Antagonists of adenosine a2a receptor

Abstract

To provide compounds that are potent adenosine A2a antagonists or adenosine A2a and A2b antagonists that retain activity in the presence of the high concentrations of adenosine that are present in the tumour microenvironment.SOLUTION: There are provided compounds of formula I shown below. The present invention relates to pharmaceutical compositions comprising these compounds, and to their use in the treatment of diseases or conditions in which adenosine A2a receptor activity is implicated, such as, for example, cancer.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to certain compounds that function as antagonists of the adenosine A2a receptor. In addition, some of the compounds are also antagonists of the A2b receptor. Also disclosed are methods for preparing these compounds, pharmaceutical compositions containing them, and adenosine A2a receptor The present invention relates to their use in the treatment of diseases or conditions in which bioactivity is implicated, such as cancer. [Background technology]

[0002] In the tumor microenvironment, many tumor cells evade elimination by cytotoxic T cells. , and reducing patients' clinical responses to immunotherapy with anti-checkpoint antibodies. The anti-PD-1 antibody pembrolizumab and nivolumab are active immunosuppressive pathways that can Mab, and the anti-PD-L1 antibodies durvalumab, avelumab, and atezolizumab It is approved for the treatment of many solid tumors, including non-small cell lung cancer, head and neck squamous cell carcinoma, and urothelial carcinoma. However, only 20-30% of patients respond to checkpoint blockade. The treatment has significant side effects (Sukari et al, 2016). Therefore, other methods to enhance the cytotoxicity of the tumor microenvironment are being actively investigated. This could be used as a monotherapy or, more likely, as a checkpoint inhibitor. These include agents that can be used in combination with inhibitors and cytotoxic agents to enhance their effectiveness. can be.

[0003] One method that has gained attention is the production and / or action of adenosine in the tumor microenvironment. Adenosine is an immunosuppressant. It has inhibitory properties and is present in high concentrations in the tumor microenvironment. Recent studies have shown that adenosine We estimate that concentrations are approximately 10 μM in tumors compared with <1 μM in normal tissues. (Houthuys et al. 2017). Adenosine contains two different substrates: It is formed at both intracellular and extracellular sites by two distinct pathways, including intracellular adenosine triphosphate (ADP). Adenosine is derived from AMP and S-adenosylhomocysteine, while during metabolic stress The high levels of extracellular adenosine observed are due to the precursors produced by the coordinated action of CD39 and CD73. Involved in the release and degradation of adenine nucleotides (ATP, ADP, and AMP) (Vij ayan et al,2017).

[0004] CD39 and CD73 are upregulated in the tumor microenvironment in response to hypoxia. D73 represents a putative patient stratification method for adenosine antagonists. Its expression in adenocarcinoma cells is also associated with poor overall prognosis in many different cancer types. These results suggest that cytokine production is involved in the undesirable immunosuppressive phenotype of the tumor microenvironment. This is because (Gao et al. 2014; Loi et al., 2013;). C D73-negative Treg cells cannot suppress effector T cell function, and therefore, tumor-infiltrating immune cells CD73 expression by cells is also important in promoting tumor immunosuppression (Deaglio et al., 2013). et al, 2007; Reinhardt et al, (2017). Furthermore, anti Patients resistant to PD1 therapy have elevated levels of CD73 (Reinhard t et al,2017).

[0005] Adenosine occupies specific GPCRs on the cell surface of the P1 purinoceptor subtype. The P1 receptor family regulates cell functions by A1, A2a, A2b, and It is further subdivided into A3.

[0006] The A2 receptors are classified into A2a and A2b receptors based on their high and low affinity for adenosine, respectively. A2a is expressed by lymphocytes, and activation of A2a occurs via the cytoplasm. This results in the suppression of IL-1 production and other effector functions. Tumor growth was observed in a syngeneic mouse model. In mice, this effect was inhibited by genetic ablation of A2a, and lymphocyte activation and It has been demonstrated that this is due to the enhancement of the injury function (Ohta et al., 2006; Wa ickman et al 2012;Beavis et al,2013;Mitt al et al, 2014; Cekic et al, 2014). A2a- / - Mau The cells show increased response to inhibition of checkpoint pathways such as PD-1, resulting in tumor-free survival. Adenosine-mediated A2a activation also improves both survival and overall survival. limiting the effectiveness of treatment (Iannone et al, 2014).

[0007] The effects of genetic deficiency of A2a in mouse models can be mimicked by pharmacological blockade of A2a. A2a antagonists enhance cytotoxic CD8+ T cells and inhibit NK cell C. It has been shown to enhance the ability of D73-expressing tumors to prevent metastasis (Beavis et al., 2011). Importantly, A2a antagonists enhance the efficacy of anti-PD1 antibodies. strengthens (Beavis et al, 2015).

[0008] These findings support the development of selective A2a antagonists for use in cancer immunotherapy. Clinical trials are underway to evaluate the drug as a monotherapy and in combination with the anti-PDL1 antibody atezolizumab. CPI-444, the first selective A2a antagonist to be evaluated in cancer, will be used in Preliminary data indicate that the compound is well tolerated and reduces tumor size. These results suggest that IFN-γ-γ reduces the number of CD8+ T cells in the tumor tissue, and shows early signs of enhancing CD8+ T cell infiltration into the tumor tissue. Summary of the Invention [Problem to be solved by the invention]

[0009] However, second-generation compounds that are potent adenosine A2a antagonists remain. In particular, potent and selective adenosine A2a antagonists are sought after. In some cases, compounds that are potent and selective adenosine A2a and A2b antagonists are Furthermore, in the presence of high concentrations of adenosine present in the tumor microenvironment, A potent adenosine A2a antagonist, or adenosine A2a and A2a antagonist, that retains activity. Compounds that are 2b antagonists are sought. [Means for solving the problem]

[0010] According to a first aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. The present invention provides salts, hydrates or solvates thereof.

[0011] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. The compound may be a salt, hydrate, or solvate of the compound, in admixture with a pharmaceutically acceptable diluent or carrier. A pharmaceutical composition comprising the compound is provided.

[0012] According to a further aspect of the present invention, adenosine A2a receptor ( and optionally A2b receptors), comprising administering to a cell a and a compound defined herein, or a pharmaceutically acceptable salt, hydrate, or solvate thereof. A method is provided comprising contacting the

[0013] According to a further aspect of the present invention, adenosine A2a receptor ( and optionally A2b receptors), comprising treating a cell with a compound according to the present invention. The compounds defined in the specification, or pharmaceutically acceptable salts, hydrates or solvates thereof, and contacting the compound with an effective amount of the compound.

[0014] According to a further aspect of the present invention, there is provided a method for inhibiting cell proliferation in vitro or in vivo, The cells are treated with a compound as defined herein, or a pharmaceutically acceptable salt or hydrate thereof. or solvate thereof, or a pharmaceutical composition as defined herein. Preferably, the compound or pharmaceutical composition further comprises one or more additional antiproliferative agents. (e.g., checkpoint inhibitors and / or cytotoxic agents) .

[0015] According to a further aspect of the present invention, a disease or disorder associated with adenosine A2a receptor activity to a patient in need of such treatment, comprising administering to said patient a or a pharmaceutically acceptable salt, hydrate or solvate thereof, or Methods are provided that include administering a therapeutically effective amount of a pharmaceutical composition as defined herein.

[0016] According to a further aspect of the present invention, treatment of a cell proliferative disorder is provided in a subject in need of such treatment. 10. A method of administering to a patient suffering from a rheumatoid arthritis, the method comprising administering to said patient a compound as defined herein, or a pharmaceutical formulation thereof. or a therapeutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein. Preferably, the compound or pharmaceutical composition is one or more additional antiproliferative agents (e.g., checkpoint inhibitors and / or cytotoxic agents) It is administered in combination with

[0017] According to a further aspect of the present invention, treatment for cancer is administered to a patient in need of such treatment. 20. A method comprising administering to said patient a compound as defined herein, or a pharmaceutically acceptable salt thereof. administering a therapeutically effective amount of a salt, hydrate or solvate, or pharmaceutical composition as defined herein; Preferably, the compound or pharmaceutical composition comprises one or more additional in combination with additional anti-cancer agents (e.g., checkpoint inhibitors and / or cytotoxic agents) It is administered.

[0018] According to a further aspect of the invention there is provided a compound as defined herein for use in therapy. or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition thereof is provided. can be.

[0019] According to a further aspect of the present invention there is provided a method for treating a cell proliferative condition comprising administering to a subject a compound as defined herein. A compound as defined above, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or There is provided a pharmaceutical composition as defined herein. Suitably, the compound or pharmaceutical composition comprises one In combination with these additional antiproliferative agents (e.g., checkpoint inhibitors and / or cytotoxic agents), They are administered in combination.

[0020] According to a further aspect of the present invention there is provided a compound as defined herein for use in the treatment of cancer. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition thereof is provided. In certain embodiments, the cancer is a human cancer. Suitably, the compound or pharmaceutical composition , one or more additional anti-cancer agents (e.g., checkpoint inhibitors and / or cytotoxic agents) It is administered in combination with

[0021] According to a further aspect of the present invention, there is provided a compound according to the invention for use as an adenosine A2a antagonist. or a pharmaceutically acceptable salt, hydrate or solvate thereof, In one embodiment, the compounds of the present invention are selective adenosine A2a antagonists. In an alternative embodiment, certain compounds of the present invention are selective adenosine A2 agonists. a antagonist and adenosine A2b antagonist.

[0022] According to a further aspect of the invention, a method for treating a disease or disorder in which adenosine A2a is involved is provided. A compound as defined herein, or a pharmaceutically acceptable salt, hydrate or the like thereof, for use in or solvates thereof.

[0023] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. Use of a salt, hydrate or solvate of the compound of formula (I) in the manufacture of a medicament for the treatment of a cell proliferative condition Preferably, the compound or pharmaceutical composition further comprises one or more additional antiproliferative agents ( For example, in combination with a checkpoint inhibitor and / or a cytotoxic agent.

[0024] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. The use of a salt, hydrate or solvate of the compound of formula (I) in the manufacture of a medicament for the treatment of cancer is provided. Preferably, the cancer is a human cancer. Preferably, the compound or pharmaceutical composition comprises one or more in combination with additional anti-cancer agents (e.g., checkpoint inhibitors and / or cytotoxic agents) It is administered as follows.

[0025] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. salts, hydrates or solvates thereof as adenosine A2a antagonists The present invention also provides a use of the compound in the manufacture of a medicament for

[0026] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. EP1337733A1 - Treatment of diseases or disorders involving adenosine A2a - Google Patents The use of the compound of formula (I) in the manufacture of a medicament is provided.

[0027] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. Also provided are methods for preparing the salts, hydrates or solvates thereof.

[0028] According to a further aspect of the present invention, by a method for preparing a compound as defined herein A compound, or a pharmaceutically acceptable salt thereof, that can be obtained, obtained, or directly obtained. The present invention provides salts, hydrates or solvates thereof.

[0029] According to a further aspect of the invention, for use in any one of the synthetic methods described herein Suitable novel intermediates as defined herein are provided.

[0030] Any suitable and preferred features relating to an aspect of the present invention may also be included in the present invention. The features may include any suitable and preferred features associated with any other aspect.

[0031] definition Unless otherwise stated, the following terms used in the specification and claims include: 2. The terms "a," "b," "c," "d," and "e" have the following meanings as set forth in

[0032] References to "treat" or "treatment" include prophylaxis, as well as the alleviation of established symptoms of a condition. Therefore, "treating" or "treatment" of a condition, disorder, or pathology should be understood as (1) may be suffering from or predisposed to a condition, disorder, or pathology; have a condition, disorder, or pathology, but have not yet experienced or exhibited any clinical or subclinical symptoms of the condition, disorder, or pathology Prevent or delay the onset of clinical symptoms of a condition, disorder or pathology that does not occur in humans. (2) to prevent a condition, disorder, or pathological state, i.e., to prevent the onset or progression of a disease; prevent the recurrence (in the case of maintenance treatment) of or at least one clinical or subclinical symptom of or (3) alleviating or attenuating the disease, i.e., the condition and regressing a condition, disorder, or pathological state, or at least one of its clinical or subclinical symptoms. This includes:

[0033] A "therapeutically effective amount" is an amount that, when administered to a mammal for treating a disease, effectively relieves the symptoms of the disease. "Therapeutically effective amount" means the amount of a compound sufficient to produce such a therapeutic effect. The dosage will vary depending on the compound, the disease and its severity, and the age, weight, etc. of the mammal being treated. do.

[0034] As used herein, the term "alkyl" includes both straight and branched chain alkyl groups. References to individual alkyl groups such as "propyl" are specific to the straight chain version only and do not include "propyl". References to individual branched chain alkyl groups, such as "isopropyl," are specific to the branched chain version only. For example, "(1-6C) alkyl" means (1-4C) alkyl, (1-3C) alkyl propyl, isopropyl and t-butyl. Similar rules apply to other groups, e.g. For example, "phenyl(1-6C)alkyl" includes phenyl(1-4C)alkyl, benzyl, Includes 1-phenylethyl and 2-phenylethyl.

[0035] The term "(m-nC)" or "(m-nC) group" used alone or as a prefix means: It refers to any group having m to n carbon atoms.

[0036] An "alkylene," "alkenylene," or "alkynylene" group is a bond between two other chemical groups. and an alkyl, alkenyl, or alkynyl group that serves to connect them. Thus, "(1-6C) alkylene" refers to a divalent linear saturated alkyl group of 1 to 6 carbon atoms. A hydrocarbon group or a divalent branched saturated hydrocarbon group of 3 to 6 carbon atoms, such as methylene , ethylene, propylene, 2-methylpropylene, pentylene, etc.

[0037] "(2-6C)alkenylene" includes, for example, ethenylene and 2,4-pentadienylene. How, a divalent linear carbon atom of 2 to 6 carbon atoms containing at least one double bond It means a hydrogen group or a divalent branched hydrocarbon group of 3 to 6 carbon atoms.

[0038] "(2-6C)alkynylene" includes, for example, ethynylene, propynylene, and butynylene. A divalent linear carbon atom of 2 to 6 carbon atoms containing at least one triple bond, such as It means a hydrogen hydride group or a divalent branched hydrocarbon group of 3 to 6 carbon atoms.

[0039] The term "(m-nC)cycloalkyl" refers to a hydrocarbon ring containing m to n carbon atoms. For example, "(3-6C)cycloalkyl" means a cycloalkyl group containing 3 to 6 carbon atoms. Hydrogen rings, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl The term "(m-nC)cycloalkyl" also refers to non-aromatic saturated or partially saturated cycloalkyl groups. It includes monocyclic, fused, bridged, or spiro bicyclic carbocyclic ring systems. "Alkyl" includes both monovalent and divalent species. Monocyclic "(m-nC)cycloalkyl" includes monocyclic "(m-nC)cycloalkyl" and "(m-nC)cycloalkyl" include ... The ring contains about 3 to 12 (preferably 3 to 8, most preferably 5 to 6) ring carbon atoms. Bicyclic "(m-nC)cycloalkyl" refers to a group having 7 to 17 ring carbon atoms, preferably 7 to 17 ring carbon atoms. Contains 12 ring carbon atoms. m~n A "cycloalkyl" ring is a fused ring system, spin It may be a bicyclic or bridged ring system.

[0040] "(3-8C)cycloalkyl" means a hydrocarbon ring or bridge containing 3 to 8 carbon atoms. Bridged systems, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclo means bicyclo[2.2.1]heptyl or bicyclo[2.2.1]heptyl.

[0041] "(3-8C)cycloalkenyl" refers to a hydrocarbon containing at least one double bond. rings such as cyclobutenyl, cyclopentenyl, cyclohexenyl or cycloheptenyl For example, 3-cyclohexen-1-yl or cyclooctenyl.

[0042] "(3-8C)cycloalkyl-(1-6C)alkylene" is (1-6C) alkylene means a (3-8C)cycloalkyl group covalently bonded to a group, both of which are defined herein. is defined.

[0043] The term "halo" or "halogen" refers to fluoro, chloro, bromo, and iodo .

[0044] The terms "heterocyclyl," "heterocyclic," or "heterocycle" refer to a non-aromatic, saturated or partially saturated monocyclic, fused, bridged or spiro bicyclic heterocyclic ring systems. The ring contains about 3 to 12 (preferably 3 to 7) ring atoms, and no nitrogen, oxygen, or sulfur atoms are present in the ring. and the bicyclic heterocyclic ring contains 1 to 5 (preferably 1, 2 or 3) heteroatoms selected from: The ring contains 7 to 17 member atoms, preferably 7 to 12 member atoms in the ring. , fused, spiro or bridged ring systems. Examples of heterocyclic groups include oxiranyl. , oxetanyl, tetrahydrofuranyl, dioxanyl, and substituted cyclic ethers. Examples of nitrogen-containing heterocycles include azetidinyl, pyrrolidinyl, and the like. Lysinyl, piperidinyl, piperazinyl, tetrahydrotriazinyl, tetrahydropyra Representative heterocycles containing sulfur include tetrahydrothiazolyl and thiazolyl. dihydro-1,3-dithiol, tetrahydro-2H-thiopyran and hexahydro Other heterocyclic rings include dihydrooxathiolyl, tetrahydro tetrahydrooxazolyl, tetrahydrooxadiazolyl, tetrahydrodioxazolyl, tetra Hydroxathiazolyl, hexahydrotriazinyl, tetrahydrooxazinyl, mol morpholinyl, thiomorpholinyl, tetrahydropyrimidinyl, dioxolinyl, octahydropyrimidinyl Octahydrobenzofuranyl, octahydrobenzimidazolyl and octahydrobenzothiazolyl For heterocycles containing sulfur, sulfur oxides containing SO or SO2 groups are included. Yellow heterocycles are also included. Examples include tetrahydrothienyl and thiomorpholinyl sulfonyl. oxide and sulfone forms, e.g., tetrahydrothienyl 1,1-dioxide and thiomo 1 or 2 oxo (=O) or thioxo Suitable values ​​for a heterocyclyl group having an (=S) substituent are, for example, 2-oxopyrrolidine. Nyl, 2-thioxopyrrolidinyl, 2-oxoimidazolidinyl, 2-thioxoimidazolidine Lysinyl, 2-oxopiperidinyl, 2,5-dioxopyrrolidinyl, 2,5-dioxo imidazolidinyl or 2,6-dioxopiperidinyl. Particular heterocyclyl groups are saturated monocyclic rings containing 1, 2 or 3 heteroatoms selected from nitrogen, oxygen or sulfur 3- to 7-membered heterocyclyl, for example, azetidinyl, tetrahydrofuranyl, tetrahydro Pyranyl, pyrrolidinyl, morpholinyl, tetrahydrothienyl, tetrahydrothienyl , 1,1-dioxide, thiomorpholinyl, thiomorpholinyl, 1,1-dioxide, pi The aryl group is selected from the group consisting of piperidinyl, homopiperidinyl, piperazinyl, and homopiperazinyl. As will be understood, a heterocycle may be bonded via any suitable atom, for example via a carbon or nitrogen atom. However, the piperidino or morpholino groups herein may be linked to another group. Reference to a piperidin-1-yl ring or morpholin-4 is linked via a ring nitrogen. -refers to the yl ring.

[0045] A "carbon-linked heterocyclyl" is a heterocyclyl that is linked via a carbon atom rather than a heteroatom such as nitrogen. "Heterocyclic group" means a heterocyclic group as defined above, to which the ring is bonded.

[0046] A "spirocyclic ring system" is a small group of rings that have only one atom in common and are not joined by a bridge. It refers to compounds having at least two rings.

[0047] "Fused ring system" means a compound in which two rings share two adjacent atoms. For example, the rings share one covalent bond.

[0048] "Bridged ring system" means a ring system in which two rings share three or more atoms, e.g., Adv anced Organic Chemistry,by Jerry March,4 th Edition,Wiley Interscience,pages 131- 133, 1992. Examples of bridged heterocyclyl ring systems include aza-biscyl ring systems. 2-oxa-5-azabicyclo[2.2.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, Aza-bicyclo[2.2.2]octane, aza-bicyclo[3.2.1]octane and quinone Clidine is an example.

[0049] A "spirobicyclic system" is one in which two ring systems share one common spiro carbon atom, i.e. wherein the heterocycle is linked to a further carbocyclic or heterocyclic ring through a single common spiro carbon atom. An example of a spiro ring system is 6-azaspiro[3.4]octa. 2-oxa-6-azaspiro[3.4]octane, 2-azaspiro[3.3]heptane 2-oxa-6-azaspiro[3.3]heptane, 7-oxa-2-azaspiro[3 .5]nonane, 6-oxa-2-azaspiro[3.4]octane, 2-oxa-7-aza spiro[3.5]nonane and 2-oxa-6-azaspiro[3.5]nonane .

[0050] "Heterocyclyl(1-6C)alkyl" refers to a heterocyclyl group covalently linked to a (1-6C)alkylene group. and heterocyclyl groups, both of which are defined herein.

[0051] The term "heteroaryl" or "heteroaromatic" refers to a group selected from nitrogen, oxygen, or sulfur. aromatic compounds incorporating one or more (e.g., 14, especially 1, 2 or 3) heteroatoms The term "heteroaryl" refers to a monocyclic, bicyclic, or polycyclic aromatic ring. Examples of heteroaryl groups include those having 5 to 12 ring members, more usually 5 to 1 Heteroaryl groups are monocyclic and bicyclic groups containing, for example, 5 or 6 ring members. a fused 5-membered and 6-membered ring, or two fused 6-membered rings, It may be a bicyclic structure formed from fused six-membered rings. Each ring generally contains nitrogen, sulfur, and and oxygen. The ring may contain up to three heteroatoms, more usually up to two heteroatoms, e.g. In one embodiment, the heteroaryl ring contains at least one ring nitrogen atom. The nitrogen atom in the heteroaryl ring is an imidazole or pyridine. or substantially basic, as in the case of the nitrogen of an indole or pyrrole. Generally, in heteroaryl groups, including any amino group substituents on the ring, The number of basic nitrogen atoms present in is less than five.

[0052] Examples of heteroaryl include furyl, pyrrolyl, thienyl, oxazolyl, and isoxazolyl. Thiazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl , thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl pyrazinyl, 1,3,5-triazenyl, benzofuranyl, indolyl, isoindo aryl, benzothienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, Benzothiazolyl, indazolyl, purinyl, benzofurazanyl, quinolyl, isoquinolyl quinazolinyl, quinoxalinyl, cinnolinyl, pteridinyl, naphthidinyl, chlorinyl bazolyl, phenazinyl, benzoisoquinolinyl, pyridopyrazinyl, thieno[2,3b ]-furanyl-, 2H-furo[3,2b]-pyranyl-, 5H-pyrido[2,3-d]- Oxazinyl-, 1H-pyrazolo[4,3-d]-oxazinyl, 4H-imidazo[4, 5d]thiazolyl, pyrazino[2,3d]pyridazinyl, -imidazo[2,1b]thiazo -imidazo[1,2b][1,2,4]-triazinyl. "Rile" also refers to a ring in which at least one ring is aromatic and one or more of the other rings is non-aromatic. saturated or partially saturated rings, provided that at least one ring is selected from nitrogen, oxygen, or -sulfur- and partially aromatic bicyclic or polycyclic ring systems containing one or more heteroatoms. Examples of partially aromatic heteroaryl groups include, for example, tetrahydroisoquinolinyl ... tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, dihydroquinolinyl Robenzthienyl, dihydrobenzfuranyl, 2,3-dihydro-benzo[1,4]dioxide xynyl, benzo[1,3]dioxolyl, 2,2-dioxo-1,3-dihydro-2- Benzothienyl, 4,5,6,7-tetrahydrobenzofuranyl, indolinyl, 1,2 ,3,4-tetrahydro-1,8-naphthyridinyl, 1,2,3,4-tetrahydropyridinyl Do[2,3-b]pyrazinyl, 3,4-dihydro-2H-pyrido[3,2b][1,4] Oxazinyl and 6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pi Razinil is an example.

[0053] Examples of 5-membered heteroaryl groups include pyrrolyl, furanyl, thienyl, imidazolyl, Furazanyl, oxazolyl, oxadiazolyl, oxatriazolyl, isoxazolyl , thiazolyl, isothiazolyl, pyrazolyl, triazolyl and tetrazolyl groups. Examples include, but are not limited to:

[0054] Examples of 6-membered heteroaryl groups include pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, and pyrimidine. Examples include, but are not limited to, cyclohexyl and triazinyl.

[0055] The bicyclic heteroaryl group can be, for example, a group selected from: a benzene ring fused to a 5- or 6-membered ring containing 1, 2, or 3 ring heteroatoms; a pyridine ring fused to a 5- or 6-membered ring containing 1, 2, or 3 ring heteroatoms; a pyrimidine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a pyrrole ring fused to a 5- or 6-membered ring containing 1, 2, or 3 ring heteroatoms; a pyrazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a pyrazine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an imidazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an oxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an isoxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a thiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an isothiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a thiophene ring fused to a 5- or 6-membered ring containing 1, 2, or 3 ring heteroatoms; a furan ring fused to a 5- or 6-membered ring containing 1, 2, or 3 ring heteroatoms; Cyclohexyl fused to a 5- or 6-membered heteroaromatic ring containing 1, 2, or 3 ring heteroatoms ring; and Cyclopentyl fused to a 5- or 6-membered heteroaromatic ring containing 1, 2, or 3 ring heteroatoms Ru ring.

[0056] Particular examples of bicyclic heteroaryl groups containing a 6-membered ring fused to a 5-membered ring include benzophenone, ... phenyl, benzothiophenyl, benzimidazolyl, benzoxazolyl, benzisothiazolyl thiazolyl, benzothiazolyl, benzisothiazolyl, isobenzofuranyl, indole Isoindolyl, indolizinyl, indolinyl, isoindolinyl, purinyl (e.g. For example, adeninyl, guaninyl, indazolyl, benzodioxolyl and pyrazolopyri Examples of suitable alkyl groups include, but are not limited to, phenyl groups.

[0057] Particular examples of bicyclic heteroaryl groups containing two fused six-membered rings include quinolinyl, yl, methyl ... Soquinolinyl, chromanyl, thiochromanyl, chromenyl, isochromenyl, chromanyl , isochromanyl, benzodioxanyl, quinolizinyl, benzoxazinyl, benzodi Azinyl, pyridopyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl Examples of aryl include, but are not limited to, nyl, naphthyridinyl and pteridinyl groups.

[0058] "Heteroaryl(1-6C)alkyl" refers to a heteroaryl group covalently linked to a (1-6C)alkylene group. Heteroaralkyl means a heteroaryl group having a substituted or unsubstituted aryl group, both of which are defined herein. Exemplary groups include pyridin-3-ylmethyl, 3-(benzofuran-2-yl)propyl. Examples include:

[0059] The term "aryl" means a cyclic or polycyclic aromatic ring having from 5 to 12 carbon atoms. The term aryl includes both monovalent and divalent species. Examples of aryl groups include: Examples include, but are not limited to, phenyl, biphenyl, naphthyl, and the like. In certain embodiments, aryl is phenyl.

[0060] The term "aryl(1-6C)alkyl" refers to a group covalently linked to a (1-6C)alkylene group. Aryl-(1-6C)a means an aryl group, both of which are defined herein. Examples of alkyl groups include benzyl, phenylethyl, and the like.

[0061] This specification also uses some compound terms to describe groups containing two or more functional groups. Such terms will be understood by those skilled in the art. For example, heterocyclyl (m-nC) alkyl includes (m-nC) alkyl substituted by heterocyclyl. nothing.

[0062] The term "optionally substituted" refers to a group, structure, or molecule that is substituted, and "Here, R refers to a group, structure, or molecule that is not 1 One / any CH, CH2, C in the group The term "H3 groups or heteroatoms (i.e., NH) may be substituted" is preferably used. R 1 Any one of the hydrogen radicals of the group is replaced by the relevant defined group This means that...

[0063] Where an optional substituent is selected from "one or more" groups, this definition applies to one of the particular groups. It may contain all substituents selected from one of the specified groups, or substituents selected from two or more of the specified groups. I would like you to understand this.

[0064] The phrase "compounds of the invention" refers to compounds disclosed herein both generically and specifically. It means a compound.

[0065] Compounds of the Invention In a first aspect, the present invention provides a compound having structural formula I shown below, or a pharmaceutically acceptable salt thereof. Regarding acceptable salts, hydrates or solvates: [ka] [In the formula, R0 is hydrogen or deuterium; R1 is selected from aryl or heteroaryl; (wherein R1 is (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4 C) Haloalkoxy, cyano, (CH2) q1 NR 1B R 1C , (CH2) q1 OR 1B , (CH2) q1 C(O)R 1B , (CH2)q1C(O)OR 1B , (CH2) q1 O C(O)R 1B, (CH2) q1 C(O)N(R 1C )R 1B , (CH2) q1 N(R1 C )C(O)R 1B , (CH2) q1 S(O) p R 1B (where p is 0, 1 or 2) (CH2) q1 SO2N(R 1C )R 1B or (CH2) q1 N(R 1C )SO 2nd Round 1B one or more R independently selected from 1z may be substituted with a substituent, q1 is 0, 1, 2 or 3, and R 1B and R 1C are each independently hydrogen, (1 ~4C) alkyl, (3~6C) cycloalkyl or (3~6C) cycloalkyl(1~ 2C) selected from alkyl); R2 is hydrogen, cyano, halo, (1-4C) alkyl, (1-4C) haloalkyl, C( O)OR 2A , C(O)NR 2A R 2B , aryl, heteroaryl, (2-6C) aryl alkynyl, (2-6C)alkynyl or (1-4C)alkanoyl (where R 2A and R 2B are each independently hydrogen, (1-4C) alkyl, (1 ~4C)alkoxy, (3~6C)cycloalkyl or (3~6C)cycloalkyl (1-2C) alkyl; or CONR 2A R 2B In the group, R 2A and R 2B are the nitrogen atoms to which they are attached. are linked together to form a heterocycle, Alkyl, alkenyl, alkynyl, alkanoyl, aryl, heteroaryl or heteroaryl The cyclocyclyl group (R 2A and R 2B is formed by (1-4C) alkyl, Halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, amino, (1-4C) Aminoalkyl, cyano, (CH2) q2 NR 2D R 2E , (CH2) q2 OR 2D , ( CH2) q2 C(O)R 2D , (CH2) q2 C(O)OR 2D , (CH2) q2 OC( O)R 2D , (CH2)q 2C (O)N(R 2E )R 2D , (CH2) q2 N(R 2E ) C(O)R 2D , (CH2) q2 S(O)pR 2D (where p is 0, 1 or 2) ), (CH2) q2 SO2N(R 2E )R 2D or (CH2) q2 N(R 2E )SO2R 2D and q2 is optionally substituted by one or more substituents independently selected from 0, 1, 2 or 3, and R 2D and R 2E are each independently hydrogen, (1-4C) Alkyl, (3-6C)cycloalkyl or (3-6C)cycloalkyl(1-2C) selected from); R3 is hydrogen, halo, cyano or a group of the formula: -LYLq -Q (In the formula, L is absent or one or more selected from (1-2C) alkyl or oxo; is a (1-4C)alkylene optionally substituted by a substituent of Y is absent or is O, S, SO, SO2, N(R a ), C(O), C(O)O, OC(O), C(O)N(R a ), C(O)N(R a )O,N(R a )C(O),N(R a )C(O)N(R b ), N(R a )C(O)O,OC(O)N(R a ), C(=NR y )N(R a ), N(R a )C(=NRy), N(R a )C(=NR y )N(R b ), S( O)2N(R a ), N(Ra)SO2, N(R a )SO2N(R b ) or C(O)N (R a )SO2 (where R a and R b are each independently hydrogen or (1 to 4 C) alkyl, R y is hydrogen, (1-4C) alkyl, nitro or cyano selected from L q is absent or is (1-2C)alkoxy, halo, cyano, amino or o and (1-4C) alkylene optionally substituted with one or more substituents selected from oxo and can be, Q is hydrogen, (1-6C) alkyl, (2-6C) alkenyl, or (2-6C) alkynyl. , aryl, (3-8)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl aryl or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) haloalkoxy, (1-4C) aminoalkyl, (1-4C) hydroxyalkanol Kill, Cyano, NR c R d , OR c , C(O)R c , C(O)OR c ,OC(O)R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (where p is 0 , 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH2) q N R c R d (wherein q is 1, 2, or 3) may be further substituted with a group (wherein R c , R d and R e are each independently Hydrogen, (1-6C) alkyl, (3-6C) cycloalkyl or (3-6C) cyclo alkyl(1-2C)alkyl; or R c and R d together with the nitrogen atom to which they are attached, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, ( 1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino, cyano or or hydroxy, optionally substituted with one or more substituents selected from linked to form a ring), and / or Q is a group having the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or one or more selected from (1-2C) alkyl or oxo. (1-3C) alkylene optionally substituted by the above substituents, L Q1 is absent or O, S, SO, SO2, N(R f ), C(O), C(O) O, OC(O), C(O)N(R f ), N(R f )C(O),N(R f )C(O)N(R g ), N(R f )C(O)O,OC(O)N(R f ), S(O)2N(R f ), N(R f )SO2 (where R f and R g are each independently hydrogen or (1 to 2 C) alkyl), W1 is hydrogen, (1-6C) alkyl, aryl, aryl(1-2C) alkyl, (3 ~8C)cycloalkyl, (3~8C)cycloalkenyl, heteroaryl or heterocyclo and acryl (wherein W1 is oxo, (1-4C) alkyl, halo, (1-4C) halo). (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)alkoxy, (1-4C)alkoyl alkylamino, cyano, aryl, heteroaryl, heterocyclyl, (3-6C)cyclo Alkyl, NR h R i , OR h , C(O)R h , C(O)OR h ,OC(O)Rh , C( O)N(R i )R h , N(R i )C(O)R h , S(O) r R h (where r is 0, 1 or 2), SO2N(R i )R h , N(R i )SO2R h or (CH2) s NR i R h (wherein s is 1, 2, or 3) It is okay to have R h and R i are each independently hydrogen, (1-4C) alkyl, (3 Selected from (~6C)cycloalkyl or (3~6C)cycloalkyl(1~2C)alkyl And, The alkyl, alkoxy, aryl, heteroaryl, and heterocyclo groups in the substituents present in W1 are The acryl or cycloalkyl moiety may be one or more of halo, (1-4C) alkyl, (1-4C ) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, (1-4C) Alkylamino, di-[(1-4C)alkyl]amino, amino, cyano or hydroxy may be further substituted by a group, or R h and R i together with the nitrogen atom to which they are attached, oxo, (1-4C) alkyl , halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy oxy, (1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino, silyl A 4- to 7-membered heterocyclic group optionally substituted with one or more substituents selected from benzophenone and hydroxy. linked to form a heterocycle) and optionally substituted with one or more groups of is selected from the group A is selected from CR4 and N (wherein R4 is hydrogen, halo, or halo, (1-4C) haloalkyl, (1-4C) halo Alkoxy, (1-4C)aminoalkyl, (CH2) qa NR 4A R 4B , (CH2 ) qa OR 4A , (CH2) qa C(O)Rc 4A , (CH2) qa C(O)OR 4A , (CH2) qa OC(O)R 4A , (CH2) qa C(O)N(R 4B )R 4A , (CH 2) qa N(R 4B )C(O)R 4A , (CH2) qa S(O)pR 4A (where p is , 0, 1 or 2), (CH2) qa SO2N(R 4B )R 4A or (CH2) qa N(R 4B )SO2R 4A may be substituted with one or more substituents selected from (1 4C) alkyl, qa is 0, 1, 2, or 3, and R 4A and R 4B Is that each independently represents hydrogen, (1-6C) alkyl, (3-6C) cycloalkyl or (3-6C) C) selected from cycloalkyl(1-2C)alkyl); The tertiary amine in the compound of formula I may be in the form of an N-oxide, and the nitrogen in the pyridine ring The atom may be in the form of an N-oxide; Any S atom present in the heterocycle may be S(=O), S(=O)2 or S(=O)(=N R z ) (where R z is hydrogen, (1-3C) alkyl or (2-3C) alkanoyl may be present as a (selected from)].

