Imidazole Macrocycles for the Treatment of Autoimmune Diseases

Abstract

The present invention relates to a compound represented by formula (Ia) TIFF2025506393000981.tif60165 (In the formula, R 2 , M 1 , M 2 , M 3 , Q 1 and Q 2 The present invention relates to compounds of the formula:

Description

[Technical field]

[0001] The present invention relates to organic compounds useful for therapy and / or prophylaxis in mammals, in particular antagonists of STING useful for the treatment of autoimmune diseases. [Background technology]

[0002] Autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD) refer to a set of symptoms in which the immune system mistakenly attacks the body's own, resulting in unresolved, inappropriately activated inflammation that becomes pathogenic. Many of the autoimmune diseases are poorly managed by existing treatments that provide only symptomatic relief. Steroids and broad-spectrum immunosuppressants (e.g., mycophenolate and cyclophosphamide) constitute a position of care but are associated with significant treatment-related toxicity. Pathway-selective agents such as adalimumab (anti-TNF antibody, for RA and IBD) occasionally result in infection or inadequate tumor surveillance. And belimumab (anti-BAFF antibody, the only FDA-approved novel drug for SLE) shows slow onset of remission and is not very effective in the clinic. Furthermore, the heterogeneity of many autoimmune diseases without existing treatments indicates the difficulty of finding efficacy by blocking one immune pathway. Thus, currently available treatments fail to meet the greater unmet need for autoimmune inflammatory diseases and are associated with limited remissions, severe side effects, opportunistic infections, and reduced quality of life due to chronic inflammation.

[0003] Stimulator of interferon genes (STING) is a transmembrane protein located in the endoplasmic reticulum (ER) that is crucial in mediating the host's innate sensing of pathogen- / damage-associated molecular patterns (PAMPs or DAMPs). In particular, the cyclic GMP-AMP synthase (cGAS)-STING pathway has emerged as a key mechanism for linking cytosolic DNA recognition to the induction of type I interferons (IFNs) and broader immune defense programs. Binding of cGAS to double-stranded DNA (dsDNA) allosterically activates its catalytic site, leading to the production of 2'3'-cyclic GMP-AMP (cGAMP), a second messenger molecule that is agonistic for STING. Upon activation, STING translocates from the ER to the Golgi and recruits TANK-binding kinase 1 (TBK1), which phosphorylates interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB) to initiate the expression of type I IFNs and a myriad of pro-inflammatory cytokines (e.g., IL-6 and TNFα), respectively. Besides 2'3'-cGAMP, STING can be activated by other types of cyclic di-nucleotides (CDNs), such as bacterial-derived c-di-AMP, c-di-GMP, and 3',3'-cGAMP. Following signaling, STING is rapidly degraded, preventing constitutive signaling of the inflammatory response.

[0004] While inducing strong host defense responses, aberrant STING signaling fosters dysregulated immune responses associated with many pathologies. Gain-of-function (GoF) human STING mutations are the underlying cause of STING-associated vasculopathy of infancy (SAVI), a monogenic disorder characterized by the development of autoinflammatory symptoms termed type I interferon dysregulation. Mechanistically, the disease-causing substitutions trigger ligand-independent constitutive STING activation. Furthermore, STING is involved in DNA-driven inflammation, e.g., in Aicardi-Goutiéres syndrome (AGS) and genetic forms of lupus. Unlike SAVI, STING-mediated continuous innate immune activation in AGS is caused by defects in self-DNA clearance and metabolism resulting from mutations in the endonuclease genes TREX1 and / or DNASE2. Consistently, genetic and pharmacological inhibition of STING ameliorates systemic inflammation and morbidity in Trex1- / - mouse models. Apart from genetic disorders, solid preclinical and clinical evidence supports a common pathogenic role of STING in a range of inflammation-related disorders such as SLE and RA. A direct link between the cGAS-STING pathway and SLE was established by observing that PBMCs from a subset of SLE patients have elevated cytosolic cGAMP compared to healthy controls. Furthermore, apoptotic cell-derived membrane vesicles in SLE serum have high ISG stimulatory activity that is dependent on cGAS-STING. Disrupting STING signaling also ameliorated the development of lupus-like phenotypes in FcγrIIb- / - mice. Furthermore, multiple recent studies link STING to different types of neurodegeneration. Taking Parkinson's disease as an example, missense mutations in PARKIN and PINK led to the accumulation of mitochondrial DNA that triggered neuronal inflammation in a cGAS-STING-dependent manner. Absence of STING rescued motor deficits and neuronal loss in mouse disease models. Finally, STING also mediates the oncogenic DNA response triggered by chromosomal instability during cancer metastasis, and STING deficiency confers protection against colorectal and skin cancer in mice. Summary of the Invention

[0005] The present invention relates to a compound represented by formula (Ia) [ka] (In the formula, M 1 is R 1 and optionally substituted heteroarylene, wherein R 1 is deuterio, halogen, cyano, carboxy, R, RNH, (R) 2 N, RCO, RSO 2 , RNHSO 2 , R 2 NSO 2 , RSO(NR), R 3 Si, R.O.C. 1-6 Alkyl, RSC 1~6 Alkyl, RNHC 1~6 Alkyl, (R) 2 NC 1~6 Alkyl, RSO 2 C 1~6 Alkyl, RNHSO 2 C 1~6 Alkyl, R 2 NSO 2 C 1~6 Alkyl, RSO(NR)C 1~6 Alkyl or R 3 Silicon Carbide 1~6 alkyl, where R is H, R a , R b or R c and R a is R b or R c C optionally substituted with 1~6 is alkyl, R b is C 3~7 cycloalkyl, heterocyclyl, heteroaryl or aryl, 3~7Cycloalkyl, heterocyclyl, heteroaryl and aryl are unsubstituted or substituted with deuterio, halogen or R c and optionally substituted with R c ,Juterio,C 1~6 Alkyl, (C 1~6 Alkyl) 3 Si, HaloC 1~6 Alkyl, deuterio C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, Deuterio C 1~6 Alkoxy, C 2~6 Alkenyl, HaloC 2~6 Alkenyl, Deuterio C 2~6 Alkenyl, C 2~6 Alkynyl, HaloC 2~6 Alkynyl, deuterio C 2~6 Alkynyl, C 3~7 Cycloalkyl, HaloC 3~7 Cycloalkyl, deuterio C 3~7 Cycloalkyl, Amino, C 1~6 Alkylamino, (C 1~6 Alkyl) 2 Amino, C 1~6 Alkylcarbonylamino, HaloC 1~6 Alkylamino, HaloC 1~6 Alkylcarbonylamino, (HaloC 1~6 Alkyl) 2 Amino, C 3~7 Cycloalkylamino, C 3~7 Cycloalkylcarbonylamino, (C 3~7 Cycloalkyl) 2 Amino, HaloC 3~7 Cycloalkylamino, (HaloC 3~7 Cycloalkyl) 2 Amino, C 3~7 Cycloalkyl(C 1~6 Alkyl)amino, haloC 3~7 Cycloalkyl(C 1~6 Alkyl)amino, C 1~6 Alkyl sulfonyl amino, halo C 1~6 Alkyl sulfonyl amino, C1~6 Alkoxy C 1~6 Alkyl, (HaloC 1~6 Alkoxy)C 1~6 Alkyl, C 1~6 Alkoxy(halo)C 1~6 Alkyl, C 3~7 Cycloalkyl C 1~6 Alkyl, C 3~7 Cycloalkyl Halo C 1~6 Alkyl, C 1~6 Alkylcarbonyl, HaloC 1~6 Alkyl carbonyl, C 3~7 Cycloalkylcarbonyl, HaloC 3~7 Cycloalkylcarbonyl, C 1~6 Alkoxycarbonyl, HaloC 1~6 Alkoxycarbonyl, C 3~7 Cycloalkoxycarbonyl, HaloC 3~7 Cycloalkoxycarbonyl, C 1~6 Alkylaminocarbonyl, (C 1~6 Alkyl) 2 Aminocarbonyl, C 3~7 Cycloalkylaminocarbonyl, (C 3~7 Cycloalkyl) 2 Aminocarbonyl, C 1~6 Alkyl C 3~7 Cycloalkylaminocarbonyl, haloC 1~6 Alkylaminocarbonyl, halo(C 1~6 Alkyl) 2 Aminocarbonyl, HaloC 3~7 Cycloalkylaminocarbonyl, halo(C 3~7 Cycloalkyl) 2 Aminocarbonyl, HaloC 1~6 Alkyl C 3~7 Cycloalkylaminocarbonyl, C 1~6 Alkyl Halo C 3~7 Cycloalkylaminocarbonyl, (C 1~6 Alkyl) 3 Ammonio, C 1~6 Alkylsulfanyl, C 1~6 Alkylsulfinyl, C 1~6 Alkylsulfonyl, C 3~7Cycloalkylsulfanyl, C 3~7 Cycloalkylsulfinyl, C 3~7 Cycloalkylsulfonyl, HaloC 1~6 Alkylsulfanyl, HaloC 1~6 Alkylsulfinyl, HaloC 1~6 Alkylsulfonyl, HaloC 3~7 Cycloalkylsulfanyl, HaloC 3~7 Cycloalkylsulfinyl, HaloC 3~7 Cycloalkylsulfonyl, HaloC 1~6 Alkoxysulfonyl, C 1~6 Alkylaminosulfonyl, (HaloC 1~6 alkylamino)sulfonyl, (C 1~6 Alkyl) 2 Aminosulfonyl, (HaloC 1~6 Alkyl) 2 Aminosulfonyl, (C 1~6 Alkyl) 2 Phosphoryl, (C 1~6 Alkoxy) 2 Phosphoryl, hydroxy (C 1~6 Alkoxy)phosphoryl, C 1~6 Alkoxyphosphoryl, Hydroxy, HydroxyC 1~6 Alkyl, hydroxyhaloC 1~6 Alkyl, Hydroxy C 1~6 Alkoxy, Hydroxy, HaloC 1~6 Alkoxy, Hydroxy C 3~7 Cycloalkyl, hydroxyhaloC 3~7 Cycloalkyl, as well as H, C 1~6 Alkyl, C 1~6 selected from sulfonimidoyl optionally substituted with alkoxy, aryl, heteroaryl, and heterocyclyl; M 2 is arylene, heterocyclylene, or heteroarylene, and the arylene, heterocyclylene, or heteroarylene is R 1 and optionally substituted with M 3 is unsubstituted or R 3and R 2 ,Juterio,R,ROC 1~6 Alkyl, RSC 1~6 Alkyl, RSO 2 C 1~6 Alkyl, RNHC 1~6 Alkyl or (R) 2 NC 1~6 is alkyl, R 3 is heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl, or arylcarbonyl, wherein the heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl, and arylcarbonyl are unsubstituted or R 1 and optionally substituted with Q 1 -M-, -MOM-, -MSM-, -M-SO 2 -M-, -M-SO(NH)-M-, -M-SO(NR)-M-, -M-SiR 2 -M- or -MN(R)-M-, where M is unsubstituted or deuterio, halogen, cyano, carboxy, R, RO, RS, RNH, R 2 N, RSO 2 , R.O.C. 1~6 Alkyl, RSC 1~6 Alkyl, RNHC 1~6 Alkyl, (R) 2 NC 1~6 Alkyl and RSO 2 C 1~6 C, optionally substituted with substituents independently selected from alkyl 1~6 is alkylene, Q 2 NH, O, S, SO, SO 2 , P(O)R, PO(NR), Se, N(R), SiR 2 , heterocyclyl, heteroaryl or aryl) or a pharma- ceutically acceptable salt thereof.

