, type of neoplasm to be treated, degree of combination with other neoplastic inhibitors, and criteria known in the art (using standard clinical and laboratory tests and methods). A therapeutically effective amount of a compound of the invention will depend on the type of sensitivity to the site of apoptosis and incomplete flexion fracture of the cell, as well as age, weight and other criteria known to those skilled in the art.

The term "controlling growth" of a neoplasm means that the neoplasm slows, interferes with, inhibits or stops growth or metastasis of the neoplasm. In addition, the term "modulating growth" of neoplasms means killing neoplasms or their metastases.

A therapeutically effective amount of the compound of the present invention means an amount that exhibits an anti-neoplastic effect or an apoptotic inhibitory effect when administered to a patient in a single dose or multiple doses. By "neoplastic inhibitory effect" is meant to further slow, hinder, inhibit or stop the growth of neoplastic cells.

The neoplastic inhibitory effective amount of the compounds of the present invention can be readily determined by diagnostic experts skilled in the art using known techniques and observing the results obtained under similar circumstances. In determining the effective amount, there are many factors that are considered by diagnostic experts, including the species of the mammal, its size and age and general health, the specific disease involved, the degree and severity of the disease, the response of the individual patient, and the dose to be administered. Compounds of a particular structural formula, mode of administration, bioavailability of the agent to be administered, the method of administration chosen, the use of ancillary drugs, and other suitable circumstances are included.

A further embodiment of the present invention includes a method of preventing a patient at risk of developing a neoplastic disease condition comprising administering a prophylactically effective amount of a neoplastic inhibitor compound. The term “patient at risk of developing a neoplastic disease condition” refers to a neoplastic disease caused by a genetic predisposition to neoplasms or by other factors related to exposure to carcinogens, food, age, or neoplastic disease states. It means a patient who has or has a disease. Priority patients at risk of developing a neoplastic condition, including those who have a positive response to an oncogenetic virus, may be alleviating symptoms in the initial treatment of neoplasms, smoking, or in the past with carcinogens such as asbestos. By a patient who has been exposed to or has tested positive for various neoplastic gene markers.

Oncogene viruses are viruses associated with cancer. For example, chicken Raus sarcoma virus, rabbit shop papilloma virus, and rat leukemia virus are known as animal viruses that function to cause various cancers. Human papilloma virus is associated with cancer of the genitals. Infectious viruses of molluscs are associated with infectious tumors of mollusks. JC virus, a human papovavirus, is associated with reticuloendothelial diseases such as leukemia and lymphoma. Human T-cell lymphotrophic virus (HTLV) type 1 and type 2 are associated with several human leukemias and lymphomas. Human immunodeficiency virus (HIV) type 1 and type 2 cause AIDS. Epsteinba virus is associated with various malignancies, including nasopharyngeal malignancies, African Burkitt's lymphoma and lymphoma in immunosuppressive organs of transplanted receptors.

Genetic markers include BRCA 1, bcl-1 / PRAD1, cyclin D1 / CCND1, p16, cdk4, in particular Arg24Cys mutations, mutations and rearrangements at p16 ^INK4a . Genetic markers are associated with the cultivation of various neoplasms. For example, alteration of the BRCA 1 gene increases the risk of developing breast and ovarian cancer. Other gene markers include changes in the MMSC1 gene that interacts with MMCA1 in brain and prostate cancer, changes in the CtIP gene associated with the BRACA1 gene and in combination with the BRCA1 gene and associated with the E1A tumor gene pathway in breast and ovarian cancer, and apopto Activation of cis causes a change in the MKK3 gene, a cell cycle regulatory gene that acts as an inhibitor in lung cancer. In addition, patients at risk of developing neoplastic disease conditions include patients overexpressing various cell cycle proteins (including cdk4, cyclins B1 and E). Patients at risk of developing neoplastic disease conditions include patients with increased amounts of tumor markers. Known tumor markers include prostate specific antigen (PSA), a marker of prostate cancer, and insulin-like growth factor-1 (IGF-1) in plasma. Nuclear matrix protein (NMP) is associated with cancer, particularly bladder and colon cancer.

A daily effective amount of a compound of the invention is expected to be about 25 ng (25 ng / kg / day) to 500 mg / kg / day per kg body weight. Preferred effective amounts of the compounds of the invention are about 1 μg / kg / day to 500 μg / kg / day. More preferred effective amounts of the compounds of the invention are about 1 μg / kg / day to 50 μg / kg / day.

The compound of the present invention is administered in an effective amount in any form or manner in which the compound is used in vivo. The compounds of the present invention can be administered orally, subcutaneously, intramuscularly, intravenously, skin, intranasally, rectal and ocular. Oral administration is preferred. Those skilled in the art of preparing pharmaceutical compositions can readily determine suitable dosage forms of the compounds of the present invention based on the nature of the compound, the condition to be treated, the stage of the disease, the response of the other patient, and the appropriate environment.

To prepare a composition of a compound, the compound of the present invention may be mixed with a carrier, excipient or other compound. Compositions of the compounds of the present invention comprise compounds in admixture with one or more inert carriers. Compositions of the compounds of the present invention are useful compounds that are convenient for mass transport or storage. Inert carriers are substances that do not decompose and do not react covalently with the compounds of the present invention.

The inert carrier can be a solid, semisolid or liquid material. Preferred carriers are water, aqueous buffers, organic solvents and pharmaceutically acceptable carriers or excipients. Preferred aqueous buffers buffer in the range in which the compounds of the present invention are not degraded. Preferred buffer ranges are from about pH 4 to about pH 9. Preferred organic solvents are acetonitrile, ethyl acetate and hexane.

Pharmaceutical compositions of the compounds of this invention include compounds in admixture with one or more pharmaceutically acceptable carriers or excipients. Pharmaceutically acceptable carriers or excipients may be solid, semisolid or liquid materials, which can act as vehicles or media for the compounds of the present invention. Suitable as pharmaceutically acceptable carriers or excipients are well known to those skilled in the art.

Pharmaceutical compositions of the compounds of this invention may vary depending on the route of administration. When the route of administration is oral administration, parenteral administration or topical administration, preferred pharmaceutical compositions of the compounds of the invention are tablets, pills, capsules, elisers, syrups, wafers, chewing gum, suppositories, solutions or It is a suspending agent.

Preferred oral pharmaceutical compositions comprise a compound of the present invention in admixture with an inert diluent or an edible carrier. Preferred forms of the pharmaceutical composition for oral administration are tablets, pills, capsules, elixirs, syrups, wafers, chewing gum, solutions or suspensions.

Preferred pharmaceutical compositions of the present invention comprise from about 4% to about 80% of the compounds of the present invention. The pharmaceutical composition of the present invention preferably comprises about 50 ng to about 500 μg of the compound of the invention, more preferably about 1 μg to about 200 μg of the compound of the invention.

The compounds of the present invention may be administered alone or in the form of pharmaceutical compositions in combination with pharmaceutically acceptable carriers or excipients.

The following describes the abbreviations used herein. mg is milligrams, μg is micrograms, ng is nanograms, TEA is triethylamine, mmol is millimoles, mL is milliliters, C is degrees Celsius, hr is hours, TLC is thin layer chromatography , CH ₂ CL ₂ is methylene chloride, MeOH is methanol, EtOH is ethanol, N is normal, HCl is hydrochloric acid, TFA is trifluoroacetic acid, DIEA is diisopropylethylamine, RT PCR Reverse transcription polymerase chain reaction, HEPES is 4- (2-hydroxyethyl-1-piperazine ethanesulfonic acid), MgCl ₂ is magnesium chloride, EGTA is ethylene glycol-bis (β-aminoethylether) -N, N, N ', N'-tetraacetic acid, EDTA is ethylenediaminetetraacetic acid, DTT is dithiothreitol, MOI is multiplicity of infection, NaF is sodium fluoride, BSA is bovine serum albumin, po is oral administration, iv is intravenous injection, sc is subcutaneous administration.