[0066] Particular compounds of the invention include, for example, compounds of Formula I, or pharmaceutically acceptable derivatives thereof: The term "R", "R", "R' and "R'" refer to salts, hydrates and / or solvates of the compound, unless otherwise specified. Each of R1, R2, R3 and A is defined in any of the above or following paragraphs (1) to (55). has one of the meanings defined in: (1) R0 is hydrogen; (2) R0 is deuterium; (3) R1 is selected from aryl or heteroaryl (wherein R1 is (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4 C) Haloalkoxy, cyano, (CH2) q1 NR 1B R 1C , (CH2) q1 OR 1B , (CH2) q1 C(O)R 1B , (CH2) q1 C(O)OR 1B , (CH2) q1 O C(O)R 1B , (CH2) q1 C(O)N(R 1C )R 1B , (CH2) q1 N(R1 C )C(O)R 1B , (CH2) q1 S(O) p R 1B (where p is 0, 1 or 2) (CH2) q1 SO2N(R 1C )R1B or (CH2) q1 N(R 1C )SO2 R 1B one or more R independently selected from 1z may be substituted with a substituent, q1 is 0, 1, 2 or 3, and R 1B and R 1C are each independently hydrogen, (1 ~2C) alkyl, (3~4C) cycloalkyl or (3~4C) cycloalkyl(1~ 2C) selected from alkyl); (4) R1 is selected from aryl or heteroaryl (wherein R1 is (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4 C) Haloalkoxy, cyano, (CH2) q1 NR 1B R 1C , OR 1B , C(O)R1 B , C(O)OR 1B ,OC(O)R 1B , C(O)N(R 1C )R 1B , N(R 1C ) C(O)R 1B , S(O) p R 1B (wherein p is 0, 1 or 2), SO2N(R 1C )R 1B or N(R 1C )SO2R 1B one or more R independently selected from 1z Place may be substituted with a substituent, q1 is 0, 1 or 2; R 1B and R 1C are each independently hydrogen, (1-4C) alkyl, (3-6C) silyl selected from cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl); (5) R1 is selected from aryl or heteroaryl (wherein R1 is (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2 C) Haloalkoxy, cyano, (CH2) q1 NR 1B R 1C , OR 1B , C(O)R1 B , C(O)OR 1B ,OC(O)R 1B , C(O)N(R 1C )R 1B , N(R 1C ) C(O)R 1B , S(O) p R 1B (wherein p is 0, 1 or 2), SO2N(R 1C )R 1B or N(R 1C )SO2R 1B one or more R independently selected from 1z Place may be substituted with a substituent, q1 is 0, 1 or 2; R 1B and R 1C are each independently hydrogen, (1-2C) alkyl or (3-4C) selected from cycloalkyl); (5) R1 is selected from aryl or heteroaryl (wherein R1 is (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4 C) Haloalkoxy, cyano, (CH2) q1 NR 1B R 1C , (CH2) q1 OR 1B , (CH2) q1 C(O)R 1B , (CH2) q1 C(O)OR 1B , (CH2) q1 O C(O)R 1B , (CH2)q1 C(O)N(R 1C )R 1B , (CH2) q1 N(R1 C )C(O)R 1B , (CH2) q1 S(O) p R 1B (where p is 0, 1 or 2) (CH2) q1 SO2N(R 1C )R 1B or (CH2) q1 N(R 1C )SO2 R 1B one or more R independently selected from 1z may be substituted with a substituent, q1 is 0, 1 or 2; R 1B and R 1C are each independently hydrogen, (1-4C) alkyl, (3-6C) silyl selected from cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl); (6) R1 is selected from phenyl or 5- or 6-membered heteroaryl (wherein R1 is (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4 C) Haloalkoxy, cyano, (CH2) q1 NR 1B R 1C , OR 1B , C(O)R1 B , C(O)OR 1B ,OC(O)R 1B , C(O)N(R 1C )R 1B , N(R 1C ) C(O)R 1B , S(O) p R 1B (wherein p is 0, 1 or 2), SO2N(R 1C )R 1B or N(R 1C )SO2R 1Bone or more R independently selected from 1z Place may be substituted with a substituent, q1 is 0, 1 or 2; R 1B and R 1C are each independently hydrogen, (1-4C) alkyl, (3-6C) silyl selected from cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl); (7) R1 is selected from aryl or heteroaryl (wherein R1 is (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2 C) Haloalkoxy, cyano, (CH2) q1 NR 1B R 1C , OR 1B , C(O)R1 B , C(O)OR 1B ,OC(O)R 1B , C(O)N(R 1C )R 1B , N(R 1C ) C(O)R 1B , S(O) p R 1B (wherein p is 0, 1 or 2), SO2N(R 1C )R 1B or N(R 1C )SO2R 1B one or more R independently selected from 1z Place may be substituted with a substituent, q1 is 0, 1 or 2; R 1B and R 1C are each independently hydrogen, (1-2C) alkyl or (3-4C) selected from cycloalkyl); (8) R1 is selected from aryl or heteroaryl (wherein R1 is (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2 C) Haloalkoxy, cyano, (CH2)q1 NR 1B R 1C , (CH2) q1 OR 1B , (CH2) q1 C(O)R 1B , (CH2) q1 C(O)OR 1B , (CH2) q1 O C(O)R 1B , (CH2) q1 C(O)N(R 1C )R 1B , or (CH2) q1 N( R 1C )C(O)R 1B one or more R independently selected from 1z Substituted with a substituent It is okay to q1 is 0, 1, 2 or 3, and R 1B and R 1C are each independently hydrogen or ( 1-2C) are selected); (9) R1 is selected from aryl or heteroaryl (wherein R1 is (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2 C) Haloalkoxy, cyano, (CH2) q1 NR 1B R 1C , (CH2) q1 OR 1B or (CH2) q1 C(O)R 1B one or more R independently selected from 1z With substituents may be substituted, q1 is 0, 1, 2 or 3, and R 1B and R 1C are each independently hydrogen or ( 1-2C) selected from alkyl; (10) R1 is selected from phenyl or 5- or 6-membered heteroaryl (wherein R1 is (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2 C) Haloalkoxy, cyano, (CH2) q1 NR 1B R 1C , OR 1B , C(O)R1 B , C(O)OR 1B ,OC(O)R 1B , C(O)N(R 1C )R 1B , N(R 1C ) C(O)R 1B , S(O) p R 1B (wherein p is 0, 1 or 2), SO2N(R 1C )R 1B or N(R 1C )SO2R 1B one or more R independently selected from 1z Place may be substituted with a substituent, q1 is 0, 1 or 2; R 1B and R 1C are each independently selected from hydrogen or (1-2C) alkyl ); (11) R1 is one or more R1 as defined in any one of paragraphs (1) to (10) above. 1z It is an optionally substituted phenyl. (12) R1 is one or more R1s defined in any one of paragraphs (1) to (10) above. 1z It is an optionally substituted 5- or 6-membered heteroaryl. (13) R1 is phenyl, furyl, pyridyl, oxazolyl, thiazolyl, isoxa azolyl or oxazolin-2-yl (wherein phenyl, furyl, pyridinyl The aryl or oxazolyl ring may be selected from the group consisting of halo, (1-2C) alkyl, (1-2C) alkoxy, or silyl. may be substituted by an. (14) R1 is selected from phenyl, furyl, pyridyl, or oxazolyl, , phenyl, furyl, pyridyl or oxazolyl rings are halo, C 1~2 Alkoxy or cyclohexyl may be substituted by one or more of the following: (15) R1 is selected from phenyl, furyl, pyridyl, or oxazolyl, The phenyl, furyl, pyridyl or oxazolyl ring is substituted by halo or cyano. (This may be possible.) (16) R1 is 3-cyanophenyl, furyl, oxazolyl, thiazolyl, isoxazolyl, It is selected from oxazolyl and oxazolin-2-yl. (17) R1 is 3-cyanophenyl. (18) R2 is hydrogen, cyano, halo, (1-4C) alkyl, (1-4C) haloalkyl. Le, C(O)OR 2A , C(O)NR 2A R 2B , aryl, heteroaryl, (2-6 C) selected from alkenyl, (2-6C)alkynyl, or (1-4C)alkanoyl (where R 2A and R 2B are each independently hydrogen, (1-4C) alkyl, (1 ~4C)alkoxy, (3~6C)cycloalkyl or (3~6C)cycloalkyl (1-2C) alkyl; or CONR 2A R 2B In the group, R 2A and R 2B are the nitrogen atoms to which they are attached. and the alkyl group are linked together to form a 4- to 7-membered heterocycle, Alkyl, alkenyl, alkynyl, alkanoyl, aryl, heteroaryl or heteroaryl The cyclocyclyl group (R 2A and R 2Bis formed by (1-4C) alkyl, Halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, cyano, (CH2) q 2NR 2D R 2E , (CH2) q2 OR 2D , (CH2) q2 C(O)R 2D , (CH2 ) q2 C(O)OR 2D , (CH2) q2 OC(O)R 2D , (CH2)q2C(O)N (R 2E )R 2D , (CH2) q2 N(R 2E )C(O)R 12D , (CH2) q2 S( O)pR 2D (wherein p is 0, 1 or 2), (CH2) q2 SO2N(R 2E )R 2D or (CH2) q2 N(R 2E )SO2R 2D one or more independently selected from and optionally substituted by a substituent of q2 is 0, 1 or 2; R 2D and R 2E are each independently hydrogen, (1-2C) alkyl, (3-4C) silyl selected from cycloalkyl or (3-4C)cycloalkyl(1-2C)alkyl, When R2 is pyridyl, the ring nitrogen atom may be in the form of an N-oxide; (19) R2 is hydrogen, cyano, halo, (1-4C) alkyl, (1-4C) haloalkyl. Le, C(O)OR 2A , C(O)NR 2A R 2B , phenyl, 5- or 6-membered heteroaryl (2-4C)alkenyl or (1-4C)alkanoyl (where R 2A and R 2B are each independently hydrogen, (1-4C) alkyl or ( (3-6C)cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl Selected, The alkyl, alkenyl, alkanoyl, phenyl or heteroaryl group is (1-4C) Alkyl, halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, cyano, ( CH2) q2 NR 2D R 2E , (CH2) q2 OR 2D , (CH2) q2 C(O)R 2D , (CH2) q2 C(O)OR 2D , (CH2) q2 OC(O)R 2D , (CH2)q2 C (O)N(R 2E )R 2D , (CH2) q2 N(R 2E )C(O)R 12D , (CH2 ) q2 S(O)pR 2D (wherein p is 0, 1 or 2), (CH2) q2 SO2 N(R 2E )R 2D or (CH2) q2 N(R 2E )SO2R 2D are selected independently from and optionally substituted by one or more substituents such as q2 is 0, 1 or 2; R 2D and R 2E are each independently hydrogen, (1-2C) alkyl, (3-4C) silyl selected from cycloalkyl or (3-4C)cycloalkyl(1-2C)alkyl, When R2 is pyridyl, the ring nitrogen atom may be in the form of an N-oxide; (20) R2 is hydrogen, cyano, halo, (1-2C) alkyl, (1-2C) haloalkyl. Le, C(O)OR 2A , C(O)NR 2A R 2B , phenyl, 5- or 6-membered heteroaryl alkanoyl, or (1-4C)alkanoyl (where R 2A and R 2B each independently represents hydrogen or (1-4C) alkyl; Selected, The alkyl, alkenyl, alkanoyl, phenyl or heteroaryl group is (1-4C) Alkyl, halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, cyano, ( CH2) q2 NR 2D R 2E , (CH2) q2 OR 2D , (CH2) q2 C(O)R 2D , (CH2) q2 C(O)OR 2D , (CH2) q2 OC(O)R 2D , (CH2)q2 C(O)N(R 2E )R 2D , (CH2) q2 N(R 2E )C(O)R 12D , (CH2 ) q2 S(O)pR 2D (wherein p is 0, 1 or 2), (CH2) q2 SO2 N(R 2E )R 2D or (CH2) q2 N(R 2E )SO2R 2D are selected independently from and optionally substituted by one or more substituents such as q2 is 0, 1 or 2; R 2D and R 2E are each independently hydrogen, (1-2C) alkyl, (3-4C) silyl selected from cycloalkyl or (3-4C)cycloalkyl(1-2C)alkyl, When R2 is pyridyl, the ring nitrogen atom may be in the form of an N-oxide; (21) R2 is cyano, halo, methyl, CF3, C(O)OR 2A , C(O)NR 2A R 2B , 5- or 6-membered heteroaryl or (2-4C)alkanoyl (where R 2A and R 2B each independently represents hydrogen or (1-4C) alkyl; Selected, The phenyl or heteroaryl group may be (1-2C) alkyl, halo, (1-2C) haloal. Chloroalkoxy, (1-2C) haloalkoxy, cyano, (CH2) q2 NR 2D R 2E , OR 2D , C(O)R 2D , C(O)OR 2D ,OC(O)R 2D , C(O)N(R 2E )R 2D , N(R 2E )C(O)R 12D , S(O)pR 2D (where p is 0, 1 or 2. ), SO2N(R 2E )R 2D or N(R 2E )SO2R 2D are selected independently from optionally substituted by one or more substituents, q2 is 0 or 1, and R 2D and R 2Eare each independently selected from hydrogen or (1-2C) alkyl; When R2 is pyridyl, the ring nitrogen atom may be in the form of an N-oxide; (22) R2 is cyano or any of the groups defined above in any one of paragraphs (18) to (21). and optionally substituted 5- or 6-membered heteroaryl, (wherein when R2 is pyridyl, the ring nitrogen atom may be in the form of an N-oxide) ); (23) R2 is cyano, (1-2C) alkyl, halo, or (1-2C) haloalkyl , (1-2C)alkoxy, (1-2C)haloalkoxy, or cyano; and 5- or 6-membered heteroaryl optionally substituted with one or more substituents selected from (wherein when R2 is pyridyl, the ring nitrogen atom is in the form of an N-oxide. (That's good); (24) R2 is (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C )alkoxy, (1-2C)haloalkoxy, or cyano; and 5- or 6-membered heteroaryl optionally substituted with the above substituents (wherein R When 2 is pyridyl, the ring nitrogen atom may be in the form of an N-oxide; (25) R2 is one or more substituted groups independently selected from (1-2C) alkyl or halo. and 5- or 6-membered heteroaryl optionally substituted with a group (wherein R2 is pyridinyl). When the ring nitrogen atom is aryl, it may be in the form of an N-oxide; (26) R2 is (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C )alkoxy, (1-2C)haloalkoxy, or cyano; and R2 is a 6-membered heteroaryl optionally substituted by a substituent of the formula: In some cases, ring nitrogen atoms may be in the form of N-oxides; (27) R2 is one or more substituted groups independently selected from (1-2C) alkyl or halo. and a nitrogen-containing 6-membered heteroaryl optionally substituted with a group, wherein R2 is pyridyl. wherein the ring nitrogen atom may be in the form of an N-oxide; (28) R2 is substituted with one or more substituents independently selected from methyl or chloro. and optionally nitrogen-containing 6-membered heteroaryl (wherein, when R2 is pyridyl, ring nitrogen atoms may be in the form of N-oxides); (29)R2 is [ka] (In the formula, (i)R 200 and R 201 are each independently (1-2C) alkyl, hydroxy (1-2C) alkyl, aminohalo, (1-2C) haloalkyl, (1-2C) alkoxy selected from hydroxyl, (1-2C)haloalkoxy, (1-2C)alkanoyl, and cyano , (ii)R 200 and R 201 are each independently methyl, hydroxymethyl, halo , difluoromethyl, trifluoromethyl, methoxy, acetyl or cyano Ru, (iii)R 200 is methyl or chloro, and R 201 is methyl, hydroxymethyl from aryl, halo, difluoromethyl, trifluoromethyl, methoxy, acetyl or cyano selected), or [ka] (In the formula, (i)R 201 is (1-2C) alkyl, halo, (1-2C) haloalkyl, hydroxy (1-2C) alkyl, (1-2C) alkoxy, (1-2C) haloalkoxy, (1 ~2C) alkanoyl or cyano; (ii)R 201 is methyl, hydroxymethyl, halo, difluoromethyl, trifluoro methyl, methoxy, acetyl or cyano; (iii)R 201 is methyl, hydroxymethyl or chloro; (iv)R 201 is methyl; (v)R 201 is chloro) is; (30) R2 is substituted with one or more substituents independently selected from methyl or chloro. optionally pyridinyl (e.g., pyridin-4-yl); (31) R2 is 2-chloro-6-methylpyridin-4-yl or 2,6-dimethylpyridin-4-yl. Jin-4-yl, i.e., [ka] is; (32) R3 is hydrogen, halo, cyano or a group of the formula: -LYL q -Q (In the formula, L is absent or (1-4C)alkylene; Y is absent or is O, S, SO, SO2, N(R a ), C(O), C(O)O, OC(O), C(O)N(R a ), C(O)N(R a )O,N(R a )C(O),N(R a )C(O)N(R b ), N(R a )C(O)O,OC(O)N(Ra ), C(=NR y )N(R a ), N(R a )C(=NRy), N(R a )C(=NR y )N(R b ), S( O)2N(R a ), N(Ra)SO2, N(R a )SO2N(R b ) or C(O)N (R a )SO2 (where R a and R b are each independently hydrogen or (1 to 4 C) alkyl, R y is hydrogen, (1-4C) alkyl, nitro or cyano selected from L q is absent or is (1-2C)alkoxy, halo, cyano, amino or o and (1-4C) alkylene optionally substituted with one or more substituents selected from oxo and can be, Q is hydrogen, (1-6C) alkyl, (2-6C) alkenyl, or (2-6C) alkynyl. , aryl, (3-8)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl aryl or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) haloalkoxy, (1-4C) aminoalkyl, (1-4C) hydroxyalkanol Kill, Cyano, NR c R d , OR c , C(O)R c , C(O)OR c ,OC(O)R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O)p R c (where p is 0 , 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH2) q N R c R d (wherein q is 1, 2, or 3) may be further substituted with R c and R d are each independently hydrogen, (1 to 6 C) alkyl, (3-6C) cycloalkyl or (3-6C) cycloalkyl(1- 2C) alkyl; or R c and R d together with the nitrogen atom to which they are attached, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, ( 1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino, cyano or or hydroxy, optionally substituted with one or more substituents selected from linked to form a ring, and / or Q is a group having the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or (1-3C) alkylene; L Q1 is absent or O, S, SO, SO2, N(R f ), C(O), C(O) O, OC(O), C(O)N(R f ), N(R f )C(O),N(R f )C(O)N(R g ), N(R f )C(O)O,OC(O)N(R f), S(O)2N(R f ), N(R f )SO2 (where R f and R g are each independently hydrogen or (1 to 2 C) alkyl), W1 is hydrogen, (1-6C) alkyl, aryl, aryl(1-2C) alkyl, (3 ~8C)cycloalkyl, (3~8C)cycloalkenyl, heteroaryl or heterocyclo and acryl (wherein W1 is oxo, (1-4C) alkyl, halo, (1-4C) halo). (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)alkoxy, (1-4C)alkoyl alkylamino, cyano, aryl, heteroaryl, heterocyclyl, (3-6C)cyclo Alkyl, NR h R i , OR h , C(O)R h , C(O)OR h ,OC(O)R h , C( O)N(R i )R h , N(R i )C(O)R h , S(O) r R h (where r is 0, 1 or 2), SO2N(R i )R h , N(R i )SO2R h or (CH2) s NR i R h (wherein s is 1, 2, or 3) It is okay to have R h and R i are each independently hydrogen, (1-4C) alkyl, (3 Selected from (~6C)cycloalkyl or (3~6C)cycloalkyl(1~2C)alkyl And, The alkyl, alkoxy, aryl, heteroaryl, and heterocyclo groups in the substituents present in W1 are The acryl or cycloalkyl moiety may be one or more of halo, (1-4C) alkyl, (1-4C ) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, (1-4C) Alkylamino, di-[(1-4C)alkyl]amino, amino, cyano or hydroxy may be further substituted by a group, or R h and R i together with the nitrogen atom to which they are attached, oxo, (1-4C) alkyl , halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy oxy, (1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino, silyl A 4- to 7-membered heterocyclic group optionally substituted with one or more substituents selected from benzophenone and hydroxy. linked to form a heterocycle) and optionally substituted with one or more groups of is selected from the group The nitrogen atom in the tertiary amine or pyridyl ring in the R3 group may be in the form of an N-oxide. stomach; (33) R3 is hydrogen, halo, cyano or a group of the formula: -LYL q -Q (In the formula, L is absent or (1-4C)alkylene; Y is absent or is O, S, SO, SO2, N(R a ), C(O), C(O)O, OC(O), C(O)N(R a ), C(O)N(R a )O,N(R a )C(O),N(R a )C(O)N(R b ), N(R a )C(O)O,OC(O)N(Ra ), C(=NR y )N(R a ), N(R a )C(=NRy), N(R a )C(=NR y )N(R b ), S( O)2N(R a ), N(Ra)SO2, N(R a )SO2N(R b ) or C(O)N (R a )SO2 (where R a and R b are each independently hydrogen or (1 to 4 C) alkyl, R y is hydrogen, (1-4C) alkyl, nitro or cyano selected from L q is absent or is (1-2C)alkoxy, halo, cyano, amino or o and (1-4C) alkylene optionally substituted with one or more substituents selected from oxo and can be, Q is hydrogen, (1-6C) alkyl, (2-6C) alkenyl, or (2-6C) alkynyl. , aryl, (3-8)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl aryl or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) haloalkoxy, (1-4C) aminoalkyl, (1-4C) hydroxyalkanol Kill, Cyano, NR c R d , OR c , C(O)R c , C(O)OR c ,OC(O)R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O)p R c (where p is 0 , 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH2) q N R c R d (wherein q is 1, 2, or 3) may be further substituted with R c and R d are each independently hydrogen, (1 to 6 C) alkyl, (3-6C) cycloalkyl or (3-6C) cycloalkyl(1- 2C) alkyl, and / or Q is a group having the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or (1-3C) alkylene; L Q1 is absent or O, S, SO, SO2, N(R f ), C(O), C(O) O, OC(O), C(O)N(R f ), N(R f )C(O),N(R f )C(O)N(R g ), N(R f )C(O)O,OC(O)N(R f ), S(O)2N(R f ), N(R f )SO2 (where R f and R g are each independently hydrogen or (1 to 2 C) alkyl), W1 is hydrogen, (1-6C) alkyl, aryl, aryl(1-2C) alkyl, (3 ~8C)cycloalkyl, (3~8C)cycloalkenyl, heteroaryl or heterocyclo and acryl (wherein W1 is oxo, (1-4C) alkyl, halo, (1-4C) halo). (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)alkoxy, (1-4C)alkoyl alkylamino, cyano, aryl, heteroaryl, heterocyclyl, (3-6C)cyclo Alkyl, NR h R i , OR h , C(O)R h , C(O)OR h ,OC(O)R h , C( O)N(R i )R h , N(R i )C(O)R h , S(O) r R h (where r is 0, 1 or 2), SO2N(R i )R h , N(R i )SO2R h or (CH2) s NR i R h (wherein s is 1, 2, or 3) It is okay to have R h and R i are each independently hydrogen, (1-4C) alkyl, (3 Selected from (~6C)cycloalkyl or (3~6C)cycloalkyl(1~2C)alkyl will be) and optionally substituted with one or more groups of is selected from the group The nitrogen atom in the tertiary amine or pyridyl ring in the R3 group may be in the form of an N-oxide. stomach; (34) R3 is hydrogen, halo, cyano or a group of the formula: -LYL q -Q (In the formula, L is absent or (1-2C) alkylene; Y is absent or is O, S, SO, SO2, N(R a ), C(O), C(O)O, OC(O), C(O)N(R a ), C(O)N(R a )O,N(R a )C(O),N(R a )C(O)N(R b ), N(R a )C(O)O,OC(O)N(R a ), C(=NR y )N(R a ), N(R a )C(=NR y ), N(R a )C(=NR y )N(R b ), S( O)2N(R a ), N(Ra)SO2, N(R a )SO2N(R b ) or C(O)N (R a )SO2 (where R a and R b are each independently hydrogen or (1 to 4 C) alkyl, R y is hydrogen, (1-4C) alkyl, nitro or cyano selected from L q is absent or is (1-2C)alkoxy, halo, cyano, amino or o and (1-4C) alkylene optionally substituted with one or more substituents selected from oxo and can be, Q is hydrogen, (1-6C) alkyl, aryl, (3-8) cycloalkyl, heteroaryl. is aryl or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) haloalkoxy, (1-4C) aminoalkyl, (1-4C) hydroxyalkanol Kill, Cyano, NRc R d , OR c , C(O)R c , C(O)OR c ,OC(O)R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (where p is 0 , 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH2) q N R c R d (wherein q is 1, 2, or 3) may be further substituted with R c and R d are each independently hydrogen, (1 to 6 C) alkyl, (3-6C) cycloalkyl or (3-6C) cycloalkyl(1- 2C) alkyl, and / or Q is a group having the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or (1-2C) alkylene; L Q1 is absent or O, S, SO, SO2, N(R f ), C(O), C(O) O, OC(O), C(O)N(R f ), N(R f )C(O),N(R f )C(O)N(R g ), N(R f )C(O)O,OC(O)N(R f ), S(O)2N(R f ), N(R f )SO2 and Rf and R g are each independently hydrogen or (1-2C) alkane. Selected from the kill, W1 is hydrogen, (1-6C) alkyl, aryl, aryl(1-2C) alkyl, (3 -8C) cycloalkyl, heteroaryl, or heterocyclyl, and W1 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy , (1-4C)alkoxy, (1-4C)alkylamino, cyano, NR h R i , OR h , C(O)R h , C(O)OR h ,OC(O)R h , C(O)N(R i )R h , N(R i )C(O)R h , S(O) r R h (where r is 0, 1 or 2), SO2N(R i )R h , N(R i )SO2R h or (CH2) s NR i R h (where s is 1, 2 or is 3), and R h and R i teeth , each independently selected from hydrogen or (1-4C) alkyl and optionally substituted with one or more groups of is selected from the group The nitrogen atom in the tertiary amine or pyridyl ring in the R3 group may be in the form of an N-oxide. stomach; (35) R3 is hydrogen, halo, cyano or a group of the formula: -LYL q -Q (In the formula, L is absent or (1-2C) alkylene; Y is absent or O, N(R a ), C(O), C(O)O, C(O)N(R a ) , N(R a )C(O), C(O)N(R a )O,N(R a )C(O),N(R a )C(O )N(R b ), N(R a )C(O)O,OC(O)N(R a ), C(=NR y )N(R a ), N(R a )C(=NRy), N(R a )C(=NR y )N(R b ), S(O)2N( R a ), N(Ra)SO2, N(R a )SO2N(R b ) or C(O)N(R a )S O2 (where R a and R b are each independently hydrogen or (1-4C) alkyl selected from the R y is selected from hydrogen, (1-4C) alkyl, nitro or cyano ( L q is absent or is (1-2C)alkoxy, halo, cyano, amino or o and (1-4C) alkylene optionally substituted with one or more substituents selected from oxo and can be, Q is hydrogen, (1-6C) alkyl, aryl, (3-8) cycloalkyl, heteroaryl. is aryl or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) haloalkoxy, (1-4C) aminoalkyl, (1-4C) hydroxyalkanol Kill, Cyano, NR c R d , OR c , C(O)R c , C(O)OR c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (where p is 0, 1 or 2) ), SO2N(R d )R c , N(R d )SO2R c or (CH2) q NR c R d (where , q is 1, 2, or 3; R c and R d are each independently hydrogen or (1-6C) alkyl and / or Q is a group having the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or (1-2C) alkylene; L Q1 does not exist, W1 is hydrogen, (1-6C) alkyl, aryl, aryl(1-2C) alkyl, (3 -8C) cycloalkyl, heteroaryl, or heterocyclyl, and W1 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy , (1-4C)alkoxy, (1-4C)alkylamino, cyano, NR h R i , OR h , C(O)R h, C(O)OR h ,OC(O)R h , C(O)N(R i )R h , N(R i )C(O)R h , S(O) r R h (wherein r is 0, 1 or 2) may be substituted with one or more substituents, R h and R i are each independently hydrogen or is selected from (1-4C) alkyl and optionally substituted with one or more groups of is selected from the group The nitrogen atom in the tertiary amine or pyridyl ring in the R3 group may be in the form of an N-oxide. stomach; (35a) R3 is hydrogen, halo, cyano or a group of the formula: -LYL q -Q (In the formula, L is absent or (1-2C) alkylene; Y is absent or N(R a ), C(O), C(O)N(R a ), N(R a )C( =NR y )N(R b ), C(O)N(R a )O or N(R a )C(O)N(R b )in Yes (where R a and R b each independently represents hydrogen or (1-4C) alkyl; Selected, R y is selected from hydrogen, (1-4C) alkyl or cyano, L q is absent or is (1-2C)alkoxy, halo, cyano, amino or o and (1-4C) alkylene optionally substituted with one or more substituents selected from oxo and can be, Q is hydrogen, (1-6C) alkyl, (2-6C) alkenyl, (3-8) cycloalkyl aryl, or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) haloalkoxy, (1-4C) aminoalkyl, (1-4C) hydroxyalkanol Kill, Cyano, C(O)R c , C(O)OR c , C(O)N(R d )R c , N(R d )C (O)R c , S(O) p R c (wherein p is 0, 1 or 2), SO2N(R d ) R c , N(R d )SO2R c or (CH2) q NR c R d (where q is 1, 2 or 3 and R c and R d are each independently selected from hydrogen or (1-6C) alkyl, and and / or Q is a group having the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or (1-2C) alkylene; L Q1 does not exist, W1 is hydrogen, (1-6C) alkyl, aryl, aryl(1-2C) alkyl, (3 -8C) cycloalkyl, heteroaryl, or heterocyclyl, and W1 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy , (1-4C)alkoxy, (1-4C)alkylamino, cyano, NR h R i , OR h , C(O)R h , C(O)OR h ,OC(O)R h , C(O)N(R i )R h , N(R i )C(O)R h , S(O) r R h (wherein r is 0, 1 or 2) may be substituted with one or more substituents, R h and R i are each independently hydrogen or is selected from (1-4C) alkyl and optionally substituted with one or more groups of is selected from the group The nitrogen atom in the tertiary amine or pyridyl ring in the R3 group may be in the form of an N-oxide. stomach; (36) R3 is a group represented by the formula: -LYL q -Q (In the formula, L does not exist, Y is N(R a ) or C(O)N(R a ) and L q does not exist, Q is (1-6C) alkyl or (3-8) cycloalkyl (where Q is halo, cyano, NR c R d , OR c , C(O)R c , C(O)OR c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (where p is 0 , 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH2) q N R c R d (wherein q is 1, 2, or 3) may be further substituted with R c and R d are each independently hydrogen or (1- 6C) alkyl)) is the basis of; (37) R3 is a group represented by the formula: -LYL q -Q (In the formula, L does not exist, Y is N(R a ) or C(O)N(R a ) and L q does not exist, Q is (1-6C) alkyl (where Q is halo, cyano, NR c R d , OR c , C(O)OR c , S(O) p R c (wherein p is 0, 1 or 2), SO2N(R d )R c are selected independently from may be further substituted with one or more substituents, R c and R d are each independently selected from hydrogen or (1-6C) alkyl) is the basis of; (38) R3 is a group represented by the formula: -LYL q -Q (In the formula, L does not exist, Y is N(R a) or C(O)N(R a ) and L q does not exist, Q is (1-6C) alkyl (where Q is one or more OR c may be further substituted with R c is hydrogen or ( 1-4C) alkyl)) is the basis of; (39) R3 is a group represented by the formula: -LYL q -Q (In the formula, L does not exist, Y is N(R a ) or C(O)N(R a ) and L q does not exist, Q is (1-6C) alkyl (wherein Q may be further substituted with one or more OH). is the basis of; (40) R3 is a group represented by the formula: [ka] (In the formula, R 3a is hydrogen or methyl) is the basis of; (41) R3 is halo or a group of the formula: -LYQ (In the formula, L does not exist, Y is absent or is O, S, SO, SO2, N(R a ), C(O), C(O)O, OC(O), C(O)N(R a ), C(O)N(R a )O,N(R a )C(O), S(O )2N(R a ), N(R a )SO2 or N(R a )SO2N(R b ) and (where , Ra and R b are each independently selected from hydrogen or (1-2C) alkyl. , Q is (1-4C) alkyl, heteroaryl, or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) Haloalkoxy, Cyano, NR c R d , OR c , C(O)R c , C(O)OR c ,OC(O)R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (wherein p is 0, 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH2) q NR c R d (wherein q is 1, 2, or 3) and optionally further substituted with one or more substituents as defined above (wherein R c , R d and R e teeth , each independently hydrogen, (1-4C) alkyl, or (3-6C) cycloalkyl or R c and R d together with the nitrogen atom to which they are attached, (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, (1-2C) alkoxy, ( 1-2C) alkylamino, di-[(1-2C) alkyl]amino, amino, cyano or or 4- to 6-membered heterocyclic group optionally substituted with one or more substituents selected from hydroxy linked to form a ring), and / or Q is a group having the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or one or more selected from (1-2C) alkyl or oxo. (1-3C) alkylene optionally substituted by the above substituents, L Q1 is absent or O, S, SO, SO2, N(R f ), C(O), C(O) O, OC(O), C(O)N(R f ), N(R f )C(O),N(R f )C(O)O, O C(O)N(R f ), S(O)2N(R f ) or N(R f )SO2 is selected (this So, R f and R g are each independently selected from hydrogen or (1-2C) alkyl; ( W1 is hydrogen, (1-4C) alkyl, aryl, heteroaryl or heterocyclyl. (wherein W1 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl) alkoxy, (1-4C)haloalkoxy, (1-4C)alkoxy, cyano, NR h R i , OR h , C(O)R h , C(O)OR h ,OC(O)R h , C(O)N(R i )R h , N(R i )C(O)R h , S(O) r R h (where r is 0, 1 or 2), SO2N( R i )R h , N(R i )SO2R h or (CH2) s NR i R h (where s is 1, 2 or 3), wherein R h and R i are each independently hydrogen, (1-4C) alkyl, or (3-6C) cycloalkyl. alkyl, alkoxy, aryl, heteroaryl in the substituents present in W1 are selected from the group consisting of alkyl, alkoxy, aryl, heteroaryl, and heteroaryl. The aryl, heterocyclyl or cycloalkyl moiety may be one or more halo, (1-4C)alkoxy, alkyl, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy shi, (1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino, shi and may be further substituted by a hydroxyl or hydroxy group. and optionally substituted with a group is selected from the group The nitrogen atom in the tertiary amine or pyridyl ring present in the R3 group may be in the form of an N-oxide. It may be; (42) R3 is halo or a group of the formula: -Q (In the formula, Q is heteroaryl or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) Haloalkoxy, Cyano, NR c R d , OR c , C(O)R c , C(O)OR c ,OC(O)R c , C(O)N(R d )R c , N(R d )C(O)Rc , S(O) p R c (wherein p is 0, 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH2) q NR c R d (wherein q is 1, 2, or 3) and optionally further substituted with one or more substituents as defined above (wherein R c , R d and R e teeth , each independently hydrogen, (1-4C) alkyl, or (3-6C) cycloalkyl or R c and R d together with the nitrogen atom to which they are attached, (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, (1-2C) alkoxy, ( 1-2C) alkylamino, di-[(1-4C) alkyl]amino, amino, cyano or or 4- to 6-membered heterocyclic group optionally substituted with one or more substituents selected from hydroxy linked to form a ring), and / or Q is a group having the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or one or more selected from (1-2C) alkyl or oxo. (1-3C) alkylene optionally substituted by the above substituents, L Q1 is absent or O, S, SO, SO2, N(R f ), C(O), C(O) O, OC(O), C(O)N(R f ), N(R f )C(O),N(R f )C(O)O, O C(O)N(R f ), S(O)2N(R f ) or N(R f )SO2 and R f Reach BiR g are each independently selected from hydrogen or (1-2C) alkyl; W1 is hydrogen, (1-4C) alkyl, aryl, heteroaryl or heterocyclyl. can be, W1 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4C ) haloalkoxy, (1-4C) alkoxy, cyano, NR h R i , OR h , C(O)R h , C(O)OR h ,OC(O)R h , C(O)N(R i )R h , N(R i )C(O)R h , S(O) r R h (where r is 0, 1 or 2), SO2N(R i )R h , N (R i )SO2R h or (CH2) s NR i R h (where s is 1, 2, or 3) and R h and R i are each unique independently selected from hydrogen, (1-4C) alkyl, or (3-6C) cycloalkyl. Ruka, or R h and R i together with the nitrogen atom to which they are attached, form oxo, (1-4C) alkoxy, alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) a Alkoxy, (1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino , cyano, or hydroxy. are linked to form a 7-membered heterocycle, The alkyl, alkoxy, aryl, heteroaryl, and heterocyclo groups in the substituents present in W1 are The acryl or cycloalkyl moiety may be one or more of halo, (1-4C) alkyl, (1-4C ) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, (1-4C) Alkylamino, di-[(1-4C)alkyl]amino, amino, cyano or hydroxy may be further substituted by a group) and optionally substituted with a group is selected from the group The nitrogen atom in the tertiary amine or pyridyl ring present in the R3 group may be in the form of an N-oxide. It may be; (43) R3 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) Haloalkoxy, Cyano, NR c R d , OR c , C(O)R c , C(O)OR c ,OC(O)R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (wherein p is 0, 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH2) q NR c R d (wherein q is 1, 2, or 3) and heterocyclyl, which may be further substituted by one or more substituents as defined above, wherein R c , R d and R e are each independently hydrogen, (1-4C) alkyl or (3- 6C) cycloalkyl; or R c and R d together with the nitrogen atom to which they are attached, (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, (1-2C) alkoxy, ( 1-2C) alkylamino, di-[(1-2C) alkyl]amino, amino, cyano or or 4- to 6-membered heterocyclic group optionally substituted with one or more substituents selected from hydroxy linked to form a ring), and / or R3 has the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or one or more selected from (1-2C) alkyl or oxo. (1-3C) alkylene optionally substituted by the above substituents, L Q1 is absent or O, S, SO, SO2, N(R f ), C(O), C(O) O, OC(O), C(O)N(R f ), N(R f )C(O),N(R f )C(O)O, O C(O)N(R f ), S(O)2N(R f ) or N(R f )SO2 and R f and R g are each independently selected from hydrogen or (1-2C) alkyl; W1 is hydrogen, (1-4C) alkyl, aryl, heteroaryl or heterocyclyl. and W1 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1 ~4C) haloalkoxy, (1~4C) alkoxy, cyano, NR h R i , OR h , C( O)R h , C(O)OR h ,OC(O)R h , C(O)N(R i )R h , N(R i )C( O)R h , S(O) r R h (where r is 0, 1 or 2), SO2N(R i )R h , N(R i )SO2R h or (CH2) s NR i R h (where s is 1, 2, or 3. and R h and R i Is that each independently selected from hydrogen, (1-4C) alkyl, or (3-6C) cycloalkyl; Will be selected or or R h and R i together with the nitrogen atom to which they are attached, form oxo, (1-4C) alkoxy, alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) a Alkoxy, (1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino , cyano, or hydroxy. are linked to form a 7-membered heterocycle, The alkyl, alkoxy, aryl, heteroaryl, and heterocyclo groups in the substituents present in W1 are The acryl or cycloalkyl moiety may be one or more of halo, (1-4C) alkyl, (1-4C ) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, (1-4C) Alkylamino, di-[(1-4C)alkyl]amino, amino, cyano or hydroxy may be further substituted by a group) and optionally substituted with a group The nitrogen atom in the tertiary amine or pyridyl ring present in the R3 group may be in the form of an N-oxide. It may be; (44) R3 is selected from the group consisting of a 4- to 7-membered heterocyclic ring system, a 9- to 15-membered bicyclic ring system, and a 9- to 15-membered spirocyclic ring system. The nitrogen-bonded heterocycle of choice is wherein R3 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, cyano, NR c R d , OR c , C(O)R c , C(O)O R c ,OC(O)R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (wherein p is 0, 1 or 2), SO2N(R d )R c , N(R d )SO2 R c or (CH2) q NR c R d (wherein q is 1, 2, or 3) and optionally further substituted with one or more substituents selected from the group consisting of aryl, ... c , R d and R e are each independently hydrogen, (1-4C) alkyl, or (3-6C) cycloalkyl. or R c and R d together with the nitrogen atom to which they are attached, (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, (1-2C) alkoxy, ( 1-2C) alkylamino, di-[(1-2C) alkyl]amino, amino, cyano or or 4- to 6-membered heterocyclic group optionally substituted with one or more substituents selected from hydroxy linked to form a ring), and / or R3 has the formula: -L1-L Q1 -W1 (In the formula, L1 is absent or one or more selected from (1-2C) alkyl or oxo. (1-3C) alkylene optionally substituted by the above substituents, L Q1 is absent or O, S, SO, SO2, N(R f ), C(O), C(O) O, OC(O), C(O)N(R f ), N(R f )C(O),N(R f )C(O)O, O C(O)N(R f ), S(O)2N(R f ) or N(R f )SO2 and R f Reach BiR g are each independently selected from hydrogen or (1-2C) alkyl; W1 is hydrogen, (1-4C) alkyl, aryl, heteroaryl or heterocyclyl. and W1 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1 ~4C) haloalkoxy, (1~4C) alkoxy, cyano, NR h R i , OR h , C( O)Rh , C(O)OR h ,OC(O)R h , C(O)N(R i )R h , N(R i )C( O)R h , S(O) r R h (where r is 0, 1 or 2), SO2N(R i )R h , N(R i )SO2R h or (CH2) s NR i R h (where s is 1, 2, or 3. and R h and R i Is that each independently selected from hydrogen, (1-4C) alkyl, or (3-6C) cycloalkyl Can you do it? or R h and R i together with the nitrogen atom to which they are attached, form oxo, (1-4C) alkoxy, alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) a Alkoxy, (1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino , cyano, or hydroxy. are linked to form a 7-membered heterocycle, The alkyl, alkoxy, aryl, heteroaryl, and heterocyclo groups in the substituents present in W1 are The acryl or cycloalkyl moiety may be one or more of halo, (1-4C) alkyl, (1-4C ) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, (1-4C) Alkylamino, di-[(1-4C)alkyl]amino, amino, cyano or hydroxy may be further substituted by a group) and optionally substituted with a group The nitrogen atom in the tertiary amine or pyridyl ring present in the R3 group may be in the form of an N-oxide. It's okay. (45) R3 is piperazinyl, piperidinyl, pyrrolidinyl, oxetanyl, morpholinyl and heterocyclyl selected from the group consisting of aryl, diazepanyl, and azetidinyl. each of which may be further substituted with one or more R groups), or R3 has the following structure: have one of [ka] where b is an integer selected from 0, 1, 2, 3, or 4; Each R6 group is selected from the group consisting of (1-4C) alkyl, halo, (1-4C) haloalkyl, and (1-4C) halo. alkoxy, cyano, NR c R d , OR c , C(O)R c , C(O)OR c , OC(O )R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (where, p is 0, 1 or 2), SO2N(R d )R c , N(R d )SO2R c or ( CH2) q NR c R d where q is 1, 2 or 3, or a compound of the formula: -L1-L Q1 -W1 are independently selected from the group R c , R d and R eare each independently hydrogen, (1-4C) alkyl or (3- 6C) cycloalkyl or R c and R d are the nitrogen atoms to which they are attached. Together with the atom, (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C) Haloalkoxy, (1-2C)alkoxy, (1-2C)alkylamino, di-[(1- 2C) one or more selected from alkyl]amino, amino, cyano, or hydroxy are linked to form a 4- to 6-membered heterocycle which may be substituted by a substituent, where: L1 is absent or one or more selected from (1-2C) alkyl or oxo. is an optionally substituted (1-3C) alkylene; L Q1 is absent or O, S, SO, SO2, N(R f ), C(O), C(O) O, OC(O), C(O)N(R f ), N(R f )C(O),N(R f )C(O)O, O C(O)N(R f ), S(O)2N(R f ) or N(R f )SO2 and R f Reach BiR g are each independently selected from hydrogen or (1-2C) alkyl; W1 is hydrogen, (1-4C) alkyl, aryl, heteroaryl or heterocyclyl. and W1 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1 ~4C) haloalkoxy, (1~4C) alkoxy, cyano, NR h R i , OR h , C( O)R h , C(O)OR h,OC(O)R h , C(O)N(R i )R h , N(R i )C( O)R h , S(O) r R h (where r is 0, 1 or 2), SO2N(R i )R h , N(R i )SO2R h or (CH2) s NR i R h (where s is 1, 2, or 3. and R h and R i Is that each independently selected from hydrogen, (1-4C) alkyl, or (3-6C) cycloalkyl; Will be selected or or R h and R i together with the nitrogen atom to which they are attached, form oxo, (1-4C) alkoxy, alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) a Alkoxy, (1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino , cyano, or hydroxy. are linked to form a 7-membered heterocycle, The alkyl, alkoxy, aryl, heteroaryl, and heterocyclo groups in the substituents present in W1 are The acryl or cycloalkyl moiety may be one or more of halo, (1-4C) alkyl, (1-4C ) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, (1-4C) Alkylamino, di-[(1-4C)alkyl]amino, amino, cyano or hydroxy may be further substituted by groups, The nitrogen atom in the tertiary amine or pyridyl ring present in the R3 group may be in the form of an N-oxide. It's okay. (46) R3 is piperazinyl, piperidinyl, pyrrolidinyl, oxetanyl, morpholinyl aryl, diazepanyl, azetidinyl, or a heterocyclyl selected from one of the following structures: It is: [ka] . (47) R3 is selected from the group consisting of a 4- to 7-membered heterocyclic ring system, a 9- to 15-membered bicyclic ring system, and a 9- to 15-membered spirocyclic ring system. is a selected nitrogen-bonded heterocycle, where R3 is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( 1-4C) Haloalkoxy, Cyano, NR c R d , OR c , C(O)R c , C(O)OR c ,OC(O)R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (wherein p is 0, 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH2) q NR c R d (wherein q is 1, 2, or 3) and may be further substituted with one or more substituents as defined above. R c , R d and R e are each independently hydrogen, (1-4C) alkyl or (3- 6C) cycloalkyl or Rc and R d are the nitrogen atoms to which they are attached. Together with the atom, (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C) Haloalkoxy, (1-2C)alkoxy, (1-2C)alkylamino, di-[(1- 2C) one or more selected from alkyl]amino, amino, cyano, or hydroxy They are linked to form a 4- to 6-membered heterocycle which may be substituted with a substituent. (48) R3 is piperazinyl, piperidinyl, pyrrolidinyl, oxetanyl, morpholinyl and heterocyclyl selected from the group consisting of aryl, diazepanyl, and azetidinyl. each of which may be further substituted with one or more R groups), or R3 has the following structure: have one of [ka] where b is an integer selected from 0, 1, 2, 3, or 4; Each R6 group is selected from the group consisting of (1-4C) alkyl, halo, (1-4C) haloalkyl, and (1-4C) halo. alkoxy, cyano, NR c R d , OR c , C(O)R c , C(O)OR c , OC(O )R c , C(O)N(R d )R c , N(R d )C(O)R c , S(O) p R c (where, p is 0, 1 or 2), SO2N(R d )R c , N(R d )SO2R c or (CH 2) q NR c R dwhere q is 1, 2, or 3; R c and R d are each independently hydrogen, (1-4C) alkyl or (3-6C) cycloalkyl, or R c and R d are the nitrogen atoms to which they are attached. and (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C) haloa Alkoxy, (1-2C)alkoxy, (1-2C)alkylamino, di-[(1-2C) one or more substituents selected from alkyl, amino, cyano, or hydroxy; are linked together to form a 4- to 6-membered heterocycle which may be substituted with wherein the tertiary amine present in the R3 group may be in the form of an N-oxide. (49) R3 is piperazinyl, piperidinyl, pyrrolidinyl, oxetanyl, morpholinyl aryl, diazepanyl, azetidinyl, or a heterocyclyl selected from one of the following structures: It is: [ka] . (50) A is selected from CR4 and N; wherein R4 is hydrogen, halo, or halo, (1-2C) haloalkyl, (1-2C) halo Alkoxy, amino, cyano, (CH2) qa NR 4A R 4B , (CH2) qa OR 4A , (CH2) qa C(O)Rc 4A , (CH2) qa C(O)OR 4A , (CH2) qa OC(O)R 4A , (CH2) qa C(O)N(R 4B)R 4A , (CH2) qa N(R 4B )C(O)R 4A , (CH2) qa S(O) p R 4A (where p is 0, 1 or 2 ), (CH2) qa SO2N(R 4B )R 4A or (CH2) qa N(R 4B )S O2R 4A (1-2C) alkyl optionally substituted with one or more substituents selected from qa is 0, 1, 2 or 3; R 4A and R 4B are each independently Hydrogen, (1-4C) alkyl, (3-4C) cycloalkyl or (3-4C) cycloalkenyl selected from alkyl(1-2C)alkyl; (51) A is selected from CR4 and N; wherein R4 is substituted with one or more substituents selected from hydrogen, halo, or halo. may be (1-2C) alkyl; (52) A is selected from CR4 and N; where R4 is hydrogen, methyl or halo; (53) A is CR4, where R4 is hydrogen, methyl, fluoro, or chloro; (54) A is CH; (55)A is N.