[0006] Another object of the present invention relates to novel compounds of formula (I) or (Ia). Their manufacture, pharmaceuticals based on the compounds according to the present invention and their manufacture, and the use of compounds of formula (I) or (Ia) as STING antagonists and for the treatment or prevention of autoimmune diseases, inflammatory diseases, neuropathic diseases, metabolic diseases, cardiovascular diseases, or selective types of cancers involving overexpression or activation of STING. Compounds of formula (I) or (Ia) show good STING antagonistic activity. In addition, compounds of formula (I) or (Ia) also show good cytotoxicity, solubility, hPBMC, human microsome stability, and SDPK profile, as well as low CYP inhibition. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007] definition The terms "deuterio" or "deuterium" refer to an isotope of hydrogen having a single neutron as well as a proton in the nucleus.

[0008] "C 1~6 The term "alkyl" refers to saturated straight or branched chain alkyl groups containing 1 to 6, especially 1 to 4, carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, etc. 1~6 "Alkyl" groups are methyl, ethyl, and n-propyl.

[0009] "C 1~6 The term "alkylene" refers to a linear or branched saturated divalent hydrocarbon radical of 1 to 6 carbon atoms or a divalent branched saturated divalent hydrocarbon radical of 3 to 6 carbon atoms. 1~6 Examples of alkylene groups include methylene, ethylene, propylene, 2-methylpropylene, butylene, 2-ethylbutylene, pentylene, and hexylene.

[0010] "C 1~6 The term "alkoxy" refers to 1~6 It represents alkyl-O-.

[0011] "Trijuterio C 1~6 The term "alkyl" refers to 1~6 C, where three hydrogen atoms in the alkyl group have been replaced with deuterium 1~6 Indicates an alkyl group. Trideuterio C 1~6 Examples of alkyl include trideuteriomethyl.

[0012] "C 2~6 The term "alkenyl" refers to a monovalent linear or branched hydrocarbon group of 2 to 6 carbon atoms having at least one double bond. In certain embodiments, an alkenyl has 2 to 4 carbon atoms having at least one double bond. 2~6 Examples of alkenyl include ethenyl (or vinyl), propenyl, prop-2-enyl, isopropenyl, n-butenyl, and iso-butenyl.

[0013] "C 2~6 The term "alkynyl" refers to a monovalent linear or branched hydrocarbon group of 2 to 6 carbon atoms having at least one triple bond. In certain embodiments, alkynyl has 2 to 4 carbon atoms having at least one triple bond. 2-6 Examples of alkynyl include ethynyl (-C≡CH), prop-1-ynyl (-C≡CCH 3 ), prop-2-ynyl (propargyl, -CH 2 C≡CH), but-1-ynyl, but-2-ynyl and but-3-ynyl. The terms "halogen" and "halo" are used interchangeably herein and refer to fluoro, chloro, bromo or iodo.

[0014] "Haro C 1~6 The term "alkyl" refers to 1~6 At least one of the hydrogen atoms of the alkyl group is replaced by the same or different halogen atom, in particular a fluoro atom. 1~6represents an alkyl group. Examples of haloalkyl include monofluoro-, difluoro- or trifluoro-methyl, -ethyl, or -propyl, such as 3,3,3-trifluoropropyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, fluoroethyl or trifluoromethyl.

[0015] "Haro C 1~6 The term "alkoxy" refers to haloC 1~6 It represents alkyl-O-.

[0016] The term "haloazetidinyl" refers to an azetidinyl group in which at least one of the hydrogen atoms of the azetidinyl group has been replaced by the same or different halogen atom, in particular a fluoro atom. Halopiperidinyl includes fluoroazetidinyl, difluoroazetidinyl, and the like.

[0017] The term "pyrimidinyloxy" refers to pyrimidinyl-O-.

[0018] "Trijuterio C 1~6 The term "alkoxy" refers to trideuterioC 1~6 It represents alkyl-O-.

[0019] The term "carboxy" refers to --COOH.

[0020] "C 3-7 The term "cycloalkyl" means a monovalent saturated monocyclic or bicyclic hydrocarbon radical containing 3 to 7 ring carbon atoms. Bicyclic means consisting of two saturated carbocyclic rings having one or more carbon atoms in common. Examples of monocyclic cycloalkyls are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. Examples of bicyclic cycloalkyls are bicyclo[1.1.0]butyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl or bicyclo[2.2.2]octanyl.

[0021] "Haro C 3~7The term "cycloalkyl" refers to 3~7 At least one of the hydrogen atoms of the cycloalkyl group is replaced by the same or different halogen atom, in particular a fluoro atom. 3~7 This represents a cycloalkyl group.

[0022] The term "halo-1,2,3,5,6,7-hexahydropyrrolidinyl" refers to 3~7 It denotes a 1,2,3,5,6,7-hexahydropyrrolidinyl group, in which at least one of the hydrogen atoms of the cycloalkyl group is replaced by the same or different halogen atoms, in particular by fluoro atoms.

[0023] "C 3~7 The term "cycloalkoxy" refers to 3~7 Cycloalkyl-O- is represented.

[0024] The term "oxetanyloxy" means oxetanyl-O-.

[0025] The term "azetidinyloxy" refers to azetidinyl-O-.

[0026] "C 1~6 The term "alkylcarbonyloxy" refers to 1~6 It represents alkyl-C(O)-O-.

[0027] If any ring atom of the ring system is a heteroatom, the system is a heterocycle, regardless of the point of attachment of the ring system to the remainder of the molecule. In other examples, a heterocyclyl contains 4 to 10, or 5 to 10 ring atoms. In one example, a heterocyclyl contains 1 to 4 heteroatoms. In one example, a heterocyclyl contains 1 to 3 heteroatoms. In another example, a heterocyclyl contains a 3- to 7-membered monocyclic ring having 1 to 2, 1 to 3, or 1 to 4 heteroatoms selected from nitrogen, sulfur, oxygen, or silicon. In another example, a heterocyclyl contains a 4- to 6-membered monocyclic ring having 1 to 2, 1 to 3, or 1 to 4 heteroatoms selected from nitrogen, sulfur, oxygen, or silicon. In another example, a heterocyclyl contains a 3-membered monocyclic ring. In another example, a heterocyclyl contains a 4-membered monocyclic ring. In another example, a heterocyclyl contains a 5- to 6-membered monocyclic ring. In some embodiments, a heterocycloalkyl contains at least one nitrogen. In one example, a heterocyclyl group contains 0 to 3 double bonds. Any nitrogen or sulfur heteroatom may be optionally oxidized (e.g., NO, SO, SO 2 ), any nitrogen heteroatom may be optionally quaternized (e.g., [NR 4 ] + Cl - , [NR 4 ] + OH -Examples of heterocyclic rings include oxiranyl, aziridinyl, thiiranyl, azetidinyl, oxetanyl, thietanyl, 1,2-dithietanyl, 1,3-dithietanyl, pyrrolidinyl, dihydro-1H-pyrrolyl, dihydrofuranyl, tetrahydrofuranyl, dihydrothienyl, tetrahydrothienyl, imidazolidinyl, piperidinyl, piperazinyl, isoquinolinyl, tetrahydroisoquinolinyl, morpholinyl, thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, dihydropyranyl, tetrahydropyranyl, hexahydrothio ... Hydropyrimidinyl, oxazinanyl, thiazinanyl, thioxanyl, homopiperazinyl, homopiperidinyl, azepanyl, oxepanyl, thiepanyl, oxazepinyl, oxazepanyl, diazepanyl, 1,4-diazepanyl, diazepinyl, thiazepinyl, thiazepanyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, isothiazolidinyl, 1,1-dioxoisothiazolidinonyl, 1,1-dioxoisothiazolyl, oxazolidinonyl, imidazolidinonyl, 4,5,6,7-tetrahydro[2H]indazolyl, tetrahydro benzoimidazolyl, 4,5,6,7-tetrahydrobenzo[d]imidazolyl, thiazinyl, oxazinyl, thiadiazinyl, oxadiazinyl, dithiazinyl, dioxazinyl, oxathiazinyl, thiatriazinyl, oxatriazinyl, dithiadiazinyl, imidazolinyl, dihydropyrimidyl, tetrahydropyrimidyl, 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, indolinyl, thiapyranyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, pyrazolidinyl, dithianyl, dithiolanyl yl, pyrimidinonyl, pyrimidinedionyl, pyrimidine-2,4-dionyl, piperazinonyl, piperazinedionyl, pyrazolidinylimidazolinyl, 3-azabicyclo[3.1.0]hexanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 6-azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.1.1]heptanyl, 3-azabicyclo[4.1.0]heptanyl, azabicyclo[2.2.2]hexanyl, 2-azabicyclo[3.2.1]octanyl, 8-azabicyclo[3.2.1]octanyl, 2-azabicyclo[2.2.2]octanyl, 8-azabicyclo[2.2.2]octanyl, 7-oxabicyclo[2.2.1]heptane, azaspiro[3.5]nonanyl, azaspiro[2.5]octanyl, azaspiro[4.5]decanyl, 1-azaspiro[4.5]decan-2-onyl, azaspiro[5.5]undecanyl, tetrahydroindolyl, octahydroindolyl, tetrahydroisoindolyl, tetrahydroindazolyl, 1,1-dioxohexahydrothiopyranyl, and 2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl. In particular, heterocyclyl herein is. [ka] It could be.