Example 148

Cyclin-dependent kinase 4 assay

IC ₅₀ values that inhibit cdk-4 were measured by the following method.

temperament:

Glutathione S-transferase and retinoblastoma fusion protein (GST-Rb) (see Kaelin, WG, Jr., et al., Cell 64: 521-532, 1991) was obtained by Dr. William Kaelin . Plasmid pGEX-Rb (379-928) was transformed into E. coli to prepare GST-Rb. Transformed bacteria were incubated overnight, then diluted with YT medium and incubated at 37 ° C. for 2 hours. The expression of the protein was induced by incubation with 0.1 mM isopropylthioglycoside for 3 hours. After precipitation by centrifugation, the cells were sonicated in STE buffer (0.1 mM NaCl, 10 mM Tris, pH 8.0, 0.1 mM EDTA) containing 10% sarcosyl. The particulate material was removed by centrifugation and the lysate was incubated with glutathione-sepharose at 4 ° C. The beads were washed with kinase buffer, separated by SDS-PAGE, stained with Coomassie blue, and the protein was quantified using known concentrations of protein standards.

Expression of CDK4 / Cyclin D1 in Insect Cells:

Human cyclin-dependent kinase 4 (cdk4) was cloned by RT PCR using primers inferred based on published amino acid sequences (Matsushime, H, et al., Cell, 71: 323-334, 1992). The genomic DNA of MCF-7 cells was used to clone cDNA for human cyclin D1 by RT PCR. This sequence was consistent with the published sequence (Xiong, Y., et al., Cell, 65: 691-699, 1991). Both cDNAs for cdk4 and cyclin D1 were cloned into pFastBac (Life Technologies) and Bac-to-Bac baculovirus expression purchased from Life Technologies (Cat. No. # 10359-016) Using the system, recombinant Bacmid DNA containing the cDNA was prepared by position-positioned transposition. Recombinant virus was prepared using baekmid DNA to transfect Sf9 insect cells. After plaque purification of the virus, the virus preparation was amplified until the titer became a high stock solution. In both cdk4 and cyclin D1, coexpression of recombinant protein was optimal when the MOI was 0.1 at 72 hours after infection.

50 mM HEPES (pH 7.5), 10 mM MgCl ₂ , 1 mM DTT, 0.1 mM phenylmethylsulfonyl fluoride, 50 μg / ml apro, using a PARR bomb for 5 minutes under nitrogen pressure of 500 ° C. at 4 ° C. Cell lysates were prepared by lysing Sf9 cells infected with cdk4 and cyclin D1 together in a mixture of tinine and 5 μg / ml leupetin. Insoluble material was precipitated by centrifugation at 10,000 × g for 20 minutes at 4 ° C. Glycerol was added to 10% in the supernatant and stored at -81 ° C.

Kinase Analysis:

200 μl of kinase buffer (50 mM HEPES, pH 7.5, 10 mM MgCl ₂ , 1 mM EDTA) was previously added to a wet Millipore Multiscreen 96-well filter plate (0.65 μm Durapore filter paper). 50 μl of GST-Rb (0.5 μg) bound to glutathione-sepharose beads was added to each well, and the solution was removed by vacuum. The analytes were 50 mM HEPES, pH 7.5, 10 mM MgCl ₂ , 1 mM EDTA, 1 mM DTT, 1 mM EGTA, 10 mM β-glycerophosphate, 0.1 mM sodium orthovanadate, 0.1 mM NaF, 0.25% BSA, 10 μM ATP and 0.25 μCi [γ ³³ P] -ATP was included. The assay was initiated by adding 0.1 μg cdk4 / cycline D1 (insect cell lysate). Incubate at 37 ° C. for 30 minutes. The reaction was terminated by filtration with Millipore Vacuum Manifold. Washed four times with TNEN (20 mM Tris, pH 8.0, 100 mM NaCl, 1 mM EDTA, 0.5% nonidet P-40). After drying the plate at room temperature, the filter paper plate is placed in an adapter plate and 40 μl of Microsint-O® (Microscint-O) in each well. Packard was added. The plate was covered using a Top Seal A film and then counted with a Top Count Scintillation Counter.

The above results are shown in Table 1.

Example 149

cdk-2 inhibition studies

IC ₅₀ values that inhibit CDK-2 were measured by the following method.

Cyclin-dependent kinase 2 assay

Substrate: GST-Rb described above for cdk4 / cycline D1

Expression of CDK2 / Cyclin E in Insect Cells

Recombinant baculovirus against human cdk2 and cyclin E were obtained from Dr. David Morgan at the University of California, Berkeley (Desai, D. et al. Molec. Biol. Cell, 3: 571-582, 1992). Co-expression of cdk2 and Cycline E recombinant protein was optimal when the MOIs were 0.1 and 1.0 at 72 hours post infection.

Kinase Analysis:

Analytical conditions for cdk2 and cyclin E were the same as for cdk4 and cyclin D1, including the substrate. The concentrations of recombinant cdk2 and cyclin E in the assay were 0.1 μg per 100 μl of assay volume. Incubation was performed at 30 ° C. for 30 minutes.

The above results are shown in Table 1.

Example 150

ckd7 / Cyclin H Assay Protocol

Substrate: Peptide substrate called H ₂ N-RRR (YSPTSPS) ₄ -COOH based on CTD sequence of RNA polymerase II

Expression of CDK7 / Cyclin H in Insect Cells

Human cdk7 was cloned by reverse transcription PCR. Such sequences are described in Tassan, J. P., et al., J. Cell Biol. 127: 467-478, 1994 and Darbon, J. M. et al., Oncogene, 9: 3127-3138, 1994. In addition, the cDNA of cyclin H was cloned by reverse transcription PCR, and the sequence was consistent with that reported in Fisher & Morgan, Cell, 78: 713-724, 1994. Recombinant bacmid DNA and viral stocks were prepared as described above in cdk4 and Cyclin D1. At 48 hours post-infection, co-expression of cdk7 and cyclin H recombinant protein was optimal when the MOIs were 1 and 2, respectively.

Kinase Analysis:

Kinase assays measure the phosphorylation of peptide substrates (based on the C-terminal domain of RNA polymerase II) by cyclin-dependent kinase 7 achieved by cyclin H. By this enzyme [γ ³³ P] -phosphate is transferred from [γ ³³ P] -ATP to the peptide substrate. The assay was performed in 96-well V-bottom plates and transferred to 96-well Millipore multiscreen phosphocellulose filter plates after the reaction was terminated. After washing with the phosphoric acid solution, the peptide was attached to the phosphocellulose membrane.

Way :

Enzyme analysis was performed with a total volume of 100 μl in 96-well V-bottom plates. Analytes were 15 μM ATP, 0.5 μCi [γ ³³ P] -ATP, 50 mM Hepes, pH 7.5, 10 mM MgCl ₂ , 1 mM EDTA, 1 mM DTT, 10 mM β-glycerophosphate, 0.1 mM sodium orthovanadate, 0.1 mM NaF and 10 μM peptide substrate was included. To initiate the assay, 0.125 ng of cdk7 and Cycline H (insect cell lysate) were added and incubated at 24 ° C. for 5 minutes. The reaction was terminated by adding 40 [mu] l of 300 mM cold phosphoric acid to each sample. The contents of the V-bottom wells were transferred to a Millipore 96-well phosphocellulose filter plate. After stirring at room temperature for 15 minutes, the filter plate was vacuumed and washed four times with 100 μl of 75 mM cold phosphoric acid. After removing the culvert parts, the filter paper was completely dried, placed in a multiscreen microplate adapter, and 40 μl of Microsint-O was added to each well. The plate was covered with a Top-Seal A film and counted for 1.5 minutes using Packard's Peak Scintillation Counter.