[0067] Suitably, a heteroaryl or heterocyclyl group as defined herein is selected from the group consisting of N, O or monocyclic heteroaryl or monocyclic , bicyclic or bridged heterocyclyl groups.

[0068] Suitably, heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S. It is a 5- or 6-membered heteroaryl ring containing

[0069] Suitably, the heterocyclyl group comprises 1, 2 or 3 heteroatoms selected from N, O or S. It is preferably a 4-, 5-, 6-, 7- or 8-membered heterocyclyl ring containing atoms. The alkyl group is a 5, 6 or 7 alkyl group containing 1, 2 or 3 heteroatoms selected from N, O or S. membered rings [e.g., morpholinyl (e.g., 4-morpholinyl), pyridinyl, piperazinyl , homopiperazinyl or pyrrolidinonyl].

[0070] Preferably, the aryl group is phenyl.

[0071] Preferably, R0 is as defined in paragraph (1) or (2) above. In another embodiment, R is hydrogen. In another embodiment, R is deuterium.

[0072] Preferably, R1 is as defined in any one of paragraphs (3) to (17) above. More preferably, R1 is defined in any one of paragraphs (13) to (17) above. Most preferably, R1 is as defined in paragraph (13) or (17) above. is.

[0073] Preferably, R2 is as defined in any one of paragraphs (18) to (31). More preferably, R2 is cyano or any one of paragraphs (25) to (31). Most preferably, R2 is as defined in paragraph (25) or (31). That's right.

[0074] Preferably, R3 is as defined in any one of paragraphs (32) to (49). More preferably, R3 is any one of paragraphs (35) to (40) (for example, paragraph (35) Most preferably, R2 is as defined in any one of paragraphs (3 to (39)). 9) or (40).

[0075] Preferably, A is as defined in any one of paragraphs (50) to (55). Most preferably, A is as defined in paragraph (51), (54) or (55).

[0076] In certain groups of compounds of formula I above, R1 is selected from the group consisting of those described in paragraphs (3), (4), (5), (6), (7), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), (21), (22), (23), (24), (25), (26), (27), (28), (29), (3 (10), (13) or (17), and R, R, R 3 and A each have one of the definitions herein.

[0077] In a particular group of compounds of formula I above, R2 is selected from the group consisting of those described in paragraphs (18), (19), (20) and (21). ), (25), (29), (30), or (31) , R0, R1, R3 and A each have one of the definitions herein.

[0078] In a particular group of compounds of formula I above, R3 is selected from the group consisting of those described in paragraphs (32), (33), (34) and (35). ), (35), (35a), (38), (39) or (40) wherein R0, R1, R2 and A each have one of the definitions set forth herein. do.

[0079] In certain groups of compounds of formula I above, A is any of the groups listed in paragraphs (50), (51), (54) or (55), wherein R0, R1, R2 and R3 are as defined in any one of Each has one of the definitions herein.

[0080] In one embodiment of the compound of formula I above, R0 is as defined in paragraph (1) or (2); R1 is as defined in paragraphs (3) through (17) above; R2 is as defined in any one of paragraphs (18) to (31) above; R3 is as defined in any one of paragraphs (32) to (49) above, and A is as defined in any one of paragraphs (50) to (55) above.

[0081] In a particular group of compounds of formula I above, R0 is as defined in paragraph (1) or (2); R1 is as defined in paragraphs (13)-(17) above; R2 is as defined in any one of paragraphs (25) to (31) above; R3 is as defined in any one of paragraphs (35) to (40) above, and A is as defined in any one of paragraphs (51), (54) or (55) above. do.

[0082] In a particular group of compounds of formula I above, R0 is as defined in paragraph (1) or (2); R1 is as defined in paragraph (5) above; R2 is as defined in paragraph (19) above; R3 is as defined in paragraph (33) above, and A is as defined in paragraph (51) above.

[0083] In a particular group of compounds of formula I above, R0 is as defined in paragraph (1); R1 is as defined in paragraph (10) above; R2 is as defined in paragraph (20) above; R3 is as defined in paragraph (34) above, and A is as defined in paragraph (51) above.

[0084] In a particular group of compounds of formula I above, R0 is as defined in paragraph (1); R1 is as defined in paragraph (13) above; R2 is as defined in paragraph (25) above; R3 is as defined in paragraph (35) or (35a) above, and A is as defined in paragraph (53) above.

[0085] In a particular group of compounds of formula I above, R0 is as defined in paragraph (1); R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (29) above; R3 is as defined in paragraph (38) above, and A is as defined in paragraph (54) above.

[0086] In a particular group of compounds of the present invention, the compounds have the structural formula Ib shown below: subdefinitions], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof: [ka] (wherein R0, R1, R2 and R3 are as defined above, and R4 is water. methyl, fluoro or chloro).

[0087] In one embodiment of the compound of formula Ib: R0 is as defined in paragraph (1) or (2); R1 is as defined in any one of paragraphs (3) through (17) above; R2 is as defined in any one of paragraphs (18) to (31) above; R3 is as defined in any one of paragraphs (32) to (40) above, and R4 is hydrogen, methyl, fluoro or chloro.

[0088] In one embodiment of the compound of formula Ib: R0 is as defined in paragraph (1) or (2); R1 is as defined in any one of paragraphs (3) through (17) above; R2 is as defined in any one of paragraphs (18) to (31) above; R3 is as defined in any one of paragraphs (32) to (49) above, and R4 is hydrogen, methyl, fluoro or chloro.

[0089] In another embodiment of the compound of formula Ib, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (13) above; R2 is as defined in paragraph (25) above; R3 is as defined in paragraph (35) above, and R4 is hydrogen.

[0090] In another embodiment of the compound of formula Ib, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (38), (39) or (40) above, and R4 is hydrogen.

[0091] In another embodiment of the compound of formula Ib, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (40) above, and R4 is hydrogen.

[0092] In a particular group of compounds of the present invention, the compound has the structural formula Ic shown below: subdefinitions], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof: [ka] (wherein R0, R1, R2 and R3 are each as defined above).

[0093] In one embodiment of the compound of formula Ic: R0 is as defined in paragraph (1) or (2); R1 is as defined in any one of paragraphs (3) through (17) above; R2 is as defined in any one of paragraphs (18) to (31) above, and R3 is as defined in any one of paragraphs (32) to (40) above.

[0094] In another embodiment of the compound of formula Ic, R0 is as defined in paragraph (1) or (2); R1 is as defined in any one of paragraphs (3) through (17) above; R2 is as defined in any one of paragraphs (18) to (31) above, and R3 is as defined in any one of paragraphs (32) to (49) above.

[0095] In another embodiment of the compound of formula Ic, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (13) above; R2 is as defined in paragraph (25) above, and R3 is as defined in paragraph (35) above.

[0096] In another embodiment of the compound of formula Ic, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above, and R3 is as defined in paragraphs (38), (39) or (40) above.

[0097] In another embodiment of the compound of formula Ic, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (30) above, and R3 is as defined in paragraph (40) above.

[0098] In a particular group of compounds of the present invention, the compounds have the structural formula Id shown below: subdefinitions], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof: [ka] (wherein A, R1, R2 and R3 are each as defined above).

[0099] In one embodiment of the compound of formula Id, R1 is as defined in any one of paragraphs (3) through (17) above; R2 is as defined in any one of paragraphs (18) to (31) above; R3 is as defined in any one of paragraphs (32) to (40) above, and A is as defined in any one of paragraphs (50) to (55) above.

[0100] In one embodiment of the compound of formula Id, R1 is as defined in any one of paragraphs (3) through (17) above; R2 is as defined in any one of paragraphs (18) to (31) above; R3 is as defined in any one of paragraphs (32) to (49) above, and A is as defined in any one of paragraphs (50) to (55) above.

[0101] In another embodiment of the compound of formula Id, R1 is as defined in paragraph (13) above; R2 is as defined in paragraph (25) above; R3 is as defined in paragraph (35) above, and A is as defined in paragraph (51) above.

[0102] In another embodiment of the compound of formula Id, R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above, and R3 is as defined in paragraph (38), (39) or (40) above, and A is as defined in paragraph (54) or (55) above.

[0103] In another embodiment of the compound of formula Id, R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above, and R3 is as defined in paragraph (40) above, and A is as defined in paragraph (54) or (55) above.

[0104] In a particular group of compounds of the present invention, the compound has the structural formula Ie shown below: subdefinitions], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof: [ka] (Wherein A, R0, R2, R3 and R 1Z are as defined above, and m is , 0, 1 or 2).

[0105] In one embodiment of the compound of formula Ie: R0 is as defined in paragraph (1) or (2) above; R 1Z is as defined in any one of paragraphs (3) through (10) above; m is 0, 1 or 2; R2 is as defined in any one of paragraphs (18) to (31) above; R3 is as defined in any one of paragraphs (32) to (40) above, and A is as defined in any one of paragraphs (50) to (55) above.

[0106] In one embodiment of the compound of formula Ie: R0 is as defined in paragraph (1) or (2) above; R 1Z is as defined in any one of paragraphs (3) through (10) above; m is 0, 1 or 2; R2 is as defined in any one of paragraphs (18) to (31) above; R3 is as defined in any one of paragraphs (31) to (49) above, and A is as defined in any one of paragraphs (50) to (55) above.

[0107] In another embodiment of the compound of formula Ie, R0 is as defined in paragraph (1) above; R 1z is halo or cyano; m is 0 or 1; R2 is as defined in paragraph (25) above; R3 is as defined in paragraph (35) above, and A is as defined in paragraph (51) above.

[0108] In another embodiment of the compound of formula Ie, R0 is as defined in paragraph (1) above; R 1z is cyano, m is 1, R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (38), (39) or (40) above, and A is as defined in paragraph (54) or (55) above.

[0109] In another embodiment of the compound of formula Ie, R0 is as defined in paragraph (1) above; R 1z is cyano, m is 1, R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (40) above, and A is as defined in paragraph (54) or (55) above.

[0110] In a particular group of compounds of the present invention, the compound has the structural formula If shown below: subdefinitions], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof: [ka] (Wherein A, R0, R2, R3 and R 1Z are as defined above).

[0111] In one embodiment of the compound of formula If: R0 is as defined in paragraph (1) or (2) above; R 1Z is as defined in any one of paragraphs (3) through (10) above; R2 is as defined in any one of paragraphs (18) to (31) above; R3 is as defined in any one of paragraphs (32) to (40) above, and A is as defined in any one of paragraphs (50) to (55) above.

[0112] In one embodiment of the compound of formula If: R0 is as defined in paragraph (1) or (2) above; R 1Z is as defined in any one of paragraphs (3) through (10) above; R2 is as defined in any one of paragraphs (18) to (31) above; R3 is as defined in any one of paragraphs (32) to (49) above, and A is as defined in any one of paragraphs (50) to (55) above.

[0113] In another embodiment of the compound of formula If, R0 is as defined in paragraph (1) above; R 1z is halo or cyano; R2 is as defined in paragraph (25) above; R3 is as defined in paragraph (35) above, and A is as defined in paragraph (51).

[0114] In another embodiment of the compound of formula If, R0 is as defined in paragraph (1) above; R 1z is cyano, R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (38), (39) or (40) above, and A is as defined in paragraph (54) or (55) above.

[0115] In another embodiment of the compound of formula If, R0 is as defined in paragraph (1) above; R 1z is cyano, R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (40) above, and A is as defined in paragraph (54) or (55) above.

[0116] In a particular group of compounds of the present invention, the compounds have the structural formula Ig shown below: subdefinitions], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof: [ka] (wherein A, R0, R1 and R3 are as defined above, and R 200 and R 201 are each independently hydrogen, methyl, hydroxymethyl, halo, or trifluoro. methyl, difluoromethyl, methoxy or acetyl). 20 0 and R 201 are each independently selected from hydrogen, methyl, or halo.

[0117] In one embodiment of the compound of formula Ig: R0 is as defined in paragraph (1) or (2) above; R1 is as defined in any one of paragraphs (3) through (17) above; R3 is as defined in any one of paragraphs (32) to (49) above; A is as defined in any one of paragraphs (50) to (55); and R 200 and R 201 are each independently hydrogen, methyl, hydroxymethyl or halo is selected from.

[0118] In one embodiment of the compound of formula Ig: R0 is as defined in paragraph (1) or (2) above; R1 is as defined in any one of paragraphs (3) through (17) above; R3 is as defined in any one of paragraphs (32) to (40) above; A is as defined in any one of paragraphs (50) to (55); and R 200 and R 201 are each independently hydrogen, methyl, hydroxymethyl or halo is selected from.

[0119] In another embodiment of the compound of formula Ig, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (13) above; R2 is as defined in paragraph (25) above; R3 is as defined in paragraph (35) above; A is as defined in paragraph (51), and R 200 and R 201 are each independently selected from methyl or chloro.

[0120] In another embodiment of the compound of formula Ig, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (38), (39) or (40) above; A is as defined in paragraph (54) or (55) above, and R 200 is methyl and R 201 is chloro or methyl.

[0121] In another embodiment of the compound of formula Ig, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (40) above; A is as defined in paragraph (54) or (55) above, and R 200 is methyl and R 201 is chloro or methyl.

[0122] In a particular group of compounds of the present invention, the compounds have the structural formula Ig2 shown below [Formula (I): subdefinition], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof. : [ka] (Wherein A, R0, R1 and R3 are as defined above, R 201 is water from hydrogen, methyl, halo, trifluoromethyl, difluoromethyl, methoxy or acetyl selected).

[0123] In one embodiment of the compound of formula Ig2,

[0124] In one embodiment of the compound of formula Ig2, R0 is as defined in paragraph (1) or (2) above; R1 is as defined in any one of paragraphs (3) through (17) above; R3 is as defined in any one of paragraphs (32) to (40) above; A is as defined in any one of paragraphs (50) to (55); and R 201 is selected from hydrogen, methyl or halo.

[0125] In one embodiment of the compound of formula Ig2, R0 is as defined in paragraph (1) or (2) above; R1 is as defined in any one of paragraphs (3) through (17) above; R3 is as defined in any one of paragraphs (32) to (49) above; A is as defined in any one of paragraphs (50) to (55) above, and R 201 is selected from methyl, methoxy or halo.

[0126] In another embodiment of the compound of formula Ig2, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (13) above; R3 is as defined in paragraph (35) above; A is as defined in paragraph (51) above, and R 201 is selected from methyl or halo.

[0127] In another embodiment of the compound of formula Ig2, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (38), (39) or (40) above, and A is as defined in paragraph (54) or (55) above, and R 201 is selected from methyl or chloro.

[0128] In another embodiment of the compound of formula Ig2, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (40) above; A is as defined in paragraph (54) or (55) above, and R 201 is selected from methyl or chloro.

[0129] In a particular group of compounds of the present invention, the compounds have the structural formula Ih shown below: subdefinitions], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof: [ka] (wherein A, R0, R1 and R3 are each as defined above).

[0130] In one embodiment of the compound of formula Ih: R0 is as defined in paragraph (1) or (2) above; R1 is as defined in any one of paragraphs (3) through (17) above; R3 is as defined in any one of paragraphs (32) to (40) above, and A is as defined in any one of paragraphs (50) to (55).

[0131] In one embodiment of the compound of formula Ih: R0 is as defined in paragraph (1) or (2) above; R1 is as defined in any one of paragraphs (3) through (17) above; R3 is as defined in any one of paragraphs (32) to (49) above, and A is as defined in any one of paragraphs (50) to (55).

[0132] In another embodiment of the compound of formula Ih, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (13) above; R2 is as defined in paragraph (25) above; R3 is as defined in paragraph (35) above, and A is as defined in paragraph (51).

[0133] In another embodiment of the compound of formula Ih, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (38), (39) or (40) above, and A is as defined in paragraph (54) or (55).

[0134] In another embodiment of the compound of formula Ih, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (30) above; R3 is as defined in paragraph (39) or (40) above, and A is as defined in (52) or (53).

[0135] In a particular group of compounds of the present invention, the compounds have the structural formula Ih shown below: subdefinitions], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof: [ka] (wherein A, R0, R1 and R3 are each as defined above).

[0136] In one embodiment of the compound of formula Ih2, R0 is as defined in paragraph (1) or (2) above; R1 is as defined in any one of paragraphs (3) through (17) above; R3 is as defined in any one of paragraphs (32) to (40) above, and A is as defined in any one of paragraphs (50) to (55) above.

[0137] In one embodiment of the compound of formula Ih2, R0 is as defined in paragraph (1) or (2) above; R1 is as defined in any one of paragraphs (3) through (17) above; R3 is as defined in any one of paragraphs (32) to (49) above, and A is as defined in any one of paragraphs (50) to (55).

[0138] In another embodiment of the compound of formula Ih2, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (13) above; R3 is as defined in paragraph (35) above, and A is as defined in paragraph (51) above.

[0139] In another embodiment of the compound of formula Ih2, R0 is as defined in paragraph (1) above; R1 is as defined in any one of paragraphs (14) to (17) above; R3 is as defined in paragraph (38), (39) or (40) above, and A is as defined in (52) or (53).

[0140] In another embodiment of the compound of formula Ih2, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R3 is as defined in paragraph (38), (39) or (40) above, and A is as defined in (52) or (53).

[0141] In another embodiment of the compound of formula Ih2, R0 is as defined in paragraph (1) above; R1 is as defined in paragraph (17) above; R2 is as defined in paragraph (31) above; R3 is as defined in paragraph (40) above, and A is as defined in (52) or (53).

[0142] In a particular group of compounds of the present invention, the compounds have the structural formula Ii shown below: subdefinitions], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof: [ka] (Wherein A, R0, R3 and R 1Z are as defined above).

[0143] In one embodiment of the compound of formula Ii: R0 is as defined in paragraph (1) or (2) above; R1Z is as defined in any one of paragraphs (3) through (10) above; R3 is as defined in any one of paragraphs (32) to (49) above, and A is as defined in any one of paragraphs (50) to (55).

[0144] In one embodiment of the compound of formula Ii: R0 is as defined in paragraph (1) or (2) above; R 1Z is as defined in any one of paragraphs (3) through (10) above; R3 is as defined in any one of paragraphs (32) to (40) above, and A is as defined in any one of paragraphs (50) to (55).

[0145] In another embodiment of the compound of formula Ii, R0 is as defined in paragraph (1) above; R 1z is halo or cyano; R3 is as defined in paragraph (35) above, and A is as defined in paragraph (51) above.

[0146] In another embodiment of the compound of formula Ii, R0 is as defined in paragraph (1) above; R 1z is cyano, R3 is as defined in paragraph (38), (39) or (40) above, and A is as defined in paragraph (54) or (55) above.

[0147] In another embodiment of the compound of formula Ii, R0 is as defined in paragraph (1) above; R 1z is cyano, R3 is as defined in paragraph (40) above, and A is as defined in paragraph (54) or (55) above.

[0148] In a particular group of compounds of the present invention, the compounds have the structural formula Ii2 shown below [Formula (I): subdefinition], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof. : [ka] (Wherein A, R0, R3 and R 1Z are as defined above).

[0149] In one embodiment of the compound of formula Ii2, R0 is as defined in paragraph (1) or (2) above; R 1Z is as defined in any one of paragraphs (3) through (10) above; R3 is as defined in any one of paragraphs (32) to (40) above, and A is as defined in any one of paragraphs (50) to (55).

[0150] In one embodiment of the compound of formula Ii2, R0 is as defined in paragraph (1) or (2) above; R 1Z is as defined in any one of paragraphs (3) through (10) above; R3 is as defined in any one of paragraphs (32) to (49) above, and A is as defined in any one of paragraphs (50) to (55).

[0151] In another embodiment of the compound of formula Ii2, R0 is as defined in paragraph (1) above; R 1z is halo or cyano; R3 is as defined in paragraph (35) above, and A is as defined in paragraph (51) above.

[0152] In another embodiment of the compound of formula Ii2, R0 is as defined in paragraph (1) above; R 1z is cyano, R3 is as defined in paragraph (38), (39) or (40) above, and A is as defined in paragraph (54) or (55) above.

[0153] In another embodiment of the compound of formula Ii2, R0 is as defined in paragraph (1) above; R 1z is cyano, R3 is as defined in paragraph (40) above, and A is as defined in paragraph (54) or (55) above.

[0154] In a particular group of compounds of the present invention, the compounds have the structural formula Ii3 shown below [Formula (I): subdefinition], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof. : [ka] (Wherein A, R0, R3 and R 1Z are as defined above, and R 201 teeth, Hydrogen, methyl, hydroxymethyl, halo, trifluoromethyl, difluoromethyl, meth hydroxy or acetyl).

[0155] In one embodiment of the compound of formula Ii2, R0 is as defined in paragraph (1) or (2) above; R 1Zis as defined in any one of paragraphs (3) through (10) above; R3 is as defined in any one of paragraphs (32) to (40) above; A is as defined in any one of paragraphs (50) to (55) above, and R 201 is methyl, hydroxymethyl, halo, trifluoromethyl, difluoromethyl , methoxy or acetyl.

[0156] In one embodiment of the compound of formula Ii3, R0 is as defined in paragraph (1) or (2) above; R 1Z is as defined in any one of paragraphs (3) through (10) above; R3 is as defined in any one of paragraphs (32) to (49) above; A is as defined in any one of paragraphs (50) to (55) above, and R 201 is methyl, hydroxymethyl, halo, trifluoromethyl, difluoromethyl , methoxy or acetyl.

[0157] In another embodiment of the compound of formula Ii3, R0 is as defined in paragraph (1) above; R 1z is halo or cyano; R3 is as defined in paragraph (35) above; A is as defined in paragraph (50) above, and R 201 is selected from methyl, hydroxymethyl, halo, or methoxy.

[0158] In another embodiment of the compound of formula Ii3, R0 is as defined in paragraph (1) above; R 1z is cyano, R3 is as defined in paragraph (38), (39) or (40) above; A is as defined in paragraph (54) or (55) above, and R 201 is selected from methyl or chloro.

[0159] In another embodiment of the compound of formula Ii3, R0 is as defined in paragraph (1) above; R 1z is cyano, R3 is as defined in paragraph (40) above; A is as defined in paragraph (54) or (55) above, and R 201 is selected from methyl or chloro.

[0160] Specific compounds of the present invention include any of the compounds described in the Examples section of this application, or pharmaceutically acceptable salts or solvates of, in particular any of: 3-[5-amino-3-(4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl ]benzonitrile; 3-[5-amino-3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidinyl] din-2-yl]benzonitrile; 3-(5-amino-3-pyridazin-4-yl-pyrazolo[1,5-a]pyrimidine-2 -yl)benzonitrile; 3-[5-amino-3-(2-ethylpyrazol-3-yl)pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[5-amino-3-(2-chloro-6-methyl-4-pyridyl)pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1,5-a]pyridyl rimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(2-hydroxy-2- Methyl-propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy-1- Bicyclo[1.1.1]pentanyl)amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(8-methyl-3,8-di Azabicyclo[3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidine- 2-yl]benzonitrile; (3S)-4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl] (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]morpholine-3-carboxylic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-ethyl-4-piperidine) Lysyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S,4S)-4- Methoxy-1-methyl-pyrrolidin-3-yl]amino]pyrazolo[1,5-a]pyrimidin din-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-tetrahydro [1,5-a]pyrimidin-2-yl]benzodibenzofuran-3-yl]amino]pyrazolo[ ... Trill; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[3-(hydroxymethyl )-4-Methyl-piperazin-1-yl]pyrazolo[1,5-a]pyrimidin-2-yl ]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxyoxene benzo[1,5-a]pyrimidin-2-yl]benzo[1,5-a]pyrimidin-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzo nitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy-3- (methyl-butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Le; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxycyclohexyl) butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-methylsulfonyl) (4-piperidyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(8-oxa-3-azabicyclo[2.2.1. ...2.1.2.1.2.1.2.1.2.1.2.1.2 Cyclo[3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl le]benzonitrile; 3-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) Pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2,2-dimethyl-propane acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(5-oxopyrrolidine -3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-2-hydro [1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(3R,4R )-4-Hydroxytetrahydrofuran-3-yl]amino]pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(quinuclidin-3-yl) Amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxycyclohexyl) butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(2-morpholinoethyl) (amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-2-hydro [1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[2-[2-(dimethylamino)methyl] amino)ethyl]morpholin-4-yl]pyrazolo[1,5-a]pyrimidin-2-yl] Benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S)-2- Hydroxycyclobutyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4H-1,2,4-trimethyl- Azol-3-ylmethylamino)pyrazolo[1,5-a]pyrimidin-2-yl]benzo Zonitrile; (2R)-4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl] (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]morpholine-2-carboxylic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-tetrahydro [1,5-a]pyrimidin-2-yl]benzodibenzofuran-3-yl]amino]pyrazolo[ ... Trill; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-imino-1-oxo -1,4-thiazinane-4-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1,1-dioxothiazol-2-yl)methyl] (4-yl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ; 2-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) Pyrazolo[1,5-a]pyrimidin-5-yl]amino]acetamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-piperazin-1-yl-pyridyl] Lazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[2-(dimethylamino) )-1-methyl-ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]ben Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-hydroxy-pyrazolo[1 ,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1H-imidazole-2 -ylmethylamino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-morpholino-pyrazolo[1 ,5-a]pyrimidin-2-yl]benzonitrile; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]azetidine-2-carboxylic acid; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]azetidine-3-carboxylic acid; (3R)-1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl] (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]pyrrolidine-3-carboxylic acid; 4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]piperazine-1-sulfonamide; 3-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) Pyrazolo[1,5-a]pyrimidin-5-yl]amino]bicyclo[1.1.1]penta benzo-1-carboxylic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(2R)-2-hydro [1,5-a]pyrimidin-2-yl]benzonitrile ; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(2S)-2-hydro [1,5-a]pyrimidin-2-yl]benzonitrile ; 3-[5-(tert-butylamino)-3-(2-chloro-6-methyl-4-pyridyl] )pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-2-hydro [1-methyl-ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzyl benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-hydroxycyclohexyl) Propyl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Le; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4-piperidylamino) Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-morpholine -3-yl]methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; tert-Butyl(3R)-3-[[[3-(2-chloro-6-methyl-4-pyridyl) -2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino] methyl]morpholine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-3-piperidin di[amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Peridine-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-pyrrolidine -3-yl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Roridin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[rac-(4aS,7a S)-3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b][1, 4]oxazin-6-yl]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; tert-Butyl rac-(4aS,7aS)-6-[3-(2-chloro-6-methyl- 4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5- yl]-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]o Xanthazine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-morpholine -3-yl]methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; tert-Butyl(3S)-3-[[[3-(2-chloro-6-methyl-4-pyridyl) -2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino] methyl]morpholine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-pyrrolidine -3-yl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Roridin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-3-piperidin di[amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Peridine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5-a]pyridine Midine-5-carboxamide; N-tert-butyl-3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (Anophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Hydroxy-3-methyl-butyl)pyrazolo[1,5-a]pyrimidine-5-carbo oxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ 2-(4-phenylpiperazin-1-yl)ethyl]pyrazolo[1,5-a]pyrimidine -5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( Oxetan-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo [1,5-a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(morpholine-4-carbohydrate Nyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1S)-2-Hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrazole Midine-5-carboxamide; N-(2-amino-2-methyl-propyl)-3-(2-chloro-6-methyl-4-pyridyl)- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1-hydroxycyclopropyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1-hydroxycyclobutyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carbohydrate Voxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrazole Midine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (2R)-2-hydroxypropyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R)-2-hydroxy-1-methyl-ethyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-hydroxyoxetan-3-yl)methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-methyl Thilsulfonyl-pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2,3-Dihydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5 -carboxamides; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-hydroxycyclobutyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carbohydrate Voxamide; 3-(2-chloro-6-methyl-4-pyridyl)-N-(1-cyano-2-methoxy-1 -methyl-ethyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; N-(4-aminonorbornan-1-yl)-3-(2-chloro-6-methyl-4-pyridyl)- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (2S)-2,3-dihydroxypropyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3S,4S)-4-Methoxy-1-methyl-pyrrolidin-3-yl]pyrazolo[1,5 -a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (2R)-2,3-dihydroxypropyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 1-Methylazetidin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3S,4S)-4-hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-2-methyl-propyl)-N-methyl-pyrazolo[1,5-a]pyrimidin Zin-5-carboxamide; N-(3-amino-3-methyl-butyl)-3-(2-chloro-6-methyl-4-pyridinyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; N-(3-amino-1-bicyclo[1.1.1]pentanyl)-3-(2-chloro-6- Methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin thion-5-carboxamide; tert-Butyl N-[3-[[3-(2-chloro-6-methyl-4-pyridyl)-2- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino] -1-bicyclo[1.1.1]pentanyl]carbamate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ cis-(3S,4R)-4-hydroxypyrrolidin-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; tert-Butyl(3S,4R)-3-[[3-(2-chloro-6-methyl-4-pyridinyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl ]amino]-4-hydroxy-pyrrolidine-1-carboxylate; N-(2-amino-1,1-dimethyl-ethyl)-3-(2-chloro-6-methyl-4- Pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; tert-Butyl N-[2-[[3-(2-chloro-6-methyl-4-pyridyl)-2- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino] -2-methyl-propyl]carbamate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3S)-3-piperidyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide; tert-Butyl(3S)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amine no]piperidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ trans-(3S,4S)-4-hydroxypyrrolidin-3-yl]pyrazolo[1,5 -a]pyrimidine-5-carboxamide; tert-Butyl trans-(3S,4S)-3-[[3-(2-chloro-6-methyl -4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5 -carbonyl]amino]-4-hydroxy-pyrrolidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-hydroxypyrrolidin-3-yl)methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; tert-Butyl 3-[[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3 -Cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino]methyl yl]-3-hydroxy-pyrrolidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3R)-3-piperidyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amine no]piperidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Methylpyrrolidin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; tert-Butyl 3-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3- Cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino]-3- Methyl-pyrrolidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R,2S)-2,3-dihydroxy-1-methyl-propyl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl ru]pyrazolo[1,5-a]pyrimidine-5-carboxamide; N-[(1-amino-3,3-difluoro-cyclobutyl)methyl]-3-(2-chloro -6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pi Rimidine-5-carboxamide; tert-Butyl N-[1-[[[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino ]methyl]-3,3-difluoro-cyclobutyl]carbamate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( Morpholin-2-ylmethyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ; tert-Butyl 2-[[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3 -Cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino]methyl le]morpholine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(piperazine-1-carbohydrate Nyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl 4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (aminophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]piperazine-1- carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3R)-Pyrrolidin-3-yl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amine no]pyrrolidine-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-hydroxy-1-methyl) (ethyl-ethyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo [1,5-a]pyrimidine-5-carboxylic acid; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(2-phenyl) (hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(2-ethylpyrazol-3-yl)-N-(2-phenyl) (hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(2-ethyl-5-methyl-pyrazol-3-yl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-( 2-Methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2-ethyl-4-methyl-pyrazol-3-yl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-[2-(difluoromethyl)-6-methyl-4-pyridyl] [2-hydroxy-2-methyl-propyl]-N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidyl Zin-5-carboxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-( 2-Methylpyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-pyridin Rimidin-4-yl-pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-cyano-2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl) r)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(2-hydroxy-2-methyl (ethyl-propoxy)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]methanesulfonamide; (2S)-2-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyano Phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]propanoic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3R)-pyrrolidine- 3-yl]oxy-pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile phosphate Mate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(2-hydroxyethyl) (amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(morpholinomethyl)pyridine Zolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[5-(aminomethyl)-3-(2-chloro-6-methyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(3-hydroxy-3-methyl (ethyl-butyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-[2-(difluoromethyl)-6-methyl-4-pyridyl]-5-[(2-hydroxybenzoyl) (hydroxy-2-methyl-propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl le]benzonitrile; 3-[5-[(2-hydroxy-2-methyl-propyl)amino]-3-(2-methoxy -6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzodi Trill; 3-[3-(2,6-dimethyl-4-pyridyl)-5-[(2-hydroxy-2-methyl -propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-2-hydro [1-methyl-ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzyl benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(dimethylamino)pyrazo b[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4-piperidyloxy) Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-3-piperidin di[oxy]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl (3R)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]oxypiperi Zin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3S)-pyrrolidine- 3-yl]oxy-pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]oxypyrrolidone Zin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-3-piperidin di[oxy]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]oxypiperi Zin-1-carboxylate; 3-[5-amino-3-(6-amino-5-methyl-3-pyridyl)pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-[2-(difluoromethyl)-6-methyl-4-pyridyl]pyridine Zolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(2-methoxy-6-methyl-4-pyridyl)pyrazolo[1,5 -a]pyrimidin-2-yl]benzonitrile; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carbonitrile; 3-[5-amino-3-(2-fluoro-6-methyl-4-pyridyl)pyrazolo[1,5 -a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[5-amino-3-(2,6-dimethyl-1-oxide-pyridin-1-ium-4 -yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(2-amino-6-methyl-4-pyridyl)pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carboxamide; N-[4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin benzo-3-yl]-6-methyl-2-pyridyl]acetamide; 3-[5-amino-3-(5-methyl-[1,2,4]triazolo[1,5-a]pyridin (1,5-a)pyrimidin-2-yl)benzonitrile; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carboxylic acid; 3-[5-amino-3-[2-(dimethylamino)-6-methyl-4-pyridyl]pyrazo b[1,5-a]pyrimidin-2-yl]benzonitrile; [3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazo b[1,5-a]pyrimidin-5-yl]urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Iridium[1,5-a]pyrimidin-5-yl]-3-(2-hydroxy-2-methyl- lopil) urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-3-(1-ethyl-4-piperidyl)urine element; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]piperazine-1-carboxamide; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-3-[(3S)-pyrrolidin-3-yl] ]urea; 1-(2-aminoethyl)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl razolo[1,5-a]pyrimidin-5-yl]-3-[(3R)-pyrrolidin-3-yl] ]urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-2-cyano-guanidine; 3-[3-(2-ethylpyrazol-3-yl)-5-[(2-hydroxy-2-methyl -propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-[3-(hydroxymethyl)-4 -methyl-piperazin-1-yl]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(8-oxa-3-azabicyclo[3-(2-ethylpyrazol-3-yl)] ... [3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl]be benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(8-methyl-3,8-diazabiphenyl] Cyclo[3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl le]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(4-methylsulfonylpiperazine (1,5-a)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(4H-1,2,4-triazol- (3-ylmethylamino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-ethylpyrazol-3-yl)-5-piperazin-1-yl-pyrazolo [1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(1-imino-1-oxo-1, 4-Thiazinan-4-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 5-(benzylamino)-2-(2-fluorophenyl)pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; N-Benzyl-2-(2-fluorophenyl)pyrazolo[1,5-a]pyrimidine-5- amines; 2-(2-Furyl)-5-[(3-methyl-2-pyridyl)methylamino]pyrazolo[1 ,5-a]pyrimidine-3-carbonitrile; tert-Butyl(2S)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]morpholine-4-carboxylate; tert-Butyl(2R)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]pyrrolidine-1-carboxylate; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-(2-furyl)pyrazo b[1,5-a]pyrimidine-3-carbonitrile; tert-Butyl(2S)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]pyrrolidine-1-carboxylate; tert-Butyl(2R)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]morpholine-4-carboxylate; 2-(2-Furyl)-5-[4-(2-phenylethyl)piperazin-1-yl]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-(2-pyridylmethyl)piperazin-1-yl]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-(4-methylpiperazin-1-yl)pyrazolo[1,5-a] Pyrimidine-3-carbonitrile; 5-[(1-benzyl-4-piperidyl)methylamino]-2-(2-furyl)pyrazolo [1,5-a]pyrimidine-3-carbonitrile; tert-Butyl(2R)-4-[3-cyano-2-(2-furyl)pyrazolo[1,5- a]pyrimidin-5-yl]-2-methyl-piperazine-1-carboxylate; tert-Butyl(2S)-4-[3-cyano-2-(2-furyl)pyrazolo[1,5- a]pyrimidin-5-yl]-2-methyl-piperazine-1-carboxylate; 5-[2-(4-benzylpiperazin-1-yl)ethylamino]-2-(2-furyl) Pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[(3-methyl-2-pyridyl)methylamino]pyrazolo[1 ,5-a]pyrimidine-3-carboxamide; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-(2-furyl)pyrazo b[1,5-a]pyrimidine-3-carboxamide; 5-[3-(dimethylamino)azetidin-1-yl]-2-(2-furyl)pyrazolo[ 1,5-a]pyrimidine-3-carboxamide; tert-Butyl 4-[3-cyano-2-(2-furyl)pyrazolo[1,5-a]pyrimidinyl] din-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate; 2-(2-Furyl)-5-piperazin-1-yl-pyrazolo[1,5-a]pyrimidine- 3-carbonitrile; 2-(2-Furyl)-5-[[(2S)-morpholin-2-yl]methylamino]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[[(2R)-morpholin-2-yl]methylamino]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 5-(4-benzylpiperazin-1-yl)-2-(2-furyl)pyrazolo[1,5-a ]pyrimidine-3-carbonitrile; N-benzyl-3-bromo-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-5 -amine; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- carbonitrile; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carboxamides; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carboxaldehyde; N-benzyl-2-(2-furyl)pyrazolo[1,5-a]pyrimidin-5-amine; 5-Amino-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile Le; 3-Bromo-2-(2-furyl)pyrazolo[1,5-a]pyrimidin-5-amine; 2-(2-Furyl)-5-[4-[(3-methyl-2-pyridyl)methyl]piperazine- 1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-[(2,4,6-trifluorophenyl)methyl]piperidine radin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-[(1-methylimidazol-2-yl)methyl]piperidine radin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-(2-hydroxyethyl)piperazin-1-yl]pyrazin Zolo[1,5-a]pyrimidine-3-carbonitrile; N-benzyl-2-(2-furyl)-3-(1-methylpyrazol-4-yl)pyrazolo [1,5-a]pyrimidin-5-amine; N-benzyl-2-(2-furyl)-3-(2-methylpyrazol-3-yl)pyrazolo [1,5-a]pyrimidin-5-amine; Methyl (E)-3-[5-(benzylamino)-2-(2-furyl)pyrazolo[1,5- a]pyrimidin-3-yl]prop-2-enoate; (E)-3-[5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pi rimidin-3-yl]prop-2-enoic acid; 2-(2-Furyl)-5-(4-phenylpiperazin-1-yl)pyrazolo[1,5-a ]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-(3-hydroxypropylamino)pyrazolo[1,5-a]piperidin Rimidine-3-carbonitrile; 2-(2-Furyl)-5-(2-hydroxyethylamino)pyrazolo[1,5-a]pyridine Midine-3-carbonitrile; 2-(2-Furyl)-5-(3-piperidylmethylamino)pyrazolo[1,5-a]pyridine Midine-3-carbonitrile hydrochloride; 5-(benzylamino)-2-oxazol-2-yl-pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; 5-(benzylamino)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin benzo-3-carbonitrile; 2-(3-cyanophenyl)-5-[4-[(3-methyl-2-pyridyl)methyl]piperidine radin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(3-fluorophenyl)-5-[4-[(3-methyl-2-pyridyl)methyl]pyridyl Perazin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-(3-fluorophenyl) r)pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-oxazol-5-yl Ru-pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 5-(benzylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; 5-(benzylamino)-2-(5-methyl-2-furyl)pyrazolo[1,5-a]pyridine Midine-3-carbonitrile; 5-[4-[(3-methyl-2-pyridyl)methyl]piperazin-1-yl]-2-oxo Sazol-5-yl-pyrazolo[1,5-a]pyrimidine-3-carbonitrile; N-Benzyl-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidine-5- amines; 2-(3-fluorophenyl)-N-[(3-methyl-2-pyridyl)methyl]pyrazolo [1,5-a]pyrimidin-5-amine; 2-(3-fluorophenyl)-N-(2-phenylethyl)pyrazolo[1,5-a]piperidin Rimidin-5-amine; N-(1H-benzimidazol-2-ylmethyl)-2-(3-fluorophenyl)pi Lazolo[1,5-a]pyrimidin-5-amine; 2-(3-fluorophenyl)-N-(2-isoindolin-2-ylethyl)pyrazolo [1,5-a]pyrimidin-5-amine; N-Benzyl-3-chloro-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrazole mydin-5-amine; 3-Bromo-5-chloro-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin gin; N-Benzyl-3-bromo-2-(3-fluorophenyl)pyrazolo[1,5-a]pyridine mydin-5-amine; 5-(benzylamino)-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; 3-Bromo-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-5-a Min; 5-Amino-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate rubonitrile; 2-(2-Furyl)-N-(thiazol-2-ylmethyl)pyrazolo[1,5-a]pyridine mydin-5-amine; [5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3 -yl]methanol; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carboxylic acids; N-benzyl-2-(2-furyl)-3-iodo-pyrazolo[1,5-a]pyrimidine- 5-amine; 2-(2-Furyl)-3-(4-pyridyl)pyrazolo[1,5-a]pyrimidin-5-a Min; 2-(2-Furyl)-5-[[(2R)-pyrrolidin-2-yl]methylamino]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[[(2R)-1-methylpyrrolidin-2-yl]methylamine no]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[(3R)-3-methylpiperazin-1-yl]pyrazolo[1 ,5-a]pyrimidine-3-carbonitrile hydrochloride; tert-Butyl 4-[3-cyano-2-(2-furyl)pyrazolo[1,5-a]pyrimidinyl] din-5-yl]piperidine-1-carboxylate; N-benzyl-7-(2-furyl)pyrazolo[1,5-a][1,3,5]triazine- 2-amines; N-Benzyl-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-5-[4-(2-fluoroethyl)piperazin-1-yl] ]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(3-cyanophenyl)-5-[2-(4-phenylpiperazin-1-yl)ethyl] Amino]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(4-fluorophenyl)pyrazo b[1,5-a]pyrimidin-5-amine; N-tert-butyl-3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (anophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamidine; 3-(2-amino-6-methyl-4-pyridyl)-N-tert-butyl-2-(3-amino-6-methyl-4-pyridyl) (Anophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(1S )-2-Hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrimidine -5-carboxamide; 2-(3-cyanophenyl)-N-(2,3-dihydroxy-2-methyl-propyl)- 3-(2,6-dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(3-phenyl)- Hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5-a]pyrimidine -5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-5-( Sulfamoylamino)pyrazolo[1,5-a]pyrimidine; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-2-hydroxy-2-methyl-propane amide; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-2,2-dimethyl-propanamide; N-(3-amino-3-methyl-butyl)-2-(3-cyanophenyl)-3-(2,6 -Dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide.