[0028] The term "heterocyclylene" refers to a divalent heterocyclyl group.

[0029] The term "aryl" refers to a monovalent aromatic carbocyclic monocyclic or bicyclic ring system containing 6 to 10 carbon ring atoms. Examples of aryl moieties include phenyl and naphthyl. The term "arylene" refers to a divalent aryl group.

[0030] For example, Lang's Handbook of Chemistry (Dean, JA, ed.) 13 thed. Table 7-2

[1985] . This definition includes any bicyclic group in which any of the above heteroaryl rings are fused to an aryl ring, and either the aryl ring or the heteroaryl ring is attached to the remainder of the molecule. In one embodiment, heteroaryl includes 5- to 6-membered monocyclic aromatic groups in which one or more ring atoms are nitrogen, sulfur, or oxygen. In one embodiment, heteroaryl includes 7- to 12-membered bicyclic aromatic groups in which one or more ring atoms are nitrogen, sulfur, or oxygen. Exemplary heteroaryl groups include thienyl, furyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, thiatriazolyl, oxatriazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl, tetrazinyl, tetrazolo[1,5-b]pyridazinyl, imidazol[1,2-a]pyrimidinyl, 1H-pyrazolo[3,4-d]pyrimidine, 1H-pyrazolo[3,4-d]pyridazine, imidazo[1,5-a]pyrazine, and the like. Heteroaryl includes, for example, imidazo[5,1-f][1,2,4]triazine, [1,2,4]triazolo[4,3-a]pyrazine, 1H-pyrazolo[3,4-c]pyridazine, 1H-pyrazolo[3,4-b]pyridine, 1H-pyrazolo[4,3-d]pyrimidine, 1H-pyrazolo[3,4-c]pyridine, 1H-pyrazolo[4,3-c]pyridine and purinyl, as well as benzo-fused derivatives such as benzoxazolyl, benzofuryl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, benzimidazolyl, indazolyl, and indolyl. In particular, heteroaryl herein refers to [ka] It could be.

[0031] The term "heteroarylene" means a divalent heteroaryl group.

[0032] In certain embodiments, the heterocyclyl or heteroaryl group is bonded at a carbon atom of the heterocyclyl or heteroaryl group. For example, carbon-bonded heterocyclyl groups include bonded at the 2-, 3-, 4-, 5-, or 6-position of the pyridine ring, the 3-, 4-, 5-, or 6-position of the pyridazine ring, the 2-, 4-, 5-, or 6-position of the pyrimidine ring, the 2-, 3-, 5-, or 6-position of the pyrazine ring, the 2-, 3-, 4-, or 5-position of the furan, tetrahydrofuran, thiofuran, thiophene, pyrrole, or tetrahydropyrrole ring, the 2-, 4-, or 5-position of the oxazole, imidazole, or thiazole ring, the 3-, 4-, or 5-position of the isoxazole, pyrazole, or isothiazole ring, the 2-, or 3-position of the aziridine ring, the 2-, 3-, or 4-position of the azetidine ring, the 2-, 3-, 4-, 5-, 6-, 7-, or 8-position of the quinoline ring, or the 1-, 3-, 4-, 5-, 6-, 7-, or 8-position of the isoquinoline ring.

[0033] In certain embodiments, the heterocyclyl or heteroaryl group is N-linked. For example, nitrogen-linked heterocyclyl or heteroaryl groups include aziridine, azetidine, pyrrole, pyrrolidine, 2-pyrroline, 3-pyrroline, imidazole, imidazolidine, 2-imidazoline, 3-imidazoline, pyrazole, pyrazoline, 2-pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline, 1H-indazole at the 1-position, isoindole or isoindole at the 2-position, morpholine at the 4-position, and carbazole or β-carboline at the 9-position.

[0034] Unless otherwise specified, the term "optionally substituted" means that a group can be unsubstituted or substituted with one or more (e.g., 0, 1, 2, 3, 4, or 5 or more, or any of these range variables) of the substituents listed for that group, which can be the same or different. In one embodiment, an optionally substituted group has one substituent. In another embodiment, an optionally substituted group has two substituents. In another embodiment, an optionally substituted group has three substituents. In another embodiment, an optionally substituted group has four substituents. In another embodiment, an optionally substituted group has five substituents.

[0035] In one embodiment, one of ordinary skill in the art can recognize that keto-enol tautomerism exists for certain structures such as those shown below. [ka] The term "RSO(NR)" means [ka] Shows.

[0036] "SO 2 " or the term "sulfonyl" [ka] means...

[0037] The term "sulfonimidoyl" means [ka] Shows.

[0038] The term "pharmaceutically acceptable salt" means a salt that is not biologically or otherwise undesirable. Pharmaceutically acceptable salts include both acid addition salts and base addition salts.

[0039] The term "pharmaceutically acceptable acid addition salts" refers to pharmaceutically acceptable salts such as those formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, carbonic acid, phosphoric acid, and the like, and organic acids selected from aliphatic, alicyclic, aromatic, araliphatic, heterocyclic, carboxylic, and sulfonic acids, such as formic acid, acetic acid, propionic acid, glycolic acid, gluconic acid, lactic acid, pyruvic acid, oxalic acid, malic acid, maleic acid, maloneic acid, succinic acid, fumaric acid, tartaric acid, citric acid, aspartic acid, ascorbic acid, glutamic acid, anthranilic acid, benzoic acid, cinnamic acid, mandelic acid, embonic acid, phenylacetic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid.

[0040] The term "pharmaceutically acceptable base addition salt" refers to a pharmaceutically acceptable salt formed with an organic or inorganic base. Examples of acceptable inorganic bases include sodium salt, potassium salt, ammonium salt, calcium salt, magnesium salt, iron salt, zinc salt, copper salt, manganese salt, and aluminum salt. Salts derived from pharmaceutically acceptable organic non-toxic bases include the salts of primary, secondary, and tertiary amines, substituted amines, including natural substituted amines, cyclic amines, and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-diethylaminoethanol, trimethamine, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purine, piperidine, piperidine, N-ethylpiperidine, and polyamine resins.

[0041] The term "pharmacologically active metabolite" refers to a pharmacologically active product produced through metabolism in the body of a particular compound or its salt. After entering the body, most drugs become substrates for chemical reactions that can change their physical properties and biological effects. These metabolic transformations usually affect the polarity of the compounds of the invention and change the way the drug is distributed in and excreted from the body. However, in some cases, metabolism of a drug is required for therapeutic effect.

[0042] The term "therapeutically effective amount" refers to an amount of a compound or molecule of the invention that, when administered to a subject, (i) treats or prevents a particular disease, condition or disorder, (ii) reduces, ameliorates or eliminates one or more symptoms of a particular disease, condition or disorder, or (iii) prevents or delays the onset of one or more symptoms of a particular disease, condition or disorder described herein. The therapeutically effective amount will vary depending on the compound, the condition being treated, the severity of the disease being treated, the age and relative health of the subject, the route and form of administration, the judgment of the attending physician or veterinarian, and other factors.

[0043] The term "pharmaceutical composition" refers to a mixture or solution containing a therapeutically effective amount of an active ingredient together with pharma- ceutically acceptable excipients to be administered to a mammal (e.g., a human) in need thereof.