The above results are shown in Table 1.

Example 151

CDK1 / Cyclin B [ ³³ P] SPA Assay Protocol

Temperament:

Biotinylated substrate peptide (Biotin-PKTPKKAKKL) derived from the ex vivo p34 ^cdc2 phosphorylation site of histone H1 was used in this assay.

Expression of CDK1 / Cyclin B1 in Insect Cells:

Human cdk1 was cloned by reverse transcription PCR. The sequence was consistent with that reported in Lee, M. G. and Nurse, P. Nature, 327: 31-33, 1987. In addition, the cDNA of Cyclin H was cloned by RT PCR and the sequence was consistent with that reported in Pines, J. and Hunter, T., Cell, 58: 833-846, 1989. Recombinant bacmid DNA and viral stocks were prepared as described above in cdk4 and Cyclin D1. In both cdk1 and cyclin B1, coexpression of recombinant protein was optimal when the MOI was 0.1 48 hours after infection.

Kinase Analysis:

p34 ^cdc2 SPA [ ³³ P] kinase enzyme assay kit was purchased from Amersham Life Science (Cat. No. # RPNQ0170) and 96-well type analysis was performed according to the manufacturer's instructions. Each analyte contains 50 mM Tris-HCl, pH 8.0, 10 mM MgCl ₂ , 0.1 mM Na ₃ VO ₄ (sodium orthovanadate), 0.05 μM ATP, 0.2 μCi ³³ P-ATP, 2 μM DTT, in 100 μl total assay volume. 0.75 μM biotinylated peptide and 3 μg cdk1 / cycline B insect cell lysate. Incubate at 30 ° C. for 30 minutes. 200 μl of termination buffer (50 μM ATP, 5 mM EDTA and 0.1% (volume / volume) Triton X-100 in phosphate buffered saline) was added to terminate the reaction and SPA beads coated with streptavidin (2.5 mg / ml). ) Was added. The plate was left at room temperature overnight, covered with a vertex sealed A film, and counted with a Packard's vertex scintillation counter. IC ₅₀ values were measured using GraphPad Prism software to fit the S-shaped curves.

Example 152

In vitro tumor suppression

Live extracellular proliferation assay:

Skehan, P., et al., J. Natl. Cancer Inst. 82: 1107-1112, 1990 to measure the proliferation of tumor cells using a sulforhodamine B assay. Tumor cells were harvested using trypsin-EDTA, the cells blocked with trypan blue were counted, and then placed in 96-well and incubated overnight at 37 ° C. The drug was diluted in culture medium and then added to the wells. After 3 days the medium was removed and incubated for an additional 4 days after feeding the medium containing fresh drug. Cells were then fixed by treatment with 0.1 ml of 10% trichloroacetic acid at 4 ° C. for 60 minutes. The plate was washed five times with water from the faucet, dried in air, dyed with 0.4% sulforhodamine B in 1% acetic acid for 30 minutes and then dried in air. The dye was solubilized by treatment with 0.1 ml of 10 mM Tris (pH 10.5) for 5 minutes and absorbance was measured at 490 nM using a Titertek Multiscan MCC / 340 plate reader.

Alternatively, CyQUANT cell proliferation assays were used to quantify cell proliferation.

CyQUANT Cell Proliferation Assay:

Alternatively, CyQUANT cell proliferation assays were used to quantify tumor cell proliferation. Tumor cells were harvested using trypsin-EDTA, the cells blocked with trypan blue were counted, and then placed in 96-well and incubated overnight at 37 ° C. The drug was diluted in culture medium and then added to the wells. After 3 days the medium was removed and the plate was frozen at -80 ° C for at least 30 minutes. After thawing the plates, 200 μl of CyQUANT-GR in cell lysis buffer (Molecular Probes # C-7026) was added to each well and incubated at room temperature for 3-5 minutes. The fluorescence of CyQUANT-GR was measured (excitation 485 nm, emission 530 nm) in a Molecular Device Fmax fluorescence microplate reader.

Cell line:

MCF7 is a human breast adenocarcinoma that is hormone-dependent (HTB 22),

MDA-MB-231 is a human breast adenocarcinoma that is hormone-independent (HTB 26),

HT-29 is a human colorectal adenocarcinoma, relatively well differentiated to class II (HTB 38),

HCT-15 is human colon adenocarcinoma (CCL 225),

A549 is human non-small cell lung carcinoma (CCL 185),

PC-3 is a human prostate carcinoma that is hormone-independent (CRL 1435),

DU 145 is a human prostate carcinoma that is hormone-independent (HTB 81).

All of these cell lines were obtained from the American Type Culture Collection (ATCC accession numbers inserted in parentheses). MCF-7, MDA-MB-435 and MDA-MB- in modified minimum essential media (Biofluids) without phenol red and given 5% calf fetal serum, 0.01 mg / ml gentamycin and 3 mM L-glutamine 231 cell lines were cultured. All other cell lines were cultured in RPMI 1640 medium (Life Technologies) provided with 5% calf fetal serum, 0.01 mg / ml gentamycin and 3 mM L-glutamine.

The above results are shown in Table 1.

Claims (196)