[0161] Further compounds of the present invention, or pharmaceutically acceptable salts thereof, include: 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-1,1-dimethyl-ethyl)pyrazolo[1,5-a]pyrimidine-5- Carboxamides; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-[ 2-Methyl-6-(trifluoromethyl)-4-pyridyl]pyrazolo[1,5-a]pyridyl Midine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-N-(1-cyano-1-methyl-ethyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1S,2S)-2,3-dihydroxy-1-methyl-propyl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-2-cyano-3-isopropyl-guanidinium gin; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-2-hydro [1-methyl-ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzyl benzonitrile; 2-(3-cyano-2-methyl-phenyl)-3-(2,6-dimethyl-4-pyridyl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Hydroxycyclobutyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(2- Oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-1,1,2-trimethyl-propyl)pyrazolo[1,5-a]pyrimidin thion-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(1- Methyl-2-oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5 -carboxamides; 2-(3-cyanophenyl)-N-[(1S)-1,2-dimethylallyl]-3-(2, 6-Dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ; N-(2-acetamido-2-methyl-propyl)-3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; N-(3-amino-3-methyl-butyl)-3-(2-chloro-6-methyl-4-pyridinyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-methyl-4-piperidine) Lysyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(1R )-2-Hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrimidine -5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyano-2-methyl-phenoxy) N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidinyl Zin-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S)-2, 3-Dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5-a]pyrimidine -2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(4-phenyl)- (hydroxy-4-methyl-cyclohexyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate Voxamide; 3-[3-[2-(difluoromethyl)-6-methyl-4-pyridyl]-5-[(2-hydroxybenzoyl) (hydroxy-2-methyl-propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl le]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(4- Methyl-2-oxo-oxazolidin-4-yl)methyl]pyrazolo[1,5-a]pyridine Midine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(2- Methyl-5-oxo-pyrrolidin-2-yl)methyl]pyrazolo[1,5-a]pyrimidin thion-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[1-( 3-hydroxyoxetan-3-yl)ethyl]pyrazolo[1,5-a]pyrimidine-5 -carboxamides; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3- Methyl-6-oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5 -carboxamides; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-2-cyano-3-(2-hydroxy-2 -methyl-propyl)guanidine; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5-a]pyridine Midine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ rac-(2R)-2-hydroxypropyl]pyrazolo[1,5-a]pyrimidine-5- Carboxamides; 2-(3-cyano-2-methyl-phenyl)-3-(2,6-dimethyl-4-pyridyl) -N-[(1R)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5- a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(3S,4S )-4-Methoxy-1-methyl-pyrrolidin-3-yl]amino]pyrazolo[1,5-a ]pyrimidin-2-yl]benzonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-Methyl-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carbohydrate Voxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-( 2-Methoxy-6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(4- Methyl-2,5-dioxo-imidazolidin-4-yl)methyl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S,2S)-2, 3-Dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5-a]pyrimidine -2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(3-phenyl)- (hydroxy-3-methyl-cyclobutyl)pyrazolo[1,5-a]pyrimidine-5-carbo oxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(3R)-3 -piperidyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ; 2-(3-cyano-2-methyl-phenyl)-3-(2,6-dimethyl-4-pyridyl) -N-[(1S)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5- a]pyrimidine-5-carboxamide; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-3-hydroxy-3-methylbutanediol Mido; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxyoxene benzo[1,5-a]pyrimidin-2-yl]benzo[1,5-a]pyrimidin-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzo nitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[1-(2-hydroxy Ethyl)-4-piperidyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzyl benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy-3- (methyl-butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Le; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]guanidine; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1, 5-a]pyrimidine-5-carboxamidine; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(2-phenyl) (hydroxy-2-methyl-propoxy)pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(5-oxopyrrolidine -3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3S)-3-(1-chloro- (hydroxy-1-methyl-ethyl)piperazin-1-yl]pyrazolo[1,5-a]pyrimidin din-2-yl]benzonitrile; 3-[3-(2,6-dimethyl-4-pyridyl)-5-[(1-methyl-2-oxo-4 -piperidyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ; N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-5-yl]-3-hydroxy-3-methyl-butanamide; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]acetamide [2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1 ,5-a]pyrimidin-5-yl]urea; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3- (hydroxyoxetan-3-yl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-2-hydro [1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(2S)-2 -hydroxypropyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzo nitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1S,3S)-3-aminocyclopentyl]pyrazolo[1,5-a]pyrimidine-5- Carboxamides; m-{4-[({[(3S)-5-oxo-3-pyrrolidinyl]methyl}amino)carbo Nyl]-7-(2,6-dimethyl-4-pyridyl)-1,5,9-triazabicyclo[4 .3.0]nona-2,4,6,8-tetraen-8-yl}benzonitrile; 3-[5-[(2-amino-2-methyl-propyl)amino]-3-(2-chloro-6- Methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ; 3-(2-cyano-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(1R)-2 -Hydroxy-1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidin benzonitrile; N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-5-yl]-2-hydroxy-2-methyl-propanamide ; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ rac-(3S)-3-piperidyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 2-(3-cyanophenyl)-3-(3-fluoro-2,6-dimethyl-4-pyridyl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(2- Oxo-4-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(3-fluoro-2,6-dimethyl-4-pyridyl) -N-[(4-methyl-2,5-dioxo-imidazolidin-4-yl)methyl]pyrazo b[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(5-phenyl)- xopyrrolidin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1, 5-a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3R)-3-(1-chloro-6-methyl-4-pyridyl) (hydroxy-1-methyl-ethyl)piperazin-1-yl]pyrazolo[1,5-a]pyrimidin din-2-yl]benzonitrile; m-[7-(2,6-dimethyl-4-pyridyl)-4-({[(5-oxo-3-pyrrolidine) (vinyl)methyl]amino}carbonyl)-1,5,9-triazabicyclo[4.3.0] Nona-2,4,6,8-tetraen-8-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S)-2- Hydroxycyclobutyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; m-{4-[({[(3R)-5-oxo-3-pyrrolidinyl]methyl}amino)carbo Nyl]-7-(2,6-dimethyl-4-pyridyl)-1,5,9-triazabicyclo[4 .3.0]nona-2,4,6,8-tetraen-8-yl}benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxyazetyl) pyrazolo[1,5-a]pyrimidin-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzo nitrile;; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carbonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-imino-1-oxo -1,4-thiazinane-4-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[5-[(1-acetyl-4-piperidyl)amino]-3-(2,6-dimethyl-4 -pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(5- Oxomorpholin-2-yl)methyl]pyrazolo[1,5-a]pyrimidine-5-carbo oxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3R)-pyrrolidine- 3-yl]oxy-pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 1-(2-amino-2-methyl-propyl)-3-[3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl le] urea.

[0162] Specific compounds of the present invention include any of the compounds described in the Examples section of this application, or pharmaceutically acceptable salts or solvates of, in particular any of: 3-[5-amino-3-(4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl ]benzonitrile; 3-[5-amino-3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidinyl] din-2-yl]benzonitrile; 3-(5-amino-3-pyridazin-4-yl-pyrazolo[1,5-a]pyrimidine-2 -yl)benzonitrile; 3-[5-amino-3-(2-ethylpyrazol-3-yl)pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[5-amino-3-(2-chloro-6-methyl-4-pyridyl)pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1,5-a]pyridyl rimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(2-hydroxy-2- Methyl-propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy-1- Bicyclo[1.1.1]pentanyl)amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(8-methyl-3,8-di Azabicyclo[3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidine- 2-yl]benzonitrile; (3S)-4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl] (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]morpholine-3-carboxylic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-ethyl-4-piperidine) Lysyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S,4S)-4- Methoxy-1-methyl-pyrrolidin-3-yl]amino]pyrazolo[1,5-a]pyrimidin din-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-tetrahydro [1,5-a]pyrimidin-2-yl]benzodibenzofuran-3-yl]amino]pyrazolo[ ... Trill; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[3-(hydroxymethyl )-4-Methyl-piperazin-1-yl]pyrazolo[1,5-a]pyrimidin-2-yl ]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxyoxene benzo[1,5-a]pyrimidin-2-yl]benzo[1,5-a]pyrimidin-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzo nitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy-3- (methyl-butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Le; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxycyclohexyl) butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-methylsulfonyl) (4-piperidyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(8-oxa-3-azabicyclo[2.2.1. ...2.1.2.1.2.1.2.1.2.1.2.1.2 Cyclo[3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl le]benzonitrile; 3-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) Pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2,2-dimethyl-propane acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(5-oxopyrrolidine -3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-2-hydro [1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(3R,4R )-4-Hydroxytetrahydrofuran-3-yl]amino]pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(quinuclidin-3-yl) Amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxycyclohexyl) butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(2-morpholinoethyl) (amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-2-hydro [1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[2-[2-(dimethylamino)methyl] amino)ethyl]morpholin-4-yl]pyrazolo[1,5-a]pyrimidin-2-yl] Benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S)-2- Hydroxycyclobutyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4H-1,2,4-trimethyl- Azol-3-ylmethylamino)pyrazolo[1,5-a]pyrimidin-2-yl]benzo Zonitrile; (2R)-4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl] (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]morpholine-2-carboxylic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-tetrahydro [1,5-a]pyrimidin-2-yl]benzodibenzofuran-3-yl]amino]pyrazolo[ ... Trill; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-imino-1-oxo -1,4-thiazinane-4-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1,1-dioxothiazol-2-yl)methyl] (4-yl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ; 2-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) Pyrazolo[1,5-a]pyrimidin-5-yl]amino]acetamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-piperazin-1-yl-pyridyl] Lazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[2-(dimethylamino) )-1-methyl-ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]ben Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-hydroxy-pyrazolo[1 ,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1H-imidazole-2 -ylmethylamino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-morpholino-pyrazolo[1 ,5-a]pyrimidin-2-yl]benzonitrile; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]azetidine-2-carboxylic acid; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]azetidine-3-carboxylic acid; (3R)-1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl] (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]pyrrolidine-3-carboxylic acid; 4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]piperazine-1-sulfonamide; 3-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) Pyrazolo[1,5-a]pyrimidin-5-yl]amino]bicyclo[1.1.1]penta benzo-1-carboxylic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(2R)-2-hydro [1,5-a]pyrimidin-2-yl]benzonitrile ; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(2S)-2-hydro [1,5-a]pyrimidin-2-yl]benzonitrile ; 3-[5-(tert-butylamino)-3-(2-chloro-6-methyl-4-pyridyl] )pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-2-hydro [1-methyl-ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzyl benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-hydroxycyclohexyl) Propyl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Le; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4-piperidylamino) Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-morpholine -3-yl]methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; tert-Butyl(3R)-3-[[[3-(2-chloro-6-methyl-4-pyridyl) -2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino] methyl]morpholine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-3-piperidin di[amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Peridine-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-pyrrolidine -3-yl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Roridin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[rac-(4aS,7a S)-3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b][1, 4]oxazin-6-yl]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; tert-Butyl rac-(4aS,7aS)-6-[3-(2-chloro-6-methyl- 4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5- yl]-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]o Xanthazine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-morpholine -3-yl]methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; tert-Butyl(3S)-3-[[[3-(2-chloro-6-methyl-4-pyridyl) -2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino] methyl]morpholine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-pyrrolidine -3-yl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Roridin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-3-piperidin di[amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Peridine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5-a]pyridine Midine-5-carboxamide; N-tert-butyl-3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (Anophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Hydroxy-3-methyl-butyl)pyrazolo[1,5-a]pyrimidine-5-carbo oxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ 2-(4-phenylpiperazin-1-yl)ethyl]pyrazolo[1,5-a]pyrimidine -5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( Oxetan-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo [1,5-a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(morpholine-4-carbohydrate Nyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1S)-2-Hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrazole Midine-5-carboxamide; N-(2-amino-2-methyl-propyl)-3-(2-chloro-6-methyl-4-pyridyl)- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1-hydroxycyclopropyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1-hydroxycyclobutyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carbohydrate Voxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrazole Midine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (2R)-2-hydroxypropyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R)-2-hydroxy-1-methyl-ethyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-hydroxyoxetan-3-yl)methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-methyl Thilsulfonyl-pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2,3-Dihydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5 -carboxamides; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-hydroxycyclobutyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carbohydrate Voxamide; 3-(2-chloro-6-methyl-4-pyridyl)-N-(1-cyano-2-methoxy-1 -methyl-ethyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; N-(4-aminonorbornan-1-yl)-3-(2-chloro-6-methyl-4-pyridyl)- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (2S)-2,3-dihydroxypropyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3S,4S)-4-Methoxy-1-methyl-pyrrolidin-3-yl]pyrazolo[1,5 -a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (2R)-2,3-dihydroxypropyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 1-Methylazetidin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3S,4S)-4-hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-2-methyl-propyl)-N-methyl-pyrazolo[1,5-a]pyrimidin Zin-5-carboxamide; N-(3-amino-3-methyl-butyl)-3-(2-chloro-6-methyl-4-pyridinyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; N-(3-amino-1-bicyclo[1.1.1]pentanyl)-3-(2-chloro-6- Methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin thion-5-carboxamide; tert-Butyl N-[3-[[3-(2-chloro-6-methyl-4-pyridyl)-2- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino] -1-bicyclo[1.1.1]pentanyl]carbamate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ cis-(3S,4R)-4-hydroxypyrrolidin-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; tert-Butyl(3S,4R)-3-[[3-(2-chloro-6-methyl-4-pyridinyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl ]amino]-4-hydroxy-pyrrolidine-1-carboxylate; N-(2-amino-1,1-dimethyl-ethyl)-3-(2-chloro-6-methyl-4- Pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; tert-Butyl N-[2-[[3-(2-chloro-6-methyl-4-pyridyl)-2- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino] -2-methyl-propyl]carbamate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3S)-3-piperidyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide; tert-Butyl(3S)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amine no]piperidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ trans-(3S,4S)-4-hydroxypyrrolidin-3-yl]pyrazolo[1,5 -a]pyrimidine-5-carboxamide; tert-Butyl trans-(3S,4S)-3-[[3-(2-chloro-6-methyl -4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5 -carbonyl]amino]-4-hydroxy-pyrrolidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-hydroxypyrrolidin-3-yl)methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; tert-Butyl 3-[[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3 -Cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino]methyl yl]-3-hydroxy-pyrrolidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3R)-3-piperidyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amine no]piperidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Methylpyrrolidin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; tert-Butyl 3-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3- Cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino]-3- Methyl-pyrrolidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R,2S)-2,3-dihydroxy-1-methyl-propyl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl ru]pyrazolo[1,5-a]pyrimidine-5-carboxamide; N-[(1-amino-3,3-difluoro-cyclobutyl)methyl]-3-(2-chloro -6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pi Rimidine-5-carboxamide; tert-Butyl N-[1-[[[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino ]methyl]-3,3-difluoro-cyclobutyl]carbamate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( Morpholin-2-ylmethyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ; tert-Butyl 2-[[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3 -Cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino]methyl le]morpholine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(piperazine-1-carbohydrate Nyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl 4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (aminophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]piperazine-1- carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3R)-Pyrrolidin-3-yl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amine no]pyrrolidine-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-hydroxy-1-methyl) (ethyl-ethyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo [1,5-a]pyrimidine-5-carboxylic acid; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(2-phenyl) (hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(2-ethylpyrazol-3-yl)-N-(2-phenyl) (hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(2-ethyl-5-methyl-pyrazol-3-yl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-( 2-Methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2-ethyl-4-methyl-pyrazol-3-yl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-[2-(difluoromethyl)-6-methyl-4-pyridyl] [2-hydroxy-2-methyl-propyl]-N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidyl Zin-5-carboxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-( 2-Methylpyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-pyridin Rimidin-4-yl-pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-cyano-2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl) r)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(2-hydroxy-2-methyl (ethyl-propoxy)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]methanesulfonamide; (2S)-2-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyano Phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]propanoic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3R)-pyrrolidine- 3-yl]oxy-pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile phosphate Mate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(2-hydroxyethyl) (amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(morpholinomethyl)pyridine Zolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[5-(aminomethyl)-3-(2-chloro-6-methyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(3-hydroxy-3-methyl (ethyl-butyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-[2-(difluoromethyl)-6-methyl-4-pyridyl]-5-[(2-hydroxybenzoyl) (hydroxy-2-methyl-propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl le]benzonitrile; 3-[5-[(2-hydroxy-2-methyl-propyl)amino]-3-(2-methoxy -6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzodi Trill; 3-[3-(2,6-dimethyl-4-pyridyl)-5-[(2-hydroxy-2-methyl -propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-2-hydro [1-methyl-ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzyl benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(dimethylamino)pyrazo b[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4-piperidyloxy) Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-3-piperidin di[oxy]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl (3R)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]oxypiperi Zin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3S)-pyrrolidine- 3-yl]oxy-pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]oxypyrrolidone Zin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-3-piperidin di[oxy]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]oxypiperi Zin-1-carboxylate; 3-[5-amino-3-(6-amino-5-methyl-3-pyridyl)pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-[2-(difluoromethyl)-6-methyl-4-pyridyl]pyridine Zolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(2-methoxy-6-methyl-4-pyridyl)pyrazolo[1,5 -a]pyrimidin-2-yl]benzonitrile; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carbonitrile; 3-[5-amino-3-(2-fluoro-6-methyl-4-pyridyl)pyrazolo[1,5 -a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[5-amino-3-(2,6-dimethyl-1-oxide-pyridin-1-ium-4 -yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(2-amino-6-methyl-4-pyridyl)pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carboxamide; N-[4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin benzo-3-yl]-6-methyl-2-pyridyl]acetamide; 3-[5-amino-3-(5-methyl-[1,2,4]triazolo[1,5-a]pyridin (1,5-a)pyrimidin-2-yl)benzonitrile; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carboxylic acid; 3-[5-amino-3-[2-(dimethylamino)-6-methyl-4-pyridyl]pyrazo b[1,5-a]pyrimidin-2-yl]benzonitrile; [3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazo b[1,5-a]pyrimidin-5-yl]urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Iridium[1,5-a]pyrimidin-5-yl]-3-(2-hydroxy-2-methyl- lopil) urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-3-(1-ethyl-4-piperidyl)urine element; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]piperazine-1-carboxamide; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-3-[(3S)-pyrrolidin-3-yl] ]urea; 1-(2-aminoethyl)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl razolo[1,5-a]pyrimidin-5-yl]-3-[(3R)-pyrrolidin-3-yl] ]urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-2-cyano-guanidine; 3-[3-(2-ethylpyrazol-3-yl)-5-[(2-hydroxy-2-methyl -propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-[3-(hydroxymethyl)-4 -methyl-piperazin-1-yl]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(8-oxa-3-azabicyclo[3-(2-ethylpyrazol-3-yl)] ... [3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl]be benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(8-methyl-3,8-diazabiphenyl] Cyclo[3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl le]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(4-methylsulfonylpiperazine (1,5-a)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(4H-1,2,4-triazol- (3-ylmethylamino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-ethylpyrazol-3-yl)-5-piperazin-1-yl-pyrazolo [1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(1-imino-1-oxo-1, 4-Thiazinan-4-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 5-(benzylamino)-2-(2-fluorophenyl)pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; N-Benzyl-2-(2-fluorophenyl)pyrazolo[1,5-a]pyrimidine-5- amines; 2-(2-Furyl)-5-[(3-methyl-2-pyridyl)methylamino]pyrazolo[1 ,5-a]pyrimidine-3-carbonitrile; tert-Butyl(2S)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]morpholine-4-carboxylate; tert-Butyl(2R)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]pyrrolidine-1-carboxylate; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-(2-furyl)pyrazo b[1,5-a]pyrimidine-3-carbonitrile; tert-Butyl(2S)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]pyrrolidine-1-carboxylate; tert-Butyl(2R)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]morpholine-4-carboxylate; 2-(2-Furyl)-5-[4-(2-phenylethyl)piperazin-1-yl]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-(2-pyridylmethyl)piperazin-1-yl]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-(4-methylpiperazin-1-yl)pyrazolo[1,5-a] Pyrimidine-3-carbonitrile; 5-[(1-benzyl-4-piperidyl)methylamino]-2-(2-furyl)pyrazolo [1,5-a]pyrimidine-3-carbonitrile; tert-Butyl(2R)-4-[3-cyano-2-(2-furyl)pyrazolo[1,5- a]pyrimidin-5-yl]-2-methyl-piperazine-1-carboxylate; tert-Butyl(2S)-4-[3-cyano-2-(2-furyl)pyrazolo[1,5- a]pyrimidin-5-yl]-2-methyl-piperazine-1-carboxylate; 5-[2-(4-benzylpiperazin-1-yl)ethylamino]-2-(2-furyl) Pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[(3-methyl-2-pyridyl)methylamino]pyrazolo[1 ,5-a]pyrimidine-3-carboxamide; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-(2-furyl)pyrazo b[1,5-a]pyrimidine-3-carboxamide; 5-[3-(dimethylamino)azetidin-1-yl]-2-(2-furyl)pyrazolo[ 1,5-a]pyrimidine-3-carboxamide; tert-Butyl 4-[3-cyano-2-(2-furyl)pyrazolo[1,5-a]pyrimidinyl] din-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate; 2-(2-Furyl)-5-piperazin-1-yl-pyrazolo[1,5-a]pyrimidine- 3-carbonitrile; 2-(2-Furyl)-5-[[(2S)-morpholin-2-yl]methylamino]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[[(2R)-morpholin-2-yl]methylamino]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 5-(4-benzylpiperazin-1-yl)-2-(2-furyl)pyrazolo[1,5-a ]pyrimidine-3-carbonitrile; N-benzyl-3-bromo-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-5 -amine; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- carbonitrile; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carboxamides; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carboxaldehyde; N-benzyl-2-(2-furyl)pyrazolo[1,5-a]pyrimidin-5-amine; 5-Amino-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile Le; 3-Bromo-2-(2-furyl)pyrazolo[1,5-a]pyrimidin-5-amine; 2-(2-Furyl)-5-[4-[(3-methyl-2-pyridyl)methyl]piperazine- 1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-[(2,4,6-trifluorophenyl)methyl]piperidine radin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-[(1-methylimidazol-2-yl)methyl]piperidine radin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-(2-hydroxyethyl)piperazin-1-yl]pyrazin Zolo[1,5-a]pyrimidine-3-carbonitrile; N-benzyl-2-(2-furyl)-3-(1-methylpyrazol-4-yl)pyrazolo [1,5-a]pyrimidin-5-amine; N-benzyl-2-(2-furyl)-3-(2-methylpyrazol-3-yl)pyrazolo [1,5-a]pyrimidin-5-amine; Methyl (E)-3-[5-(benzylamino)-2-(2-furyl)pyrazolo[1,5- a]pyrimidin-3-yl]prop-2-enoate; (E)-3-[5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pi rimidin-3-yl]prop-2-enoic acid; 2-(2-Furyl)-5-(4-phenylpiperazin-1-yl)pyrazolo[1,5-a ]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-(3-hydroxypropylamino)pyrazolo[1,5-a]piperidin Rimidine-3-carbonitrile; 2-(2-Furyl)-5-(2-hydroxyethylamino)pyrazolo[1,5-a]pyridine Midine-3-carbonitrile; 2-(2-Furyl)-5-(3-piperidylmethylamino)pyrazolo[1,5-a]pyridine Midine-3-carbonitrile hydrochloride; 5-(benzylamino)-2-oxazol-2-yl-pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; 5-(benzylamino)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin benzo-3-carbonitrile; 2-(3-cyanophenyl)-5-[4-[(3-methyl-2-pyridyl)methyl]piperidine radin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(3-fluorophenyl)-5-[4-[(3-methyl-2-pyridyl)methyl]pyridyl Perazin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-(3-fluorophenyl) r)pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-oxazol-5-yl Ru-pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 5-(benzylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; 5-(benzylamino)-2-(5-methyl-2-furyl)pyrazolo[1,5-a]pyridine Midine-3-carbonitrile; 5-[4-[(3-methyl-2-pyridyl)methyl]piperazin-1-yl]-2-oxo Sazol-5-yl-pyrazolo[1,5-a]pyrimidine-3-carbonitrile; N-Benzyl-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidine-5- amines; 2-(3-fluorophenyl)-N-[(3-methyl-2-pyridyl)methyl]pyrazolo [1,5-a]pyrimidin-5-amine; 2-(3-fluorophenyl)-N-(2-phenylethyl)pyrazolo[1,5-a]piperidin Rimidin-5-amine; N-(1H-benzimidazol-2-ylmethyl)-2-(3-fluorophenyl)pi Lazolo[1,5-a]pyrimidin-5-amine; 2-(3-fluorophenyl)-N-(2-isoindolin-2-ylethyl)pyrazolo [1,5-a]pyrimidin-5-amine; N-Benzyl-3-chloro-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrazole mydin-5-amine; 3-Bromo-5-chloro-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin gin; N-Benzyl-3-bromo-2-(3-fluorophenyl)pyrazolo[1,5-a]pyridine mydin-5-amine; 5-(benzylamino)-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; 3-Bromo-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-5-a Min; 5-Amino-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate rubonitrile; 2-(2-Furyl)-N-(thiazol-2-ylmethyl)pyrazolo[1,5-a]pyridine mydin-5-amine; [5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3 -yl]methanol; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carboxylic acids; N-benzyl-2-(2-furyl)-3-iodo-pyrazolo[1,5-a]pyrimidine- 5-amine; 2-(2-Furyl)-3-(4-pyridyl)pyrazolo[1,5-a]pyrimidin-5-a Min; 2-(2-Furyl)-5-[[(2R)-pyrrolidin-2-yl]methylamino]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[[(2R)-1-methylpyrrolidin-2-yl]methylamine no]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[(3R)-3-methylpiperazin-1-yl]pyrazolo[1 ,5-a]pyrimidine-3-carbonitrile hydrochloride; tert-Butyl 4-[3-cyano-2-(2-furyl)pyrazolo[1,5-a]pyrimidinyl] din-5-yl]piperidine-1-carboxylate; N-benzyl-7-(2-furyl)pyrazolo[1,5-a][1,3,5]triazine- 2-amines; N-Benzyl-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-5-[4-(2-fluoroethyl)piperazin-1-yl] ]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(3-cyanophenyl)-5-[2-(4-phenylpiperazin-1-yl)ethyl] Amino]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(4-fluorophenyl)pyrazo b[1,5-a]pyrimidin-5-amine; N-tert-butyl-3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (anophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamidine; 3-(2-amino-6-methyl-4-pyridyl)-N-tert-butyl-2-(3-amino-6-methyl-4-pyridyl) (Anophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(1S )-2-Hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrimidine -5-carboxamide; 2-(3-cyanophenyl)-N-(2,3-dihydroxy-2-methyl-propyl)- 3-(2,6-dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(3-phenyl)- Hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5-a]pyrimidine -5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-5-( Sulfamoylamino)pyrazolo[1,5-a]pyrimidine; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-2-hydroxy-2-methyl-propane amide; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-2,2-dimethyl-propanamide; N-(3-amino-3-methyl-butyl)-2-(3-cyanophenyl)-3-(2,6 -Dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-1,1-dimethyl-ethyl)pyrazolo[1,5-a]pyrimidine-5- Carboxamides; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-[ 2-Methyl-6-(trifluoromethyl)-4-pyridyl]pyrazolo[1,5-a]pyridyl Midine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-N-(1-cyano-1-methyl-ethyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1S,2S)-2,3-dihydroxy-1-methyl-propyl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-2-cyano-3-isopropyl-guanidinium gin; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-2-hydro [1-methyl-ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzyl benzonitrile; 2-(3-cyano-2-methyl-phenyl)-3-(2,6-dimethyl-4-pyridyl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Hydroxycyclobutyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(2- Oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-1,1,2-trimethyl-propyl)pyrazolo[1,5-a]pyrimidin thion-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(1- Methyl-2-oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5 -carboxamides; 2-(3-cyanophenyl)-N-[(1S)-1,2-dimethylallyl]-3-(2, 6-Dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ; N-(2-acetamido-2-methyl-propyl)-3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; N-(3-amino-3-methyl-butyl)-3-(2-chloro-6-methyl-4-pyridinyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-methyl-4-piperidine) Lysyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(1R )-2-Hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrimidine -5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyano-2-methyl-phenoxy) N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidinyl Zin-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S)-2, 3-Dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5-a]pyrimidine -2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(4-phenyl)- (hydroxy-4-methyl-cyclohexyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate Voxamide; 3-[3-[2-(difluoromethyl)-6-methyl-4-pyridyl]-5-[(2-hydroxybenzoyl) (hydroxy-2-methyl-propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl le]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(4- Methyl-2-oxo-oxazolidin-4-yl)methyl]pyrazolo[1,5-a]pyridine Midine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(2- Methyl-5-oxo-pyrrolidin-2-yl)methyl]pyrazolo[1,5-a]pyrimidin thion-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[1-( 3-hydroxyoxetan-3-yl)ethyl]pyrazolo[1,5-a]pyrimidine-5 -carboxamides; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3- Methyl-6-oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5 -carboxamides; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]-2-cyano-3-(2-hydroxy-2 -methyl-propyl)guanidine; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-Hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5-a]pyridine Midine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ rac-(2R)-2-hydroxypropyl]pyrazolo[1,5-a]pyrimidine-5- Carboxamides; 2-(3-cyano-2-methyl-phenyl)-3-(2,6-dimethyl-4-pyridyl) -N-[(1R)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5- a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(3S,4S )-4-Methoxy-1-methyl-pyrrolidin-3-yl]amino]pyrazolo[1,5-a ]pyrimidin-2-yl]benzonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-Methyl-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carbohydrate Voxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-( 2-Methoxy-6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(4- Methyl-2,5-dioxo-imidazolidin-4-yl)methyl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S,2S)-2, 3-Dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5-a]pyrimidine -2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(3-phenyl)- (hydroxy-3-methyl-cyclobutyl)pyrazolo[1,5-a]pyrimidine-5-carbo oxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(3R)-3 -piperidyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ; 2-(3-cyano-2-methyl-phenyl)-3-(2,6-dimethyl-4-pyridyl) -N-[(1S)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5- a]pyrimidine-5-carboxamide; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-3-hydroxy-3-methylbutanediol Mido; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxyoxene benzo[1,5-a]pyrimidin-2-yl]benzo[1,5-a]pyrimidin-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzo nitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[1-(2-hydroxy Ethyl)-4-piperidyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzyl benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy-3- (methyl-butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Le; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl Lazolo[1,5-a]pyrimidin-5-yl]guanidine; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1, 5-a]pyrimidine-5-carboxamidine; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(2-phenyl) (hydroxy-2-methyl-propoxy)pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(5-oxopyrrolidine -3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3S)-3-(1-chloro- (hydroxy-1-methyl-ethyl)piperazin-1-yl]pyrazolo[1,5-a]pyrimidin din-2-yl]benzonitrile; 3-[3-(2,6-dimethyl-4-pyridyl)-5-[(1-methyl-2-oxo-4 -piperidyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ; N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-5-yl]-3-hydroxy-3-methyl-butanamide; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]acetamide [2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1 ,5-a]pyrimidin-5-yl]urea; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3- (hydroxyoxetan-3-yl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate ruboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-2-hydro [1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(2S)-2 -hydroxypropyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzo nitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1S,3S)-3-aminocyclopentyl]pyrazolo[1,5-a]pyrimidine-5- Carboxamides; m-{4-[({[(3S)-5-oxo-3-pyrrolidinyl]methyl}amino)carbo Nyl]-7-(2,6-dimethyl-4-pyridyl)-1,5,9-triazabicyclo[4 .3.0]nona-2,4,6,8-tetraen-8-yl}benzonitrile; 3-[5-[(2-amino-2-methyl-propyl)amino]-3-(2-chloro-6- Methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ; 3-(2-cyano-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-Hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(1R)-2 -Hydroxy-1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidin benzonitrile; N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-5-yl]-2-hydroxy-2-methyl-propanamide ; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ rac-(3S)-3-piperidyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 2-(3-cyanophenyl)-3-(3-fluoro-2,6-dimethyl-4-pyridyl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(2- Oxo-4-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(3-fluoro-2,6-dimethyl-4-pyridyl) -N-[(4-methyl-2,5-dioxo-imidazolidin-4-yl)methyl]pyrazo b[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(5-phenyl)- xopyrrolidin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1, 5-a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3R)-3-(1-chloro-6-methyl-4-pyridyl) (hydroxy-1-methyl-ethyl)piperazin-1-yl]pyrazolo[1,5-a]pyrimidin din-2-yl]benzonitrile; m-[7-(2,6-dimethyl-4-pyridyl)-4-({[(5-oxo-3-pyrrolidine) (vinyl)methyl]amino}carbonyl)-1,5,9-triazabicyclo[4.3.0] Nona-2,4,6,8-tetraen-8-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S)-2- Hydroxycyclobutyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; m-{4-[({[(3R)-5-oxo-3-pyrrolidinyl]methyl}amino)carbo Nyl]-7-(2,6-dimethyl-4-pyridyl)-1,5,9-triazabicyclo[4 .3.0]nona-2,4,6,8-tetraen-8-yl}benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxyazetyl) pyrazolo[1,5-a]pyrimidin-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzo nitrile;; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carbonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-imino-1-oxo -1,4-thiazinane-4-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[5-[(1-acetyl-4-piperidyl)amino]-3-(2,6-dimethyl-4 -pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(5- Oxomorpholin-2-yl)methyl]pyrazolo[1,5-a]pyrimidine-5-carbo oxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3R)-pyrrolidine- 3-yl]oxy-pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 1-(2-amino-2-methyl-propyl)-3-[3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl le]urea; 3-[3-(2,6-dimethyl-4-pyridyl)-5-(2,4-dioxo-1,3,8 -triazaspiro[4.5]decane-8-carbonyl)pyrazolo[1,5-a]pyrimidin benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3S ,4S)-4-Hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a]pyridine Midine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[[(2 R)-5-oxopyrrolidin-2-yl]methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4R)-4-hydroxy-4-methyl-tetrahydrofuran-3-yl]pyrazolo[1 ,5-a]pyrimidine-5-carboxamide 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4S)-4-Hydroxy-4-methyl-tetrahydrofuran-3-yl]pyrazolo[1 ,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(6- Oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3S ,4R)-4-hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a]pyrazole Midine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4R)-4-hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a]pyrazole Midine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4S)-4-Hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a]pyridine Midine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4R)-4-hydroxy-1-methyl-pyrrolidin-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[[(2 S)-5-oxopyrrolidin-2-yl]methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3S ,4R)-4-hydroxy-1-methyl-pyrrolidin-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-thio Azol-5-yl-pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-[5-[(2-amino-2-methyl-propyl)amino]-3-(2-chloro-6- Methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ;; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 4-piperidyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 4-Cyano-4-piperidyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ; N-(4-carbamoyl-4-piperidyl)-3-(2-chloro-6-methyl-4-pyridyl)- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-[3-(2,6-dimethyl-4-pyridyl)-5-(piperazin-1-ylmethyl) Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile;; 2-(3-cyanophenyl)-N-[(1S)-2-hydroxy-1,2-dimethyl- propyl]-3-[2-(hydroxymethyl)-6-methyl-4-pyridyl]pyrazolo[1 ,5-a]pyrimidine-5-carboxamide; 3-[3-(2,6-dimethyl-4-pyridyl)-5-(3-oxo-2,8-diazas Pyrro[4.5]decan-8-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2,6-dimethyl-4-pyridyl)-5-[[1-(2-hydroxy-2- Methyl-propyl)-4-piperidyl]amino]pyrazolo[1,5-a]pyrimidine-2 -yl]benzonitrile; (2S)-N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl] ) Pyrazolo[1,5-a]pyrimidin-5-yl]-3,3,3-trifluoro-2-hydroxybenzoate hydroxy-2-methyl-propanamide; N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-5-yl]-2-oxa-6-azaspiro[3.3]hepta benzo-6-carboxamide; and 4-cyano-N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridinyl] pyrazolo[1,5-a]pyrimidin-5-yl]-4-methyl-piperidine-1-carboxylate Ruboxamide.

[0163] The various functional groups and substituents that make up the compound of formula (I) are generally The molecular weight of the compound is selected to be no more than 1000. More generally, the molecular weight of the compound is , less than 900, for example, less than 800, or less than 750, or less than 700, or less than 650 More preferably, the molecular weight is less than 600, for example, 550 or less.

[0164] Suitable pharmaceutically acceptable salts of the compounds of the invention include, for example, the compounds of the invention which are sufficiently basic. Acid addition salts of the compounds of the present invention may be prepared by addition of, for example, inorganic or organic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, liquor, Acid addition with carboxylic acid, trifluoroacetic acid, formic acid, citric acid, methanesulfonic acid or maleic acid Additionally, suitable pharmaceutically acceptable salts of compounds of the invention that are sufficiently acidic are: Alkali metal salts, such as sodium or potassium salts, alkaline earth metal salts, such as , calcium or magnesium salts, ammonium salts, or pharmaceutically acceptable cations salts with organic bases giving amines, e.g., methylamine, dimethylamine, trimethylamine , piperidine, morpholine, or tris-(2-hydroxyethyl)amine salts be.

[0165] have the same molecular formula but differ in the nature or arrangement of bonding of their atoms or their position in space. Compounds that differ in the arrangement of their atoms in space are called "isomers." Isomers that differ in the configuration of Stereoisomers, called "diastereomers," are non-superimposable mirror images of each other. If a compound has an asymmetric center, e.g., four asymmetric chiral molecules, When a compound is bonded to a group having a substituent, a pair of enantiomers is possible. Cahn and Prelog's R and S Depending on the ordering rules, or molecules rotate the plane of polarized light to produce dextrorotatory or levorotatory (i.e. They are described in this way, i.e., as the (+) or (-) isomer, respectively. A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of enantiomers is called a "racemic mixture."

[0166] The compounds of the present invention may have one or more asymmetric centers, and such compounds may Therefore, it may occur as an individual (R) or (S) stereoisomer or as a mixture thereof. Unless otherwise indicated, certain The description or naming of compounds includes both individual enantiomers and mixtures thereof, racemic or otherwise. For example, by synthesis from optically active starting materials. Methods for determining stereochemistry and separating stereoisomers by means of the resolution of racemates or racemates are well known in the art. Well-known in the field of organic chemistry ("Advanced Organic Chemistry" try”,4th edition J.March,John Wiley and (See the discussion in Chapter 4 of "Sons, New York, 2001"). Some of the compounds may have geometric isomeric centers (E and Z isomers). All optical isomers, diastereoisomers and geometric isomers, and mixtures thereof It should be understood that this includes:

[0167] The present invention also provides compounds of the invention as defined herein that include one or more isotopic substitutions. For example, H in any isotopic form including 1H, 2H (D) and 3H (T). C may be in any isotopic form, including C, C, and C; may be in any isotopic form, including 16O and 18O.