[0044] STING antagonist The present invention relates to a compound represented by the formula (Ia): [ka] (In the formula, M 1 is R 1 and optionally substituted heteroarylene, wherein R 1 is deuterio, halogen, cyano, carboxy, R, RNH, (R) 2 N, RCO, RSO 2 , RNHSO 2 , R 2 NSO2 , RSO(NR), R 3 Si, R.O.C. 1-6 Alkyl, RSC 1~6 Alkyl, RNHC 1~6 Alkyl, (R) 2 NC 1~6 Alkyl, RSO 2 C 1~6 Alkyl, RNHSO 2 C 1~6 Alkyl, R 2 NSO 2 C 1~6 Alkyl, RSO(NR)C 1~6 Alkyl or R 3 Silicon Carbide 1~6 alkyl, where R is H, R a , R b or R c and R a is R b or R c C optionally substituted with 1~6 is alkyl, R b is C 3~7 cycloalkyl, heterocyclyl, heteroaryl or aryl, 3~7 Cycloalkyl, heterocyclyl, heteroaryl and aryl are unsubstituted or substituted with deuterio, halogen or R c and optionally substituted with R c ,Juterio,C 1~6 Alkyl, (C 1~6 Alkyl) 3 Si, HaloC 1~6 Alkyl, deuterio C 1~6 Alkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, Deuterio C 1~6 Alkoxy, C 2~6 Alkenyl, HaloC 2~6 Alkenyl, Deuterio C 2~6 Alkenyl, C 2~6 Alkynyl, HaloC 2~6 Alkynyl, deuterio C 2~6 Alkynyl, C3~7 Cycloalkyl, HaloC 3~7 Cycloalkyl, deuterio C 3~7 Cycloalkyl, Amino, C 1~6 Alkylamino, (C 1~6 Alkyl) 2 Amino, C 1~6 Alkylcarbonylamino, HaloC 1~6 Alkylamino, HaloC 1~6 Alkylcarbonylamino, (HaloC 1~6 Alkyl) 2 Amino, C 3~7 Cycloalkylamino, C 3~7 Cycloalkylcarbonylamino, (C 3~7 Cycloalkyl) 2 Amino, HaloC 3~7 Cycloalkylamino, (HaloC 3~7 Cycloalkyl) 2 Amino, C 3~7 Cycloalkyl(C 1~6 Alkyl)amino, haloC 3~7 Cycloalkyl(C 1~6 Alkyl)amino, C 1~6 Alkyl sulfonyl amino, halo C 1~6 Alkyl sulfonyl amino, C 1~6 Alkoxy C 1~6 Alkyl, (HaloC 1~6 Alkoxy)C 1~6 Alkyl, C 1~6 Alkoxy(halo)C 1~6 Alkyl, C 3~7 Cycloalkyl C 1~6 Alkyl, C 3~7 Cycloalkyl Halo C 1~6 Alkyl, C 1~6 Alkylcarbonyl, HaloC 1~6 Alkyl carbonyl, C 3~7 Cycloalkylcarbonyl, HaloC 3~7 Cycloalkylcarbonyl, C 1~6 Alkoxycarbonyl, HaloC 1~6 Alkoxycarbonyl, C 3~7 Cycloalkoxycarbonyl, HaloC 3~7 Cycloalkoxycarbonyl, C 1~6Alkylaminocarbonyl, (C 1~6 Alkyl) 2 Aminocarbonyl, C 3~7 Cycloalkylaminocarbonyl, (C 3~7 Cycloalkyl) 2 Aminocarbonyl, C 1~6 Alkyl C 3~7 Cycloalkylaminocarbonyl, haloC 1~6 Alkylaminocarbonyl, halo(C 1~6 Alkyl) 2 Aminocarbonyl, HaloC 3~7 Cycloalkylaminocarbonyl, halo(C 3~7 Cycloalkyl) 2 Aminocarbonyl, HaloC 1~6 Alkyl C 3~7 Cycloalkylaminocarbonyl, C 1~6 Alkyl Halo C 3~7 Cycloalkylaminocarbonyl, (C 1~6 Alkyl) 3 Ammonio, C 1~6 Alkylsulfanyl, C 1~6 Alkylsulfinyl, C 1~6 Alkylsulfonyl, C 3~7 Cycloalkylsulfanyl, C 3~7 Cycloalkylsulfinyl, C 3~7 Cycloalkylsulfonyl, HaloC 1~6 Alkylsulfanyl, HaloC 1~6 Alkylsulfinyl, HaloC 1~6 Alkylsulfonyl, HaloC 3~7 Cycloalkylsulfanyl, HaloC 3~7 Cycloalkylsulfinyl, HaloC 3~7 Cycloalkylsulfonyl, HaloC 1~6 Alkoxysulfonyl, C 1~6 Alkylaminosulfonyl, (HaloC 1~6 alkylamino)sulfonyl, (C 1~6 Alkyl) 2 Aminosulfonyl, (HaloC 1~6 Alkyl) 2 Aminosulfonyl, (C 1~6 Alkyl) 2Phosphoryl, (C 1~6 Alkoxy) 2 Phosphoryl, hydroxy (C 1~6 Alkoxy)phosphoryl, C 1~6 Alkoxyphosphoryl, Hydroxy, HydroxyC 1~6 Alkyl, hydroxyhaloC 1~6 Alkyl, Hydroxy C 1~6 Alkoxy, Hydroxy, HaloC 1~6 Alkoxy, Hydroxy C 3~7 Cycloalkyl, hydroxyhaloC 3~7 Cycloalkyl, as well as H, C 1~6 Alkyl, C 1~6 selected from sulfonimidoyl optionally substituted with alkoxy, aryl, heteroaryl, and heterocyclyl; M 2 is arylene, heterocyclylene, or heteroarylene, and the arylene, heterocyclylene, or heteroarylene is R 1 and optionally substituted with M 3 is unsubstituted or R 3 and R 2 ,Juterio,R,ROC 1~6 Alkyl, RSC 1~6 Alkyl, RSO 2 C 1~6 Alkyl, RNHC 1~6 Alkyl or (R) 2 NC 1~6 is alkyl, R 3 is heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl, or arylcarbonyl, wherein the heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl, and arylcarbonyl are unsubstituted or R 1 and optionally substituted with Q 1 -M-, -MOM-, -MSM-, -M-SO 2-M-, -M-SO(NH)-M-, -M-SO(NR)-M-, -M-SiR 2 -M- or -MN(R)-M-, where M is unsubstituted or deuterio, halogen, cyano, carboxy, R, RO, RS, RNH, R 2 N, RSO 2 , R.O.C. 1~6 Alkyl, RSC 1~6 Alkyl, RNHC 1~6 Alkyl, (R) 2 NC 1~6 Alkyl and RSO 2 C 1~6 C, optionally substituted with substituents independently selected from alkyl 1~6 is alkylene, Q 2 NH, O, S, SO, SO 2 , P(O)R, PO(NR), Se, N(R), SiR 2 , heterocyclyl, heteroaryl or aryl) or a pharma- ceutically acceptable salt thereof.