A compound of formula 1, pharmaceutically acceptable salts, optical isomers or hydrates thereof. <Formula 1> Where R is selected from the group consisting of R2, R2NH- or R3R4N-R5-; R 2 is selected from the group consisting of C ₉ -C ₁₂ alkyl, formula 2 and formula 3; <Formula 2> <Formula 3> In Formulas 2 and 3, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer from 0 to 8) X is an integer from 1 to 8, n is an integer from 0 to 8, Z is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, M is hydrogen, C ₁ -C ₄ alkyl, 4 and Formula 5; <Formula 4> <Formula 5> In Formulas 4 and 5, R6 'is each selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m' -phenyl (m' is an integer from 0 to 8) Independently selected, n 'is an integer from 0 to 8, x' is an integer from 1 to 8, Q is hydrogen or C ₁ -C ₄ alkyl, Z 'is phenyl, heterocycle, cycloalkyl and naphthalene Selected from the group consisting of; Of the substituents, C ₉ -C ₁₂ alkyl or Z is optionally substituted with 1 to 3 substituents, identical or different, selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9, respectively; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8 and x" Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 1 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; R 3 and R 4 are selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl and (CH ₂ ) _y -phenyl (y is an integer from 0 to 8), wherein R 3 and R 4 are not both hydrogen; R 5 is C ₁ -C ₈ alkylene; R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl; Provided that when R 2 is of formula 3 wherein n is at least 1, R 1 is isopropyl or cyclopentyl, R 6 is hydrogen, C ₁ -C ₄ alkyl or (CH ₂ ) _m -phenyl, Z is phenyl, Heterocycle or cycloalkyl, optionally substituted by 1 to 3 substituents, identical or different, selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9 as defined above. The method of claim 1, R is R2; R 2 is C ₉ -C ₁₂ alkyl selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9, optionally substituted by 1 to 3 substituents, the same or different; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, and R6 "is each hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m" -phenyl ( m "is an integer from 0 to 8), x" is an integer from 1 to 8, n "is an integer from 0 to 8, Z" is phenyl, heterocycle, cycloalkyl and naphthalene M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 1 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The compound of claim 2, wherein R 2 is C ₁₁ -C ₁₂ alkyl. The compound of claim 3, wherein R 2 is C ₁₂ alkyl. The 2- [trans- (4-aminocyclohexyl) amino] -6- (dodecylamino) -9-cyclopentylpurine dihydrochloride according to claim 4. The method of claim 1, R is R2; R 2 is formula (2); <Formula 2> In Formula 2, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), x is an integer from 1 to 8, M is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 4 and formula 5; <Formula 4> <Formula 5> In Formulas 4 and 5, R6 'is each selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m' -phenyl (m' is an integer from 0 to 8) Independently selected, n 'is an integer from 0 to 8, x' is an integer from 1 to 8, Q is hydrogen or C ₁ -C ₄ alkyl, Z 'is phenyl, heterocycle, cycloalkyl and naphthalene Selected from the group consisting of; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The compound of claim 6, wherein M is hydrogen. The compound of claim 6, wherein M is C ₁ -C ₄ alkyl. The compound of claim 8, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- (2-methoxyethylamino) -9-cyclopentylpurine dihydrochloride, 2- [trans- (4-amino Cyclohexyl) amino] -6- (3-methoxypropylamino) -9-cyclopentylpurine dihydrochloride or 2- [trans- (4-aminocyclohexyl) amino] -6- (4-methoxybutylamino ) -9-cyclopentylpurine dihydrochloride. 7. Compounds according to claim 6, wherein M is a group of formula (4). <Formula 4> Wherein R6 ', x' and Q are as defined in claim 6. The compound of claim 10, wherein Q is hydrogen. The 2- [trans- (4-aminocyclohexyl) amino] -6- (2-hydroxyethoxyethylamino) -9-cyclopentylpurine dihydrochloride according to claim 11. The compound of claim 10, wherein Q is C ₁ -C ₄ alkyl. The 2- [trans- (4-aminocyclohexyl) amino] -6- [3- (2-methoxyethoxy) propylamino] -9-cyclopentylpurine dihydrochloride according to claim 13. 7. Compounds according to claim 6, wherein M is a group of formula (5). <Formula 5> Wherein R6 ', n' and Z 'are as defined in claim 6. The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer from 0 to 8, Z is naphthalene which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9. ; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, and R6 "is each hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m" -phenyl ( m "is an integer from 0 to 8), x" is an integer from 1 to 8, n "is an integer from 0 to 8, Z" is phenyl, heterocycle, cycloalkyl and naphthalene M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 1 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The 2- [trans- (4-aminocyclohexyl) amino] -6-[(1-naphthyl) methylamino] -9-cyclopentylpurine dihydrochloride according to claim 16. The method of claim 1, R is R2; R 2 is Z; Z is phenyl which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, and R 6 ″ is each hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m ”} -phenyl Independently selected from the group consisting of: x "is an integer from 1 to 8, n" is an integer from 0 to 8, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and M 'is Hydrogen, C ₁ -C ₄ alkyl, selected from the group consisting of Formula 10 and Formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 1 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The 2- [trans- (4-aminocyclohexyl) amino] -6- (phenylamino) -9-cyclopentylpurine dihydrochloride of claim 18. The compound of claim 18, wherein Z is substituted by D. 19. The 2- [trans- (4-aminocyclohexyl) amino] -6-[(4-fluoromethoxy) phenylamino] -9-cyclopentylpurine dihydrochloride according to claim 20. The compound of claim 18, wherein Z is substituted by E. 19. The compound of claim 22, wherein E is Hal. The 2- [trans- (4-aminocyclohexyl) amino] -6- (3-fluorophenylamino) -9-cyclopentylpurine dihydrochloride of claim 23. The compound of claim 22, wherein E is C ₁ -C ₈ alkyl. 26. The 2- [trans- (4-aminocyclohexyl) amino] -6-[(4-pentyl) phenylamino] -9-cyclopentylpurine dihydrochloride of claim 25. The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is independently hydrogen or C ₃ -C ₈ cycloalkyl, wherein at least one R 6 is C ₃ -C ₈ cycloalkyl, n is an integer of 1 to 8, Z is each D, E Phenyl optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, and R6 "is each hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m" -phenyl ( m "is an integer from 0 to 8), x" is an integer from 1 to 8, n "is an integer from 0 to 8, Z" is phenyl, heterocycle, cycloalkyl and naphthalene M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 27, wherein the (+/-)-2- [trans- (4-aminocyclohexyl) amino] -6-[(α-cyclopropyl-4-chlorobenzyl) amino] -9-cyclopentylpurine di Hydrochloride. The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer of 1 to 8 , Z is phenyl which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In D and Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, b is an integer of 0 to 2, and Z ″ is phenyl , Heterocycle, cycloalkyl and naphthalene, and R6 ″ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is 0 to Is an integer of 8), n "is an integer from 0 to 8, x" is an integer from 1 to 8, M 'is hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11 It is selected from the group consisting of; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (1) wherein R 1 is selected from the group consisting of cyclopentyl and isopropyl, pharmaceutically acceptable salts, optical isomers or hydrates thereof. 30. The compound of claim 29, wherein Z is substituted with D. 31. The compound of claim 30, wherein D is trifluoromethyl. 32. The compound of claim 31 wherein 2- [trans- (4-aminocyclohexyl) amino] -6-[(4-trifluorobenzyl) amino] -9-cyclopentylpurine dihydrochloride or 2- [trans- ( 4-aminocyclohexyl) amino] -6-[(2-trifluorobenzyl) amino] -9-cyclopentylpurine dihydrochloride. The compound of claim 30, wherein D is C ₁ -C ₄ alkoxy. The method of claim 33, wherein the 2- [trans- (4-aminocyclohexyl) amino] -6- (3,4,5-triethoxybenzylamino) -9-cyclopentylpurine dihydrochloride, 2- [trans -(4-aminocyclohexyl) amino] -6-[(2,6-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride, 2- [trans- (4-aminocyclohexyl) amino]- 6-[(4-methoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6-[(2-methoxybenzyl) amino]- 9-cyclopentylpurine dihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6-[(2,3-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride, 2- [Trans- (4-aminocyclohexyl) amino] -6-[(2- (4-methoxyphenyl) ethylamino] -9-cyclopentylpurine dihydrochloride, 2- [trans- (4-aminocyclohexyl ) Amino] -6-[(2,4-dimethoxybenzyl) amino] -9-cyclophene Tilpurine dihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6-[(3,4-dimethoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride, 2- [Trans- (4-aminocyclohexyl) amino] -6-[(2- (3-methoxyphenyl) ethylamino] -9-cyclopentylpurine dihydrochloride, 2- [trans- (4-aminocyclohexyl ) Amino] -6-[(3,5-dimethoxybenzyl) amino] -9-cyclopentylpurine dihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6-[(2,3 -Dimethoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6-[(3,4-dimethoxybenzyl) amino]- 9-cyclopentylpurine dihydrochloride or 2- [trans- (4-aminocyclohexyl) amino] -6- (4-methoxybenzyl) amino] -9- (2-propyl) purine dihydrochloride. The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer from 0 to 8, Z is phenyl optionally substituted by 1 to 3 substituents, identical or different, selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9. ; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'and Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 0 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula 1 wherein R 1 is cyclopentenyl, a pharmaceutically acceptable salt, optical isomer or hydrate thereof. 