[0168] Certain compounds of formula (I) may also be present in solvated and unsolvated forms, e.g., hydrated forms. It is also understood that the present invention provides all such solvates that have antiproliferative activity. It should be understood that the term encompasses forms.

[0169] Certain compounds of formula I may also exhibit polymorphism, and the present invention provides that all compounds possessing antiproliferative activity. It should also be understood that such forms are encompassed.

[0170] Compounds of formula I can exist in many different tautomeric forms, and references to compounds of formula I For the avoidance of doubt, it is understood that the compounds may exhibit some tautomeric forms. When a substance can exist in one of two forms and only one is specifically described or shown, Nevertheless, all others are encompassed by Formula I. Examples of tautomeric forms include Examples include the keto, enol, and enolate forms, such as the following tautomeric pair: Examples include: keto / enol (shown below), imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enethiol, and nitro / acid -Nitro. [ka]

[0171] Compounds of formula I containing an amine function may also form N-oxides. References herein to compounds of formula I containing a group also include the N-oxide. If it contains some amine functional groups, one or more nitrogen atoms can be oxidized to form N-oxides. Particular examples of N-oxides are those of the nitrogen atoms of tertiary amines or nitrogen-containing heterocycles. N-oxides are the N-oxides of the corresponding amines. For example, they can be formed by treatment with an oxidizing agent such as a peroxycarboxylic acid. For example, Advanced Organic Ch emistry,4th Edition,Wiley Interscience,p More specifically, the N-oxide is LWDready (Sy n.Comm.1977,7,509-514) In this case, the amine compound is reacted with m-chloropentaerythritol in an inert solvent such as dichloromethane. React with mCPBA.

[0172] The compounds of formula (I) are compounds that are degraded in the human or animal body to release the compounds of the present invention. A prodrug can be administered in the form of a drug. Prodrugs may be used to modify the pharmacokinetic and / or pharmacokinetic properties of the compounds of the present invention. The compound may be formed when it contains a suitable group or substituent to which a property-modifying group can be attached. Examples of prodrugs include those which react with the carboxy or hydrochloride groups in the compounds of formula (I). In vivo cleavable ester derivatives that can be formed at the oxy group and compounds of formula (I) In vivo cleavable amide derivatives that can be formed at the carboxy or amino groups in Examples include:

[0173] Thus, the present invention is made available by organic synthesis and is directed to the cleavage of the prodrug. Thus, when made available in the human or animal body, the compound of formula (I) as defined above The present invention therefore includes compounds of formula I produced by organic synthesis means, as well as the All compounds, including those compounds produced in the human or animal body by metabolism of precursor compounds. That is, the compounds of formula (I) are synthetically produced compounds or metabolically produced compounds. could be.

[0174] Suitable pharmaceutically acceptable prodrugs of compounds of formula (I) are those which do not induce undesirable pharmacological It is believed to be inactive and not excessively toxic, and suitable for administration to the human or animal body. It is based on reasonable medical judgment.

[0175] Various forms of prodrugs are described, for example, in the following documents: a)Methods in Enzymology,Vol.42,p.309-396 , edited by K. Widder, et al. (Academic Press, 1985); b) Design of Pro-drugs, edited by H. Bundgaard, (Else vier, 1985); c)A Textbook of Drug Design and Development ent, Krogsgaard-Larsen and H. Bundgaard, eds., C. hapter 5“Design and Application of Pro-d rugs”, H. Bundgaard p.113-191(1991); d) H. Bundgaard, Advanced Drug Delivery Rev. iews,8,1-38(1992); e) H. Bundgaard, et al., Journal of Pharmace utical Sciences,77,285(1988); f) N.Kakeya,et al.,Chem.Pharm.Bull.,32,69 2(1984); g) T. Higuchi and V. Stella, “Pro-Drugs as N ovel Delivery Systems”,ACSSymposium S eries,Volume 14; and h) E. Roche (editor), “Bioreversible Carriers in Drug Design”, Pergamon Press, 1987.

[0176] Suitable pharmaceutically acceptable prodrugs of compounds of formula I having a carboxy group include, for example, For example, an in vivo cleavable ester thereof. In vivo cleavable esters are cleaved, for example, in the human or animal body to produce the parent acid. Suitable pharmaceutically acceptable esters for carboxy are Examples of esters include C1-6 alkyl esters such as methyl, ethyl, and tert-butyl. , C1-6 alkoxymethyl esters such as methoxymethyl ester, pivaloyloxy C1-6 alkanoyloxymethyl esters such as methyl esters, for example, pivaloyloxymethyl esters oxymethyl ester, 3-phthalidyl ester, cyclopentylcarbonyloxymethyl and C3-8 cycloalkyl such as 1-cyclohexylcarbonyloxyethyl ester Carbonyloxy-C1~6 alkyl ester, 5-methyl-2-oxo-1,3-dioxide 2-oxo-1,3-dioxolenylmethyl esters such as oxolen-4-ylmethyl ester esters, and methoxycarbonyloxymethyl and 1-methoxycarbonyloxyethyl Examples of such alkoxycarbonyloxy C1-6 alkyl esters include C1-6 alkoxycarbonyloxy C1-6 alkyl esters. can be done.

[0177] Suitable pharmaceutically acceptable prodrugs of compounds of formula (I) having a hydroxy group are For example, an in vivo cleavable ester or ether thereof. In vivo cleavable esters or ethers of compounds of formula I can be used in, for example, humans or animals. A pharmaceutically acceptable ester or ether which is cleaved in the body to produce the parent hydroxy compound. Suitable pharmaceutically acceptable ester-forming groups for the hydroxy group include aryl, Examples of suitable esters include inorganic esters such as phosphate esters (including phosphoramido cyclic esters). Further suitable pharmaceutically acceptable ester-forming groups for hydroxy groups include acetonitriles, benzoyl, benzoyl, phenylacetyl, and substituted benzoyl and phenylacetyl groups. Any C1-10 alkanoyl group, ethoxycarbonyl, N,N-(C1-6)2 carbamo C1-10 acetyl groups such as 2-dialkylaminoacetyl and 2-carboxyacetyl groups The ring substituents on the phenylacetyl and benzoyl groups include alkoxycarbonyl groups. Examples include aminomethyl, N-alkylaminomethyl, and N,N-dialkylaminomethyl. methyl, morpholinomethyl, piperazin-1-ylmethyl, and 4-(C1-4 alkyl)piperazin-1-ylmethyl. Suitable pharmaceutically acceptable groups for the hydroxy group include hydroxyl-1-ylmethyl. Ether-forming groups include α-aryl groups such as acetoxymethyl and pivaloyloxymethyl groups. Examples thereof include siloxyalkyl groups.

[0178] Suitable pharmaceutically acceptable prodrugs of compounds of formula (I) having a carboxy group are For example, amides that are cleavable in vivo, amines such as ammonia, methyl C1-4 alkylamines such as amine, dimethylamine, N-ethyl-N-methylamine or (C1-4 alkyl) 2-amines such as diethylamine, 2-methoxyethylamine, etc. C1-4 alkoxy-C2-4 alkylamines, benzylamines, etc. ~4 alkylamines and amides formed with amino acids such as glycine or its esters is.

[0179] Suitable pharmaceutically acceptable prodrugs of compounds of formula I having an amino group are, for example: Suitable pharmaceutically acceptable derivatives of the amino group are cleavable in vivo. Examples of amides include acetyl, benzoyl, phenylacetyl, and substituted benzoyl. Examples include amides formed with C1-10 alkanoyl groups such as phenylacetyl and phenylacetyl groups. Examples of ring substituents on the phenylacetyl and benzoyl groups include aminomethyl , N-alkylaminomethyl, N,N-dialkylaminomethyl, morpholinomethyl, Perazin-1-ylmethyl and 4-(C1-4 alkyl)piperazin-1-ylmethyl Examples include:

[0180] The in vivo effects of the compounds of formula (I) are determined, in part, by the administration of the compounds of formula (I) to a human or animal This effect may be exerted by one or more metabolic products formed in the body of the compound of formula (I). The in vivo effects of the compounds of (I) are also exerted by the metabolism of the precursor compounds (prodrugs). It can be done.

[0181] The present invention may be modified by any preferred or advantageous feature or by a particular embodiment. The present invention may relate to any compound or specific group of compounds defined herein, but the present invention also relates to , any of the foregoing, preferred or advantageous features, or any that specifically exclude a particular embodiment. It may also relate to a compound or a particular group of compounds.

[0182] Preferably, the present invention does not include any individual compound that does not have biological activity as defined herein. Exclude things.

[0183] synthesis The compounds of the present invention may be prepared by any suitable technique known in the art. Specific processes for preparing compounds of the present invention are described in the Examples section below. Reaction schemes for preparing such compounds are shown in Figures 1-18. do. [Brief explanation of the drawings]

[0184] [Figure 1] FIG. 1 shows a reaction scheme for preparing compounds of formula I, where A is CH, R1 is 3-cyanophenyl, R2 is 2-chloro-6-methylpyridin-4-yl, and R3 is an amide-linked substituent of formula —C(O)NRR, where each R is hydrogen or a substituent. [Figure 2] FIG. 2 shows a reaction scheme for preparing intermediate B (described in the accompanying Examples section). [Figure 3]FIG. 3 shows a reaction scheme for preparing compounds of Formula I, where A is CH, R1 is 3-cyanophenyl, R2 is 2-chloro-6-methylpyridin-4-yl, and R3 is an amine-linked substituent represented by the formula —NH—R. [Figure 4] FIG. 4 shows a reaction scheme for preparing compounds of formula I, where A is CH, R1 is 3-cyanophenyl, R2 is a group as defined herein, and R3 is an amine group (which can be further reacted to form an amine-linked substituent). [Figure 5] FIG. 5 shows a reaction scheme for preparing a compound of formula I, where A is CH, R1 is 3-cyanophenyl, R2 is 2-chloro-6-methylpyridin-4-yl, and R3 is a urea moiety of formula —NH—C(O)NH2. [Figure 6] FIG. 6 shows a reaction scheme for preparing intermediate G (described in the accompanying Examples section). [Figure 7] FIG. 7 shows a reaction scheme for preparing the compounds of Examples 35 and 36 herein. [Figure 8] FIG. 8 shows intermediate compounds T, P, and R, as well as a reaction scheme for preparing compounds of formula I, where A is CH, R1 is furan-2-yl, R2 is cyano, and R3 is an amine-linked substituent of formula —NH—R. [Figure 9] FIG. 9 shows intermediate Q and a reaction scheme for preparing compounds of formula I, where A is CH, R1 is furan-2-yl, R2 is Br, cyano, or —C(O)NH2, and R3 is benzylamino. [Figure 10] FIG. 10 shows a reaction scheme for preparing intermediate S and compounds of formula I, where A is CH, R is furan-2-yl, R is a group defined herein, and R is benzylamino. [Figure 11] FIG. 11 shows a reaction scheme for preparing compounds of formula I via intermediate X, where A is CH, R1 is furan-2-yl, R2 is hydrogen, and R3 is benzylamino. [Figure 12] FIG. 12 shows intermediate U and a reaction scheme for preparing compounds of formula I, where A is CH, R is a group defined herein, R is cyano, and R is benzylamino. [Figure 13] FIG. 13 shows the reaction scheme for preparing intermediate compounds V and W, as well as compounds of formula I, where A is CH, R1 is 3-fluorophenyl, R2 is cyano or bromo, and R3 is an amine-linked substituent represented by the formula -NHR. [Figure 14] FIG. 14 shows a reaction scheme for preparing a compound of formula I, wherein A is CH, R1 is 4-fluorophenyl, R2 is a group as defined herein, and R3 is an amine-linked substituent represented by the formula "-NRR" (where each R is hydrogen or a substituent). [Figure 15] FIG. 15 shows the reaction scheme for preparing the intermediate compounds shown in Steps 2a and 2b of Example 92, as well as compounds of Formula I, where A is CH, R1 is 3-cyanophenyl, R2 is 2,6-dimethylpyridin-4-yl, and R3 is an amide-linked substituent represented by the formula —C(O)—NRR, where each R is hydrogen or a substituent. [Figure 16] FIG. 16 shows a reaction scheme for preparing intermediate compound Y. [Figure 17] FIG. 17 shows a reaction scheme for preparing intermediate compound Z. [Figure 18] FIG. 18 shows a reaction scheme for preparing intermediate compound AB. DETAILED DESCRIPTION OF THE INVENTION

[0185] The description of the synthetic methods described herein and any compounds used to prepare the starting materials In the reference synthesis method of the present invention, the solvent, reaction atmosphere, reaction temperature, duration of the experiment and post-treatment procedure It is understood that all suggested reaction conditions, including the selection of the reaction conditions, can be selected by one skilled in the art. I want to be.

[0186] Those skilled in the art of organic synthesis will appreciate that the functional groups present on various parts of the molecule determine the availability of reagents and reactions. It is understood that applicable conditions must be met.

[0187] During the synthesis of the compounds of the invention in the processes defined herein or as specific starting materials During the synthesis of , it may be desirable to protect certain substituents to prevent their undesired reactions. It will be appreciated that there may be cases where such protection is necessary. A skilled chemist will be able to determine when such protection is necessary. and how such protecting groups can be placed and subsequently removed. It would be.

[0188] For examples of protecting groups, see one of the many general texts on the subject, e.g., The Protective Groups in Organizations by Odora Green nic Synthesis" (Publisher: John Wiley & Sons) Protecting groups are described in the literature as being appropriate for the removal of the protecting group in question. or may be removed by any convenient method known to the skilled chemist. Such a method allows the protecting groups to be attached with minimal interference to groups elsewhere in the molecule. is selected for removal.

[0189] Thus, if the reactants contain groups such as amino, carboxy, or hydroxy, In some cases, it may be desirable to protect groups in some of the reactions mentioned herein. .

[0190] For example, suitable protecting groups for an amino or alkylamino group are for example acyl groups, e.g. Alkanoyl groups such as acetyl, alkoxycarbonyl groups such as methoxycarbonyl , ethoxycarbonyl or t-butoxycarbonyl group, arylmethoxycarbonyl group , for example, benzyloxycarbonyl, or an aroyl group, for example, benzoyl. The deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group. Acyl groups such as alkanoyl or alkoxycarbonyl groups or aroyl groups are, for example, , alkali metal hydroxides, for example, lithium hydroxide or sodium hydroxide, or other suitable salts. Alternatively, the tert-butoxycarbonyl group or the like can be removed by hydrolysis. The acyl group of the formula (I) can be reacted with a suitable acid such as hydrochloric acid, sulfuric acid or phosphoric acid, or trifluoroacetic acid. It can be removed by treatment with acid and is an aryl group such as a benzyloxycarbonyl group. The alkoxycarbonyl group can be removed by, for example, hydrogenation over a catalyst such as palladium on carbon, or Removed by treatment with a Lewis acid, e.g., borontris (trifluoroacetate) Suitable alternative protecting groups for primary amino groups are, for example, alkylamines, For example, fluorescein can be removed by treatment with dimethylaminopropylamine or hydrazine. It is a thallous group.

[0191] Suitable protecting groups for hydroxy groups are, for example, acyl groups, e.g. alkano groups such as acetyl. an aryl group, an aroyl group, for example, benzoyl, or an arylmethyl group, for example, benzyl; The deprotection conditions for the above protecting groups will necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or aroyl group may be substituted with, for example, an alkali metal Suitable salts such as hydroxides, for example lithium hydroxide, sodium hydroxide, or ammonia Alternatively, the arylmethyl group, such as a benzyl group, may be removed by hydrolysis. can be removed, for example, by hydrogenation over a catalyst such as palladium on carbon.

[0192] Suitable protecting groups for carboxy groups are, for example, esterifying groups, such as sodium hydroxide. a methyl or ethyl group which can be removed by hydrolysis with any base, or e.g. a t-butyl group which can be removed by treatment with an acid, e.g., an organic acid such as trifluoroacetic acid; or a benzyl group which can be removed by hydrogenation over a catalyst such as palladium on carbon. be.

[0193] Resins can also be used as protecting groups.

[0194] The methodology used to synthesize compounds of formula (I) is The process suitable for their preparation will vary depending on the nature of the aryl group and any substituents associated therewith. The process is further described in the accompanying examples.

[0195] A compound of formula (I) synthesized by any one of the processes defined herein If so, the process may then further comprise one or more of the following additional steps: (i) removing any protecting groups present; (ii) converting a compound of formula (I) into another compound of formula (I); (iii) forming a pharmaceutically acceptable salt, hydrate or solvate of a compound of formula I; and / or (iv) forming a prodrug of a compound of formula I.

[0196] The above example (ii) is a method of synthesizing a compound of formula (I) and then One or more of the groups may be further reacted to change the nature of the group to provide alternative compounds of formula (I). This is the case.

[0197] The resulting compound of formula (I) can be isolated and purified using techniques well known in the art. It is possible.

[0198] Certain compounds of formula I as defined herein are (i) a compound of formula IIa [ka] wherein A, R0, R1 and R2 are each as defined above, and X1 is a suitable Leaving groups (e.g., bromo, chloro, iodo, -SMe, -S(O)Me, or -S(O)M e) is with the group [R3-X2]-H, where X2 is N, S or O, and [R3-X2] together and reacts with the X2 atom, which is linked to the R3 group as defined above. to make can be prepared by Optionally, the process may then further comprise one or more of the following additional steps: can: (i) removing any protecting groups that may be present; (ii) converting a compound of formula (I) into another compound of formula (I) (e.g., by removing an R3 substituent to another R3 substituent as defined herein; (iii) forming a pharmaceutically acceptable salt, hydrate or solvate of a compound of formula I; and / or (iv) forming a prodrug of a compound of formula I.

[0199] For the avoidance of any doubt, the X2 atom is a heteroatom present in the group R3, i.e. That is, [R3-X2] is an R3 group containing the X2 heteroatom.

[0200] In the above reaction, when a compound of formula II is reacted with a group [R3-X2]-H, the group X1 is substituted with the H atom of the [R3-X2]-H group, and the R3 substituent is connected to the group of formula II through the X2 atom. It will be understood that the compound is attached to

[0201] Those skilled in the art will readily recognize suitable reaction conditions for the reaction between a compound of formula II and the [R3-X2]-H group. Examples of suitable reaction conditions can be readily selected. It is described in the section.

[0202] Compounds of formula II can be prepared by any of the preferred methods known in the art, as will be apparent from the accompanying Examples section. Specific examples of the preparation of compounds of formula II are described herein. are described in the accompanying Examples section of the same.

[0203] Compounds of formula I can also be prepared by Suzuki-Miyaura coupling or Stille coupling reactions. For example, certain compounds of formula I defined herein can also be prepared by (i) a compound of formula III [ka] (wherein A, R0, R2 and R3 are each as defined above, and X3 is a halo atom) (e.g., bromo, chloro, or iodo) in a group of the following formula: R1-M wherein M is a coupling reagent (e.g., a boron coupling agent as defined herein). or a tin coupling agent), wherein R1 is as defined above. and; or (ii) a compound of formula IV [ka] (wherein A, R0, R1 and R3 are each as defined above, and X3 is a halo atom) (e.g., bromo, chloro, or iodo) in a group of the following formula: R2-M wherein M is a coupling reagent (e.g., a boron coupling agent as defined herein). or a tin coupling agent), and R2 is as defined above. and; or (iii) a compound of formula V [ka] (wherein A, R0, R1 and R2 are each as defined above, and X3 is a halo atom) (e.g., bromo, chloro, or iodo) in a group of the following formula: R3-M wherein M is a coupling reagent (e.g., a boron coupling agent as defined herein). or a tin coupling agent), and R3 is as defined above. and can be prepared by Optionally, the process may then further comprise one or more of the following additional steps: can: (i) removing any protecting groups that may be present; (ii) converting a compound of formula (I) into another compound of formula (I); (iii) forming a pharmaceutically acceptable salt, hydrate or solvate of a compound of formula I; and / or (iv) forming a prodrug of a compound of formula I.

[0204] The group M may be any suitable boron carboxylate known in the art for Suzuki-Miyaura coupling reactions. Examples of suitable boron reagents include boronic acids and boronic acid esters. (e.g., catecholboronic acid ester, pinacolboronic acid ester, triisopropylboronic acid ester, arylboronates, MIDA boronates, cyclic triol boronates), boranes (e.g., 9 -BBN borane), organic trifluoroborates or boronamides (e.g., 1,8-diazoborane, Specific examples include -B(OH)2 or -B(OCH 3)2.

[0205] The Suzuki-Miyaura coupling reaction is well known, and those skilled in the art will be able to identify suitable reaction conditions for this reaction. You will be able to easily select the item.

[0206] In the Stille coupling reaction, M is a tin coupling agent, preferably of the formula -Sn [(1-6C) alkyl]3, e.g., -Sn(butyl)3, a tin coupling agent .

[0207] The Stille coupling reaction is well known, and those skilled in the art will recognize suitable reaction conditions for this reaction. Such reactions are usually carried out in the presence of a palladium catalyst. This will be carried out under the supervision of the

[0208] biological activity The biological assays described in the Examples section (Biological Examples 1-3) were used to determine the activity of the compounds of the present invention. The pharmacological effect of the compound can be measured.

[0209] The pharmacological properties of the compounds of formula I vary with structural changes, as would be expected. The compounds of the invention are active in the assays described in Biological Examples 1, 2 and 3. I found out that...

[0210] Generally, with respect to adenosine A2a antagonism, the compounds of the present invention exhibit the same activity as in Biological Example 1. IC of 1 μM or less in the assay described 50 and the preferred compound of the present invention is 20 IC below 0 nM 50 and the most preferred compounds of the present invention exhibit an IC of 50 nM or less. 50 of show.

[0211] Preferably, compounds of the invention inhibit adenosine in the assay described in Biological Example 1. IC at A1, A2b or A3 receptors 50 IC at adenosine A2a receptors 50 at least two times higher, more preferably at least five times higher, and even more preferably , at least 10 times higher.

[0212] Pharmaceutical Composition According to a further aspect of the invention, there is provided a compound of the invention as defined above, or a pharmaceutical composition thereof. a pharmaceutically acceptable salt, hydrate or solvate thereof, together with a pharmaceutically acceptable diluent or carrier. A pharmaceutical composition comprising:

[0213] The compositions of the present invention can be administered orally (e.g., as tablets, lozenges, hard or soft capsules, or in water). Water or oily suspensions, emulsions, dispersible powders or granules, syrups or emulsions as lixil), topical use (e.g., cream, ointment, gel, or aqueous or oily as a solution or suspension), by inhalation (e.g., as a finely divided powder or liquid aerosol), administration by insufflation (e.g., as a micronized powder), or parenteral administration (e.g., Aqueous or oily sterile solutions for intravenous, subcutaneous, intramuscular, intraperitoneal or intramuscular administration The pharmaceutical composition may be in a form suitable for administration as a suppository (for example, as a bolus or as a suppository for rectal administration).

[0214] The compositions of the present invention may be prepared in a conventional manner using conventional pharmaceutical excipients well known in the art. Thus, compositions intended for oral use can be obtained by procedures such as It may contain one or more coloring agents, sweetening agents, flavoring agents and / or preservatives.

[0215] An effective amount of a compound of the invention for use in therapy will be that which will treat the proliferative conditions referred to herein. to treat or prevent, slow the progression of, and / or alleviate the symptoms associated with the condition It's a sufficient amount.

[0216] The amount of active ingredient that is combined with one or more excipients to produce a single dosage form may vary depending on the therapeutic The results will necessarily vary depending on the individual and the specific route of administration. For example, The illustrated formulations generally contain, for example, 0.5 mg to 0.5 g of active agent (more preferably, 0. 5 to 100 mg, for example, 1 to 30 mg), varying from about 5 to about 98% by weight of the total composition. The pharmaceutical composition may contain, in admixture with suitable and convenient amounts of excipients to obtain the desired results.

[0217] The size of the dose of a compound of formula I for therapeutic or prophylactic purposes will, of course, be determined by well-known medical principles. The nature and severity of the condition, the age and sex of the animal or patient, and the administration history are taken into account in accordance with established principles. It changes depending on the road.

[0218] The compounds of the invention, when used for therapeutic or prophylactic purposes, will generally be administered in doses of, for example, 0.1 Daily doses ranging from 100 mg / kg to 75 mg / kg body weight given in divided doses if necessary Generally, smaller doses are administered when parenteral routes are used. Therefore, for example, in intravenous or intraperitoneal administration, the dose is, for example, 0.1 mg / kg to 30 mg / kg. Doses in the range of 1000 mg / kg body weight are generally used. Similarly, for administration by inhalation, e.g. Doses ranging from 0.05 mg / kg to 25 mg / kg of body weight are used. Oral administration, especially tablets The dosage form may also be suitable. Typically, a unit dosage form contains a compound of the invention in an amount of about 0.5 mg to 0. Contains 0.5g.

[0219] Therapeutic Uses and Applications The present invention relates to an antagonist of the adenosine A2 receptor, particularly the adenosine A2a receptor. The present invention provides compounds that function as

[0220] According to a further aspect of the present invention, adenosine A2a receptors are detected in vitro or in vivo. A method of antagonizing a cellular response, comprising treating a cell with a compound as defined herein, or a pharmaceutically acceptable salt thereof. In accordance with another aspect of the present invention, a method is provided comprising contacting the compound with an effective amount of a salt, hydrate, or solvate thereof.

[0221] According to a further aspect of the present invention, adenosine A2a receptors are detected in vitro or in vivo. A method of selectively antagonizing a cell by treating the cell with a compound as defined herein, or a pharmaceutically acceptable salt thereof. and contacting the compound with an effective amount of an acceptable salt, hydrate, or solvate thereof. do.

[0222] According to a further aspect of the present invention, there is provided a method for inhibiting cell proliferation in vitro or in vivo. The cells are treated with a compound defined herein, or a pharmaceutically acceptable salt or hydrate thereof. or solvate thereof, or a pharmaceutical composition as defined herein. Preferably, the compound or pharmaceutical composition further comprises one or more additional antiproliferative agents. (e.g., checkpoint inhibitors and / or cytotoxic agents) .

[0223] According to a further aspect of the present invention, a disease or disorder associated with adenosine A2a receptor activity to a patient in need of such treatment, comprising administering to said patient a or a pharmaceutically acceptable salt, hydrate or solvate thereof, or Methods are provided that include administering a therapeutically effective amount of a pharmaceutical composition as defined herein.

[0224] According to a further aspect of the present invention, treatment of a cell proliferative disorder is provided in a subject in need of such treatment. 10. A method of administering to a patient suffering from a rheumatoid arthritis, the method comprising administering to said patient a compound as defined herein, or a pharmaceutical formulation thereof. or a therapeutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein. Preferably, the compound or pharmaceutical composition is one or more additional antiproliferative agents (e.g., checkpoint inhibitors and / or cytotoxic agents) It is administered in combination with

[0225] According to a further aspect of the present invention, treatment for cancer is administered to a patient in need of such treatment. 20. A method comprising administering to said patient a compound as defined herein, or a pharmaceutically acceptable salt thereof. administering a therapeutically effective amount of a salt, hydrate or solvate, or pharmaceutical composition as defined herein; Preferably, the compound or pharmaceutical composition comprises one or more additional in combination with additional anti-cancer agents (e.g., checkpoint inhibitors and / or cytotoxic agents) It is administered.

[0226] According to a further aspect of the invention there is provided a compound as defined herein for use in therapy. or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition thereof is provided. can be.

[0227] According to a further aspect of the present invention there is provided a method for treating a cell proliferative condition comprising administering to a subject a compound as defined herein. A compound as defined above, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or There is provided a pharmaceutical composition as defined herein. Suitably, the compound or pharmaceutical composition comprises one In combination with these additional antiproliferative agents (e.g., checkpoint inhibitors and / or cytotoxic agents), They are administered in combination.

[0228] According to a further aspect of the present invention there is provided a compound as defined herein for use in the treatment of cancer. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition thereof is provided. In certain embodiments, the cancer is a human cancer. Suitably, the compound or pharmaceutical composition , one or more additional anti-cancer agents (e.g., checkpoint inhibitors and / or cytotoxic agents) It is administered in combination with

[0229] According to a further aspect of the present invention, there is provided a compound according to the invention for use as an adenosine A2a antagonist. or a pharmaceutically acceptable salt, hydrate or solvate thereof, In one embodiment, the compounds of the present invention are selective adenosine A2a antagonists. In an alternative embodiment, certain compounds of the present invention are selective adenosine A2 agonists. a antagonist and adenosine A2b antagonist.

[0230] According to a further aspect of the invention, a method for treating a disease or disorder in which adenosine A2a is involved is provided. A compound as defined herein, or a pharmaceutically acceptable salt, hydrate or the like thereof, for use in or solvates thereof.

[0231] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. Use of a salt, hydrate or solvate of the compound of formula (I) in the manufacture of a medicament for the treatment of a cell proliferative condition Preferably, the compound or pharmaceutical composition further comprises one or more additional antiproliferative agents ( For example, in combination with a checkpoint inhibitor and / or a cytotoxic agent.

[0232] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. The use of a salt, hydrate or solvate of the compound of formula (I) in the manufacture of a medicament for the treatment of cancer is provided. Preferably, the cancer is a human cancer. Preferably, the compound or pharmaceutical composition comprises one or more in combination with additional anti-cancer agents (e.g., checkpoint inhibitors and / or cytotoxic agents) It is administered as follows.

[0233] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. salts, hydrates or solvates thereof as adenosine A2a antagonists The present invention also provides a use of the compound in the manufacture of a medicament for

[0234] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. salts, hydrates or solvates thereof as adenosine A2a antagonists The present invention also provides a use of the compound in the manufacture of a medicament for

[0235] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt thereof. adenosine A2a receptor activity-related disease or There is provided a use in the manufacture of a medicament for the treatment of a disorder.

[0236] The term "proliferative disorder" is used interchangeably herein and refers to a disorder that is caused by an in vitro or in vivo and unwanted or excessive growth of undesired or abnormal cells, such as neoplastic or hyperplastic growth. Associated with uncontrolled cell proliferation. Examples of cell proliferative conditions include malignant neoplasms and tumors. , cancer, leukemia, psoriasis, bone diseases, fibroproliferative disorders (e.g., of connective tissue), and atheroma These include, but are not limited to, premalignant and malignant cell proliferation, including atherosclerosis. These include, but are not limited to, lung, colon, breast, ovary, prostate, liver, pancreas, brain, and skin. Any type of cell can be treated, including but not limited to:

[0237] The antiproliferative effects of the compounds of the present invention are due to their adenosine A2a antagonist activity. It is particularly applicable to the treatment of human cancers.

[0238] More specifically, cancer, in particular solid tumors, such as non-small cell lung cancer or small cell lung cancer, head and neck cancer, Compounds of general formula (I) are provided for use in the treatment of squamous cell carcinoma and urothelial carcinoma.

[0239] More specifically, it is used to treat cancer, for example lung cancer, such as small cell lung cancer or non-small cell lung cancer. Compounds of general formula (I) are provided for:

[0240] Cancer, in particular solid tumors, such as non-small cell lung cancer or small cell lung cancer, head and neck squamous cell carcinoma, and urinary The use of a compound of general formula (I) in the manufacture of a medicament for use in the treatment of urothelial carcinoma is also Provided.

[0241] The present invention further relates to the treatment of cancer, particularly solid tumors, such as non-small cell lung cancer or small cell lung cancer, head and neck cancer, A method for treating squamous cell carcinoma and urothelial carcinoma, said method being effective in patients in need of such treatment. The method comprises administering an amount of a compound of general formula (I).

[0242] The patient to be treated is preferably a mammal, more preferably a human.

[0243] Administration route The compounds of the present invention or pharmaceutical compositions containing these compounds may be administered systemically / peripherally or locally (i.e. The compound may be administered to a subject by any convenient route of administration, regardless of the intended site of action (i.e., the desired site of action). This can be done.

[0244] Routes of administration include oral (e.g., by ingestion), buccal, sublingual, and transdermal (e.g., transmucosal (e.g., via patches, plasters, etc.) intranasally (e.g., by a nasal spray); intraocularly (e.g., by eye drops), lungs (e.g., by aerosols, e.g., by inhalation through the mouth or nose), by insufflation), rectum (e.g., by suppository or enema), vagina (e.g., in a pessary) by), parenteral (e.g., subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal) , intrathecal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, subarachnoid, substernal and by injection, including intratumoral, and in a depot or reservoir, e.g., subcutaneously or intramuscularly. These include, but are not limited to, implants.

[0245] The compounds of the present invention or pharmaceutical compositions containing these compounds are administered by intratumoral delivery. It is possible.

[0246] Combination therapy The compounds of formula I are useful for the treatment and / or prevention of cell proliferative disorders, such as, for example, cancer. The compounds of formula I as defined herein may be administered in combination with one or more additional anti-proliferative / anti-cancer therapies, e.g. For example, chemotherapy with one or more additional antiproliferative / anticancer agents, radiation therapy and / or conventional treatment It can be used in combination with other techniques.

[0247] The additional antiproliferative / anticancer agent may be combined with a compound of formula (I) as defined herein in a pharmaceutical composition. or may be added separately, simultaneously with the compound of formula (I), or earlier or later. It may be administered sooner or later.

[0248] Thus, in a further aspect of the invention, simultaneous, sequential or separate use in the treatment of cancer a compound of general formula (I) and a compound useful for treating or preventing cancer as a combined preparation for A product containing the additional agent is provided.

[0249] The present invention also provides a combination preparation for simultaneous, sequential or separate use in the treatment of cancer. in combination with one or more additional antiproliferative / anticancer agents for use in the treatment of cancer, as a The present invention provides a compound of general formula (I)

[0250] In particular, the combination therapy as defined herein is directed to the treatment of solid tumors, such as non-small cell lung cancer or It is suitable for the treatment of small cell lung cancer, head and neck squamous cell carcinoma, and urothelial carcinoma.

[0251] Suitable additional antiproliferative agents that may be used in combination with compounds of formula I as defined herein / Anticancer drugs [separately or as part of a pharmaceutical composition in combination with a compound of general formula (I)] or as part of a combined preparation] include: 1) other forms of cancer immunotherapy and anti-cancer chemotherapeutic agents; 2) Adenosine pathway modulators (A2b antagonists, CD73 inhibitors and CD3 9 inhibitors); 3) Anti-PD-1 and PDL-1 antibodies (cetrelimab, pembrolizumab, nivolumab, dextromethorphan, including, but not limited to, urvalumab, avelumab, and atezolizumab; and to 4) Anti-CTLA4 antibodies (including but not limited to ipilimumab).

[0252] Compounds of formula I as defined herein are useful in treating PD-1 and PDL-1 diseases, including PD-1, PD-2, and PD-L1. Limulus, pembrolizumab, nivolumab, durvalumab, avelumab and atezolizumab The present invention is particularly suitable for use in combination with a variety of different ion exchangers, including but not limited to ion exchangers.

[0253] Preferably, the anti-PD1 antibody is one described in U.S. Patent Application Publication No. 2019 / 0225689 or No. 2017 / 0121409, the entire contents of which are incorporated herein by reference. One such antibody is cetrelimab, for example, one of the antibodies disclosed in US Pat. Limab (JNJ-63723283, CET) inhibits programmed death with high affinity and specificity. Fully human immunoglobulin (Ig) G4 kappa monoclonal antibody that binds to the PD-1 receptor (PD-1) Cetrelimab is a monoclonal antibody that has shown activity in solid tumors. ski P,et al.Journal of Clinical Oncology .2019;37(8):31.

[0254] The compounds of formula I as defined herein are in particular adenosine pathway modulators, e.g. including, but not limited to, A2b antagonists, CD73 inhibitors and CD39 inhibitors. Suitable for use in combination.

[0255] The A2a antagonists of general formula (I) may also be used in, but are not limited to, CAR-T cells The present invention can be used in combination with cell-based immunotherapies and cancer vaccines, including immunotherapy. .