[0045] Another embodiment of the present invention is a compound represented by the formula (I): [ka] (In the formula, R 1 is deuterio, H, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C 1~6 Alkyl, (C 1~6 Alkylsulfonylpiperazinyl)C 1~6 Alkyl, Amino, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkoxycarbonyl, C 1~6 Alkyl, C 1~6 Alkylaminocarbonyl, C 1~6 Alkylcarbonylamino, C 3~7 Cycloalkyl, HaloC 1~6 Alkyl, Hydroxy C1~6 Alkyl, morpholinyl C 1~6 Alkyl, Hydroxy, Pyrazolyl C 1~6 Alkyl or triazolyl C 1~6 is alkyl, R 2 H, (2-oxa-5-azabicyclo[2.2.1]heptanyl)C 1~6 Alkyl, (2-oxa-6-azaspiro[3.3]heptanyl)C 1~6 Alkyl, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C 1~6 Alkyl, ((C 1~6 Alkyl) 3 Ammonio)C 1~6 Alkyl, (C 1~6 Alkylsulfonylpiperazinyl)C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkyl, C 3~7 Cycloalkyl C 1~6 Alkyl, haloC 1~6 Alkyl, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkyl, Phenyl C 1~6 Alkyl, pyrimidinyloxy C 1~6 Alkyl, Tetrazolyl C 1~6 Alkyl or trideuterio C 1~6 is alkyl, R 3 teeth, [ka] where: R 4 H, (C 1~6 Alkyl) 2 amino, (C 1~6 Alkyl) 2 Aminocarbonyl, (C 1~6 Alkyl) 2 Phosphoryl, 1,1-dioxotianil, C 1~6 Alkyl-substituted 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrolyl; HaroC 1~6 1,6-diazaspiro[3.3]heptanyl substituted with alkyl or oxetanyl; HaroC 1~6 1,7-diazaspiro[3.5]nonanyl substituted with alkyl or oxetanyl; 2,2-dioxo-2λ 6 -thia-6-azaspiro[3.3]heptanyl, C 1~6 2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazinyl substituted with alkyl, C 1~6 Alkyl, haloC 1~6 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, HaroC 1~6 2-azaspiro[3.3]heptanyl substituted once or twice with substituents independently selected from alkyl and hydroxy; 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazinyl, 3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazinyl, (Halooxetanyl)C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkyl, C 3~7 Cycloalkylcarbonyl, cyano C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 Alkylcarbonyl, HaloC 3~7 Cycloalkyl, Hydroxy C 1~6Alkyl, Hydroxy C 1~6 Alkylcarbonyl, HydroxyC 3~7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, oxetanyl-substituted 3,6-diazabicyclo[3.2.0]heptanyl; 3,7-diazabicyclo[4.2.0]octanyl substituted with oxetanyl, HaroC 1~6 alkyl-substituted 3,8-diazabicyclo[3.2.1]octanyl; 3-oxa-6-azabicyclo[3.1.1]heptanyl, C 1~6 alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl; 3-oxa-8-azabicyclo[3.2.1]octanyl, Unsubstituted or C 1~6 alkyl-substituted 4,7-diazaspiro[2.5]octanyl; 4-oxo-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazinyl, HaroC 1~6 Alkyl or C 1~6 Alkoxy C 1~6 Alkyl-substituted 5-oxa-2,8-diazaspiro[3.5]nonanyl, 6,6-dioxo-6λ 6 -thia-1-azaspiro[3.3]heptanyl, 6-oxa-1-azaspiro[3.3]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, HaroC 1~6 Alkyl-substituted 8-oxa-2,5-diazaspiro[3.5]nonanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, amino, Aminocarbonyl, Unsubstituted, or (C 1~6 Alkyl) 2 Amino, (C 1~6 Alkyl)2 Amino C 1~6 Alkyl, Amino, C 1~6 Alkyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylsulfonyl, C 1~6 Alkyl Sulfonyl C 1~6 Alkyl, C 3~7 Cycloalkyl, cyano, cyanoC 1~6 Alkyl, haloC 1~6 Alkyl, Hydroxy C 1~6 Alkyl, morpholinyl and morpholinyl C 1~6 azetidinyl substituted once or twice with substituents independently selected from alkyl; HaroC 1~6 Alkyl or C 3~7 cycloalkyl-substituted azetidinyloxy; Unsubstituted or (HaloC 1~6 Alkylcarbonyl)azetidinyl, C 1~6 Alkylazetidinyl, C 1~6 Alkylpiperazinyl, C 1~6 Alkylpyrrolidinyl, halo-1,2,3,5,6,7-hexahydropyrrolidinyl, haloC 1~6 C substituted with alkylazetidinyl, morpholinyl, oxetanyl or tetrahydrofuranyl 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkylamino, C 1~6 Alkoxycarbonyl, Unsubstituted, or (C 1~6 Alkoxy C 1~6 Alkylcarbonyl)azetidinyl, (haloC 1~6 (alkylcarbonyl)pyrrolidinyl, 1,1-dioxothietanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, 4,7-diazaspiro[2.5]octanyl, C 1~6 Alkoxy, C 1~6 Alkylcarbonylazetidinyl, C 1~6 Alkylcarbonyloxy, C 1~6Alkylcarbonylpyrrolidinyl, C 1~6 Alkylsulfonylazetidinyl, C 1~6 Alkylsulfonylpyrrolidinyl, C 3~7 Cycloalkylsulfonylazetidinyl, cyano, haloC 1~6 Alkylazetidinyl, Hydroxy, HydroxyC 1~6 C substituted once or twice with substituents independently selected from alkyl, morpholinyl and oxetanyl 1~6 Alkyl, C 1~6 Alkylamino, Unsubstituted or substituted with 1,1-dioxothietanyl 1~6 Alkylsulfanyl, C 1~6 Alkylsulfonyl, Unsubstituted, or C 1~6 Alkoxy or hydroxy substituted C 3~7 Cycloalkyl, Carboxy, Cyano, HaroC 1~6 Alkoxy, Hydroxy-substituted haloC 1~6 Alkyl, Hydroxy, Hydroxy C 1~6 Alkylcarbamoyl, Imidazolyl, morpholinyl, morpholinylcarbonyl, Oxetanyl, oxomorpholinyl, oxooxazolidinyl, C 1~6 alkyl-substituted oxopiperazinyl; Unsubstituted, or C 1~6 alkyl- or hydroxy-substituted oxopyrrolidinyl; C 1~6 Alkyl, carboxy, oxetanyl and phenyl C 1~6 piperazinyl substituted once or twice with substituents independently selected from alkyl; C 1~6piperidinyl substituted with alkyl, 2H-tetrazolyl or oxazolyl; Amino, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl carbonyl, C 1~6 Alkyl sulfonyl, cyano, halo C 1~6 pyrrolidinyl substituted once or twice with substituents independently selected from alkylcarbonyl and halogen; pyrrolidinyl carbonyl, tetrahydrofuranyl, or tetrahydropyranyl, R 5 is 1,3-dihydroisobenzofuranyl, halogen-substituted 1H-indazolyl; C 2~6 Alkynyl, Thienyl, Unsubstituted, or halogen or C 1~6 alkyl-substituted bicyclo[1.1.1]pentanyl, (C 1~6 Alkoxy C 1~6 Alkyl)C 3~7 Cycloalkyloxy, (C 1~6 Alkyl) 2 Phosphoryl, (C 1~6 Alkylmorpholinyl)C 1~6 Alkoxy, (C 1~6 Alkylsulfonylazetidinyl)C 1~6 Alkoxy, 2-oxa-6-azaspiro[3.3]heptanyl, azetidinyl, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkoxy C 2~6 Alkynyl, C 1~6 Alkoxy C 3~7 Cycloalkyloxy, C 1~6 Alkoxypyrrolidinyl, C 1~6 Alkyl, C 1~6 Alkylamino, C1~6 Alkylsulfanyl, C 1~6 Alkylsulfinyl, C 1~6 Alkylsulfonyl, C 2~6 Alkenyl, C 3~7 Cycloalkyl, C 3~7 Cycloalkyloxy, carboxy, cyano, cyano C 1~6 Alkoxy, HaloC 1~6 Alkoxy, HaloC 1~6 Alkyl, halogen, hydroxy, morpholinyl, morpholinyl C 1~6 Alkoxy, oxetanyl C 1~6 Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl, tetrahydrofuranyloxy and trideuterioC 1~6 phenyl substituted once, twice or three times with substituents independently selected from alkoxy; Unsubstituted or halogen, hydroxy, C 1~6 Alkylsulfanyl and C 1~6 pyridinyl substituted once or twice with substituents independently selected from alkoxy, or pyrimidinyl, unsubstituted or substituted by halogen; R 6 is H or C 1~6 is alkyl, R 7 is C 1~6 is alkyl, R 7a is C 1~6 Alkyl, C 3~7 Cycloalkyl or C 1~6 Alkoxy C 1~6 is alkyl, R 7b , H, C 1~6 Alkoxy or Phenyl C 1~6 is an alkoxy; R 7c is H or C 1~6 is an alkoxy; R 7d is C 1~6 Alkyl, C 3~7 Cycloalkyl C 1~6 Alkyl or C1~6 Alkoxy C 1~6 is alkyl, R 7e H, amino, phenyl C 1~6 Alkylamino or morpholinyl C 1~6 is alkylamino, R 7f is C 1~6 Alkyl, Phenyl C 1~6 alkyl or oxetanyl; R 7g is H or C 1~6 Alkoxy C 1~6 is alkyl, Q 1 is unsubstituted or C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkoxy, C 1~6 Alkyl, C 1~6 Alkylcarbonyloxy, carboxy, hydroxy, hydroxyC 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkoxy and trideuterioC 1~6 C substituted once or twice with substituents independently selected from alkoxy 1~6 is alkylene, or -MOM-, where M is C 1~6 is alkylene, Q 2 is NH, O or S, A 1 is CH or N, A 2 , CH, CR 7h or N, where R 7h is C 1~6 is alkyl, A 3 CR 8 or N, where R 8 , H, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7Cycloalkoxy, C 3~7 Cycloalkoxyamino, cyano, haloazetidinyl C 1~6 Alkyl, haloC 1~6 Alkoxy, halogen, morpholinyl C 1~6 alkyl or oxetanyl; A 4 is CR 9 or N, where R 9 is H, or R 8 and R 9 together with the atoms to which they are attached form a heterocyclyl, A 5 is CR 10 or N, where R 10 is H or a halogen, A 6 CR 11 or N, where R 11 is H, deuterio, halogen, C 1~6 Alkyl or C 1~6 is an alkoxy; A 7 is CR 12 or N, where R 12 is H or a halogen, However, A 1 , A 2 , A 3 and A 4 Two or less of the following are simultaneously N and A 5 , A 6 and A 7 (exactly one of is N) or a pharma- ceutically acceptable salt thereof.