36. The compound of claim 35, wherein Z is substituted with E. The compound of claim 36, wherein E is Hal. The hydrochloride of claim 37 wherein 2- [trans- (4-aminocyclohexyl) amino] -6-[(3-iodobenzyl) amino] -9- (2-cyclopentenyl) purine hydrochloride. The method of claim 1, R is R2; R 2 is Z; Z is a heterocycle which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 0 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. 40. The compound of claim 39, wherein Z is piperidine. 41. The compound of claim 40, wherein Z is substituted with D. 41. The compound of claim 40, wherein Z is substituted with E. 43. The compound of claim 42, wherein E is C ₁ -C ₈ alkyl. 44. The compound of claim 43, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-propyl) piperidinylamino) -9-cyclopentylpurine, 2- [trans- (4 -Aminocyclohexyl) amino] -6- [4- (1-butyl) piperidinylamino) -9-cyclopentylpurine or 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-allyl) piperidinylamino) -9-cyclopentylpurine. 41. The compound of claim 40, wherein Z is substituted with a group of formula (6). <Formula 6> Wherein R6 ″, X ″ and b are as defined in claim 39. 46. The compound of claim 45, wherein b is zero. The 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-thiomethoxy) ethyl) piperidinylamino) -9-cyclopentylpurine according to claim 46. 46. The compound of claim 45, wherein b is 1. The 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenylsulfinyl) ethyl) piperidinylamino) -9-cyclopentylpurine according to claim 48. 41. The compound of claim 40, wherein Z is substituted with a group of formula 7. <Formula 7> Wherein R 6 ″ and x ″ are as defined in claim 39. 51. The compound of claim 50, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dimethylaminoethyl)) piperidinylamino] -9-cyclo Pentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dimethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dimethylaminobutyl)) piperidinylamino] -9-cyclopentylpurine, 2- [ Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dimethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- ( 4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-diethylaminoethyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4- Aminocyclohexyl) amino] -6- [4- (1- (3-N, N-diethylaminopropyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclo Hexyl) amino] -6- [4- (1- (4-N, N-diethylaminobutyl)) piperidi Amino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-diethylaminopentyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dipropylaminoethyl)) piperidinylamino] -9 -Cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dipropylaminopropyl)) piperidinylamino] -9-cyclo Pentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dipropylaminobutyl)) piperidinylamino] -9-cyclopentylpurine , 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dipropylaminopentyl)) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dibutylaminoethyl)) piperidinylamino] -9-cyclopentylpurine, 2- [ Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dibutylamimi Nopropyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dibutylaminobutyl )) Piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dibutylaminopentyl)) Piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-dibenzylaminoethyl)) piperidi Nylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-N, N-dibenzylaminopropyl)) piperidinylamino ] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-dibenzylaminobutyl)) piperidinylamino]- 9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-dibenzylaminopentyl)) piperidinylamino] -9- Cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N -Di- (2-phenylethylene) aminoethyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3 -N, N-di- (2-phenylethylene) aminopropyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- ( 1- (4-N, N-di- (2-phenylethylene) aminobutyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (2-phenylethylene) aminopentyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino ] -6- [4- (1- (2-N, N-di- (3-phenylpropylene) aminoethyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-amino Cyclohexyl) amino] -6- [4- (1- (3-N, N-di- (3-phenylpropylene) aminopropyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-N, N-di- (3-phenylpropylene) amino part Til)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-N, N-di- (3- Phenylpropylene) aminopentyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-N, N-di -(4-phenylbutylene) aminoethyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- N, N-di- (4-phenylbutylene) aminopropyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- ( 1- (4-N, N-di- (4-phenylbutylene) aminobutyl)) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4-aminocyclohexyl) amino] -6 -[4- (1- (5-N, N-di- (4-phenylbutylene) aminopentyl)) piperidinylamino] -9-cyclopentylpurine. 41. The compound of claim 40, wherein Z is substituted with a group of formula (8). <Formula 8> Wherein R 6 ″, x ″ and M ′ are as defined in claim 39. 53. The compound of claim 52, wherein M 'is hydrogen. The compound of claim 53, wherein x ″ is 2. 55. The compound of claim 54, wherein (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenyl-2-hydroxyethyl)) piperidinyl Amino] -9-cyclopentylpurine. The compound of claim 53, wherein x ″ is 3. The 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-hydroxy) propyl) piperidinylamino] -9-cyclopentylpurine according to claim 56. The compound of claim 53, wherein x ″ is 4. The 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-hydroxy) butyl) piperidinylamino] -9-cyclopentylpurine according to claim 58. The compound of claim 53, wherein x ″ is 5. 61. The 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-hydroxypentyl)) piperidinylamino] -9-cyclopentylpurine according to claim 60. 55. The compound of claim 53, wherein x "is 6. 63. The compound of claim 62, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-hydroxy) hexyl) piperidinylamino] -9-cyclopentylpurine. The compound of claim 52, wherein M ′ is C ₁ -C ₄ alkyl. 65. The compound of claim 64, wherein x "is one. 65. The compound of claim 64, wherein x "is 2. 67. The compound of claim 65, wherein x "is 3. 68. The compound of claim 67, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-methoxy) propyl) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-ethoxy) propyl) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4- Aminocyclohexyl) amino] -6- [4- (1- (3-propoxy) propyl) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4-aminocyclohexyl) amino]- 6- [4- (1- (3-butoxy) propyl) piperidinylamino] -9-cyclopentylpurine. 67. The compound of claim 65, wherein x "is 4. The method of claim 69, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methoxy) butyl) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-ethoxy) butyl) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4- Aminocyclohexyl) amino] -6- [4- (1- (4-propoxy) butyl) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4-aminocyclohexyl) amino]- 6- [4- (1- (4-butoxy) butyl) piperidinylamino] -9-cyclopentylpurine. 67. The compound of claim 65, wherein x "is 5. The compound of claim 71, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-methoxypentyl)) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-ethoxypentyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4- Aminocyclohexyl) amino] -6- [4- (1- (5-propoxypentyl)) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4-aminocyclohexyl) amino]- 6- [4- (1- (5-butoxypentyl)) piperidinylamino] -9-cyclopentylpurine. 67. The compound of claim 65, wherein x "is 6. 74. The compound of claim 73, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-methoxy) hexyl) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-ethoxy) hexyl) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4- Aminocyclohexyl) amino] -6- [4- (1- (6-propoxy) hexyl) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4-aminocyclohexyl) amino]- 6- [4- (1- (6-butoxy) hexyl) piperidinylamino] -9-cyclopentylpurine. 