[0256] Examples of additional anti-proliferative / anti-cancer chemotherapeutic agents include, but are not limited to, the following: One or more of the following: MEK (e.g., MEK1, MEK2, or MEK1 and MEK2) inhibitors (e.g., X L518, CI-1040, PD035901, selumetinib / AZD6244, GSK 1 120212 / trametinib, GDC-0973, ARRY-162, ARRY-3 00, AZD8330, PD0325901, U0126, PD98059, TAK-7 33, PD3 18088, AS703026, BAY 869766), alkylating agent (e.g., cyclophosphamide, ifosfamide, chlorambucil, busulfan, melphalan, Phalan, mechlorethamine, uramustine, thiotepa, nitrosoureas, nitrogen Mustard (e.g., mechloroethamine, cyclophosphamide, chlorambucil, mayfenib) methyl melamines (e.g., hexamethyl melamine, thiomethyl melamine), ethyleneimine and methyl melamines (e.g., hexamethyl melamine, thiomethyl melamine), alkyl sulfonates (e.g., busulfan), nitrosoureas (e.g., carbohydrates) Streptozocin, Lomustine, Semustine, Streptozocin), Triazene (Dacarbazine) , antimetabolites (e.g., 5-azathioprine, leucovorin, capecitabine, fludarabine) methadone, gemcitabine, pemetrexed, raltitrexed, folic acid analogs (e.g., methotrexate, Rexate), or pyrimidine analogs (e.g., fluorouracil, floxouridine) , cytarabine), purine analogs (e.g., mercaptopurine, thioguanine, pentosulfamethoxazole, plant alkaloids (e.g., vincristine, vinblastine, vinoresin, etc.), Rubin, vindesine, podophyllotoxin, paclitaxel, docetaxel, etc.), topo Isomerase inhibitors (e.g., irinotecan, topotecan, amsacrine, etoposide ( VP16), etoposide phosphate, teniposide, etc.), anticancer antibiotics (e.g., doxorubicin, Bicine, Adriamycin, Daunorubicin, Epirubicin, Actinomycin, Bleomycin mycin, mitomycin, mitoxantrone, plicamycin, etc.), platinum compounds or Platinum-containing agents (e.g., cisplatin, oxaloplatin, alboplatin), anthracycline, Senediones (e.g., mitoxantrone), substituted ureas (e.g., hydroxyurea), methyl hydrazine derivatives (e.g., procarbazine), adrenal cortex suppressants (e.g., mitotane, aminoglutethimide), epipodophyllotoxins (e.g., etoposide), antibiotics (e.g., Daunorubicin, doxorubicin, bleomycin), enzymes (e.g., L-aspartate ligase), mitogen-activated protein kinase signaling inhibitors (e.g., U 0126, PD98059, PD184352, PD0325901, ARRY-142 886, SB239063, SP600125, BAY 43-9006, Waltman or LY294002, Syk inhibitors, mTOR inhibitors, antibodies (e.g., Rituxan gossyphol, genacense, polyphenol E, chlorophyll Syn, all-trans retinoic acid (ATRA), bryostatin, tumor necrosis factor-related Apoptosis-inducing ligand (TRAIL), 5-aza-2'-deoxycytidine, ol Trans-retinoic acid, doxorubicin, vincristine, etoposide, gemcitabine , imatinib (Gleevec.RTM.), geldanamycin, 17-N-allylamine No-17-demethoxygeldanamycin (17-AAG), flavopiridol, LY29 4002, bortezomib, trastuzumab, BAY 11-7082, PKC412, P D184352, 20-epi-1,25-dihydroxyvitamin D3; 5-ethynyluracil Sil; Abiraterone; Aclarubicin; Achilfulvene; Adecipenol; Adzelesin ;Aldesleukin;ALL-TK antagonist;Altretamine;Ambamastine; Amidox; Amifostine; Aminolevulinic acid; Amrubicin; Amsacrine; Anagnoside Relide; Anastrozole; Andrographolide; Angiogenesis inhibitor; Antagonist D; Antagonist G; Antarelix; Anti-adsorption morphogenetic protein-1; Anti-and Antiestrogens (prostate cancer); Antiestrogens; Antineoplastons; Antisense oligonucleotides Reotide; Aphidicolin glycinate; Apoptosis gene modulator; Apotho Cis-regulator; apurinic acid; ara-CDP-DL-PTBA; arginine deaminase Nase; Aslaculin; Atamestane; Atrimastin; Axinastatin 1; Axin Nastatin 2; Axinastatin 3; Azasetron; Azatoxin; Azatyrosine; Bacillus annuus Cathine III derivative; Balanol; Batimastat; BCR / ABL antagonist; Benzochlorin; Benzoylstaurosporin; Beta-lactam derivatives; Beta-arretin ;Betaclamycin B;Betulinic acid;bFGF inhibitor;bicalutamide;bisantrene;bi Suaziridinylspermine; Bisnafide; Bistraten A; Bizelesin; Breflate ;Bropirimine;Budotitanium;Buthionine sulfoximine;Calcipotriol;Calpho Staphylococcus aureus; Camptothecin derivatives; Canaripox IL-2; Capecitabine; Carboxylic Acid Mido-amino-triazole; Carboxyamidotriazole; CaRest M3; C ARN 700; Cartilage-derived inhibitor; Carzelesin; Casein kinase inhibitor (ICOS );Castanospermine;Cecropin B;Cetrorelix;Chlorin;Chloroquinoxa Phosphorus sulfonamides; Cicaprost; cis-porphyrins; Cladribine; Clomiphene Collismycin A; Collismycin B; Combretastatin Chin A4; Combretastatin analogues; Conagenin; Crambesidin 816; Krisna Thor; Cryptophycin 8; Cryptophycin A derivatives; Curacin A; Cyclopentaa Diclofenac; Cycloplatin; Cytarabine ocfosfate; Cell lysis factor; cytostatin; dacliximab; decitabine; dehydrodidemine B; deslorelin ;Dexamethasone;Dexphosphamide;Dexrazoxane;Dexverapamil;Zia Dicon; Didemnin B; Didox; Diethylnorspermine; Dihydro-5-azacytidine gin; 9-dioxamycin; diphenylspiromustine; docosanol; dolasetron ;Doxifluridine;Droloxifene;Dronabinol;Duocarmycin SA;E Buseren; Ecomustine; Edelfosine; Edrecolomab; Eflornithine; Elemene ;Emiteful;Epirubicin;Epristeride;Estramustine analogues;Estro Estrogen agonists; estrogen antagonists; etanidazole; etoposide phosphate; Xemestane; Fadrozole; Fazarabine; Fenretinide; Filgrastim; Finasteride; Flavopiridol; Flazelastine; Fluasterone; Fludarabine; Luorodaunornithine hydrochloride; Forfenimex; Formestane; Fostriecin ;Fotemustine;Gadolinium texapyrin;Gallium nitrate;Galocitabine;Ganirel gelatinase inhibitors; gemcitabine; glutathione inhibitors; hepsulfam; hele Glyn; Hexamethylenebisacetamide; Hypericin; Ibandronic acid; Idarbi Syn; Idoxifene; Idramanton; Ilmofosine; Ilmostat; Imidazoa Cridone; Imiquimod; Immunostimulant peptides; Insulin-like growth factor-1 receptor inhibitors; Interferon agonists; interferons; interleukins; iobenguane; Iododoxorubicin; Ipomeanol, 4-; Ilopract; Irsogladine; Isobe Isohomohalichondrin B; Itasetron; Jasplakinolide; Kahalari DoF; Lamellarin-N triacetate; Lanreotide; Leinamycin; Lenograstim ;Lentinan sulfate;Leptolstatin;Letrozole;Leukemia inhibitory factor;Leukocyte alpha Interferon; leuprolide + estrogen + progesterone; leuprorelin; Levamisole; Liarozole; Linear polyamine analogue; Lipophilic disaccharide peptide; Lipophilic Active platinum compounds; lissoclinamide 7; lobaplatin; Lonbricin; lometrexol; lonidamine; losoxantrone; lovastatin; Loxacin Sorivine; Lurtotecan; Lutetium texaphyrin; Lisofylline; Cytolytic peptides maytansine; mannostatin A; marimastat; massoprocol; maspin; Trilysine inhibitors; matrix metalloproteinase inhibitors; menogaril; merbaron; Meterelin; methioninase; metoclopramide; MIF inhibitor; mifepristone; mi Lutefosine; Millimostim; Mismatched double-stranded RNA; Mitoguazone; Mitolactol; My Mitomycin analogue; Mitonafide; Mitotoxin fibroblast growth factor-saporin; Mitotoxin Toxantrone; Mofalotene; Molgramostim; Monoclonal antibody, human chorionic gonadotropin Nadotrophin; monophosphoryl lipid A + mycobacterium Cell wall sk; mopidamol; multidrug resistance gene inhibitor; multiple tumor suppressor 1-based therapeutic agent ;Mustard anticancer agent;Mycaperoxide B;Mycobacterial cell wall extract;Miliaporo N-acetyldinaline; N-substituted benzamides; Nafarelin; Nagrestipp; Naloxone + pentazocine; napavine; naftarpine; nartograstim; nedaplatin ;Nemorubicin;Neridronic acid;Neutral endopeptidase;Nilutamide;Nisamycin; Nitric oxide modulators; Nitroxide antioxidants; Nitrulline; 06-benzylguanidine octreotide; oxenon; oligonucleotides; onapristone; ondancet Ondansetron; Oracin; Oral cytokine inducer; Ormaplatin; Osateron; Oxaliplatin; Oxaunomycin; Palauamine; Palmitoyl lysozyme Pamidronic acid; Panaxytriol; Panomyphen; Parabactin; Pazelliptin Pegaspargase; Perdecin; Pentosan polysulfate sodium; Pentostatin; Pen Perflubron; Perfosfamide; Perillyl alcohol; Phenazino Mycin; Phenylephrine acetate; Phosphatase inhibitors; Picibanil; Pilocarpine hydrochloride; Pirarubicin; Piritrexim; Prasetin A; Prasetin B; Plasminogen activator Factor inhibitors; Platinum complexes; Platinum compounds; Platinum triamine complexes; Porfimer sodium ;Porfiromycin;Prednisone;Propylbis-acridone;Prostaglandins J2; Proteasome inhibitor; Protein A system immunomodulator; Protein kinase C inhibitor; protein kinase C inhibitor, microalgae; tyrosine phosphatase protein inhibitors;purine nucleoside phosphorylase inhibitors;purpurins;pyrazoloacridines; Pyridoxylated hemoglobin polyoxyethylene Conjugate; raf antagonist; raltitrexed; ramosetron; ras farnesyl Protein transferase inhibitors; ras inhibitors; ras-GAP inhibitors; demethylation Reterliptin; Rhenium Re186 etidronate; Rhizoxin; Ribozyme; RII Retinamide; Rogletimide; Rohitukin; Romurtide; Roquinimex; Rubidinone B 1; Ruboxyl; Safingol; Saintpin; SarCNU; Sarcofitol A; Sa Rugramostim; Sdi 1 mimetic; Semustine; Senescense-derived inhibitor 1; Se Signal transduction inhibitors; signal transduction modulators; single-chain antigens Binding protein; Sizofiran; Sobuzoxane; Borocaptate sodium; Phenylephrine Sodium sorbitol; Sorberool; Somatomedin binding protein; Sonermin; Sparfos acid ;Spicamycin D;Spiromustine;Splenopentin;Spongistatin 1;Squam Lamin;Stem cell inhibitor;Stem cell division inhibitor;Stipiamide;Stromelysin inhibitor;S Rufinosine; hyperactive vasoactive intestinal peptide antagonist; Suradista; Suramin ;Swansonine;Synthetic glycosaminoglycan;Talimustine;Tamoxifen methiodide ; Tauromustine; Tazarotene; Tecogalan sodium; Tegafur; Terlapyrylium; Telomerase inhibitors; temoporfin; temozolomide; teniposide; tetrachlorodecanoic acid oxide; tetrazomine; thaliblastine; thiocoraline; thrombopoietin; thrombo Thymopoietin mimetic; Thymalfadine; Thymopoietin receptor agonist; Thymotri Naan; Thyroid-stimulating hormone; Stannous ethyl etiopurpurin; Tirapazamine; Titanocene diamine Chloride; Topsentin; Toremifene; Totipotent stem cell factor; Translation inhibitors; Tretinoin; Triacetyluridine; Triciribine; Trimetrexate; Triptorelin; Tropice Tron; Turosteride; Tyrosine kinase inhibitor; Tyrphostin; UBC inhibitor; Ube Nimex; urogenital sinus-derived growth inhibitor; urokinase receptor antagonist; Vapreo Tide; Variolin B; Vector system, red blood cell gene therapy drug; Veraresol; Veramine ;Bardine;Verteporfin;Vinorelbine;Vinxartin;Vitaxin;Borozole Zinostatin; Zanoterone; Zeniplatin; Zilascorb; Zinostatin stimalamer, Adri amycin, dactinomycin, bleomycin, vinblastine, cisplatin, Civicin; Aclarubicin; Acodazole hydrochloride; Acronin; Adzelesin; Ardes Leukin; Altretamine; Ambomycin; Amethantrone acetate; Aminoglutethimide ;Amsacrine;Anastrozole;Anthramycin;Asparaginase;Aspergillus Azacitidine; Azetapro; Azotomycin; Batimastat; Benzodepa; Bical Tamide; Bisantrene hydrochloride; Bisnafide dimesylate; Bizelesin; Bleomycin sulfate Synthon; Brequinar sodium; Bropirimine; Busulfan; Cactinomycin; Callus Telon; Caracemide; Carbetimer; Carboplatin; Carmustine; Carbicin Hydrochloride Salt; Carzelcin; Cedefingol; Chlorambucil; Cilolemycin; Cladribine; Crisnatol mesylate; Cyclophosphamide; Cytarabine; Dacarbazine; Daunol Bicine hydrochloride; Decitabine; Dextromaplatin; Dezaguamine; Dezaguamine mesylate Diaziconazole; Doxorubicin; Doxorubicin hydrochloride; Droloxifene; Citric acid Droloxifene; Dromostanolone propionate; Duazomycin; Edatrexate Eflornithine hydrochloride; Elsamitrucin; Enloplatin; Enpromate; E Pipropizine; Epirubicin hydrochloride; Elbrozole; Esorubicin hydrochloride; Estram estramustine; estramustine sodium phosphate; etanidazole; etoposide; etoposide phosphate Poside; Etoprine; Fadrozole hydrochloride; Fazarabine; Fenretinide; Flox Uridine; Fludarabine phosphate; Fluorouracil; Flurocitabine; Foscidone; Fostriecin sodium; gemcitabine; gemcitabine hydrochloride; hydroxyurea; salt Idarubicin; Ifosfamide; Imofosine; Interleukin II (recombinant interleukin 2 or rlL.sub.2), interferon alpha-2a; Interferon alfa-2b; interferon alfa-n1; interferon alpha-n3; interferon beta-la; interferon gamma-lb; ip Loplatin; Irinotecan hydrochloride; Lanreotide acetate; Letrozole; Leuprolide acetate ;Liarozole hydrochloride;Lometrexol sodium;Lomustine;Losoxantrone salt acid salt; masoprocol; maytansine; mechlorethamine hydrochloride; megestrol acetate; vinegar Melengestrol acetate; Melphalan; Menogaril; Mercaptopurine; Methotrexor methotrexate sodium; metoprine; meturedepa; mitindomide; mitocalcin Mitochromin; Mitogillin; Mitomarcin; Mitomycin; Mitospel; Mitotane ;Mitoxantrone hydrochloride;Mycophenolic acid;Nocodazoie ;Nogalamycin;Ormaplatin;Oxisuran;Pegaspargase;Periomycin ;Pentamustine;Peplomycin sulfate;Perfosfamide;Pipobroman;Piposul Phan; Piroxantrone hydrochloride; Plicamycin; Promestane; Porfimer sodium Porfiromycin; Prednimustine; Procarbazine hydrochloride; Puromycin; Puromycin hydrochloride; Pyrazofurin; Ribopurin; Rogletimide; Safingol; Safi Angol hydrochloride; Semustine; Simtrazene; Sparfosate sodium; Sparsomy Spirogermanium hydrochloride; Spiromustine; Spiroplatin; Streptonigrin Streptozocin; Sulofenur; Tallysomycin; Tecogalan sodium; Tega Ful;Teloxantrone hydrochloride;Temoporfin;Teniposide;Teroxylon;Test Lactone; Thiamiprine; Thioguanine; Thiotepa; Tiazofurin; Tirapazamine; Quercus Toremifene phosphate; Trestrone acetate; Trisivirine phosphate; Trimetrexate; Gluconate Trimetrexate chlorate; Triptorelin; Tubrozole hydrochloride; Uracil masterbate d;Uredep;Vapreotide;Verteporfin;Vinblastine sulfate;Vincris sulfate Vindesine; Vindesine sulfate; Vinepidine sulfate; Vinglycinate sulfate; Vin sulfate Leurosine; Vinorelbine tartrate; Vinrocidine sulfate; Vinzoxidine sulfate; Vorozole; Zeniplatin; Zinostatin; Zorubicin hydrochloride, arresting cells in the G2-M phase and / or or agents that modulate microtubule formation or stability (e.g., Taxol™ (i.e., (i.e., paclitaxel), Taxotere™ (a compound containing a taxane skeleton), Rubrozole (i.e., R-55104), Dolastatin 10 (i.e., DLS-1 0 and NSC-376128), mivobulin isethionate (i.e., CI-980) ), vincristine, NSC-639829, discodermolide (i.e., NV P-XX-A-296), ABT-751 (Abbott, i.e., E-701 0), altritol (e.g., altritol A and altritol C), spongiform activator Spongestatin (e.g., spongistatin 1, spongistatin 2, spongistatin 3, spongistatin Distatin 4, spongistatin 5, spongistatin 6, spongistatin 7, spongistatin distatin 8 and spongistatin 9), cemadotin hydrochloride (i.e., LU-1037 93 and NSC-D-669356), epothilones (e.g., epothilone A, epothilone B, epothilone C (i.e., desoxyepothilone A or dEpoA), epothilone D ( KOS-862, dEpoB and desoxyepothilone B), epothilone E, Epothilone F, epothilone B N-oxide, epothilone A N-oxide, 16-aza - Epothilone B, 21-aminoepothilone B (i.e., BMS-3-10705), 2 1-hydroxyepothilone D (i.e., desoxyepothilone F and dEpoF), 2 6-Fluoroepothilone, auristatin PE (i.e., NSC-654663), Bridotin (i.e., TZT-1027), vincristine sulfate, cryptophycin 5 2 (i.e., LY-355703), bitilebuamide, tubulysin A, canadensol , sendaureidin (i.e., NSC-106969), oncocidin Al (i.e., , BTO-956 and DF E), physianolide B, laulimalide, narcosine (NS (also known as C-5366), nascapine, hemiasterin, vanadocene acetylacetone Setonate, Monsatrol, Inanosin (i.e., NSC-698666), Eleuthero Desmethyleleutherobin, Desaetyeleutherobin leutherobin), Lusoeleutherobin A and Zeleutherobin), Caribe Osid, Calibaeolin, Halichondrin B, Diazonamide A, Taccalonolide A, Geo Zostatin, (-)-phenylahisteine ​​(i.e., NSCL-96F037), myostatin, Severin B, resberastatin sodium phosphate, steroids (e.g., dexamethasone) ), finasteride, aromatase inhibitors, gonadotropin-releasing hormone agonists (G nRH), e.g., goserelin or leuprolide, adrenocorticosteroids (e.g. , prednisone), progestins (e.g., hydroxyprogesterone caproate, acetate megestrol, medroxyprogesterone acetate), estrogens (e.g., diethylsulfone tilbestrol, ethinylestradiol), antiestrogens (e.g., tamoxifen androgens (e.g., testosterone propionate, fluoxymesterone) , antiandrogens (e.g., flutamide), immunostimulants (e.g., bacillus calmette- Guerlain (BCG), levamisole, interleukin-2, alpha-interferon etc.), monoclonal antibodies (e.g., anti-CD20, anti-F¢ER2, anti-CD52, anti-UL A-DR and anti-VEGF monoclonal antibodies), immunotoxins (e.g., anti-CD33 monoclonal antibodies), Anti-CD22 monoclonal antibody-calicheamicin conjugate, anti-CD22 monoclonal antibody-pure Iodomonas exotoxin conjugates, etc.), radioimmunotherapeutic agents (e.g., conjugated to ln, 0Y, or I conjugated anti-CD20 monoclonal antibodies, triptolide, homohalogenation Tonin, dactinomycin, doxorubicin, epirubicin, topotecan, itraconazole vindesine, cerivastatin, vincristine, deoxyadenosine, sertralil , pitavastatin, irinotecan, clofazimine, 5-nonyloxytryptamine, Vemurafenib, dabrafenib, erlotinib, gefitinib, EGFR inhibitors, epithelial Growth factor receptor (EGFR) targeted therapy or therapeutic agent (e.g., gefitinib (Iressa) (TM), erlotinib (Tarceva™), cetuximab (Erbitux®), (TM), lapatinib (Tykerb(TM), panitumumab (Vectibix( vandetanib (Caprelsa™), afatinib / BIBW299 2. CI-1033 / canertinib, neratinib / HKI-272, CP-724714 , TAK-285, AST-1306, ARRY334543, ARRY-380, AG -1478, dacomitinib / PF299804, OSI-420 / desmethylerlotinib AZD8931, AEE788, pelitinib / EKB-569, CUDC-101, WZ8040, WZ4002, WZ3146, AG-490, XL647, PD1530 35, BMS-599626), sorafenib, imatinib, sunitinib, dasatinib, Or hormone therapy.

[0257] As noted above, the combination therapies of the present invention may involve the simultaneous, sequential or separate administration of the individual components of the treatment. Such combination products may be administered in the dosage ranges described above. Use the compounds of the invention and other pharmaceutically active agents within their approved dosage ranges.

[0258] According to this aspect of the invention, a compound of the invention as defined above, or a pharmaceutically acceptable salt thereof, is provided. and one or more additional antiproliferative / anticancer agents. For example, combinations are provided for use in the treatment of cancer, including solid tumors.

[0259] According to this aspect of the invention, the treatment of cell proliferative conditions such as cancer (e.g., cancers including solid tumors) is A combination for use in therapy comprising a compound of the invention as defined above, or a drug thereof and physiologically acceptable salts, hydrates or solvates thereof, and those selected from those listed above. Also provided are combinations comprising one or more additional antiproliferative / anticancer agents.

[0260] In a further aspect of the present invention, another compound selected from those listed hereinabove is 2. A compound of the present invention, or a pharmaceutical composition thereof, for use in the treatment of cancer in combination with an antitumor agent of the present invention Acceptable salts, hydrates or solvates thereof are provided.

[0261] As used herein, the term "combination" refers to simultaneous, separate or consecutive In one aspect of the invention, "combination" refers to simultaneous administration. In another aspect of the invention, "combination" refers to separate administration. "In combination" refers to sequential administration. When administration is sequential or separate, the second component The delay in administration of should not be such as to eliminate the beneficial effect of the combination.

[0262] According to a further aspect of the present invention, a compound of the present invention, or a pharmaceutically acceptable salt thereof, water The solvate or the solvate may be combined with a pharmaceutically acceptable diluent or carrier (as defined herein). a pharmaceutical composition comprising the compound of formula (I) in combination with an antitumor agent (any of which is selected from those listed above in A composition is provided. [Example]

[0263] General conditions: Mass spectra were performed on an LC-MS system using electrospray ionization. These were analyzed using a Waters Acquity H-Cl with PDA and QDa mass detection. Ass UPLC, Acquity UPLC (binary pump / PDA detector) + ZQ Mass spectrometer or Acquity i-Class (quaternary pump / PDA detection) Instrument) + Quattro Micro mass spectrometer, Waters PDA and ELS detector Waters Acquity uPLC system with Shimadzu L The measurements were carried out using a C-MS-2010EV system. [M+H]+ is a monoisotopic This refers to the molecular weight of the block.

[0264] NMR spectra were obtained using a Bruker Ultrashield 500MHz NMR spectrometer. Spectrometer, Bruker Avance III HD 400MHz NMR Spectrometer, B ruker Avance DPX 300MHz NMR Spectrometer, Bruker Av Avance III HD 500MHz or Bruker Avance III HD The spectrum was recorded at 298 K and referenced to the solvent peak.

[0265] The following examples are intended to illustrate the present invention but are not intended to limit it. Temperatures are given in degrees Celsius. Unless otherwise stated, all evaporations are carried out under vacuum, preferably at about 1 The pressure is 5mmHg to 100mmHg (=20 to 133mbar). The structures of the compounds and starting materials are confirmed by standard analytical methods, e.g., MS and NMR. Abbreviations used are conventional in the art. , these terms have their generally accepted meanings.

[0266] Abbreviation Appearance br Broad d double line dd compound double line DABCO (1,4-diazabicyclo[2.2.2]octane) DBU 1,8-diazabicyclo[5.4.0]undec-7-ene DCM dichloromethane DIPEA Diisopropylethylamine DMA Dimethylacetamide DMF N,N-dimethylformamide EtOAc ethyl acetate HPLC High Performance Liquid Chromatography HBTU Hexafluorophosphate Benzotriazole Tetramethyluranium IMS Industrial Denatured Alcohol LC-MS Liquid Chromatography Mass Spectrometry mCPBA 3-chloroperbenzoic acid MeOH Methanol MeCN acetonitrile MS mass spectrometry m multiplet min mL milliliter m / z mass-to-charge ratio NBS N-Bromosuccinimide NMR nuclear magnetic resonance Pd(amphos)2Cl2bis(di-tert-butyl(4-dimethylamino) Phenyl)phosphine)dichloropalladium(II) Pd(tBu3P)2 Bis(tri-tert-butylphosphine)palladium(0) ppm parts per million PS polymer support Rt retention time s single line t triple line T3P Propanephosphonic Anhydride TFA trifluoroacetic acid THF tetrahydrofuran.

[0267] With reference to the following examples, compounds of preferred embodiments are shown to be useful in treating cancer in the context of the methods described herein or in the context of the present invention. It was synthesized using other methods known in the art.

[0268] The various starting materials, intermediates and compounds of the preferred embodiments may be optionally precipitated, filtered, or otherwise processed. The compound may be isolated and purified using conventional techniques such as crystallization, evaporation, distillation, and chromatography. Unless otherwise stated, all starting materials were obtained from commercial suppliers and Salts are prepared from the compounds by known salt-forming procedures and are used without further purification. It is possible.

[0269] It is understood that the organic compounds according to the preferred embodiments may exhibit the phenomenon of tautomerism. Since the chemical structures within this specification may represent only one of the possible tautomeric forms, It is to be understood that preferred embodiments encompass any tautomeric forms of the depicted structures.

[0270] Unless otherwise stated, analytical HPLC conditions were as follows:

[0271] Method 2A Column: Kinetex Core-Shell C18 2.1 x 50 mm 5 μm Column temperature: 40°C Eluent: A: H2O + 0.1% formic acid, B: MeCN + 0.1% formic acid Flow rate: 1.2mL / min Gradient: 0-1.83 min, 5-100% B, 1.83-2.25 min, 100% B, 2.25 ~2.26 minutes 100~5%B

[0272] Method 2.5B Column: Phenomenex Gemini-NX C18 2 x 50 mm 3 μm Column temperature: 40℃ Eluents: A: 2 mM ammonium bicarbonate buffered to pH 10, B: MeCN Flow rate: 1mL / min Gradient: 0-1.80 min, 1-100% B, 1.80-2.10 min, 100% B, 2.10 ~2.30 minutes 100~1%B

[0273] Method 3A Column: Acquity UPLC CSH C18 2.1 x 50 mm, 1.7 μm Column temperature: 50℃ Eluent: A: HO, B: MeCN, 0.1% formic acid Flow rate: 1mL / min Gradient: 0.2-2.5 min 2-98%B, 2.5-3.0 min 98%B

[0274] Method 3B Column: Acquity UPLC BEH C18 2.1 x 50 mm, 1.7 μm Column temperature: 50℃ Eluent: A: HO, B: MeCN, 0.1% ammonia Flow rate: 1mL / min Gradient: 0.2-2.5 min 2-98%B, 2.5-3.0 min 98%B

[0275] Method 5A Column: YMC-Triart C18 2 x 50 mm, 5 μm Flow rate: 0.8mL / min Eluent: A: H2O, B: MeCN, C: 50% H2O / 50% MeCN + 1.0% formic acid Gradient: 0.0–4.0 min 0–95% B, 5% C; 4.0–4.4 min 95% B, 5% C ;4.4~4.5 minutes 95%A, 5%B

[0276] Method 5B Column: YMC-Triart C18 2 x 50 mm, 5 μm Flow rate: 0.8mL / min Eluent: A: H2O, B: MeCN, C: 50% H2O / 50% MeCN + 1.0% ammonium hydroxide Monia (water-based) Gradient: 0.0–4.0 min 0–95% B, 5% C; 4.0–4.4 min 95% B, 5% C ;4.4~4.5 minutes 95%A, 5%B

[0277] Method 7A Column: Phenomenex Kinetix-XB C18 2.1 x 100 mm, 1.7 μm Column temperature: 40℃ Eluent: A: HO + 0.1% formic acid, B: MeCN + 0.1% formic acid Flow rate: 0.6mL / min Gradient: 0-5.3.0 min 5-100%B, 5.3-5.8 min 100%B, 5.8-5 .82 minutes 100~5%B, 5.82~7.00 minutes 5%B

[0278] Method 7B Column: Waters UPLC® BEH™ C18, 2.1 mm x 10 0mm, 1.7μm column Column temperature: 40℃ Eluents: A: 2 mM ammonium bicarbonate buffered to pH 10, B: MeCN Flow rate: 0.6mL / min Gradient: 0-5.3.0 min 5-100%B, 5.3-5.8 min 100%B, 5.8-5 .82 minutes 100~5%B, 5.82~7.00 minutes 5%B

[0279] Method 8A Column: Acquity UPLC CSH C18 2.1 x 100 mm, 1.7 μm Column temperature: 50℃ Eluent: A: HO, B: MeCN, 0.1% formic acid Flow rate: 0.6mL / min Gradient: 0.5-6.5 min 2-98%B, 6.5-7.5 min 98%B

[0280] Method 8B Column: Acquity UPLC BEH C18 2.1 x 100 mm, 1.7 μm Column temperature: 50℃ Eluent: A: HO, B: MeCN, 0.1% ammonia Flow rate: 0.6mL / min Gradient: 0.5-6.5 min 2-98%B, 6.5-7.5 min 98%B

[0281] Method 15A Column: YMC-Triart C18 2 x 50 mm, 5 μm Flow rate: 0.8mL / min Eluent: A: H2O, B: MeCN, C: 50% H2O / 50% MeCN + 1.0% formic acid Gradient: 0.0–12.0 min 0–95% B, 5% C; 12.0–14.0 min 95% B, 5%C; 14.0~14.2 minutes 95%A, 5%B

[0282] Method 15B Column: YMC-Triart C18 50 x 2 mm, 5 μm Flow rate: 0.8mL / min Eluent: A: H2O, B: MeCN, C: 50% H2O / 50% MeCN + 1.0% ammonium hydroxide Monia (water-based) Gradient: 0.0–12.0 min 0–95% B, 5% C; 12.0–14.0 min 95% B, 5%C; 14.0~14.2 minutes 95%A, 5%B

[0283] Example 1 - 3-[5-amino-3-(4-pyridyl)pyrazolo[1,5-a]pyrimidine -2-yl]benzonitrile [ka] 3-(5-amino-3-bromo-)- Pyrazolo[1,5-a]pyrimidin-2-yl)benzonitrile (Intermediate E) (89 mg , 0.28 mmol), 4-pyridylboronic acid (52 mg, 0.42 mmol) and K2 A mixture of CO3 (78 mg, 0.57 mmol) was degassed under N2 flow. Bu3P2 (14 mg, 0.03 mmol) was added and the reaction mixture was heated to 120 °C (preheated bath). The mixture was heated to rt for 1 h, and the resulting mixture was cooled to room temperature and added dropwise to stirred water (50 mL). The precipitate was collected by filtration and purified by silica chromatography eluting with a gradient of 5-10% MeOH / DCM. The resulting material was triturated with MeOH (3 mL) and purified by HPLC. Subsequent trituration with EtOAc (5 mL) afforded the title compound as a beige solid. obtained. LC-MS (Method 15A): Rt5.14 min; MS m / z313.2=[M+H]+ 1 H NMR(500MHz,DMSO-d6)δ 8.62(d,J=7.5Hz,1 H),8.44(d,J=5.5Hz,2H),7.91(t,J=3.3Hz,2H) ,7.78(d,J=7.9Hz,1H),7.65(t,J=8.0Hz,1H),7 .40(d,J=5.2Hz,2H),7.25(s,2H),6.39(d,J=7. 5Hz, 1H).

[0284] The compounds of the examples shown in the following table (Table Ex1) were prepared by the reaction of 3-(5-amino-3-bromo-pyridinyl) (Iso[1,5-a]pyrimidin-2-yl)benzonitrile (Intermediate E) and the appropriate Prepared as in Example 1 from boronic acid or boronic ester.

[0285] [Table 1]

[0286] [Table 2]

[0287] [Table 3]

[0288] Example 2-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(2-hydro (2-methyl-propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl] Benzonitrile [ka] 3-[5-chloro-3-(2-chloro-6-methyl-4-pyridyl)methyl]propanol in NMP (15 mL) (1,5-a)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile (Intermediate C) (9 00mg, 2.37mmol), 1-amino-2-methyl-propan-2-ol (31 6 mg, 3.55 mmol) and DIPEA (2.06 mL, 11.83 mmol) The suspension was heated at 50° C. for 3 hours. After cooling to room temperature, the mixture was diluted with 90% brine solution (10 The organic layer was partitioned between 50% brine solution ( 3 x 50 mL), dried over MgSO4 and concentrated in vacuo. The crude material was purified by silica chromatography eluting with a gradient of 1000 mg / DCM to give a colorless solid. The title compound was obtained as a compound. LC-MS (Method 8B): Rt4.24 min; MS m / z431.2 / 433.2=[ MH]- 1 H NMR(500MHz,DMSO-d6)δ 8.57(d,J=7.6Hz,1 H),8.01-7.90(m,3H),7.83(d,J=7.8Hz,1H),7. 68(t,J=7.8Hz,1H),7.41(s,1H),7.27(s,1H),6 .61(d,J=7.6Hz,1H),4.63(s,1H),3.44(d,J=5. 8Hz, 2H), 2.33(s, 3H), 1.19(s, 6H).

[0289] The compounds of the examples shown in the following table (Table Ex2) were prepared by the reaction of 3-[5-chloro-3-(2-chloro- (6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzo Prepared analogously to Example 2 from the nitrile (Intermediate C) and the appropriate amine.

[0290] [Table 4]

[0291] [Table 5]

[0292] [Table 6]

[0293] [Table 7]

[0294] [Table 8]

[0295] [Table 9]

[0296] [Table 10]

[0297] [Table 11]

[0298] [Table 12]

[0299] [Table 13]

[0300] [Table 14]

[0301] [Table 15]

[0302] [Table 16]

[0303] Example 3-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(2R)- 2-hydroxypropyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile [ka] 3-[5-chloro-3-(2-chloro-6-methyl-4-pyridinyl)methyl]propanol in DMF (1 mL) 1,5-a-pyrimidin-2-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile (Intermediate C) (10 0 mg, 0.26 mmol) with (2R)-1-aminopropan-2-ol (0.08 mL, 1.05 mmol) was added and stirred at 60°C for 45 minutes. The mixture was cooled and added dropwise to stirred water (20 mL). EtOAc (50 mL) was added and the aqueous layer was separated. The organic layer was washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo. The crude material was purified by reversed-phase chromatography eluting with 40-50% MeCN / water (+0.1 wt% NH4OH). Purification was performed by chromatography followed by silica gel eluting with a gradient of 0-8% MeOH / DCM. Purification by column chromatography gave the title compound as a colorless solid. LC-MS (Method 15B): Rt7.23 min; MS m / z419.2 / 421.1= [M+H]+ 1 H NMR(500MHz,DMSO-d6)δ 8.59(d,J=7.5Hz,1 H),8.05(s,1H),8.00-7.94(m,2H),7.84(dt,J= 7.9,1.4Hz,1H),7.70(t,J=7.7Hz,1H),7.38(s, 1H),7.29(s,1H),6.53(d,J=7.6Hz,1H),4.83(d ,J=4.8Hz,1H),4.01-3.92(m,1H),3.56-3.45(m ,1H),3.22(dt,J=13.0,6.1Hz,1H),2.34(s,3H) ,1.16(d,J=6.2Hz,3H).

[0304] The compounds of the examples shown in the following table (Table Ex3) were prepared by the reaction of 3-[5-chloro-3-(2-chloro- (6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzo Prepared analogously to Example 3 from the nitrile (Intermediate C) and the appropriate amine.

[0305] [Table 17]

[0306] [Table 18]

[0307] Example 4-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4-piperidinyl) (amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile [ka] Step 1: tert-butyl 4-[[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]piperidine Lysine-1-carboxylate [ka] tert-Butyl 4-aminopiperidine-1-carboxylate (69 mg, 0.34 (0.06 mL, 0.34 mmol) in DMF (1 mL) and 3-[5-chloro-3-(2-chloro-6-methyl-4-pyridyl)pyrazolo[1,5 [-a]pyrimidin-2-yl]benzonitrile (Intermediate C) (100 mg, 0.26 mm ol) and stirred at 60°C overnight. After cooling to room temperature, the mixture was 20 mL) and the resulting precipitate was collected by filtration and washed with water (2 x 5 mL). The solid was azeotroped from acetone (20 ml) and 40-65% MeCN / water (+0.1 wt%). Purification by reverse phase eluting with a gradient of HCl (NH4OH) gave the title compound as a colorless solid. . LC-MS (Method 5B): Rt3.89 min; MS m / z544.2=[M+H]+ 1 H NMR(500MHz,DMSO-d6)δ 8.63(d,J=7.6Hz,1 H),8.03-7.93(m,3H),7.86(dt,J=8.0,1.5Hz,1 H),7.72(t,J=7.8Hz,1H),7.43(s,1H),7.30(s, 1H),6.45(d,J=7.6Hz,1H),4.06-3.94(m,3H),2 .97(br s,2H),2.36(s,3H),2.15-2.03(m,2H), 1.48-1.34(m,11H).

[0308] Step 2: 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4-piperidyl Amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile 4M HCl in 1,4-dioxane (0.55 mL, 2.19 mmol) was dissolved in MeO tert-Butyl 4-[[3-(2-chloro-6-methyl-4- Pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl ]amino]piperidine-1-carboxylate (Step 1) (119 mg, 0.22 mmol) The mixture was concentrated in vacuo and the resulting mixture was stirred at room temperature for 1 hour. Purification was performed by reverse phase elution with a gradient of 60% MeCN / water (+0.1% NH4OH by weight). , to give the title compound as a colorless solid. LC-MS (Method 8B): Rt4.78 min; MS m / z444.2 / 446.2=[M +H]+ 1 H NMR(500MHz,DMSO-d6)δ 8.58(d,J=7.6Hz,1 H),8.02-7.94(m,2H),7.92(d,J=6.8Hz,1H),7. 85(dt,J=7.9,1.5Hz,1H),7.70(t,J=7.8Hz,1H) ,7.45(s,1H),7.28(s,1H),6.43(d,J=7.6Hz,1H ),3.94-3.82(m,1H),3.07-2.97(m,2H),2.64-2 .55(m,2H),2.33(s,3H),2.06-1.96(m,2H),1.4 5-1.29 (m, 2H). No NH protons were observed.

[0309] The compounds of the examples shown in the following table (Table Ex4) were prepared by the reaction of 3-[5-chloro-3-(2-chloro- (6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzo Prepared analogously to Example 4 from the nitrile (Intermediate C) and the appropriate amine (Step 1), This was followed by deprotection using 4M HCl / dioxane (Step 2).

[0310] [Table 19]

[0311] [Table 20]

[0312] [Table 21]

[0313] [Table 22]

[0314] [Table 23]

[0315] [Table 24]

[0316] [Table 25]

[0317] Example 4.8-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R ,2S)-2,3-dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile [ka] Step 1-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-1 -[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]amino] Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile [ka] In the same manner as in Step 1 of Example 4, 3-[5-chloro-3-(2-chloro-6-methyl- 4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile (intermediate C) and (1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolane-4-yl] The title compound was prepared from methylethanamine. LC-MS (Method 5B): Rt3.84 min; MS m / z489.2 / 491.1=[ M+H]+ 1H NMR(500MHz,DMSO-d6)δ 8.60(d,J=7.6Hz,1 H),8.02-7.93(m,2H),7.89-7.80(m,2H),7.69( t,J=7.8Hz,1H),7.34(s,1H),7.31(s,1H),6.50 (d,J=7.6Hz,1H),4.29(s,2H),4.03(dd,J=8.2, 6.2Hz,1H),3.72(dd,J=8.2,6.2Hz,1H),2.35(s ,3H),1.36(s,3H),1.30(s,3H),1.21(d,J=6.0H z,3H).

[0318] Step 2-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S )-2,3-dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5-a]pi Rimidin-2-yl]benzonitrile 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[ [(1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]e [1,5-a]pyrimidin-2-yl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile (Step 1 ) (49.1 mg, 0.1000 mmol) was added to a suspension of 2 M aqueous HCl (0.5 m L, 1 mmol) was added, and the reaction mixture was stirred at room temperature for 16 hours. The mixture was partitioned between ethyl acetate (15 mL) and water (15 mL). The organic layer was separated, and the aqueous layer was diluted with ethyl acetate ( The combined organic layers were washed with brine (15 mL) and Dried over a2SO4, filtered and concentrated in vacuo. Gradient of 2-10% MeOH / DCM Purification by silica chromatography eluting with hexane gave the title compound as a white solid. . LC-MS (Method 8B): Rt4.06 min; MS m / z449.2 / 451.2=[ M+H]+ 1H NMR(500MHz,DMSO-d6)δ 8.56(d,J=7.6Hz,1 H),7.99-7.93(m,2H),7.83(d,J=8.1,1.5Hz,1H ),7.73-7.62(m,2H),7.38(s,1H),7.31(s,1H), 6.62(d,J=7.6Hz,1H),5.03(d,J=4.7Hz,1H),4. 56(t,J=5.5Hz,1H),4.40-4.26(m,1H),3.65-3. 54(m,1H),3.38(t,J=6.0Hz,2H),2.34(s,3H),1 .26(d,J=6.7Hz,3H).

[0319] Example 4.9-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S ,2S)-2,3-dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile [ka] Step 1-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-1 -[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]amino] Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile [ka] In the same manner as in Step 1 of Example 4, 3-[5-chloro-3-(2-chloro-6-methyl- 4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile (intermediate C) and (1S)-1-[(4S)-2,2-dimethyl-1,3-dioxolane-4-yl] The title compound was prepared from methylethanamine. LC-MS (Method 5B): Rt2.29 min; MS m / z489.4 / 491.1=[ M+H]+ 1H NMR(500MHz,DMSO-d6)δ 8.61(d,J=7.5Hz,1 H),8.00-7.93(m,2H),7.92(d,J=8.0Hz,1H),7. 83(d,J=8.0Hz,1H),7.69(t,J=7.8Hz,1H),7.34 (s,1H),7.28(s,1H),6.45(d,J=7.6Hz,1H),4.2 5(q,J=7.1Hz,1H),4.15(q,J=6.2Hz,1H),4.04( dd,J=8.4,6.5Hz,1H),3.85(dd,J=8.4,5.5Hz,1 H),2.34(s,3H),1.40(s,3H),1.30(s,3H),1.24 (d, J = 6.6 Hz, 3H).

[0320] Step 2-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S,2S )-2,3-dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5-a]pi Rimidin-2-yl]benzonitrile 3-[3-(2-chloro-6-methyl-4-pyridyl)-2-methylpropional]-4-pyridyl]-2-methylpropional was prepared in the same manner as in Step 2 of Example 4.8. (1S)-1-[(4S)-2,2-dimethyl-1,3-dioxolane -4-yl]ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzodi The title compound was prepared from tolyl (Step 1) and 2M aqueous HCl. LC-MS (Method 8B): Rt4.01 min; MS m / z449.2 / 451.2=[ M+H]+ 1H NMR(500MHz,DMSO-d6)δ 8.57(d,J=7.5Hz,1 H),8.00-7.93(m,2H),7.88-7.79(m,2H),7.70( t,J=7.7Hz,1H),7.44(s,1H),7.22(s,1H),6.52 (d,J=7.6Hz,1H),4.86(d,J=5.3Hz,1H),4.60(t ,J=5.4Hz,1H),4.30-4.17(m,1H),3.75-3.66(m ,1H),3.43(t,J=5.9Hz,2H),2.36(s,3H),1.18( d, J = 6.7 Hz, 3H).

[0321] Example 4.10-[5-[(2-amino-2-methyl-propyl)amino]-3-(2- Chloro-6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzyl Benzonitrile trifluoroacetate [ka] Step 1-tert-butyl N-[2-[[3-(2-chloro-6-methyl-4-pyridyl) )-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino ]-1,1-dimethyl-ethyl]carbamate: [ka] In the same manner as in Step 1 of Example 4, 3-[5-chloro-3-(2-chloro-6-methyl- 4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile (intermediate C) and tert-butyl N-(2-amino-1,1-dimethyl-ethyl)carbamate The title compound was prepared from LC-MS (Method 5B): Rt3.34 min; MS m / z530.3 / 532.3=[ MH]- 1H NMR(500MHz,DMSO-d6)δ 8.61(d,J=7.6Hz,1 H),8.02-7.92(m,3H),7.83(d,J=7.8Hz,1H),7. 70(t,J=7.8Hz,1H),7.41(s,1H),7.32(s,1H),6 .67(s,1H),6.57(d,J=7.6Hz,1H),3.65(d,J=6. 1Hz, 2H), 2.37 (s, 3H), 1.32-1.24 (m, 15H).

[0322] Step 2-[5-[(2-amino-2-methyl-propyl)amino]-3-(2-chloro- 6-Methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lythrifluacetate Trifluoroacetic acid (0.14 mL, 1.84 mmol) was dissolved in DCM (1 mL) rt-Butyl N-[2-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3 -cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-1,1- Dimethyl-ethyl]carbamate (Step 1) (65.4 mg, 0.1200 mmol) The mixture was concentrated in vacuo and then The solid residue was triturated with diethyl ether (2 mL) and acetonitrile (2 mL). This afforded the title compound as an off-white solid. LC-MS (Method 8B): Rt4.51 min; MS m / z432.2 / 434.2=[ MH]+ 1H NMR(500MHz,DMSO-d6)δ 8.69(d,J=7.6Hz,1 H),8.03(s,1H),7.99-7.94(m,2H),7.90(br s, 3H),7.84-7.78(m,1H),7.69(t,J=8.0Hz,1H),7 .34(s,1H),7.27(s,1H),6.55(d,J=7.7Hz,1H), 3.62(d,J=6.2Hz,2H),2.37(s,3H),1.33(s,6H) .