[0046] Another embodiment of the present invention is a compound represented by the formula (Ib): [ka] (In the formula, R 1 is deuterio, H, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C 1~6Alkyl, (C 1~6 Alkylsulfonylpiperazinyl)C 1~6 Alkyl, Amino, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkoxycarbonyl, C 1~6 Alkyl, C 1~6 Alkylaminocarbonyl, C 1~6 Alkylcarbonylamino, C 3~7 Cycloalkyl, HaloC 1~6 Alkyl, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkyl, Hydroxy, Pyrazolyl C 1~6 Alkyl or triazolyl C 1~6 is alkyl, R 2 H, (2-oxa-5-azabicyclo[2.2.1]heptanyl)C 1~6 Alkyl, (2-oxa-6-azaspiro[3.3]heptanyl)C 1~6 Alkyl, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C 1~6 Alkyl, ((C 1~6 Alkyl) 3 Ammonio)C 1~6 Alkyl, (C 1~6 Alkylsulfonylpiperazinyl)C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkyl, C 3~7 Cycloalkyl C 1~6 Alkyl, haloC 1~6 Alkyl, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkyl, Phenyl C 1~6 Alkyl, pyrimidinyloxy C 1~6 Alkyl, Tetrazolyl C 1~6 Alkyl or trideuterio C 1~6 is alkyl, R 3 teeth, [ka] where: R 4 H, (C 1~6 Alkyl) 2 amino, (C 1~6 Alkyl) 2 Aminocarbonyl, (C 1~6 Alkyl) 2 Phosphoryl, 1,1-dioxotianil, C 1~6 Alkyl-substituted 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrolyl; HaroC 1~6 1,6-diazaspiro[3.3]heptanyl substituted with alkyl or oxetanyl; HaroC 1~6 1,7-diazaspiro[3.5]nonanyl substituted with alkyl or oxetanyl; 2,2-dioxo-2λ 6 -thia-6-azaspiro[3.3]heptanyl, C 1~6 2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazinyl substituted with alkyl, C 1~6 Alkyl, haloC 1~6 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, HaroC 1~6 2-azaspiro[3.3]heptanyl substituted once or twice with substituents independently selected from alkyl and hydroxy; 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazinyl, 3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazinyl, (Halooxetanyl)C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkyl, C 3~7 Cycloalkylcarbonyl, cyano C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 Alkylcarbonyl, HaloC 3~7 Cycloalkyl, Hydroxy C 1~6 Alkyl, Hydroxy C 1~6 Alkylcarbonyl, HydroxyC 3~7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, oxetanyl-substituted 3,6-diazabicyclo[3.2.0]heptanyl; 3,7-diazabicyclo[4.2.0]octanyl substituted with oxetanyl, HaroC 1~6 alkyl-substituted 3,8-diazabicyclo[3.2.1]octanyl; 3-oxa-6-azabicyclo[3.1.1]heptanyl, C 1~6 alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl; 3-oxa-8-azabicyclo[3.2.1]octanyl, Unsubstituted or C 1~6 alkyl-substituted 4,7-diazaspiro[2.5]octanyl; 4-oxo-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazinyl, HaroC 1~6 Alkyl or C 1~6 Alkoxy C 1~6 Alkyl-substituted 5-oxa-2,8-diazaspiro[3.5]nonanyl, 6,6-dioxo-6λ 6 -thia-1-azaspiro[3.3]heptanyl, 6-oxa-1-azaspiro[3.3]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, HaroC 1~6 Alkyl-substituted 8-oxa-2,5-diazaspiro[3.5]nonanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, amino, Aminocarbonyl, Unsubstituted, or (C 1~6 Alkyl) 2 Amino, (C 1~6 Alkyl) 2 Amino C 1~6 Alkyl, Amino, C 1~6 Alkyl, C 1~6 Alkyl carbonyl, C 1~6 Alkylsulfonyl, C 1~6 Alkyl Sulfonyl C 1~6 Alkyl, C 3~7 Cycloalkyl, cyano, cyanoC 1~6 Alkyl, haloC 1~6 Alkyl, Hydroxy C 1~6 Alkyl, morpholinyl and morpholinyl C 1~6 azetidinyl substituted once or twice with substituents independently selected from alkyl; HaroC 1~6 Alkyl or C 3~7 cycloalkyl-substituted azetidinyloxy; Unsubstituted or (HaloC 1~6 Alkylcarbonyl)azetidinyl, C 1~6 Alkylazetidinyl, C 1~6 Alkylpiperazinyl, C 1~6 Alkylpyrrolidinyl, halo-1,2,3,5,6,7-hexahydropyrrolidinyl, haloC 1~6 C substituted with alkylazetidinyl, morpholinyl, oxetanyl or tetrahydrofuranyl 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkylamino, C 1~6 Alkoxycarbonyl, Unsubstituted, or (C 1~6Alkoxy C 1~6 Alkylcarbonyl)azetidinyl, (haloC 1~6 (alkylcarbonyl)pyrrolidinyl, 1,1-dioxothietanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, 4,7-diazaspiro[2.5]octanyl, C 1~6 Alkoxy, C 1~6 Alkylcarbonylazetidinyl, C 1~6 Alkylcarbonyloxy, C 1~6 Alkylcarbonylpyrrolidinyl, C 1~6 Alkylsulfonylazetidinyl, C 1~6 Alkylsulfonylpyrrolidinyl, C 3~7 Cycloalkylsulfonylazetidinyl, cyano, haloC 1~6 Alkylazetidinyl, Hydroxy, HydroxyC 1~6 C substituted once or twice with substituents independently selected from alkyl, morpholinyl and oxetanyl 1~6 Alkyl, C 1~6 Alkylamino, Unsubstituted or substituted with 1,1-dioxothietanyl 1~6 Alkylsulfanyl, C 1~6 Alkylsulfonyl, Unsubstituted, or C 1~6 Alkoxy or hydroxy substituted C 3~7 Cycloalkyl, Carboxy, Cyano, HaroC 1~6 Alkoxy, Hydroxy-substituted haloC 1~6 Alkyl, Hydroxy, Hydroxy C 1~6 Alkylcarbamoyl, Imidazolyl, morpholinyl, morpholinylcarbonyl, Oxetanyl, oxomorpholinyl, oxooxazolidinyl, C 1~6 alkyl-substituted oxopiperazinyl; Unsubstituted, or C 1~6 alkyl- or hydroxy-substituted oxopyrrolidinyl; C 1~6 Alkyl, carboxy, oxetanyl and phenyl C 1~6 piperazinyl substituted once or twice with substituents independently selected from alkyl; C 1~6 piperidinyl substituted with alkyl, 2H-tetrazolyl or oxazolyl; Amino, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl carbonyl, C 1~6 Alkyl sulfonyl, cyano, halo C 1~6 pyrrolidinyl substituted once or twice with substituents independently selected from alkylcarbonyl and halogen; pyrrolidinyl carbonyl, tetrahydrofuranyl, or tetrahydropyranyl, R 5 is 1,3-dihydroisobenzofuranyl, halogen-substituted 1H-indazolyl; C 2~6 Alkynyl, Thienyl, Unsubstituted, or halogen or C 1~6 alkyl-substituted bicyclo[1.1.1]pentanyl, (C 1~6 Alkoxy C 1~6 Alkyl)C 3~7 Cycloalkyloxy, (C 1~6 Alkyl) 2 Phosphoryl, (C 1~6 Alkylmorpholinyl)C 1~6 Alkoxy, (C 1~6 Alkylsulfonylazetidinyl)C 1~6 Alkoxy, 2-oxa-6-azaspiro[3.3]heptanyl, azetidinyl, C1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkoxy C 2~6 Alkynyl, C 1~6 Alkoxy C 3~7 Cycloalkyloxy, C 1~6 Alkoxypyrrolidinyl, C 1~6 Alkyl, C 1~6 Alkylamino, C 1~6 Alkylsulfanyl, C 1~6 Alkylsulfinyl, C 1~6 Alkylsulfonyl, C 2~6 Alkenyl, C 3~7 Cycloalkyl, C 3~7 Cycloalkyloxy, carboxy, cyano, cyano C 1~6 Alkoxy, HaloC 1~6 Alkoxy, HaloC 1~6 Alkyl, halogen, hydroxy, morpholinyl, morpholinyl C 1~6 Alkoxy, oxetanyl C 1~6 Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl, tetrahydrofuranyloxy and trideuterioC 1~6 phenyl substituted once, twice or three times with substituents independently selected from alkoxy; Unsubstituted or halogen, hydroxy, C 1~6 Alkylsulfanyl and C 1~6 pyridinyl substituted once or twice with substituents independently selected from alkoxy, or pyrimidinyl, unsubstituted or substituted by halogen; R 6 is H or C 1~6 is alkyl, R 7 is C 1~6 is alkyl, R 7a is C 1~6 Alkyl, C 3~7 Cycloalkyl or C 1~6 Alkoxy C1~6 is alkyl, R 7b , H, C 1~6 Alkoxy or Phenyl C 1~6 is an alkoxy; R 7c is H or C 1~6 is an alkoxy; R 7d is C 1~6 Alkyl, C 3~7 Cycloalkyl C 1~6 Alkyl or C 1~6 Alkoxy C 1~6 is alkyl, R 7e H, amino, phenyl C 1~6 Alkylamino or morpholinyl C 1~6 is alkylamino, R 7f is C 1~6 Alkyl, Phenyl C 1~6 alkyl or oxetanyl; R 7g is H or C 1~6 Alkoxy C 1~6 is alkyl, Q 1 is unsubstituted or C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkoxy, C 1~6 Alkyl, C 1~6 Alkylcarbonyloxy, carboxy, hydroxy, hydroxyC 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkoxy and trideuterioC 1~6 C substituted once or twice with substituents independently selected from alkoxy 1~6 is alkylene, or -MOM-, where M is C 1~6 is alkylene, Q 2 is NH, O or S, A 1 is CH or N, A2 , CH, CR 7h or N, where R 7h is C 1~6 is alkyl, A 3 CR 8 or N, where R 8 , H, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkoxy, C 3~7 Cycloalkoxyamino, cyano, haloazetidinyl C 1~6 Alkyl, haloC 1~6 Alkoxy, halogen, morpholinyl C 1~6 alkyl or oxetanyl; A 4 is CR 9 or N, where R 9 is H, or R 8 and R 9 together with the atoms to which they are attached form a heterocyclyl, A 5 is CR 10 or N, where R 10 is H or a halogen, A 6 CR 11 or N, where R 11 is H, deuterio, halogen, C 1~6 Alkyl or C 1~6 is an alkoxy; A 7 is CR 12 or N, where R 12 is H or a halogen, However, A 1 , A 2 , A 3 and A 4 Two or less of the following are simultaneously N and A 5 , A 6 and A 7 (exactly one of is N) or a pharma- ceutically acceptable salt thereof.