53. The compound of claim 52, wherein M 'is a group of formula 10. <Formula 10> Wherein R6 "', x"' and Q 'are as defined in claim 39. 76. The compound of claim 75, wherein Q 'is hydrogen. 77. The compound of claim 76, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (2-hydroxyethyleneoxy) ethyl)) piperidinylamino] -9 Cyclopentylpurine. 76. The compound of claim 75, wherein Q 'is C ₁ -C ₄ alkyl. 53. The compound of claim 52, wherein M 'is a group of formula (11). <Formula 11> Wherein R6 "', n"' and Z "'are as defined in claim 39. 80. The compound of claim 79, wherein Z "'is phenyl. 81. The compound of claim 80, wherein x "is two. 84. The compound of claim 81, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenoxyethyl)) piperidinylamino] -9-cyclopentylpurine. 81. The compound of claim 80, wherein x "is 3. 84. The compound of claim 83, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-phenoxypropyl)) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-benzyloxy) propyl) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4- Aminocyclohexyl) amino] -6- [4- (1- (3- (2-phenylethyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl ) Amino] -6- [4- (1- (3- (3-phenylpropyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (4-phenylbutyleneoxy) propyl) piperidinylamino] -9-cyclopentylpurine. 81. The compound of claim 80, wherein x "is 4. 86. The compound of claim 85, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-benzyloxy) butyl) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (2-phenylethyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine, 2- [trans -(4-aminocyclohexyl) amino] -6- [4- (1- (4- (3-phenylpropyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4 -Aminocyclohexyl) amino] -6- [4- (1- (4- (4-phenylbutyleneoxy) butyl) piperidinylamino] -9-cyclopentylpurine. 81. The compound of claim 80, wherein x "is 5. 88. The compound of claim 87, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5-benzyloxypentyl)) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (2-phenylethyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine, 2- [ Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (3-phenylpropyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (5- (4-phenylbutyleneoxy) pentyl)) piperidinylamino] -9-cyclopentylpurine. 81. The compound of claim 80, wherein x "is 6. 90. The compound of claim 89 wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6-benzyloxy) hexyl) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (6- (2-phenylethyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine, 2- [trans -(4-aminocyclohexyl) amino] -6- [4- (1- (6- (3-phenylpropyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4 -Aminocyclohexyl) amino] -6- [4- (1- (6- (4-phenylbutyleneoxy) hexyl) piperidinylamino] -9-cyclopentylpurine. The compound of claim 40, wherein Z is substituted with a group of formula 9. <Formula 9> Wherein R 6 ″, n ″ and Z ″ are as defined in claim 39. 92. The compound of claim 91, wherein Z "is phenyl. 93. The compound of claim 92, wherein n "is 1. 94. The compound of claim 93, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-benzyl) piperidinylamino] -9-cyclopentylpurine trihydrochloride, (R, S ) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-benzyl-3-methyl) piperidinylamino] -9-cyclopentylpurine or (+/-)-2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (α-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine. 93. The compound of claim 92, wherein n "is 2. 96. The compound of claim 95, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-phenylethyl)) piperidinylamino] -9-cyclopentylpurine trihydrochloride . The compound of claim 63, wherein Z ″ is substituted with D ′. 98. The compound of claim 97, wherein D 'is C ₁ -C ₄ alkoxy. 99. The compound of claim 98, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methoxybenzyl)) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-methoxybenzyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4- Aminocyclohexyl) amino] -6- [4- [1- (3,5-dimethoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride or 2- [trans- (4-aminocyclo Hexyl) amino] -6- [4- [1- (2-methoxybenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride. 98. The compound of claim 97, wherein D 'is trifluoromethyl. 101. The compound of claim 100, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-trifluoromethylbenzyl)) piperidinylamino] -9-cyclopentylpurine , 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- [1- [3,5-bis (trifluoromethyl) benzyl]] piperidinylamino] -9-cyclopentylpurine trihydro Chloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride or 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-bis-trifluoromethylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydro Chloride. 93. The compound of claim 92, wherein Z "is substituted with E '. 109. The compound of claim 102, wherein E 'is C ₁ -C ₈ alkyl. 103. The compound of claim 103, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine, 2- [Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclo Hexyl) amino] -6- [4- (1- (3-methylbenzyl)) piperidinylamino] -9-cyclopentylpurine trihydrochloride or 2- [trans- (4-aminocyclohexyl) amino]- 6- [4- [1- (3-chloro-4-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride. 107. The compound of claim 102, wherein E 'is Hal. 105. The compound of claim 105, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4-chlorobenzyl)) piperidinylamino] -9-cyclopentylpurine, 2- [Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-chlorobenzyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclo Hexyl) amino] -6- [4- (1- (2-chlorobenzyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [ 4- (1- (2,6-dichlorobenzyl)) piperidinylamino] -9-cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- ( 2,3-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2 , 5-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3, 5-difluorobenzyl)] piperidi Amino] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,4-difluorobenzyl)] piperidinylamino ] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3-fluorobenzyl)] piperidinylamino] -9- Cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine tree Hydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- [1- (4-fluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-dichlorobenzyl )] Piperidinylamino] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2,5-dichlorobenzyl)] pipe Ridinylamino] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-chloro-4-fluorobenzyl)] pipe Ridinylamino] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-difluorobenzyl)] piperidi Nylamino] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-difluorobenzyl)] piperidinyl Amino] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (3,4-difluorobenzyl)] piperidinylamino ] -9-cyclopentylpurine trihydrochloride, 2- [trans- (4-aminocyclohexyl) a Mino] -6- [4- [1- (3,4-difluorobenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride or 2- [trans- (4-aminocyclohexyl) amino ] -6- [4- [1- (3-chloro-4-methylbenzyl)] piperidinylamino] -9-cyclopentylpurine trihydrochloride. 92. The compound of claim 91, wherein Z "is a heterocycle. 107. The compound of claim 107, wherein Z "is 1,3-benzodioxolyl. 109. The compound of claim 108, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3,4-methylenedioxybenzyl)) piperidinylamino] -9-cyclopentyl Purine. 107. The compound of claim 107, wherein Z "is pyridinyl. 111. The compound of claim 110, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine, 2 -[Trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4- Aminocyclohexyl) amino] -6- [4- (1- (4-pyridinylmethyl)) piperidinylamino] -9-cyclopentylpurine. 107. The compound of claim 107, wherein Z "is isoxoxazolyl. 112. The compound of claim 112, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (2,4-dimethylisoxazolyl)) methyl) piperidinylamino] -9-cyclopentylpurine. 107. The compound of claim 107, wherein Z "is tetrahydrofuranyl. 117. The compound of claim 114, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3-tetrahydrofuranyl) methyl) piperidinylamino] -9-cyclopentylpurine . 107. The compound of claim 107, wherein Z "is pyrrolidinyl. 116. The compound of claim 116, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1-pyrrolidinyl) ethyl)) piperidinylamino] -9- Cyclopentylpurine or (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (3- (1-methyl) pyrrolidinyl) ethyl) ) Piperidinylamino] -9-cyclopentylpurine. 107. The compound of claim 107, wherein Z "is piperidinyl. 118. The composition of claim 118, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1-piperidinyl) ethyl)) piperidinylamino] -9- Cyclopentylpurine, 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (1-piperidinyl) propyl)) piperidinylamino] -9-cyclopentyl Purine or (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (3- (1-methyl) piperidinyl) methyl)) piperidinylamino ] -9-cyclopentylpurine. 