[0323] Example 4.11-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3- Hydroxyazetidin-3-yl)methylamino]pyrazolo[1,5-a]pyrimidine- 2-yl]benzonitrile trifluoroacetate [ka] Step 1-tert-butyl 3-[[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl ethyl]-3-hydroxy-azetidine-1-carboxylate [ka] In the same manner as in Step 1 of Example 4, 3-[5-chloro-3-(2-chloro-6-methyl- 4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile (intermediate C) and tert-butyl 3-(aminomethyl)-3-hydroxy-azetidine-1-carboxylate The title compound was prepared from the carboxylate. LC-MS (Method 5B): Rt3.15 min; MS m / z546.2=[M+H]+ 1 H NMR(500MHz,DMSO-d6)δ 8.62(d,J=7.5Hz,1 H),8.16-8.06(m,1H),8.01-7.92(m,2H),7.84( d,J=7.9Hz,1H),7.70(t,J=7.8Hz,1H),7.41(s, 1H),7.24(s,1H),6.57(d,J=7.6Hz,1H),6.07(s ,1H),3.91(s,2H),3.81-3.66(m,4H),2.35(s,3 H), 1.34(s,9H).

[0324] Step 2-3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy Thiazetidin-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl ]benzonitrile trifluoroacetate tert-Butyl 3-[[[3-(2-chloro- -6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pi Rimidin-5-yl]amino]methyl]-3-hydroxy-azetidine-1-carboxy The title compound was prepared from methyl ester (step 1) and TFA. LC-MS (Method 15B): Rt8.34 min; MS m / z446.1=[M+H]+ 1H NMR(500MHz,DMSO-d6)δ 8.84(s,1H),8.75- 8.60(m,2H),8.11(s,1H),8.02-7.91(m,2H),7. 81(d,J=7.9Hz,1H),7.69(t,J=7.9Hz,1H),7.33 (s,1H),7.26(s,1H),6.58(d,J=7.6Hz,1H),6.4 7(s,1H),4.12-4.00(m,2H),3.86(dd,J=11.4,5 .8Hz,2H),3.68(d,J=5.5Hz,2H),2.38(s,3H).

[0325] Example 5 - 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)- )-N-(3-hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5 -a]pyrimidine-5-carboxamide [ka] 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro ...3-chloro-4-pyridyl)-2-(3-chloro-4-pyridyl)-2-(3-chloro (aminophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylic acid (intermediate A) (50 A suspension of 1 mg (0.13 mmol) of 1000 mg ... DCM (1 mL) and HCl (0.38 mmol) were added dropwise and the mixture was stirred at room temperature for 5 minutes. Add oxalyl chloride (0.02 mL, 0.26 mmol) and refrigerate the mixture for an additional 5 min. After stirring, the resulting mixture was concentrated in vacuo to give the acid chloride.

[0326] 3-Aminobicyclo[1.1.1]pentan-1-ol hydrochloride in DCM (1 mL) (26 mg, 0.19 mmol) and DIPEA (89 μL, 0.51 mmol) To this was added dropwise a suspension of the acid chloride in DCM (1 mL) and the mixture was stirred for 45 min. 3-aminobicyclo[1.1.1]pentan-1-ol hydrochloride (9 mg, 0.06 The resulting mixture was diluted with HO (10 The aqueous solution was partitioned between DCM (2 mL) and DCM (10 mL) and the organic portion was separated. × 10 mL), and the combined organic extracts were washed with brine (10 mL) and The mixture was dried over gSO4 and the solvent was removed in vacuo. Elution was with a gradient of 0-2% MeOH / DCM Purification by silica chromatography gave the title compound as a yellow solid. LC-MS (Method 8B): Rt4.32 min; MS m / z471.2 / 473.1=[ M+H]+ 1 H NMR(500MHz,DMSO-d6)δ 9.41(d,J=7.2Hz,1 H),9.24(s,1H),8.05(s,1H),7.99(d,J=7.8Hz, 1H),7.87(d,J=7.8Hz,1H),7.71(t,J=7.8Hz,1H ),7.65(d,J=7.2Hz,1H),7.52(s,1H),7.33(s,1 H),6.30(s,1H),2.46(s,3H),2.18(s,6H).

[0327] The compounds of the examples shown in the following table (Table Ex5) were prepared by the reaction of 3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate Prepared in the same manner as in Example 5 from carboxylic acid (Intermediate A), oxalyl chloride and the appropriate amine. Made.

[0328] [Table 26]

[0329] [Table 27]

[0330] [Table 28]

[0331] Example 5.8-2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl) Pyrazolo[1,5-a]pyrimidine-5-carboxamide [ka] 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1 ,5-a]pyrimidine-5-carboxylic acid (Example 92, Step 2b) oxalyl chloride and water The title compound was prepared in a similar manner to Example 5 from ammonium oxide. LC-MS (Method 8B): Rt3.74 min; MS m / z369.2=[M+H]+ 1H NMR(500MHz,DMSO-d6)δ 9.37(d,J=7.2Hz,1 H),8.12(s,1H),8.04-8.00(m,1H),7.99-7.94( m,2H),7.86(d,J=7.9Hz,1H),7.71-7.65(m,2H) ,7.18(s,2H),2.41(s,6H).

[0332] Example 6 - 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)- )-N-[(1S)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5 -a]pyrimidine-5-carboxamide [ka] 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (aminophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylic acid (intermediate A) (40 mg, 0.10 mmol) and (3S)-3-amino-2-methyl-butan-2-ol A mixture of the hydrochloride (21 mg, 0.15 mmol) and DIPEA (89 μL, 0.51 m mol), followed by T3P® (50% in DMF) (0.14 mL, 0.21 The resulting mixture was stirred at room temperature for 1 hour. (10 mL) and water (10 mL). The layers were separated and the aqueous layer was diluted with EtOAc (2×10 The combined organic layers were washed with 50% brine (3 x 10 mL) and extracted with MgS The mixture was dried over O4, filtered, and concentrated in vacuo. Elution was performed with a gradient of 0-3% MeOH / DCM. Purification by silica chromatography gave the title compound as a yellow solid. LC-MS (Method 8B): Rt4.57 min; MS m / z475.2 / 477.2=[ M+H]+ 1 H NMR(500MHz,DMSO-d6)δ 9.45(d,J=7.1Hz,1 H),8.27(d,J=9.0Hz,1H),8.10(s,1H),8.02(d, J=7.8Hz,1H),7.93(d,J=8.0Hz,1H),7.77-7.69 (m,2H),7.55(s,1H),7.30(s,1H),4.73(s,1H), 3.95-3.83(m,1H),2.45(s,3H),1.22-1.13(m,9 H).

[0333] The compounds of the examples shown in the following table (Table Ex6) were prepared by the reaction of 3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate From carboxylic acid (Intermediate A), T3P®, DIPEA and the appropriate amine, Example Prepared in the same manner as in 6.

[0334] [Table 29]

[0335] [Table 30]

[0336] [Table 31]

[0337] [Table 32]

[0338] [Table 33]

[0339] [Table 34]

[0340] [Table 35]

[0341] [Table 36]

[0342] [Table 37]

[0343] [Table 38]

[0344] Example 7 - N-(3-amino-3-methyl-butyl)-3-(2-chloro-6-methyl- 4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5- Carboxamide [ka] Step 1-tert-butyl N-[3-[[3-(2-chloro-6-methyl-4-pyridyl) )-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl] Amino]-1,1-dimethyl-ethyl]carbamate [ka] 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazo [1,5-A]pyrimidine-5-carboxylic acid (intermediate A) (50 mg, 0.13 mmol) l), T3P® (50 wt% in EtOAc) (91 μL, 0.26 mmol ), DIPEA (112 μL, 0.64 mmol) and tert-butyl N-(3-aminopropyl) (1,1-dimethyl-propyl)carbamate (38.92 mg, 0.19 mmol) A solution of this in DMF (1 mL) was stirred at 60°C for 4 hours. The mixture was diluted with water (5 mL) and the resulting The precipitate was collected by vacuum filtration. The solid was dissolved in DCM (20 ml) and subjected to phase separation. Filtration through a cartridge and concentration in vacuo gave the title compound as a yellow solid. LC-MS (Method 2A): Rt1.37 min; MS m / z574.3 / 576.3=[ M+H]+ 1H NMR(400MHz,DMSO-d6)δ 9.41(d,J=7.2Hz,1 H),8.70(t,J=5.8Hz,1H),8.06(t,J=1.4Hz,1H) ,8.00(dt,J=7.7,1.3Hz,1H),7.88(dt,J=7.9,1 .3Hz,1H),7.73(t,J=7.8Hz,1H),7.69(d,J=7.2 Hz,1H),7.51(s,1H),7.32(s,1H),6.43(s,1H), 2.47(s,3H),1.91(t,J=7.5Hz,2H),1.35(s,9H) , 1.24 (s, 6H). HSQC shows 1×CH2 silicide under the water peak. Gunnar.

[0345] Step 2: N-(3-amino-3-methyl-butyl)-3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate Ruboxamide tert-Butyl N-[3-[[3-(2-chloro-6-methyl) -4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5 -carbonyl]amino]-1,1-dimethyl-propyl]carbamate (Step 1) (62 mg, 0.10 mmol) and 4M in 1,4-dioxane (251 μL, 1 mmol). The solution of HCl was stirred at room temperature for 18 hours. The resulting mixture was concentrated in vacuo and then 1g Isolute® SCX cartridge eluted with 7M NH3 in MeOH The filtrate was concentrated in vacuo and lyophilized to give the title compound as a yellow powder. I got something. LC-MS (Method 7A): Rt2.09 min; MS m / z474.2 / 476.2=[ M+H]+ 1 H NMR(500MHz,DMSO-d6)δ 9.57-9.51(m,1H), 9.41(d,J=7.2Hz,1H),8.06(t,J=1.4Hz,1H),8. 00(dt,J=7.8,1.3Hz,1H),7.87(dt,J=7.9,1.3H z,1H),7.75-7.68(m,2H),7.38(d,J=12.1Hz,2H ),3.45(q,J=6.4Hz,2H),2.44(s,3H),1.61(t,J = 6.8 Hz, 2H), 1.12 (s, 6H). No NH2 protons were observed.

[0346] The compounds of the examples shown in the following table (Table Ex7) were prepared by the reaction of 3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate From carboxylic acid (Intermediate A), T3P®, DIPEA and the appropriate amine, Example Prepared similarly to 7 (step 1) followed by 4M HCl in 1,4-dioxane and deprotected (Step 2).

[0347] [Table 39]

[0348] [Table 40]

[0349] [Table 41]

[0350] [Table 42]

[0351] Table 43

[0352] Table 44

[0353] Table 45

[0354] Table 46

[0355] Table 47

[0356] Table 48

[0357] Table 49

[0358] Table 50

[0359] Table 51

[0360] Table 52

[0361] Table 53

[0362] [Table 54]

[0363] [Table 55]

[0364] Example 7.19-3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl) (phenyl)-N-[(1S,2S)-2,3-dihydroxy-1-methyl-propyl]pyra Zolo[1,5-a]pyrimidine-5-carboxamide [ka] Step 1: 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) -N-[(1S)-1-[(4S)-2,2-dimethyl-1,3-dioxolane-4-yl] [1,5-a]pyrimidine-5-carboxamide [ka] 3-(2-chloro-6-methyl-4-pyridyl)-2-(2-chloro-6-methyl-4-pyridyl)-2-methylpropional was prepared in the same manner as in Step 1 of Example 7. -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylic acid (intermediate A) and (1S)-1-[(4S)-2,2-dimethyl-1,3-dioxolane-4-yl] The title compound was prepared from methylethanamine. LC-MS (Method 5B): Rt3.08 min; MS m / z517.2 / 519.2=[ M+H]+ 1H NMR(500MHz,DMSO-d6)δ 9.44(d,J=7.2Hz,1 H),8.50(d,J=8.8Hz,1H),8.09(s,1H),8.01(d, J=7.9Hz,1H),7.91(d,J=7.9Hz,1H),7.73(t,J= 7.9Hz,1H),7.70(d,J=7.2Hz,1H),7.54(s,1H), 7.33(s,1H),4.23-4.17(m,1H),4.14-4.08(m,1 H),4.03(dd,J=8.7,6.6Hz,1H),3.90(dd,J=8.7 ,5.3Hz,1H),2.46(s,3H),1.33-1.20(m,9H)

[0365] Step 2-3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) -N-[(1S,2S)-2,3-dihydroxy-1-methyl-propyl]pyrazolo[1 ,5-a]pyrimidine-5-carboxamide 3-(2-chloro-6-methyl-4-pyridyl) -2-(3-cyanophenyl)-N-[(1S)-1-[(4S)-2,2-dimethyl- 1,3-dioxolan-4-yl]ethyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate The title compound was prepared from ruboxamide (Step 1) and 2M aqueous HCl. LC-MS (Method 8B): Rt3.99 min; MS m / z477.2=[M+H]+ 1H NMR(500MHz,DMSO-d6)δ 9.44(d,J=7.2Hz,1 H),8.57(d,J=8.8Hz,1H),8.09(t,J=1.7Hz,1H) ,8.01(dt,J=7.8,1.4Hz,1H),7.91(dt,J=8.1,1 .4Hz,1H),7.77-7.71(m,2H),7.58(s,1H),7.25 (s,1H),5.02(d,J=5.2Hz,1H),4.73(t,J=5.5Hz ,1H),4.20-4.10(m,1H),3.65-3.57(m,1H),3.5 3-3.47(m,1H),3.44-3.39(m,1H),2.47(s,3H), 1.15(d,J=6.7Hz,3H).

[0366] Example 8 - 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-hydroxybenzoyl) (1-methyl-ethyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile L [ka] Step 1: 3-[3-bromo-5-(1-hydroxy-1-methyl-ethyl)pyrazolo[1 ,5-a]pyrimidin-2-yl]benzonitrile [ka] Ethyl 3-bromo-2-(3-cyanophenyl)pyrazolo[ 1,5-a]pyrimidine-5-carboxylate (Intermediate A5) (96 mg, 0.26 m To a mixture of MeMgCl (3 M in THF) (0.2 mL, 0.60 mmol The resulting mixture was diluted with DCM (40 mL). The organic phase was dried over MgSO4 and concentrated in vacuo. The mixture was concentrated under reduced pressure and chromatographed on silica eluting with a gradient of 0-2% MeOH / DCM. Further purification gave the title compound as a colorless solid. LC-MS (Method 5B): Rt3.80 min; MS m / z357.0 / 359.0=[ M+H]+ 1H NMR(500MHz,DMSO-d6)δ 9.16(d,J=7.2Hz,1 H),8.39-8.36(m,1H),8.35-8.30(m,1H),8.01- 7.98(m,1H),7.79(t,J=7.9Hz,1H),7.46(d,J=7 .2Hz,1H),5.61(s,1H),1.52(s,6H).

[0367] Step 2: 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-hydroxy (1-methyl-ethyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile 3-(3-bromo-5-( 1-hydroxy-1-methyl-ethyl)pyrazolo[1,5-a]pyrimidin-2-yl) Benzonitrile (Step 1) (65 mg, 0.18 mmol), 2-chloro-6-methyl- 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine of gin (62 mg, 0.24 mmol) and K2CO3 (75 mg, 0.55 mmol). The mixture was degassed under N flow. Pd(tBuP) (9 mg, 0.02 mmol) ) was added and the reaction mixture was heated to 80° C. for 15 minutes. The resulting mixture was cooled to room temperature and (30 mL) and extracted with DCM (2 x 30 mL). The organic extract was dried over MgSO4. The mixture was dried and concentrated in vacuo. followed by a gradient of 40–80% MeCN / water (+0.1 wt% NH4OH). Purify by C18 reverse phase chromatography eluting with 0-10% MeOH / DCM. A final re-purification on gradient eluted silica gave the title compound as a colorless solid. Got it. LC-MS (Method 15B): Rt7.79 min; MS m / z404.1 / 406.0= [M+H]+ 1H NMR(500MHz,DMSO-d6)δ 9.23(d,J=7.3Hz,1 H),8.05(s,1H),8.00(d,J=7.7Hz,1H),7.89(d, J=7.8Hz,1H),7.72(t,J=7.8Hz,1H),7.52(d,J= 7.3Hz,1H),7.42(s,1H),7.35(s,1H),5.64(s,1 H), 2.39(s,3H), 1.54(s,6H).

[0368] Example 9 (= Intermediate A) -3-(2-chloro-6-methyl-4-pyridyl)-2-(3- Cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylic acid [ka] A solution of lithium hydroxide (273 mg, 11.42 mmol) in water (20 mL) was added to 1,4 -ethyl 3-(2-chloro-6-methyl-4-pyridyl)- in dioxane (50 mL) 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate Add to a stirred partial suspension of (Intermediate A6) (1.59 g, 3.81 mmol) and react The mixture was stirred at room temperature for 1 h. The resulting mixture was diluted with H2O (100 mL) and Et2O (1 The organic fraction was removed and the aqueous portion was acidified with 2M HCl. The resulting solid was collected by filtration and azeotroped from MeOH (x2) to give a yellow solid. The title compound was obtained. LC-MS (Method 3B): Rt1.09 min; MS m / z390.1=[M+H]+ 1H NMR(500MHz,DMSO-d6)δ 9.37(d,J=7.2Hz,1 H),8.06(s,1H),7.99(d,J=7.8Hz,1H),7.87(d, J=7.8Hz,1H),7.71(t,J=7.8Hz,1H),7.66(d,J= 7.2Hz,1H),7.43(s,1H),7.33(s,1H),2.42(s,3 H).OH protons were not observed.

[0369] Example 10 - 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)- N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5 -Carboxamide [ka] 3-Bromo-2-(3-chloro-2-methylpropional) in 1,4-dioxane (2 mL) and water (0.40 mL) (aminophenyl)-N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a ] Solution of pyrimidine-5-carboxamide (Intermediate B) (85 mg, 0.21 mmol) The mixture was degassed with N2 and (2,6-dimethyl-4-pyridyl)boronic acid (46 mg, 0.31 m mol), K2CO3 (57 mg, 0.41 mmol) and Pd(tBu3P)2 (5 m g, 0.01 mmol). The resulting mixture was heated to 50°C for 1 hour. (2,6-Dimethyl-4-pyridyl)boronic acid (46 mg, 0.31 mmol), K2C O3 (57 mg, 0.41 mmol) and Pd(tBu3P)2 (5 mg, 0.01 mmol) ol) was added and the reaction mixture was heated to 50° C. for an additional hour. -4-pyridyl)boronic acid (46 mg, 0.31 mmol) in two doses at 30-minute intervals. The reaction mixture was heated to 50° C. for an additional 30 minutes. (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (48mg, 0.21mmol), Pd(tBu3P)2 (5mg, 0.01mmol) and a solution of K2CO3 (57 mg, 0.41 mmol) in water (0.2 mL) was added, and the mixture The mixture was heated to 50° C. for an additional hour, after which the reaction was cooled to room temperature. Partition between 20 mL (15 mL) and EtOAc (20 mL), separate the organic po...

Claims

1. A compound having the structural formula Ia shown below, or a pharmaceutically acceptable salt thereof: 【Chemistry 1】 [In the formula, R ０ is hydrogen or deuterium; R １ is selected from aryl or heteroaryl (where R １ is (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4 C) haloalkoxy, cyano, (CH ２ ) ｑ１ NR １Ｂ R １Ｃ , (CH ２ ) ｑ１ OR １Ｂ 、(CH ２ ) ｑ１ C(O)R １Ｂ 、(CH ２ ) ｑ１ C(O)OR １Ｂ 、(CH ２ ) ｑ１ O C(O)R １Ｂ 、(CH ２ ) ｑ１ C(O)N(R １Ｃ )R １Ｂ 、(CH ２ ) ｑ１ N(R １ Ｃ ) C(O)R １Ｂ , (CH ２ ) ｑ１ S (O) ｐ R １Ｂ (where p is 0, 1 or 2) There is), (CH ２ ) ｑ１ SO ２ N (R １Ｃ ) R １Ｂ or (CH ２ ) ｑ１ N (R １Ｃ ) SO ２ R １Ｂ one or more R independently selected from １ｚ may be substituted with a substituent, q1 is 0, 1, 2 or 3, R １Ｂ and R １Ｃ are each independently hydrogen, (1 -4C) alkyl, (3-6C) cycloalkyl or (3-6C) cycloalkyl(1- 2C) selected from alkyl); R ２ is hydrogen, cyano, halo, (1-4C) alkyl, (1-4C) haloalkyl, C( O) OR ２Ａ , C(O)NR ２Ａ R ２Ｂ , aryl, heteroaryl, (2-6C) aryl alkynyl, (2-6C)alkynyl or (1-4C)alkanoyl (where R ２Ａ and R ２Ｂ are each independently hydrogen, (1-4C) alkyl, (1 -4C)alkoxy, (3-6C)cycloalkyl or (3-6C)cycloalkyl (1-2C) alkyl; or CONR ２Ａ R ２Ｂ In the group, R ２Ａ and R ２Ｂ are the nitrogen atoms to which they are bonded. are linked together to form a heterocycle, Any alkyl, alkenyl, alkynyl, alkanoyl, aryl, heteroaryl or is a heterocyclyl group (R ２Ａ and R ２Ｂ is formed by (1-4C) aluminum alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, amino, (1- 4C) aminoalkyl, cyano, (CH ２ ) ｑ２ NR ２Ｄ R ２Ｅ , (CH ２ ) ｑ２ OR ２ Ｄ 、(CH ２ ) ｑ２ C(O)R ２Ｄ 、(CH ２ ) ｑ２ C(O)OR ２Ｄ 、(CH ２ ) ｑ２ OC(O)R ２Ｄ 、(CH ２ )q ２ C(O)N(R ２Ｅ )R ２Ｄ 、(CH ２ ) ｑ２ N(R ２Ｅ ) C(O)R ２Ｄ , (CH ２ ) ｑ２ S (O) ｐ R ２Ｄ (where p is 0, 1 or 2) (CH ２ ) ｑ２ SO ２ N (R ２Ｅ ) R ２Ｄ or (CH ２ ) ｑ２ N (R ２Ｅ ) S O ２ R ２Ｄ and q 2 is 0, 1, 2 or 3; R ２Ｄ and R ２Ｅ are each independently hydrogen, (1 to 4C) alkyl, (3-6C) cycloalkyl or (3-6C) cycloalkyl(1-2 C) alkyl); R ３ is hydrogen, halo, cyano or the formula: -L-Y-L ｑ -Q (In the formula, L is absent or one or more selected from (1-2C) alkyl or oxo. is (1-4C) alkylene optionally substituted by a substituent of Y is absent or O, S, SO, SO ２ , N(R ａ ), C(O), C(O)O, OC(O)、C(O)N(R ａ )、C(O)N(R ａ )O、N(R ａ )C(O)、N(R ａ )C(O)N(R ｂ )、N(R ａ )C(O)O、OC(O)N(R ａ )、C(=NR ｙ )N(R ａ )、N(R ａ )C(=NR ｙ )、N(R ａ )C(=NR ｙ )N(R ｂ )、S( O) ２ N (R ａ ), N(R ａ ) SO ２ , N(R ａ ) SO ２ N (R ｂ ) or C(O)N (R ａ ) SO ２ (where R ａ and R ｂ are each independently hydrogen or (1 to 4 C) alkyl, R ｙ is hydrogen, (1-4C) alkyl, nitro or cyano selected from L ｑ is absent or is selected from (1-2C)alkoxy, halo, cyano, amino or o and (1-4C) alkylene optionally substituted with one or more substituents selected from oxo and oxo. can be, Q is hydrogen, (1-6C) alkyl, (2-6C) alkenyl, (2-6C) alkynyl , aryl, (3-8)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl aryl or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( (1-4C) haloalkoxy, (1-4C) aminoalkyl, (1-4C) hydroxyalkanol Kill, Cyano, NR ｃ R ｄ , OR ｃ , C(O)R ｃ , C(O)OR ｃ , O.C.(O.)R ｃ , C(O)N(R ｄ ) R ｃ , N(R ｄ ) C(O)R ｃ , S(O) ｐ R ｃ (where p is 0 , 1 or 2), SO ２ N (R ｄ ) R ｃ , N(R ｄ ) SO ２ R ｃ Or (CH ２ ) ｑ NR ｃ R ｄ (wherein q is 1, 2, or 3) may be further substituted with a substituent (wherein R ｃ , R ｄ and R ｅ are independent of each other. and hydrogen, (1-6C) alkyl, (3-6C) cycloalkyl or (3-6C) cycloalkyl. chloroalkyl(1-2C)alkyl; or R ｃ and R ｄ together with the nitrogen atom to which they are attached represent (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, ( 1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino, cyano or or 4- to 7-membered heterocyclic rings optionally substituted with one or more substituents selected from the group consisting of hydroxyl, linked to form a ring), and / or Q is a group of the formula: -L １ -L Ｑ１ -W １ (In the formula, L １ is absent or is one or more selected from (1-2C) alkyl or oxo (1-3C) alkylene optionally substituted by the above substituents, L Ｑ１ is not present or O, S, SO, SO ２ , N(R ｆ ), C(O), C(O) O、OC(O)、C(O)N(R ｆ )、N(R ｆ )C(O)、N(R ｆ )C(O)N(R ｇ )、N(R ｆ )C(O)O、OC(O)N(R ｆ )、S(O) ２ N(R ｆ )、N(R ｆ ) SO ２ is selected from ｆ and R ｇ are each independently hydrogen or (1 to 2 C) alkyl), W １ is hydrogen, (1-6C) alkyl, aryl, aryl(1-2C) alkyl, (3 3-8C) cycloalkyl, (3-8C) cycloalkenyl, heteroaryl or heterocyclo Krill (where W １ is oxo, (1-4C) alkyl, halo, (1-4C) halo (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)alkoxy, (1-4C)alkenyl alkylamino, cyano, aryl, heteroaryl, heterocyclyl, (3-6C)cyclo Alkyl, NR ｈ R ｉ , OR ｈ , C(O)R ｈ , C(O)OR ｈ , O.C.(O.)R ｈ , C( O)N(R ｉ ) R ｈ , N(R ｉ ) C(O)R ｈ , S(O) ｒ R ｈ (where r is 0, 1 or 2), SO ２ N (R ｉ ) R ｈ , N(R ｉ ) SO ２ R ｈ or (CH ２ ) ｓ NR ｉ R ｈ (wherein s is 1, 2, or 3) It may be R ｈ and R ｉ are each independently hydrogen, (1-4C) alkyl, (3 -6C)cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl And, W １ Any alkyl, alkoxy, aryl, heteroaryl, or heteroaryl group in the substituents The terecyclyl or cycloalkyl moiety may be one or more of halo, (1-4C) alkyl, (1 (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy, (1- 4C) alkylamino, di-[(1-4C)alkyl]amino, amino, cyano or hydroxy may be further substituted by an alkoxy group, or R ｈ and R ｉ together with the nitrogen atom to which they are attached, represent oxo, (1-4C) alkyl , halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, (1-4C) alkoxy oxy, (1-4C) alkylamino, di-[(1-4C) alkyl]amino, amino, silyl 4- to 7-membered alkyl groups optionally substituted with one or more substituents selected from benzoate, benzophenone, benzotriazole ... linked to form a heterocycle) and optionally substituted with one or more groups of is selected from the group A is CR ４ and N (where R ４ is hydrogen, halo, or halo, (1-4C) haloalkyl, (1-4C) halo alkoxy, (1-4C)aminoalkyl, cyano, (CH ２ ) ｑａ NR ４Ａ R ４Ｂ , (CH ２ ) ｑａ OR ４Ａ 、(CH ２ ) ｑａ C(O)R ｃ４Ａ 、(CH ２ ) ｑａ C(O)O R ４Ａ 、(CH ２ ) ｑａ OC(O)R ４Ａ 、(CH ２ ) ｑａ C(O)N(R ４Ｂ )R ４Ａ , (CH ２ ) ｑａ N (R ４Ｂ ) C(O)R ４Ａ , (CH ２ ) ｑａ S (O) ｐ R ４Ａ (here and p is 0, 1 or 2), (CH ２ ) ｑａ SO ２ N (R ４Ｂ ) R ４Ａ Or ( CH ２ ) ｑａ N (R ４Ｂ ) SO ２ R ４Ａ substituted with one or more substituents selected from optionally (1-4C) alkyl, qa is 0, 1, 2 or 3, R ４Ａ and R ４Ｂ are each independently hydrogen, (1-6C) alkyl, or (3-6C) cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl); Any tertiary amine in the compounds of formula I may be in the form of an N-oxide, and the pyridyl ring the nitrogen atom in may be in the form of an N-oxide; Any S atom present in the heterocycle may be S(=O), S(=O) ２ Or S(=O)( =NR ｚ ) (where R ｚ is hydrogen, (1-3C) alkyl or (2-3C) alkanoyl The hydroxybenzoates may be present as a group selected from the group consisting of hydroxybenzoates, ...

2. R １ is selected from aryl or heteroaryl, where R １ (1-4C) Alkyl, halo, (1-4C) haloalkyl, (1-4C) haloalkoxy, cyano, ( CH ２ ) ｑ１ NR １Ｂ R １Ｃ 、OR １Ｂ 、C(O)R １Ｂ 、C(O)OR １Ｂ 、OC(O )R １Ｂ 、C(O)N(R １Ｃ )R １Ｂ 、N(R １Ｃ )C(O)R １Ｂ 、S(O) ｐ R １ Ｂ (wherein p is 0, 1 or 2), SO ２ N (R １Ｃ ) R １Ｂ or N(R １Ｃ ) SO ２ R １Ｂ one or more R independently selected from １ｚ may be substituted with a substituent, q1 is 0, 1 or 2; R １Ｂ and R １Ｃ are each independently hydrogen, (1-4C) alkyl, (3-6C) cyclohexyl cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl), 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof.

3. R １ is selected from aryl or heteroaryl, where R １ (1-2C) Alkyl, halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, cyano, ( CH ２ ) ｑ１ NR １Ｂ R １Ｃ 、OR １Ｂ 、C(O)R １Ｂ 、C(O)OR １Ｂ 、OC(O )R １Ｂ 、C(O)N(R １Ｃ )R １Ｂ 、N(R １Ｃ )C(O)R １Ｂ 、S(O) ｐ R １ Ｂ (wherein p is 0, 1 or 2), SO ２ N (R １Ｃ ) R １Ｂ or N(R １Ｃ ) S O ２ R １Ｂ one or more R independently selected from １ｚ may be substituted with a substituent, q1 is 0, 1 or 2; R １Ｂ and R １Ｃ are each independently hydrogen, (1-2C) alkyl or (3-4C) cycloalkyl) 3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof.

4. R １ is selected from phenyl, furyl, pyridyl or oxazolyl, where phenyl The nyl, furyl, pyridyl or oxazolyl ring is optionally substituted with halo, (1-2C) alkyl, (1-2C) aryl ... C) optionally substituted with one or more of alkoxy or cyano), The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof.

5. R １ is selected from phenyl, furyl, pyridyl or oxazolyl, where phenyl The yl, furyl, pyridyl or oxazolyl ring is substituted by halo or cyano.

5. The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

6. R １ is 3-cyanophenyl; or and pharmaceutically acceptable salts thereof.

7. R ２ is hydrogen, cyano, halo, (1-4C) alkyl, (1-4C) haloalkyl, C (O) OR ２Ａ , C(O)NR ２Ａ R ２Ｂ , aryl, heteroaryl, (2-6C) a alkenyl, (2-6C)alkynyl or (1-4C)alkanoyl (where R ２Ａ and R ２Ｂ are each independently hydrogen, (1-4C) alkyl, (1 -4C)alkoxy, (3-6C)cycloalkyl or (3-6C)cycloalkyl (1-2C) alkyl; or CONR ２Ａ R ２Ｂ In the group, R ２Ａ and R ２Ｂ are the nitrogen atoms to which they are bonded. are linked together to form a 4- to 7-membered heterocycle; Any alkyl, alkenyl, alkynyl, alkanoyl, aryl, heteroaryl or is a heterocyclyl group (R ２Ａ and R ２Ｂ is formed by (1-4C) aluminum alkyl, halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, cyano, (CH ２ ) ｑ２ NR ２Ｄ R ２Ｅ 、(CH ２ ) ｑ２ OR ２Ｄ 、(CH ２ ) ｑ２ C(O)R ２Ｄ 、( CH ２ ) ｑ２ C(O)OR ２Ｄ 、(CH ２ ) ｑ２ OC(O)R ２Ｄ 、(CH ２ ) ｑ２ C( O)N(R ２Ｅ )R ２Ｄ 、(CH ２ ) ｑ２ N(R ２Ｅ )C(O)R １２Ｄ 、(CH ２ ) ｑ ２ S (O) ｐ R ２Ｄ (wherein p is 0, 1 or 2), (CH ２ ) ｑ２ SO ２ N ( R ２Ｅ ) R ２Ｄ or (CH ２ ) ｑ２ N (R ２Ｅ ) SO ２ R ２Ｄ 1 independently selected from may be substituted by one or more substituents, q2 is 0, 1 or 2; R ２Ｄ and R ２Ｅ are each independently hydrogen, (1-2C) alkyl, (3-4C) cyclohexyl cycloalkyl or (3-4C)cycloalkyl(1-2C)alkyl), The compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof.

8. R ２ is cyano, halo, methyl, CF ３ , C(O)OR ２Ａ , C(O)NR ２Ａ R ２Ｂ , 5- or 6-membered heteroaryl or (2-4C)alkanoyl (where R ２Ａ and R ２Ｂ each independently represents hydrogen or (1-4C) alkyl; Selected, Any heteroaryl group can be (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2C) haloalkoxy, cyano, (CH ２ ) ｑ２ NR ２Ｄ R ２Ｅ , OR ２Ｄ , C( O)R ２Ｄ 、C(O)OR ２Ｄ 、OC(O)R ２Ｄ 、C(O)N(R ２Ｅ )R ２Ｄ 、N( R ２Ｅ ) C(O)R １２Ｄ , S(O) ｐ R ２Ｄ where p is 0, 1 or 2; SO ２ N (R ２Ｅ ) R ２Ｄ or N(R ２Ｅ ) SO ２ R ２Ｄ one or more independently selected from q2 is 0 or 1, and R ２Ｄ and R ２Ｅ are each independently selected from hydrogen or (1-2C) alkyl; The compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof.

9. R ２ is cyano or substituted as defined above in claim 7 or 8.

10. The compound according to claim 1, wherein the aryl is selected from the group consisting of 5- and 6-membered heteroaryls. Item 1. The compound according to item 1, or a pharmaceutically acceptable salt thereof.

10. R ２ is a cyano, or 【Chemistry 2】 (In the formula, (i) R ２００ and R ２０１ are each independently (1-2C) alkyl, halo, (1 (1-2C) haloalkyl, (1-2C) hydroxyalkyl, (1-2C) alkoxy, ( (1-2C) selected from haloalkoxy, (1-2C)alkanoyl, or cyano; (ii) R ２００ and R ２０１ are each independently methyl, hydroxymethyl, halo , difluoromethyl, trifluoromethyl, methoxy, acetyl or cyano will be (iii) R ２００ is methyl or chloro, R ２０１ is methyl, hydroxy Methyl, halo, difluoromethyl, trifluoromethyl, methoxy, acetyl or chloromethyl (selected from Ano) or 【Transformation 3】 (In the formula, (i) R ２０１ is (1-2C) alkyl, halo, (1-2C) haloalkyl, (1-2 C) hydroxyalkyl (1-2C) alkoxy, (1-2C) haloalkoxy, (1- 2C) alkanoyl or cyano; (ii) R ２０１ is methyl, hydroxymethyl, halo, difluoromethyl, trifluoro methyl, methoxy, acetyl or cyano; (iii) R ２０１ is methyl, hydroxymethyl or chloro; (iv) R ２０１ is methyl; (v) R ２０１ is chloro) is selected from the group Optionally, R ２ is cyano or 2-chloro-6-methylpyridin-4-yl or 2 , 6-dimethylpyridin-4-yl; The compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof.

11. R ３ is hydrogen, halo, cyano or the formula: -L-Y-L ｑ -Q (In the formula, L is absent or (1-4C)alkylene; Y is absent or O, S, SO, SO ２ , N(R ａ ), C(O), C(O)O, OC(O)、C(O)N(R ａ )、C(O)N(R ａ )O、N(R ａ )C(O)、N(R ａ )C(O)N(R ｂ )、N(R ａ )C(O)O、OC(O)N(R ａ )、C(=NR ｙ )N(R ａ )、N(R ａ )C(=NR ｙ )、N(R ａ )C(=NR ｙ )N(R ｂ )、S( O) ２ N (R ａ ), N(R ａ ) SO ２ , C(O)N(R ａ ) SO ２ Or N(R ａ ) S O ２ N (R ｂ ) where R ａ and R ｂ are each independently hydrogen or (1 to 4 C) alkyl, R ｙ is hydrogen, (1-4C) alkyl, nitro or cyano selected from L ｑ is absent or is selected from (1-2C)alkoxy, halo, cyano, amino or o and (1-4C) alkylene optionally substituted with one or more substituents selected from oxo and oxo. can be, Q is hydrogen, (1-6C) alkyl, (2-6C) alkenyl, (2-6C) alkynyl , aryl, (3-8)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl aryl or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( (1-4C) haloalkoxy, (1-4C) aminoalkyl, (1-4C) hydroxyalkanol Kill, Cyano, NR ｃ R ｄ , OR ｃ , C(O)R ｃ , C(O)OR ｃ , O.C.(O.)R ｃ , C(O)N(R ｄ ) R ｃ , N(R ｄ ) C(O)R ｃ , S(O) ｐ R ｃ (where p is 0 , 1 or 2), SO ２ N (R ｄ ) R ｃ , N(R ｄ ) SO ２ R ｃ or (CH ２ ) ｑ N R ｃ R ｄ (wherein q is 1, 2, or 3) may be further substituted with a group (wherein R ｃ and R ｄ are each independently hydrogen, (1-6C) alkyl, (3-6C) cycloalkyl or (3-6C) cycloalkoxy aryl(1-2C)alkyl), and / or Q is a group of the formula: -L １ -L Ｑ１ -W １ (In the formula, L １ is absent or is (1-3C) alkylene, L Ｑ１ is not present or O, S, SO, SO ２ , N(R ｆ ), C(O), C(O) O、OC(O)、C(O)N(R ｆ )、N(R ｆ )C(O)、N(R ｆ )C(O)N(R ｇ )、N(R ｆ )C(O)O、OC(O)N(R ｆ )、S(O) ２ N(R ｆ )、N(R ｆ ) SO ２ is selected from ｆ and R ｇ are each independently hydrogen or (1 to 2 C) alkyl), W １ is hydrogen, (1-6C) alkyl, aryl, aryl(1-2C) alkyl, (3 3-8C) cycloalkyl, (3-8C) cycloalkenyl, heteroaryl or heterocyclo Krill (where W １ is oxo, (1-4C) alkyl, halo, (1-4C) halo (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)alkoxy, (1-4C)alkenyl alkylamino, cyano, aryl, heteroaryl, heterocyclyl, (3-6C)cyclo Alkyl, NR ｈ R ｉ , OR ｈ , C(O)R ｈ , C(O)OR ｈ , O.C.(O.)R ｈ , C( O)N(R ｉ ) R ｈ , N(R ｉ ) C(O)R ｈ , S(O) ｒ R ｈ (where r is 0, 1 or 2), SO ２ N (R ｉ ) R ｈ , N(R ｉ ) SO ２ R ｈ or (CH ２ ) ｓ NR ｉ R ｈ (wherein s is 1, 2, or 3) It may be R ｈ and R ｉ are each independently hydrogen, (1-4C) alkyl, (3 -6C)cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl It will be) and optionally substituted with one or more groups of is selected from the group R ３ Any tertiary amine in the group or nitrogen atom in the pyridyl ring may be in the form of an N-oxide. That's fine, The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof.