[0047] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to (iv)(i) or (iii), or a pharma- ceutically acceptable salt thereof, wherein R 1 is H or C 1~6 It is an alkyl.

[0048] A further embodiment of the present invention is (v) a compound of formula (I) or (Ia) according to any one of (i) to (iv), or a pharma- ceutically acceptable salt thereof, wherein R 1 is H or methyl.

[0049] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (v), wherein R 2 is C 1~6 Alkyl or trideuterio C 1~6 It is an alkyl.

[0050] A further embodiment of the present invention is (vii) a compound of formula (I) or (Ia) according to any one of (i) to (vi), or a pharma- ceutically acceptable salt thereof, wherein R 2 is methyl, ethyl or trideuteriomethyl.

[0051] A further embodiment of the present invention is (viii) a compound of formula (I) or (Ia) according to any one of (i) to (vii), or a pharma- ceutically acceptable salt thereof, wherein R 3 teeth, [ka] and During the ceremony, R 4 H, HaroC 1~6 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, C 1~6 Alkoxy C 1~6 Alkyl, C1~6 Alkyl, C 3~7 Cycloalkylcarbonyl, HaloC 1~6 Alkyl, haloC 1~6 Alkylcarbonyl, HydroxyC 1~6 Alkyl, Hydroxy C 1~6 Alkylcarbonyl, HydroxyC 3~7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C 1~6 alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl; amino, C 1~6 Alkyl carbonyl, C 1~6 azetidinyl substituted with alkylsulfonyl or cyano; C 1~6 Alkoxy, Unsubstituted, or C 1~6 Alkoxy, C 1~6 Alkylcarbonylazetidinyl, C 1~6 Alkylsulfonylazetidinyl, C 3~7 Cycloalkylsulfonylazetidinyl, haloC 1~6 C substituted with alkylazetidinyl, hydroxy, morpholinyl or oxetanyl 1~6 Alkyl, Oxetanyl, oxooxazolidinyl, or Unsubstituted, or C 1~6 is an oxopyrrolidinyl substituted with alkyl or hydroxy; R 5 is C 1~6 Alkoxy, C 3~7 Cycloalkyloxy, cyano, haloC 1~6 Alkoxy, halogen, hydroxy and trideuterioC 1~6 phenyl substituted once, twice or three times with substituents independently selected from alkoxy; pyridinyl substituted twice with halogen, or pyrimidinyl substituted with halogen; R 6 is H, R 7a is C 1~6 is alkyl, R 7e is amino, R 7f is C 1~6 is alkyl, R 7g But H or C 1~6 Alkoxy C 1~6 It is an alkyl.

[0052] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (ix)(i) to (viii), or a pharma- ceutically acceptable salt thereof, wherein R 3 teeth, [ka] where: R 4 H, R 4is H, (1-acetylazetidin-3-yl)methyl, (1-cyclopropylsulfonylazetidin-3-yl)methyl, (1-ethylsulfonylazetidin-3-yl)methyl, (1-methylsulfonylazetidin-3-yl)methyl, [1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl, 1-acetylazetidin-3-yl, 1-methylsulfonylazetidin-3-yl, 2-oxooxazolidin-3-yl, 2-oxopyrrolidin-1-yl, 3-(1-hydroxycyclobutanecarbonyl)-3,6-diphenylphosphine ... Azabicyclo[3.1.1]heptan-6-yl, 3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3. 1.1]heptan-6-yl, 3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, Anoazetidin-1-yl, 3-hydroxy-2-oxo-pyrrolidin-1-yl, 3-methyl-2-oxo-pyrrolidin-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, 5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl, amino, azetidin-1-yl, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl, oxetan-2-ylmethyl or oxetan-3-yl. R 5 is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropoxy, cyano, difluoromethoxy, fluoro, hydroxy and trideuteriomethoxy; pyridinyl substituted twice with fluoro, or pyrimidinyl substituted with fluoro; R 6 is H, R 7a is methyl, R 7e is amino, R 7f is methyl, R 7g is H or methoxymethyl. A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (x)(i) to (ix), or a pharma- ceutically acceptable salt thereof, wherein R 3 teeth [ka] where: R 4 H, HaroC 1~6 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkylcarbonyl, HaloC 1~6 Alkyl, haloC 1~6 Alkylcarbonyl, HydroxyC 1~6 Alkyl, Hydroxy C 1~6Alkylcarbonyl, HydroxyC 3~7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C 1~6 alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl; amino, C 1~6 Alkyl carbonyl, C 1~6 azetidinyl substituted with alkylsulfonyl or cyano; C 1~6 Alkoxy, Unsubstituted, or C 1~6 Alkoxy, C 1~6 Alkylcarbonylazetidinyl, C 1~6 Alkylsulfonylazetidinyl, C 3~7 Cycloalkylsulfonylazetidinyl, haloC 1~6 C substituted with alkylazetidinyl, hydroxy, morpholinyl or oxetanyl 1~6 Alkyl, Oxetanyl, oxooxazolidinyl, or Unsubstituted, or C 1~6 is an oxopyrrolidinyl substituted with alkyl or hydroxy; R 5 is C 1~6 Alkoxy, C 3~7 Cycloalkyloxy, cyano, haloC 1~6 Alkoxy, halogen, hydroxy and trideuterioC 1~6 phenyl substituted once, twice or three times with substituents independently selected from alkoxy; pyridinyl substituted twice with halogen, or pyrimidinyl substituted with halogen; R 6 is H. A further embodiment of the present invention is (xi) a compound of formula (I) or (Ia) according to any one of (i) to (x), or a pharma- ceutically acceptable salt thereof, wherein R3 teeth, [ka] where: R 4is H, (1-acetylazetidin-3-yl)methyl, (1-cyclopropylsulfonylazetidin-3-yl)methyl, (1-ethylsulfonylazetidin-3-yl)methyl, (1-methylsulfonylazetidin-3-yl)methyl, [1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl, 1-acetylazetidin-3-yl, 1-methylsulfonylazetidin-3-yl, 2-oxooxazolidin-3-yl, 2-oxopyrrolidin-1-yl, 3-(1-hydroxycyclobutanecarbonyl)-3,6-diphenylphosphine ... Azabicyclo[3.1.1]heptan-6-yl, 3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3. 1.1]heptan-6-yl, 3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, Anoazetidin-1-yl, 3-hydroxy-2-oxo-pyrrolidin-1-yl, 3-methyl-2-oxo-pyrrolidin-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, 5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl, amino, azetidin-1-yl, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl, oxetan-2-ylmethyl or oxetan-3-yl. R 5 is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropoxy, cyano, difluoromethoxy, fluoro, hydroxy and trideuteriomethoxy; pyridinyl substituted twice with fluoro, or pyrimidinyl substituted with fluoro; R 6 is H.

[0053] A further embodiment of the present invention is (xii) a compound of formula (I) or (Ia) according to any one of (i) to (xi), or a pharma- ceutically acceptable salt thereof, wherein Q 1 is C 1~6 Alkoxy, C 1~6 Alkylcarbonyloxy, Hydroxy, C 1~6 Alkyl and trideuterio C 1~6 substituted once or twice with substituents independently selected from alkoxy 1~6 It is alkylene.

[0054] A further embodiment of the present invention is (xiii) a compound of formula (I) or (Ia) according to any one of (i) to (xii), or a pharma- ceutically acceptable salt thereof, wherein Q 1 is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl, acetoxy and trideuteriomethoxy.

[0055] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (xiii), or a pharma- ceutically acceptable salt thereof, wherein Q 1 is C1~6 Alkoxy-substituted C 1~6 It is alkylene.

[0056] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xv)(i) to (xiv), or a pharma- ceutically acceptable salt thereof, wherein Q 1 is methoxy or ethoxy substituted propylene.

[0057] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (xv), or a pharma- ceutically acceptable salt thereof, wherein Q 2 is NH or O.

[0058] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (xvi), or a pharma- ceutically acceptable salt thereof, wherein A 1 is N.

[0059] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (xvii), or a pharma- ceutically acceptable salt thereof, wherein A 3 is CR 8 and R 8 is H, C 1~6 Alkoxy, C 1~6 Alkyl, C 3~7 Cycloalkoxy, HaloC 1~6 It is alkoxy or halogen.

[0060] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xix)(i) to (xviii), or a pharma- ceutically acceptable salt thereof, wherein A 3 is CR 8 and R 8 is H, methoxy, methyl, cyclopropoxy, difluoromethoxy or fluoro.

[0061] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xx)(i) to (xix), or a pharma- ceutically acceptable salt thereof, wherein A 3 is CR 8 and R 8 is H.

[0062] A further embodiment of the present invention is (xxi) a compound of formula (I) or (Ia) according to any one of (i) to (xx), or a pharma- ceutically acceptable salt thereof, wherein A 4 is CR 9 and R 9 is H.

[0063] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (xxi), or a pharma- ceutically acceptable salt thereof, wherein A 5 is CR 10 or N and R 10 is H or fluoro.

[0064] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (xxii), or a pharma- ceutically acceptable salt thereof, wherein A 5 is CR 10 and R 10 is H.

[0065] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxiv) (i) to (xxiii), or a pharma- ceutically acceptable salt thereof, wherein A 6 is CR 11 and R 11 is H or a halogen.

[0066] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxv)(i) to (xxiv), or a pharma- ceutically acceptable salt thereof, wherein A 6 is CR 11 and R 11is H or fluoro.