107. The compound of claim 107, wherein Z "is morpholinyl. 121. The compound of claim 120, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (4-morpholinyl) ethyl)) piperidinylamino] -9- Cyclopentylpurine. 107. The compound of claim 107, wherein Z "is piperazinyl. 123. The compound of claim 122, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2- (1- (4-methyl) piperidinyl) ethyl)) piperidinyl Amino] -9-cyclopentylpurine. 107. The compound of claim 107, wherein Z "is benzimidazolinyl. 124. The compound of claim 124, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-benzimidazolinyl) methyl) piperidinylamino] -9-cyclopentyl Purine. 107. The compound of claim 107, wherein Z "is thiazolinyl. 126. The compound of claim 126, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (4- (2-methyl) thiazolinyl) methyl) piperidinylamino] -9 Cyclopentylpurine. 107. The compound of claim 107, wherein Z "is thiopheneyl. 129. The 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1- (2-thiophenyl) methyl) piperidinylamino] -9-cyclopentylpurine according to claim 128. 92. The compound of claim 91, wherein Z "is cycloalkyl. 131. The compound of claim 130, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-cyclopropylmethyl) piperidinylamino] -9-cyclopentylpurine or 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (1-cyclohexylmethyl) piperidinylamino] -9-cyclopentylpurine dihydrochloride. 40. The compound of claim 39, wherein Z is pyrrolidine. 134. The compound of claim 132, wherein Z is substituted with a group of formula 9. <Formula 9> Wherein R 6 ″, n ″ and Z ″ are as defined in claim 39. 134. The compound of Claim 133, wherein Z "is phenyl. 134. The compound of claim 134, wherein (R) -2- [trans- (4-aminocyclohexyl) amino] -6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine or -2- [trans- (4-aminocyclohexyl) amino] -6- [3- (1-benzyl) pyrrolidinylamino] -9-cyclopentylpurine. The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is independently hydrogen or C ₃ -C ₈ cycloalkyl, wherein at least one R 6 is C ₃ -C ₈ cycloalkyl, n is an integer of 1 to 8, Z is D, E, Heterocycle which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is each independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, and (CH ₂ ) _n′ -phenyl (n ′ is an integer of 0 to 8), and n is 1 to 8 An integer, Z is a heterocycle, which may be optionally substituted by one or three substituents, identical or different, selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In D and Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, b is an integer of 0 to 2, and Z ″ is phenyl , Heterocycle, cycloalkyl and naphthalene, and R6 ″ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is 0 to Is an integer of 8), n "is an integer from 0 to 8, x" is an integer from 1 to 8, M 'is hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11 It is selected from the group consisting of; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'and Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 0 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein M 1 is selected from the group consisting of cyclopentyl and isopropyl. 137. The compound of claim 137, wherein Z is substituted with D. 138. The compound of claim 138, wherein D is C ₁ -C ₄ alkoxy. 139. The compound of claim 139, wherein 2- [trans- (4-aminocyclohexyl) amino] -6-[(3- (5-methoxyindolyl))-2-ethylamino] -9-cyclopentylpurine dihydrochloride . The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _n -phenyl, n is an integer from 0 to 8, Z is a heterocycle which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, M 'and Z "are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula 1 wherein R 1 is cyclopentenyl, a pharmaceutically acceptable salt, optical isomer or hydrate thereof. The method of claim 1, R is R2; R 2 is Z; Z is cycloalkyl which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, M 'and Z "are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. 142. The compound of Claim 142, wherein Z is substituted with E. 143. The compound of claim 143, wherein E is OH. 145. The compound of claim 144, wherein trans-2- [trans- (4-aminocyclohexyl) amino] -6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine dihydrochloride or cis-2- [Trans- (4-aminocyclohexyl) amino] -6-[(4-hydroxy) cyclohexylamino] -9-cyclopentylpurine dihydrochloride. 142. The compound of claim 142, wherein Z is substituted with a group of formula 8. <Formula 8> Wherein R 6 ″, x ″ and M ′ are as defined in claim 142. 146. The compound of claim 146, wherein M 'is hydrogen. 147. The compound of claim 147, wherein (R, S) -2- [trans- (4-aminocyclohexyl) amino] -6-[(1-hydroxymethyl) cyclopentylamino] -9-cyclopentylpurine dihydrochloride . The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is independently hydrogen or C ₃ -C ₈ cycloalkyl, wherein at least one R 6 is C ₃ -C ₈ cycloalkyl, n is an integer from 1 to 8, Z is D, E, Cycloalkyl which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 0 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is each independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, and (CH ₂ ) _n′ -phenyl (n ′ is an integer of 0 to 8), and n is 1 to 8 An integer, Z is cycloalkyl, which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In D and Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, b is an integer of 0 to 2, and Z ″ is phenyl , Heterocycle, cycloalkyl and naphthalene, and R6 ″ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is 0 to Is an integer of 8), n "is an integer from 0 to 8, x" is an integer from 1 to 8, M 'is hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11 It is selected from the group consisting of; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (1) wherein R 1 is selected from the group consisting of cyclopentyl and isopropyl, pharmaceutically acceptable salts, optical isomers or hydrates thereof. 153. The compound of claim 150, wherein Z is substituted with a group of formula 8. <Formula 8> Wherein R 6 ″, x ″ and M ′ are as defined in claim 145. 153. The compound of claim 151, wherein M 'is hydrogen. 152. The 2- [trans- (4-aminocyclohexyl) amino] -6- [4- (hydroxymethyl) cyclohexanemethylamino] -9-cyclopentylpurine dihydrochloride. The method of claim 1, R is R2; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _n -phenyl, n is an integer from 0 to 8, Z is cycloalkyl, which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula 1 wherein R 1 is cyclopentyl, a pharmaceutically acceptable salt, optical isomer or hydrate thereof. The method of claim 1, R is R2NH-; R 2 is optionally substituted by 1 to 3 substituents, identical or different, selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 0 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2NH-; R 2 is formula (2); <Formula 2> In Formula 2, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), x is an integer from 1 to 8, M is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 4 and formula 5, <Formula 4> <Formula 5> In Formulas 4 and 5, R6 'is each selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m' -phenyl (m' is an integer from 0 to 8) Independently selected, n 'is an integer from 0 to 8, x' is an integer from 1 to 8, Q is hydrogen or C ₁ -C ₄ alkyl, Z 'is phenyl, heterocycle, cycloalkyl and naphthalene Selected from the group consisting of; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer of 0 to 8 , Z is naphthalene, which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2NH-; R 2 is Z; Z is phenyl optionally substituted by one or three substituents, identical or different, selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. 158. The compound of claim 158, wherein Z is substituted with E. 162. The compound of claim 159, wherein E is Hal. 161. The compound of claim 160, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [2,6-dichlorophenylhydrazino] -9-cyclopentylpurine dihydrochloride, 2- [trans- (4 -Aminocyclohexyl) amino] -6- (2-chlorophenylhydrazino] -9-cyclopentylpurine dihydrochloride, 2- [trans- (4-aminocyclohexyl) amino] -6- [2-fluoro Phenylhydrazino] -9-cyclopentylpurine dihydrochloride or 2- [trans- (4-aminocyclohexyl) amino] -6- (2,4-dichlorophenylhydrazino] -9-cyclopentylpurine dihydrochloride . The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is independently hydrogen or C ₃ -C ₈ cycloalkyl, wherein at least one R 6 is C ₃ -C ₈ cycloalkyl, n is an integer of 1 to 8, Z is D, E, Phenyl optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 0 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer of 1 to 8 , Z is phenyl which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D and Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, and E is Hal, OH and C ₁ -C ₈ alkyl, respectively Independently selected from the group consisting of b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ cycloalkyl , C ₁ -C ₄ alkyl and (CH ₂ ) _{m ″} -phenyl (m ″ is an integer from 0 to 8), n ″ is an integer from 0 to 8 and x ″ is 1 to Is an integer of 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M ′ and Z ″ substituents are optionally substituted by D ′, E ′ or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (1) wherein R 1 is selected from the group consisting of cyclopentyl and isopropyl, pharmaceutically acceptable salts, optical isomers or hydrates thereof. The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer from 0 to 8, Z is phenyl optionally substituted by 1 to 3 substituents, identical or different, selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9. ; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula 1 wherein R 1 is cyclopentyl, a pharmaceutically acceptable salt, optical isomer or hydrate thereof. The method of claim 1, R is R2NH-; R 2 is Z; Z is a heterocycle which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is independently hydrogen or C ₃ -C ₈ cycloalkyl, wherein at least one R 6 is C ₃ -C ₈ cycloalkyl, n is an integer from 1 to 8, Z is D, E, Heterocycle which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). are independently selected, x "from" is an integer from 0 to 8, Q "is hydrogen or C ₁ -C ₄ alkyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ alkoxy Are independently selected from the group consisting of E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer of 1 to 8 , Z is a heterocycle which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (1) wherein R 1 is selected from the group consisting of cyclopentyl and isopropyl, pharmaceutically acceptable salts, optical isomers or hydrates thereof. The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer from 0 to 8, Z is a heterocycle that may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9. Is; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula 1 wherein R 1 is cyclopentenyl, a pharmaceutically acceptable salt, optical isomer or hydrate thereof. The method of claim 1, R is R2NH-; R 2 is Z; Z is cycloalkyl, which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R 6 is independently hydrogen or C ₃ -C ₈ cycloalkyl, wherein at least one R 6 is C ₃ -C ₈ cycloalkyl, n is an integer from 1 to 8, Z is D, E, Cycloalkyl which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer of 1 to 8 , Z is cycloalkyl, which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, Formula 6, Formula 7, Formula 8 and Formula 9; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D and Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, and E is Hal, OH and C ₁ -C ₈ alkyl, respectively Independently selected from the group consisting of b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ cycloalkyl , C ₁ -C ₄ alkyl and (CH ₂ ) _{m ″} -phenyl (m ″ is an integer from 0 to 8), n ″ is an integer from 0 to 8 and x ″ is 1 to Is an integer of 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula (1) wherein R 1 is selected from the group consisting of cyclopentyl and isopropyl, pharmaceutically acceptable salts, optical isomers or hydrates thereof. The method of claim 1, R is R2NH-; R 2 is Formula 3; <Formula 3> In Formula 3, R6 is each independently selected from the group consisting of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _m -phenyl (m is an integer of 0 to 8), n is an integer from 0 to 8 and Z is cycloalkyl, which may be optionally substituted by the same or different 1 to 3 substituents selected from the group consisting of D, E, Formula 6, Formula 7, Formula 8 and Formula 9 Is; <Formula 6> <Formula 7> <Formula 8> <Formula 9> In the above D, E and in Chemical Formulas 6 to 9, D is each independently selected from the group consisting of trifluoromethyl, trifluoromethoxy and C ₁ -C ₄ alkoxy, E is Hal, OH and C ₁ -C respectively ₈ is independently selected from the group consisting of alkyl, b is an integer from 0 to 2, Z "is selected from the group consisting of phenyl, heterocycle, cycloalkyl and naphthalene, and R6" are each hydrogen, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₄ alkyl and (CH ₂ ) _{m "} -phenyl (m" is an integer from 0 to 8), n "is an integer from 0 to 8, x" is Is an integer from 1 to 8 and M 'is selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl, formula 10 and formula 11; <Formula 10> <Formula 11> In Formulas 10 and 11, R 6 ″ ′ is hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ′} -phenyl (m ″ ′ is an integer of 0 to 8), respectively. Independently selected from the group consisting of n ″ ′ is an integer from 0 to 8, x ″ ′ is an integer from 1 to 8, Q ′ is hydrogen or C ₁ -C ₄ alkyl and Z ″ ′ is phenyl, hetero Selected from the group consisting of cycles, cycloalkyls and naphthalenes, The M 'and Z "substituents are optionally substituted by D', E 'or Formula 12; <Formula 12> In Formula 12, R6 ″ ″ is each of hydrogen, C ₃ -C ₈ cycloalkyl, C ₁ -C ₄ alkyl, and (CH ₂ ) _{m ″ ″} -phenyl (m ″ ″ is an integer of 0 to 8). from independently selected, x "" is an integer from 0 to 8, Q "is hydrogen, C ₁ -C ₄ alkyl or phenyl, D 'are each trifluoromethyl, trifluoromethoxy, and C ₁ -C ₄ is independently selected from the group consisting of alkoxy, E 'is each independently selected from the group consisting of Hal, OH and C ₁ -C ₈ alkyl; A compound of formula 1 wherein R 1 is cyclopentenyl, a pharmaceutically acceptable salt, optical isomer or hydrate thereof. The method of claim 1, R is R3R4N-R5-; R 3 and R 4 are selected from the group consisting of hydrogen, C ₁ -C ₄ alkyl and (CH ₂ ) _n -phenyl, where n is an integer from 0 to 8, wherein both R 3 and R 4 are not hydrogen; R 5 is C ₁ -C ₈ alkylene; A compound of formula (I), pharmaceutically acceptable salts, optical isomers or hydrates thereof, wherein R 1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl. 172. The compound of claim 173, wherein 2- [trans- (4-aminocyclohexyl) amino] -6- [2-N, N-diethylamino) ethylamino] -9-cyclopentylpurine trihydrochloride, 2- [ Trans- (4-aminocyclohexyl) amino] -6- [3-N, N-diethylamino) propylamino] -9-cyclopentylpurine trihydrochloride or 2- [trans- (4-aminocyclohexyl) Amino] -6- [2- (phenylamino) ethylamino] -9-cyclopentylpurine trihydrochloride. A method of treating said disease, comprising administering a compound of claim 1 to a patient of a hyperproliferative disease. 175. The method of claim 175, wherein the hyperproliferative disease is a neoplastic disease state. 176. The method of claim 176, wherein the neoplastic disease condition is selected from leukemia, carcinoma, adenocarcinoma, sarcoma, melanoma, or a mixed type of neoplasm. 178. The method of claim 177, wherein the leukemia is selected from acute lymphoblastic leukemia, chronic leukemia, acute myeloid leukemia and chronic myeloid leukemia. 177. The method of claim 177, wherein the carcinoma is selected from cervical cancer, breast cancer, prostate cancer, esophageal cancer, gastric cancer, small intestine cancer, colon cancer, ovarian cancer, and lung cancer. 177. The method of claim 177, wherein the adenocarcinoma is selected from cervical cancer, breast cancer, prostate cancer, esophageal cancer, gastric cancer, small intestine cancer, colon cancer, ovarian cancer and lung cancer. 178. The method of claim 177, wherein the sarcoma is selected from osteosarcoma, osteosarcoma, lipoma, liposarcoma, hemangioma, angiosarcoma. 177. The method of claim 177, wherein the melanoma is selected from melanin deficient melanoma and melaninous melanoma. 181. The method of claim 177, wherein the mixed type of neoplasia is selected from carcinosarcoma disease, lymphoid tissue type disease, follicular reticulum disease, cell sarcoma disease, and Hodgkin's disease. 175. The method of claim 175, wherein the hyperproliferative disease is a neoplastic disease state. Method of inhibiting apoptosis in neurons. 185. The method of claim 185, wherein the apoptosis is induced by a neoplastic inhibitor. 185. The method of claim 185, wherein the apoptosis is induced by cerebrovascular disease. 185. The method of claim 185, wherein the apoptosis is induced by stroke or incomplete flex fracture. A method for inhibiting apoptosis of a cell, comprising administering a compound of claim 1 to a nerve cell. A method of inhibiting damage to a cell induced by a neoplastic inhibitor comprising administering a compound of claim 1 to a nerve cell. A composition in admixture with or associated with an inert carrier, comprising an assayable amount of the compound of claim 1. A pharmaceutical composition in admixture or association with one or more pharmaceutically acceptable carriers or excipients comprising a cdk-2 inhibitory effective amount of the compound of claim 1. The compound of claim 1, wherein Z is a heterocycle substituted with C _n- (R 6 ") ₂ -Z". 194. The compound of claim 193, wherein Z "is naphthalene. 204. The compound of claim 194, wherein n "is 1. 194. The composition of claim 193, wherein the 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (2-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine trihydro Chloride or 2- [trans- (4-aminocyclohexyl) amino] -6- [4- [1- (1-naphthyl) methyl] piperidinylamino] -9-cyclopentylpurine trihydrochloride.