12. R ３ is hydrogen, halo, cyano or the formula: -L-Y-L ｑ -Q (In the formula, L is absent or (1-2C)alkylene; Y is absent or O, N(R ａ ), C(O), C(O)O, C(O)N(R ａ ) 、C(O)N(R ａ )O、N(R ａ )C(O)、N(R ａ )C(O)N(R ｂ )、N(R ａ )C(O)O、OC(O)N(R ａ )、C(=NR ｙ )N(R ａ )、N(R ａ )C(= NR ｙ )、N(R ａ )C(=NR ｙ )N(R ｂ )、S(O) ２ N(R ａ )、N(R ａ )S O ２ , C(O)N(R ａ ) SO ２ Or N(R ａ ) SO ２ N (R ｂ ) (where: R ａ and R ｂ are each independently selected from hydrogen or (1-4C) alkyl; R ｙ is selected from hydrogen, (1-4C) alkyl, nitro or cyano), L ｑ is absent or is selected from (1-2C)alkoxy, halo, cyano, amino or o and (1-4C) alkylene optionally substituted with one or more substituents selected from oxo and oxo. can be, Q is hydrogen, (1-6C) alkyl, aryl, (3-8) cycloalkyl, heteroaryl is aryl or heterocyclyl (wherein Q is oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, ( (1-4C) haloalkoxy, (1-4C) aminoalkyl, (1-4C) hydroxyalkanol Kill, Cyano, NR ｃ R ｄ , OR ｃ , C(O)R ｃ , C(O)OR ｃ , C(O)N(R ｄ ) R ｃ , N(R ｄ ) C(O)R ｃ , S(O) ｐ R ｃ (where p is 0, 1 or 2) ), SO ２ N (R ｄ ) R ｃ , N(R ｄ ) SO ２ R ｃ Or (CH ２ ) ｑ NR ｃ R ｄ (child wherein q is 1, 2, or 3. may be replaced (where R ｃ and R ｄ are each independently hydrogen or (1 to 6C) alkyl), and / or Q is a group of the formula: -L １ -L Ｑ１ -W １ (In the formula, L １ is absent or is (1-2C) alkylene, L Ｑ１ does not exist, W １ is hydrogen, (1-6C) alkyl, aryl, aryl(1-2C) alkyl, (3 -8C) cycloalkyl, heteroaryl, or heterocyclyl (wherein W １ teeth, oxo, (1-4C) alkyl, halo, (1-4C) haloalkyl, (1-4C) haloa alkoxy, (1-4C)alkoxy, (1-4C)alkylamino, cyano, NR ｈ R ｉ 、OR ｈ 、C(O)R ｈ 、C(O)OR ｈ 、OC(O)R ｈ 、C(O)N(R ｉ )R ｈ 、 N (R ｉ ) C(O)R ｈ , S(O) ｒ R ｈ (where r is 0, 1 or 2) may be substituted with one or more substituents selected from the group consisting of aryl, ... ｈ and R ｉ are each independently , hydrogen or (1-4C) alkyl) and optionally substituted with one or more groups of is selected from the group R ３ Any tertiary amine in the group or nitrogen atom in the pyridyl ring may be in the form of an N-oxide. That's fine, 12. The compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof.

13. R ３ is the formula: -L-Y-L ｑ -Q (In the formula, L does not exist, Y is N(R ａ ) or C(O)N(R ａ ) and L ｑ does not exist, Q is (1-6C) alkyl or (3-8C) cycloalkyl (where Q is halo, cyano, NR ｃ R ｄ , OR ｃ , C(O)R ｃ , C(O)OR ｃ , C(O)N(R ｄ ) R ｃ , N(R ｄ ) C(O)R ｃ , S(O) ｐ R ｃ (where p is 0 , 1 or 2), SO ２ N (R ｄ ) R ｃ , N(R ｄ ) SO ２ R ｃ or (CH ２ ) ｑ N R ｃ R ｄ (wherein q is 1, 2, or 3) may be further substituted with a group, R ｃ and R ｄ are each independently hydrogen or (1 to 6C) selected from alkyl) The compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, salt.

14. R ３ is the formula: 【Chemistry 4】 (In the formula, R ３ａ is hydrogen or methyl) The compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, salt.

15. A is CR ４ and N (where R ４ is hydrogen, halo, or halo, (1-2C) haloalkyl, (1-2C) halo Alkoxy, amino, cyano, (CH ２ ) ｑａ NR ４Ａ R ４Ｂ , (CH ２ ) ｑａ OR ４ Ａ 、(CH ２ ) ｑａ C(O)R ｃ４Ａ 、(CH ２ ) ｑａ C(O)OR ４Ａ 、(CH ２ ) ｑ ａ OC(O)R ４Ａ 、(CH ２ ) ｑａ C(O)N(R ４Ｂ )R ４Ａ 、(CH ２ ) ｑａ N( R ４Ｂ ) C(O)R ４Ａ , (CH ２ ) ｑａ S (O) ｐ R ４Ａ (where p is 0, 1 or 2), (CH ２ ) ｑａ SO ２ N (R ４Ｂ ) R ４Ａ Or (CH ２ ) ｑａ N (R ４ Ｂ ) SO ２ R ４Ａ (1-2C) alkyl, qa is 0, 1, 2 or 3, R ４Ａ and R ４Ｂ are independent of each other and hydrogen, (1-4C) alkyl, (3-4C) cycloalkyl or (3-4C) cycloalkyl. methyl(1-2C)alkyl); 15. The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt thereof.

16. A is CR ４ and N, where R ４ is selected from hydrogen, halo, or halo and optionally (1-2C) alkyl, optionally substituted with one or more substituents selected from the group consisting of aryl, aryl, aryl, aryl and aryl. Therefore, A is CR ４ and N, where R ４ is hydrogen, methyl or halo 16. The compound according to any one of claims 1 to 15, or a pharmaceutically acceptable salt thereof.

17. formula: 【Transformation 5】 【Transformation 6】 (In the formula, A, R ０ , R １ , R ２ , R ３ and R １ｚ are any of claims 1 to 15, respectively. as defined in paragraph 1; m is 0, 1 or 2; R ２００ and R ２０１ are each independently hydrogen, methyl, hydroxymethyl or halo (selected from or a pharmaceutically acceptable salt thereof.

18. A compound selected from any one of the following, or a pharmaceutically acceptable salt thereof: 3-[5-amino-3-(4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl ]benzonitrile; 3-[5-amino-3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidinyl] dibenzonitrile; 3-(5-amino-3-pyridazin-4-yl-pyrazolo[1,5-a]pyrimidine-2 -yl)benzonitrile; 3-[5-amino-3-(2-ethylpyrazol-3-yl)pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[5-amino-3-(2-chloro-6-methyl-4-pyridyl)pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(2,6-dimethyl-4-pyridyl)pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(2-hydroxy-2- (methyl-propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy-1- Bicyclo[1.1.1]pentanyl)amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(8-methyl-3,8-di Azabicyclo[3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidine- 2-yl]benzonitrile; (3S)-4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl] (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]morpholine-3-carboxylic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-ethyl-4-piperidine) lysyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S,4S)-4- Methoxy-1-methyl-pyrrolidin-3-yl]amino]pyrazolo[1,5-a]pyrimidin dibenzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-tetrahydro pyrazolo[1,5-a]pyrimidin-2-yl]benzodihydrofuran-3-yl]amino]pyrazolo ... Trill; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[3-(hydroxymethyl )-4-methyl-piperazin-1-yl]pyrazolo[1,5-a]pyrimidin-2-yl ]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxyoxene [1,5-a]pyrimidin-2-yl]benzo[1,5-a]pyrazolo[1,5-a]pyrimidin-2-yl]benzo[1,5-a]pyrimidin-3-yl]methylamino ... Nitriles; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy-3- (methyl-butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Lu; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxycyclo butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-methylsulfonyl (4-piperidyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(8-oxa-3-azabicyclo[2.2.1.2.2.1]phenyl]propanol] Cyclo[3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl benzonitrile; 3-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) Pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2,2-dimethyl-propane acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(5-oxopyrrolidine -3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-2-hydro [1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(3R,4R )-4-hydroxytetrahydrofuran-3-yl]amino]pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(quinuclidin-3-yl Amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxycyclo butyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(2-morpholinoethyl] amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-2-hydro [1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidine-2- yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[2-[2-(dimethylamino) 4-amino)ethyl]morpholin-4-yl]pyrazolo[1,5-a]pyrimidin-2-yl] Benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S)-2- hydroxycyclobutyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4H-1,2,4-trimethyl- azole-3-ylmethylamino)pyrazolo[1,5-a]pyrimidin-2-yl]benzo Zonitrile; (2R)-4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl] (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]morpholine-2-carboxylic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-tetrahydro pyrazolo[1,5-a]pyrimidin-2-yl]benzodihydrofuran-3-yl]amino]pyrazolo ... Trill; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-imino-1-oxo -1,4-thiazinane-4-yl)pyrazolo[1,5-a]pyrimidin-2-yl]ben Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1,1-dioxothiazol-2-yl)methyl] [1,5-a]pyrimidin-2-yl]benzonitrile ； 2-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) Pyrazolo[1,5-a]pyrimidin-5-yl]amino]acetamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-piperazin-1-yl-pyridyl] lazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[2-(dimethylamino )-1-methyl-ethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-hydroxy-pyrazolo[1 ,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1H-imidazole-2 -ylmethylamino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-morpholino-pyrazolo[1 ,5-a]pyrimidin-2-yl]benzonitrile; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] lazolo[1,5-a]pyrimidin-5-yl]azetidine-2-carboxylic acid; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] lazolo[1,5-a]pyrimidin-5-yl]azetidine-3-carboxylic acid; (3R)-1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanopropyl] (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]pyrrolidine-3-carboxylic acid; 4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl lazolo[1,5-a]pyrimidin-5-yl]piperazine-1-sulfonamide; 3-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl) Pyrazolo[1,5-a]pyrimidin-5-yl]amino]bicyclo[1.1.1]penta benzo-1-carboxylic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(2R)-2-hydro [1,5-a]pyrimidin-2-yl]benzonitrile ； 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(2S)-2-hydro [1,5-a]pyrimidin-2-yl]benzonitrile ； 3-[5-(tert-butylamino)-3-(2-chloro-6-methyl-4-pyridyl ) pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-2-hydro [1,5-a]pyrimidin-2-yl]benzyloxy-1-methyl-ethyl]amino]pyrazolo[ ... benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-hydroxycyclo propyl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Lu; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4-piperidylamino) Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-morpholine -3-yl]methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; tert-butyl(3R)-3-[[[3-(2-chloro-6-methyl-4-pyridyl) -2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino] methyl]morpholine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-3-piperidin diethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Peridine-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-pyrrolidine -3-yl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Roridin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[rac-(4aS, 7a S)-3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b][1, 4]oxazin-6-yl]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Lil; tert-Butyl rac-(4aS,7aS)-6-[3-(2-chloro-6-methyl- 4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5- yl]-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]o Xanthazine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-morpholine -3-yl]methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; tert-Butyl(3S)-3-[[[3-(2-chloro-6-methyl-4-pyridyl) -2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino] methyl]morpholine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-pyrrolidine -3-yl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Roridin-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-3-piperidin diethyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]pyrimidin Peridine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5-a]pyridine mydine-5-carboxamide; N-tert-butyl-3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (aminophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-hydroxy-3-methyl-butyl)pyrazolo[1,5-a]pyrimidine-5-carbo oxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ 2-(4-phenylpiperazin-1-yl)ethyl]pyrazolo[1,5-a]pyrimidine -5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( Oxetan-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo [1,5-a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(morpholine-4-carbohydrate Nyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1S)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrazole mydine-5-carboxamide; N-(2-amino-2-methyl-propyl)-3-(2-chloro-6-methyl-4-pyridyl) pyrazolo[1,5-a]pyrimidine-5-carboxylate Samid; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1-hydroxycyclopropyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate Ruboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1-hydroxycyclobutyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate Voxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrazole mydine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (2R)-2-hydroxypropyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R)-2-hydroxy-1-methyl-ethyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-hydroxyoxetan-3-yl)methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-methyl Thilsulfonyl-pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2,3-dihydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5 -carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-hydroxycyclobutyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate Voxamide; 3-(2-chloro-6-methyl-4-pyridyl)-N-(1-cyano-2-methoxy-1 -methyl-ethyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; N-(4-aminonorbornan-1-yl)-3-(2-chloro-6-methyl-4-pyridyl) pyrazolo[1,5-a]pyrimidine-5-carboxylate Samid; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (2S)-2,3-dihydroxypropyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate Ruboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3S,4S)-4-Methoxy-1-methyl-pyrrolidin-3-yl]pyrazolo[1,5 -a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (2R)-2,3-dihydroxypropyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate Ruboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 1-methylazetidin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3S,4S)-4-hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-hydroxy-2-methyl-propyl)-N-methyl-pyrazolo[1,5-a]pyrimidin Zine-5-carboxamide; N-(3-amino-3-methyl-butyl)-3-(2-chloro-6-methyl-4-pyridinyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; N-(3-amino-1-bicyclo[1.1.1]pentanyl)-3-(2-chloro-6- Methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin thiazol-5-carboxamide; tert-Butyl N-[3-[[3-(2-chloro-6-methyl-4-pyridyl)-2- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino] -1-bicyclo[1.1.1]pentanyl]carbamate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ cis-(3S,4R)-4-hydroxypyrrolidin-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; tert-Butyl(3S,4R)-3-[[3-(2-chloro-6-methyl-4-pyridinyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl ]amino]-4-hydroxy-pyrrolidine-1-carboxylate; N-(2-amino-1,1-dimethyl-ethyl)-3-(2-chloro-6-methyl-4- pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; tert-Butyl N-[2-[[3-(2-chloro-6-methyl-4-pyridyl)-2- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino] -2-methyl-propyl]carbamate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3S)-3-piperidyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide; tert-Butyl(3S)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amine no]piperidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ trans-(3S,4S)-4-hydroxypyrrolidin-3-yl]pyrazolo[1,5 -a]pyrimidine-5-carboxamide; tert-Butyl trans-(3S,4S)-3-[[3-(2-chloro-6-methyl -4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5 -carbonyl]amino]-4-hydroxy-pyrrolidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-hydroxypyrrolidin-3-yl)methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; tert-Butyl 3-[[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3 -cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino]methyl yl]-3-hydroxy-pyrrolidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3R)-3-piperidyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amine no]piperidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-methylpyrrolidin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; tert-Butyl 3-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3- cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino]-3- Methyl-pyrrolidine-1-carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R,2S)-2,3-dihydroxy-1-methyl-propyl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl pyrazolo[1,5-a]pyrimidine-5-carboxamide; N-[(1-amino-3,3-difluoro-cyclobutyl)methyl]-3-(2-chloro -6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pi Rimidine-5-carboxamide; tert-Butyl N-[1-[[[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino ]methyl]-3,3-difluoro-cyclobutyl]carbamate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( Morpholin-2-ylmethyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ； tert-Butyl 2-[[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3 -cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amino]methyl methyl]morpholine-4-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(piperazine-1-carbo Nyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl 4-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (aminophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]piperazine-1- Carboxylate; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3R)-pyrrolidin-3-yl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; tert-Butyl(3R)-3-[[3-(2-chloro-6-methyl-4-pyridyl)- 2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carbonyl]amine no]pyrrolidine-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-hydroxy-1-methyl (ethyl-ethyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazolo [1,5-a]pyrimidine-5-carboxylic acid; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(2-phenyl) (hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(2-ethylpyrazol-3-yl)-N-(2-phenyl) (hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(2-ethyl-5-methyl-pyrazol-3-yl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-( 2-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2-ethyl-4-methyl-pyrazol-3-yl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-[2-(difluoromethyl)-6-methyl-4-pyridine pyrazolo[1,5-a]pyrimidyl]-N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidyl Zine-5-carboxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-( 2-methylpyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-pyridin Rimidin-4-yl-pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-cyano-2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl) (l)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(2-hydroxy-2-methyl (ethyl-propoxy)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] lazolo[1,5-a]pyrimidin-5-yl]methanesulfonamide; (2S)-2-[[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyano (phenyl)pyrazolo[1,5-a]pyrimidin-5-yl]amino]propanoic acid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3R)-pyrrolidine- 3-yl]oxy-pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile phosphate Mate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(2-hydroxyethyl) amino)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(morpholinomethyl)pyridine Zolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[5-(aminomethyl)-3-(2-chloro-6-methyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(3-hydroxy-3-methyl (ethyl-butyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-[2-(difluoromethyl)-6-methyl-4-pyridyl]-5-[(2-fluoromethyl)- [hydroxy-2-methyl-propyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl benzonitrile; 3-[5-[(2-hydroxy-2-methyl-propyl)amino]-3-(2-methoxy -6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzodi Trill; 3-[3-(2,6-dimethyl-4-pyridyl)-5-[(2-hydroxy-2-methyl -propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-2-hydro [1,5-a]pyrimidin-2-yl]benzyloxy-1-methyl-ethyl]amino]pyrazolo[ ... benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(dimethylamino)pyrazo b[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(4-piperidyloxy) Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3R)-3-piperidin pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3R)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]oxypiperidin Din-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3S)-pyrrolidine- 3-yl]oxy-pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]oxypyrrolidone Din-1-carboxylate; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(3S)-3-piperidin pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; tert-Butyl(3S)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]oxypiperidin Din-1-carboxylate; 3-[5-amino-3-(6-amino-5-methyl-3-pyridyl)pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-[2-(difluoromethyl)-6-methyl-4-pyridyl]pyridine Zolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(2-methoxy-6-methyl-4-pyridyl)pyrazolo[1,5 -a]pyrimidin-2-yl]benzonitrile; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carbonitrile; 3-[5-amino-3-(2-fluoro-6-methyl-4-pyridyl)pyrazolo[1,5 -a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pi rimidin-2-yl]benzonitrile; 3-[5-amino-3-(2,6-dimethyl-1-oxide-pyridin-1-ium-4 -yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[5-amino-3-(2-amino-6-methyl-4-pyridyl)pyrazolo[1,5- a]pyrimidin-2-yl]benzonitrile; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carboxamide; N-[4-[5-amino-2- (3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]-6-methyl- 2-pyridyl]acetamide; 3-[5-amino-3-(5-methyl-[1,2,4]triazolo[1,5-a]pyridin (1,5-a)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl]-6-methyl-pyridine-2-carboxylic acid; 3-[5-amino-3-[2-(dimethylamino)-6-methyl-4-pyridyl]pyrazo b[1,5-a]pyrimidin-2-yl]benzonitrile; [3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyrazo b[1,5-a]pyrimidin-5-yl]urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Iridium[1,5-a]pyrimidin-5-yl]-3-(2-hydroxy-2-methyl- lopil) urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-3-(1-ethyl-4-piperidyl)uria element; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]piperazine-1-carboxamide; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-3-[(3S)-pyrrolidin-3-yl ]urea; 1-(2-aminoethyl)-3-[3-(2-chloro-6-methyl-4-pyridyl)-2 -(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl]urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] azolo[1,5-a]pyrimidin-5-yl]-3-[(3R)-pyrrolidin-3-yl ]urea; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-2-cyano-guanidine; 3-[3-(2-ethylpyrazol-3-yl)-5-[(2-hydroxy-2-methyl -propyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-[3-(hydroxymethyl)-4 -methyl-piperazin-1-yl]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(8-oxa-3-azabicyclo [3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzyl benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(8-methyl-3,8-diazabiphenyl] Cyclo[3.2.1]octan-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(4-methylsulfonylpiperazine (1,5-a)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(4H-1,2,4-triazol- (pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile Lil; 3-[3-(2-ethylpyrazol-3-yl)-5-piperazin-1-yl-pyrazolo [1,5-a]pyrimidin-2-yl]benzonitrile; 3-[3-(2-ethylpyrazol-3-yl)-5-(1-imino-1-oxo-1, 4-thiazinane-4-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonite Lil; 5-(benzylamino)-2-(2-fluorophenyl)pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; N-benzyl-2-(2-fluorophenyl)pyrazolo[1,5-a]pyrimidine-5- amines; 2-(2-furyl)-5-[(3-methyl-2-pyridyl)methylamino]pyrazolo[1 ,5-a]pyrimidine-3-carbonitrile; tert-Butyl(2S)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]morpholine-4-carboxylate; tert-Butyl(2R)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]pyrrolidine-1-carboxylate; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-(2-furyl)pyrazo b[1,5-a]pyrimidine-3-carbonitrile; tert-Butyl(2S)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]pyrrolidine-1-carboxylate; tert-Butyl(2R)-2-[[[3-cyano-2-(2-furyl)pyrazolo[1, 5-a]pyrimidin-5-yl]amino]methyl]morpholine-4-carboxylate; 2-(2-furyl)-5-[4-(2-phenylethyl)piperazin-1-yl]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-(2-pyridylmethyl)piperazin-1-yl]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-furyl)-5-(4-methylpiperazin-1-yl)pyrazolo[1,5-a] Pyrimidine-3-carbonitrile; 5-[(1-benzyl-4-piperidyl)methylamino]-2-(2-furyl)pyrazolo [1,5-a]pyrimidine-3-carbonitrile; tert-Butyl(2R)-4-[3-cyano-2-(2-furyl)pyrazolo[1,5- a]pyrimidin-5-yl]-2-methyl-piperazine-1-carboxylate; tert-Butyl(2S)-4-[3-cyano-2-(2-furyl)pyrazolo[1,5- a]pyrimidin-5-yl]-2-methyl-piperazine-1-carboxylate; 5-[2-(4-benzylpiperazin-1-yl)ethylamino]-2-(2-furyl) Pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-furyl)-5-[(3-methyl-2-pyridyl)methylamino]pyrazolo[1 ,5-a]pyrimidine-3-carboxamide; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-(2-furyl)pyrazo b[1,5-a]pyrimidine-3-carboxamide; 5-[3-(dimethylamino)azetidin-1-yl]-2-(2-furyl)pyrazolo[ 1,5-a]pyrimidine-3-carboxamide; tert-Butyl 4-[3-cyano-2-(2-furyl)pyrazolo[1,5-a]pyrimidinyl] din-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylate; 2-(2-Furyl)-5-piperazin-1-yl-pyrazolo[1,5-a]pyrimidine- 3-carbonitrile; 2-(2-furyl)-5-[[(2S)-morpholin-2-yl]methylamino]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-furyl)-5-[[(2R)-morpholin-2-yl]methylamino]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 5-(4-benzylpiperazin-1-yl)-2-(2-furyl)pyrazolo[1,5-a ]pyrimidine-3-carbonitrile; N-benzyl-3-bromo-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-5 -amines; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carbonitrile; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carboxamides; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carboxaldehyde; N-benzyl-2-(2-furyl)pyrazolo[1,5-a]pyrimidin-5-amine; 5-amino-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile Lu; 3-bromo-2-(2-furyl)pyrazolo[1,5-a]pyrimidin-5-amine; 2-(2-furyl)-5-[4-[(3-methyl-2-pyridyl)methyl]piperazine- 1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-[(2,4,6-trifluorophenyl)methyl]piperidine [radin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-[(1-methylimidazol-2-yl)methyl]piperidine [radin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[4-(2-hydroxyethyl)piperazin-1-yl]pyra Zolo[1,5-a]pyrimidine-3-carbonitrile; N-benzyl-2-(2-furyl)-3-(1-methylpyrazol-4-yl)pyrazolo [1,5-a]pyrimidin-5-amine; N-benzyl-2-(2-furyl)-3-(2-methylpyrazol-3-yl)pyrazolo [1,5-a]pyrimidin-5-amine; Methyl (E)-3-[5-(benzylamino)-2-(2-furyl)pyrazolo[1,5- a]pyrimidin-3-yl]prop-2-enoate; (E)-3-[5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pi rimidin-3-yl]prop-2-enoic acid; 2-(2-furyl)-5-(4-phenylpiperazin-1-yl)pyrazolo[1,5-a ]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-(3-hydroxypropylamino)pyrazolo[1,5-a]pyrazole rimidine-3-carbonitrile; 2-(2-Furyl)-5-(2-hydroxyethylamino)pyrazolo[1,5-a]pyridine amide-3-carbonitrile; 2-(2-Furyl)-5-(3-piperidylmethylamino)pyrazolo[1,5-a]pyridine amide-3-carbonitrile hydrochloride; 5-(benzylamino)-2-oxazol-2-yl-pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; 5-(benzylamino)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin benzo-3-carbonitrile; 2-(3-cyanophenyl)-5-[4-[(3-methyl-2-pyridyl)methyl]piperidine [radin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(3-fluorophenyl)-5-[4-[(3-methyl-2-pyridyl)methyl]pyridyl Perazin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-(3-fluorophenyl) (l) pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 5-[4-(2-fluoroethyl)piperazin-1-yl]-2-oxazol-5-yl ru-pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 5-(benzylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; 5-(benzylamino)-2-(5-methyl-2-furyl)pyrazolo[1,5-a]pyridine amide-3-carbonitrile; 5-[4-[(3-methyl-2-pyridyl)methyl]piperazin-1-yl]-2-oxo Sazol-5-yl-pyrazolo[1,5-a]pyrimidine-3-carbonitrile; N-benzyl-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidine-5- amines; 2-(3-fluorophenyl)-N-[(3-methyl-2-pyridyl)methyl]pyrazolo [1,5-a]pyrimidin-5-amine; 2-(3-fluorophenyl)-N-(2-phenylethyl)pyrazolo[1,5-a]pyrazole Rimidin-5-amine; N-(1H-benzimidazol-2-ylmethyl)-2-(3-fluorophenyl)pyrrolidone lazolo[1,5-a]pyrimidin-5-amine; 2-(3-fluorophenyl)-N-(2-isoindolin-2-ylethyl)pyrazolo [1,5-a]pyrimidin-5-amine; N-benzyl-3-chloro-2-(3-fluorophenyl)pyrazolo[1,5-a]pyridine imidin-5-amine; 3-Bromo-5-chloro-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin gin; N-benzyl-3-bromo-2-(3-fluorophenyl)pyrazolo[1,5-a]pyridine imidin-5-amine; 5-(benzylamino)-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin di-3-carbonitrile; 3-Bromo-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-5-a Min; 5-amino-2-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate Carbonitrile; 2-(2-Furyl)-N-(thiazol-2-ylmethyl)pyrazolo[1,5-a]pyridine imidin-5-amine; [5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3 -yl]methanol; 5-(benzylamino)-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3- Carboxylic acid; N-benzyl-2-(2-furyl)-3-iodo-pyrazolo[1,5-a]pyrimidine- 5-amine; 2-(2-Furyl)-3-(4-pyridyl)pyrazolo[1,5-a]pyrimidin-5-a Min; 2-(2-Furyl)-5-[[(2R)-pyrrolidin-2-yl]methylamino]pyrazo b[1,5-a]pyrimidine-3-carbonitrile; 2-(2-Furyl)-5-[[(2R)-1-methylpyrrolidin-2-yl]methylamine no]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(2-furyl)-5-[(3R)-3-methylpiperazin-1-yl]pyrazolo[1 ,5-a]pyrimidine-3-carbonitrile hydrochloride; tert-Butyl 4-[3-cyano-2-(2-furyl)pyrazolo[1,5-a]pyrimidinyl] zinzyl]piperidine-1-carboxylate; N-benzyl-7-(2-furyl)pyrazolo[1,5-a][1,3,5]triazine 2-amine; N-benzyl-2-(2-furyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-5-[4-(2-fluoroethyl)piperazin-1-yl ]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 2-(3-cyanophenyl)-5-[2-(4-phenylpiperazin-1-yl)ethyl Amino]pyrazolo[1,5-a]pyrimidine-3-carbonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(4-fluorophenyl)pyrazo b[1,5-a]pyrimidin-5-amine; N-tert-butyl-3-(2-chloro-6-methyl-4-pyridyl)-2-(3-chloro- (anophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamidine; 3-(2-amino-6-methyl-4-pyridyl)-N-tert-butyl-2-(3-amino-6-methyl-4-pyridyl) (aminophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(1S )-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrimidine -5-carboxamide; 2-(3-cyanophenyl)-N-(2,3-dihydroxy-2-methyl-propyl)- 3-(2,6-dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate Voxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(3-phenyl) hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5-a]pyrimidine -5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-5-( sulfamoylamino)pyrazolo[1,5-a]pyrimidine; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-2-hydroxy-2-methyl-propane amides; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-2,2-dimethyl-propanamide; N-(3-amino-3-methyl-butyl)-2-(3-cyanophenyl)-3-(2,6 -dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-hydroxy-1,1-dimethyl-ethyl)pyrazolo[1,5-a]pyrimidine-5- Carboxamides; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-[ 2-methyl-6-(trifluoromethyl)-4-pyridyl]pyrazolo[1,5-a]pyridyl mydine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-N-(1-cyano-1-methyl-ethyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1S,2S)-2,3-dihydroxy-1-methyl-propyl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-2-cyano-3-isopropyl-guanidinium gin; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R)-2-hydro [1,5-a]pyrimidin-2-yl]benzyloxy-1-methyl-ethyl]amino]pyrazolo[ ... benzonitrile; 2-(3-cyano-2-methyl-phenyl)-3-(2,6-dimethyl-4-pyridyl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-hydroxycyclobutyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ； 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(2- Oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-hydroxy-1,1,2-trimethyl-propyl)pyrazolo[1,5-a]pyrimidin thiazol-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(1- Methyl-2-oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5 -carboxamide; 2-(3-cyanophenyl)-N-[(1S)-1,2-dimethylallyl]-3-(2, 6-dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ； N-(2-acetamido-2-methyl-propyl)-3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate Ruboxamide; N-(3-amino-3-methyl-butyl)-3-(2-chloro-6-methyl-4-pyridinyl) (phenyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(1-methyl-4-piperidine) lysyl)amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(1R )-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5-a]pyrimidine -5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyano-2-methyl-phenanthroline N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidinyl Zine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S)-2, 3-dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5-a]pyrimidine -2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(4-phenyl) (hydroxy-4-methyl-cyclohexyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate Voxamide; 3-[3-[2-(difluoromethyl)-6-methyl-4-pyridyl]-5-[(2-fluoromethyl)- [hydroxy-2-methyl-propyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(4- Methyl-2-oxo-oxazolidin-4-yl)methyl]pyrazolo[1,5-a]pyrazole mydine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(2- Methyl-5-oxo-pyrrolidin-2-yl)methyl]pyrazolo[1,5-a]pyrimidin thiazol-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[1-( 3-hydroxyoxetan-3-yl)ethyl]pyrazolo[1,5-a]pyrimidine-5 -carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3- Methyl-6-oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5 -carboxamide; 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-2-cyano-3-(2-hydroxy-2 -methyl-propyl)guanidine; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 3-hydroxy-1-bicyclo[1.1.1]pentanyl)pyrazolo[1,5-a]pyridine mydine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ rac-(2R)-2-hydroxypropyl]pyrazolo[1,5-a]pyrimidine-5- Carboxamides; 2-(3-cyano-2-methyl-phenyl)-3-(2,6-dimethyl-4-pyridyl) -N-[(1R)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5- a] pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(3S,4S )-4-methoxy-1-methyl-pyrrolidin-3-yl]amino]pyrazolo[1,5-a ]pyrimidin-2-yl]benzonitrile; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (3-methyl-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-( 2-Methoxy-6-methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate Ruboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(4- Methyl-2,5-dioxo-imidazolidin-4-yl)methyl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S,2S)-2, 3-dihydroxy-1-methyl-propyl]amino]pyrazolo[1,5-a]pyrimidine -2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(3-phenyl) (hydroxy-3-methyl-cyclobutyl)pyrazolo[1,5-a]pyrimidine-5-carbo oxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(3R)-3 -piperidyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ； 2-(3-cyano-2-methyl-phenyl)-3-(2,6-dimethyl-4-pyridyl) -N-[(1S)-2-hydroxy-1,2-dimethyl-propyl]pyrazolo[1,5- a] pyrimidine-5-carboxamide; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-yl]-3-hydroxy-3-methylbutane Mido; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxyoxene [1,5-a]pyrimidin-2-yl]benzo[1,5-a]pyrazolo[1,5-a]pyrimidin-2-yl]benzo[1,5-a]pyrimidin-3-yl]methylamino ... Nitriles; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[1-(2-hydroxy Ethyl)-4-piperidyl]amino]pyrazolo[1,5-a]pyrimidin-2-ylbene Zonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxy-3- (methyl-butyl)amino]pyrazolo[1,5-a]pyrimidin-2-ylbenzonitrile ； 1-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-ylguanidine; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1, 5-a]pyrimidine-5-carboxamidine; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(2-phenyl) (hydroxy-2-methyl-propoxy)pyrazolo[1,5-a]pyrimidine-5-carboxylate Samid; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(5-oxopyrrolidine -3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-ylbenzonitrile Lu; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3S)-3-(1-chloro- (hydroxy-1-methyl-ethyl)piperazin-1-ylpyrazolo[1,5-a]pyrimidin benzo-2-ylbenzonitrile; 3-[3-(2,6-dimethyl-4-pyridyl)-5-[(1-methyl-2-oxo-4 -piperidyl)amino]pyrazolo[1,5-a]pyrimidin-2-ylbenzonitrile; N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-5-yl-3-hydroxy-3-methyl-butanamide; N-[3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)pyridyl] Lazolo[1,5-a]pyrimidin-5-ylacetamide [2-(3-cyanophenyl) -3-(2,6-dimethyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-5-yl urea; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3- hydroxyoxetan-3-yl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxylate Ruboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1S)-2-hydro [1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidine-2- Ilbenzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(2S)-2 -hydroxypropyl]amino]pyrazolo[1,5-a]pyrimidin-2-ylbenzodiphenyl ether Trill; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ (1S,3S)-3-aminocyclopentyl]pyrazolo[1,5-a]pyrimidine-5- Carboxamides; m-{4-[({[(3S)-5-oxo-3-pyrrolidinyl]methyl}amino)carbo nyl]-7-(2,6-dimethyl-4-pyridyl)-1,5,9-triazabicyclo[4 .3.0]nona-2,4,6,8-tetraen-8-yl}benzonitrile; 3-[5-[(2-amino-2-methyl-propyl)amino]-3-(2-chloro-6- Methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ； 3-(2-cyano-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide Voxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[rac-(1R)-2 -hydroxy-1,2-dimethyl-propyl]amino]pyrazolo[1,5-a]pyrimidin benzonitrile; N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-5-yl-2-hydroxy-2-methyl-propanamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-[ rac-(3S)-3-piperidyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Samid; 2-(3-cyanophenyl)-3-(3-fluoro-2,6-dimethyl-4-pyridyl) -N-(2-hydroxy-2-methyl-propyl)pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(2- Oxo-4-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(3-fluoro-2,6-dimethyl-4-pyridyl) -N-[(4-methyl-2,5-dioxo-imidazolidin-4-yl)methyl]pyrazo b[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-(5-octyl) xopyrrolidin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1, 5-a]pyrimidine-5-carboxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3R)-3-(1-chloro- (hydroxy-1-methyl-ethyl)piperazin-1-ylpyrazolo[1,5-a]pyrimidin benzonitrile; m-[7-(2,6-dimethyl-4-pyridyl)-4-({[(5-oxo-3-pyrrolidine (vinyl)methyl]amino}carbonyl)-1,5,9-triazabicyclo[4.3.0] Nona-2,4,6,8-tetraen-8-yl]benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[[(1R,2S)-2- hydroxycyclobutyl]amino]pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; m-{4-[({[(3R)-5-oxo-3-pyrrolidinyl]methyl}amino)carbo nyl]-7-(2,6-dimethyl-4-pyridyl)-1,5,9-triazabicyclo[4 .3.0]nona-2,4,6,8-tetraen-8-yl}benzonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3-hydroxyazetyl) pyrazolo[1,5-a]pyrimidin-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-2-yl]benzo Nitriles; 2,2,2-trifluoroacetic acid; 4-[5-amino-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3 -yl-6-methyl-pyridine-2-carbonitrile; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-(1-imino-1-oxo -1,4-thiazinane-4-yl)pyrazolo[1,5-a]pyrimidin-2-yl]ben Zonitrile; 3-[5-[(1-acetyl-4-piperidyl)amino]-3-(2,6-dimethyl-4 -pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(5- (oxomorpholin-2-yl)methyl]pyrazolo[1,5-a]pyrimidine-5-carbo oxamide; 3-[3-(2-chloro-6-methyl-4-pyridyl)-5-[(3R)-pyrrolidine- 3-yl]oxy-pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; 1-(2-amino-2-methyl-propyl)-3-[3-(2-chloro-6-methyl-4 -pyridyl)-2-(3-cyanophenyl)pyrazolo[1,5-a]pyrimidin-5-yl le]urea; 3-[3-(2,6-dimethyl-4-pyridyl)-5-(2,4-dioxo-1,3,8 -triazaspiro[4.5]decane-8-carbonyl)pyrazolo[1,5-a]pyrimidin benzonitrile; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3S ,4S)-4-hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a]pyridine mydine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[[(2 R)-5-oxopyrrolidin-2-yl]methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4R)-4-hydroxy-4-methyl-tetrahydrofuran-3-yl]pyrazolo[1 ,5-a]pyrimidine-5-carboxamide 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4S)-4-hydroxy-4-methyl-tetrahydrofuran-3-yl]pyrazolo[1 ,5-a]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(6- Oxo-3-piperidyl)methyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide Mido; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3S ,4R)-4-hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a]pyrazole mydine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4R)-4-hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a]pyrazole mydine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4S)-4-hydroxytetrahydrofuran-3-yl]pyrazolo[1,5-a]pyridine mydine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3R ,4R)-4-hydroxy-1-methyl-pyrrolidin-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[[(2 S)-5-oxopyrrolidin-2-yl]methyl]pyrazolo[1,5-a]pyrimidine- 5-carboxamide; 2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)-N-[(3S ,4R)-4-hydroxy-1-methyl-pyrrolidin-3-yl]pyrazolo[1,5-a ]pyrimidine-5-carboxamide; 2-(3-cyanophenyl)-N-(2-hydroxy-2-methyl-propyl)-3-thio Azol-5-yl-pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-[5-[(2-amino-2-methyl-propyl)amino]-3-(2-chloro-6- Methyl-4-pyridyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile ； ； 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 4-piperidyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide; 3-(2-chloro-6-methyl-4-pyridyl)-2-(3-cyanophenyl)-N-( 4-cyano-4-piperidyl)pyrazolo[1,5-a]pyrimidine-5-carboxamide ； N-(4-carbamoyl-4-piperidyl)-3-(2-chloro-6-methyl-4-pyridyl) pyrazolo[1,5-a]pyrimidine-5-carboxylate Samid; 3-[3-(2,6-dimethyl-4-pyridyl)-5-(piperazin-1-ylmethyl) Pyrazolo[1,5-a]pyrimidin-2-yl]benzonitrile; ； 2-(3-cyanophenyl)-N-[(1S)-2-hydroxy-1,2-dimethyl- propyl]-3-[2-(hydroxymethyl)-6-methyl-4-pyridyl]pyrazolo[1 ,5-a]pyrimidine-5-carboxamide; 3-[3-(2,6-dimethyl-4-pyridyl)-5-(3-oxo-2,8-diaza pyrro[4.5]decan-8-yl)pyrazolo[1,5-a]pyrimidin-2-yl]benzoate Zonitrile; 3-[3-(2,6-dimethyl-4-pyridyl)-5-[[1-(2-hydroxy-2- Methyl-propyl)-4-piperidyl]amino]pyrazolo[1,5-a]pyrimidine-2 -yl]benzonitrile; (2S)-N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl] ) pyrazolo[1,5-a]pyrimidin-5-yl]-3,3,3-trifluoro-2-hydroxybenzoate hydroxy-2-methyl-propanamide; N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridyl)pyrazolo [1,5-a]pyrimidin-5-yl]-2-oxa-6-azaspiro[3.3]hepta thiazol-6-carboxamide; or 4-cyano-N-[2-(3-cyanophenyl)-3-(2,6-dimethyl-4-pyridinyl] pyrazolo[1,5-a]pyrimidin-5-yl]-4-methyl-piperidine-1-carboxylate Ruboxamide.

19. The compound according to any one of claims 1 to 18 or a pharmaceutically acceptable salt thereof is administered by a pharmaceutical A pharmaceutical composition comprising the compound of formula (I) in combination with a physiologically acceptable diluent or carrier.

20. A compound or a drug thereof according to any one of claims 1 to 18 for use in therapy.

20. The pharmaceutical composition of claim 19, wherein the compound is a physiologically acceptable salt thereof.

21. A compound according to any one of claims 1 to 18 or a pharmaceutically acceptable salt thereof, or 20. The pharmaceutical composition according to claim 19, (i) treatment of cell proliferative conditions; (ii) the treatment of cancer; (iii) the treatment of cancer, wherein said compound or pharmaceutical composition contains one or more additional anti-cancer agents administered in combination with (iv) the treatment of cancer, wherein said compound or pharmaceutical composition is 1) other forms of cancer immunotherapy and anti-cancer chemotherapeutic agents; 2) adenosine pathway modulators (for example, but not limited to, A2b antagonists) st, CD73 inhibitor and CD39 inhibitor); 3) Anti-PD-1 and PDL-1 antibodies (e.g., cetrelimab, pembrolizumab, nivolumab) mab, durvalumab, avelumab and atezolizumab); and 4) Anti-CTLA4 antibodies (e.g., ipilimumab) and (iii) administering the compound in combination with one or more additional anti-cancer agents selected from the group consisting of:

2. A compound or pharmaceutical composition for use in

22. A method of treating a cell proliferative disorder in a patient in need of such treatment, comprising: Item 19. A compound according to any one of items 1 to 18 or a pharmaceutically acceptable salt thereof, or 20. A method comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 19.

23. A method for administering cancer treatment to a patient in need of such treatment, comprising administering to said patient a compound according to any one of claims 1 to 18.

20. A compound according to any one of claims 19 or a pharmaceutically acceptable salt thereof, Administering a therapeutically effective amount of the pharmaceutical composition of claim 1.

24. A method of treating a cell proliferative disorder in a patient in need of such treatment, comprising: Item 19. A compound according to any one of items 1 to 18 or a pharmaceutically acceptable salt thereof, or 20. Administering a therapeutically effective amount of the pharmaceutical composition according to claim 19 in combination with one or more additional anticancer agents. The method includes:

25. the one or more additional anti-cancer agents 1) other forms of cancer immunotherapy and anti-cancer chemotherapeutic agents; 2) adenosine pathway modulators (for example, but not limited to, A2b antagonists) st, CD73 inhibitor and CD39 inhibitor); 3) Anti-PD-1 and PDL-1 antibodies (e.g., cetrelimab, pembrolizumab, nivolumab) mab, durvalumab, avelumab and atezolizumab); and 4) Anti-CTLA4 antibodies (e.g., ipilimumab) 25. The method of claim 24, wherein the compound is selected from the group consisting of:

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