[0067] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxvi)(i) to (xxv), or a pharma- ceutically acceptable salt thereof, wherein A 6 is CR 11 and R 11 is a halogen.

[0068] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxvii)(i) to (xxvi), or a pharma- ceutically acceptable salt thereof, wherein A 6 is CR 11 and R 11 is fluoro.

[0069] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxviii) (i) to (xxvii), or a pharma- ceutically acceptable salt thereof, wherein A 7 is CR 12 and R 12 is H or a halogen.

[0070] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxix)(i) to (xxviii), or a pharma- ceutically acceptable salt thereof, wherein A 7 is CR 12 and R 12 is H or fluoro.

[0071] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxx)(i) to (xxix), or a pharma- ceutically acceptable salt thereof, wherein A 7 is CR 12 and R 12 is H. A further embodiment of the invention is a compound of formula (I) or formula (Ia) according to any one of (xxxi) (i) or (ii) or (iii), wherein R1 is H or C 1~6 is alkyl, R 2 is C 1~6 Alkyl or trideuterio C 1~6 is alkyl, R 3 teeth, [ka] where: R 4 H, HaroC 1~6 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkylcarbonyl, HaloC 1~6 Alkyl, haloC 1~6 Alkylcarbonyl, HydroxyC 1~6 Alkyl, Hydroxy C 1~6 Alkylcarbonyl, HydroxyC 3~7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C 1~6 alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl; amino, C 1~6 Alkyl carbonyl, C 1~6 azetidinyl substituted with alkylsulfonyl or cyano; C 1~6 Alkoxy, Unsubstituted, or C 1~6 Alkoxy, C 1~6 Alkylcarbonylazetidinyl, C 1~6 Alkylsulfonylazetidinyl, C 3~7 Cycloalkylsulfonylazetidinyl, haloC 1~6C substituted with alkylazetidinyl, hydroxy, morpholinyl or oxetanyl 1~6 Alkyl, Oxetanyl, oxooxazolidinyl, Unsubstituted, or C 1~6 is an oxopyrrolidinyl substituted with alkyl or hydroxy; R 5 is C 1~6 Alkoxy, C 3~7 Cycloalkyloxy, cyano, haloC 1~6 Alkoxy, halogen, hydroxy and trideuterioC 1~6 phenyl substituted once, twice or three times with substituents independently selected from alkoxy; pyridinyl substituted twice with halogen, or pyrimidinyl substituted with halogen; R 6 is H, R 7a is C 1~6 is alkyl, R 7e is amino, R 7f is C 1~6 is alkyl, R 7g is H or C 1~6 Alkoxy C 1~6 is alkyl, Q 1 is C 1~6 Alkoxy, C 1~6 Alkylcarbonyloxy, Hydroxy, C 1~6 Alkyl and trideuterio C 1~6 C substituted once or twice with substituents independently selected from alkoxy 1~6 is alkylene, Q 2 is NH or O, A 1 is N, A 2 , CH, CR 7h or N, where R 7h is C 1~6is alkyl, A 3 is CR 8 where R 8 is H, C 1~6 Alkoxy, C 1~6 Alkyl, C 3~7 Cycloalkoxy, HaloC 1~6 alkoxy or halogen; A 4 is CR 9 where R 9 is H, A 5 is CR 10 or N, where R 10 is H or a halogen, A 6 is CR 11 where R 11 is H or a halogen, A 7 is CR 12 where R 12 is H or a halogen; or a pharma- ceutically acceptable salt thereof. A further embodiment of the present invention is a compound of formula (I) or (Ia) according to (xxxii)(xxxi), wherein R 1 is H or methyl, R 2 is methyl, ethyl or trideuteriomethyl, R 3 teeth, [ka] where: R 4 H, R 4is H, (1-acetylazetidin-3-yl)methyl, (1-cyclopropylsulfonylazetidin-3-yl)methyl, (1-ethylsulfonylazetidin-3-yl)methyl, (1-methylsulfonylazetidin-3-yl)methyl, [1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl, 1-acetylazetidin-3-yl, 1-methylsulfonylazetidin-3-yl, 2-oxooxazolidin-3-yl, 2-oxopyrrolidin-1-yl, 3-(1-hydroxycyclobutanecarbonyl)-3,6-diphenylphosphine ... Azabicyclo[3.1.1]heptan-6-yl, 3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3. 1.1]heptan-6-yl, 3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, Anoazetidin-1-yl, 3-hydroxy-2-oxo-pyrrolidin-1-yl, 3-methyl-2-oxo-pyrrolidin-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, 5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl, amino, azetidin-1-yl, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl, oxetan-2-ylmethyl or oxetan-3-yl. R 5 is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropoxy, cyano, difluoromethoxy, fluoro, hydroxy and trideuteriomethoxy; pyridinyl substituted twice with fluoro, or pyrimidinyl substituted with fluoro; R 6 is H, R 7a is methyl, R 7e is amino, R 7f is methyl, R 7g is H or methoxymethyl, Q 1 is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl, acetoxy and trideuteriomethoxy; Q 2 is NH or O, A 1 is N, A 2 , CH, CR 7h or N, where R 7h is methyl, A 3 is CR 8 where R 8 is H, methoxy, methyl, cyclopropoxy, difluoromethoxy or fluoro; A 4 is CR 9 where R 9 is H, A 5 is CR 10 or N, where R10 is H or fluoro, A 6 is CR 11 where R 11 is H or fluoro, A 7 is CR 12 where R 12 is H or fluoro; or a pharma- ceutically acceptable salt thereof. A further embodiment of the present invention is a compound of formula (I) or (Ia) according to (xxxiii)(xxxii), wherein R 1 is C 1~6 is alkyl, R 2 is C 1~6 is alkyl, R 3 teeth, [ka] where: R 4 H, HaroC 1~6 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkylcarbonyl, HaloC 1~6 Alkyl, haloC 1~6 Alkylcarbonyl, HydroxyC 1~6 Alkyl, Hydroxy C 1~6 Alkylcarbonyl, HydroxyC 3~7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C 1~6 alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl; amino, C 1~6 Alkyl carbonyl, C 1~6 azetidinyl substituted with alkylsulfonyl or cyano; C 1~6 Alkoxy, Unsubstituted, or C 1~6 Alkoxy, C 1~6 Alkylcarbonylazetidinyl, C 1~6 Alkylsulfonylazetidinyl, C 3~7 Cycloalkylsulfonylazetidinyl, haloC 1~6 C substituted with alkylazetidinyl, hydroxy, morpholinyl or oxetanyl 1~6 Alkyl, Oxetanyl, oxooxazolidinyl, Unsubstituted, or C 1~6 is an oxopyrrolidinyl substituted with alkyl or hydroxy; R 5 is C 1~6 Alkoxy, C 3~7 Cycloalkyloxy, cyano, haloC 1~6 Alkoxy, halogen, hydroxy and trideuterioC 1~6 phenyl substituted once, twice or three times with substituents independently selected from alkoxy; pyridinyl substituted twice with halogen, or pyrimidinyl substituted with halogen; R 6 is H, Q 1 is C 1~6 Alkoxy-substituted C 1~6 is alkylene, Q 2 is NH or O, A 1 is N, A 2 is CH or N, A 3 is CR 8 where R 8 is H, A 4 is CR9 where R 9 is H, A 5 is CR 10 or N, where R 10 is H, A 6 is CR 11 where R 11 is a halogen, A 7 is CR 12 where R 12 is H, or a pharma- ceutically acceptable salt thereof. A further embodiment of the present invention is a compound of formula (I) or (Ia) according to (xxxiv)(xxxiii), wherein R 1 is methyl, R 2 is methyl, R 3 teeth, [ka] where: R 4is H, (1-acetylazetidin-3-yl)methyl, (1-cyclopropylsulfonylazetidin-3-yl)methyl, (1-ethylsulfonylazetidin-3-yl)methyl, (1-methylsulfonylazetidin-3-yl)methyl, [1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl, 1-acetylazetidin-3-yl, 1-methylsulfonylazetidin-3-yl, 2-oxooxazolidin-3-yl, 2-oxopyrrolidin-1-yl, 3-(1-hydroxycyclobutanecarbonyl)-3,6-diphenylphosphine ... Azabicyclo[3.1.1]heptan-6-yl, 3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3. 1.1]heptan-6-yl, 3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, Anoazetidin-1-yl, 3-hydroxy-2-oxo-pyrrolidin-1-yl, 3-methyl-2-oxo-pyrrolidin-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, 5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl, amino, azetidin-1-yl, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl, oxetan-2-ylmethyl or oxetan-3-yl. R 5 is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropoxy, cyano, difluoromethoxy, fluoro, hydroxy and trideuteriomethoxy; pyridinyl substituted twice with fluoro, or pyrimidinyl substituted with fluoro; R 6 is H, Q 1 is methoxy or ethoxy substituted propylene; Q 2 is NH or O, A 1 is N, A 2 is CH or N, A 3 is CR 8 where R 8 is H, A 4 is CR 9 where R 9 is H, A 5 is CR 10 or N, where R 10 is H, A 6 is CR 11 where R 11 is fluoro, A 7 is CR 12 where R 12 is H, or a pharma- ceutically acceptable salt thereof. The present invention relates to a compound represented by the formula (Ia) [ka] (In the formula, M 1 is R 1 and optionally substituted heteroarylene, wherein R 1 is deuterio, halogen, cyano, carboxy, R, RO, RS, RNH, (R) 2 N, RCO, RSO 2 , RNHSO 2 , R 2 NSO 2 , RSO(NR), ROC 1~6 Alkyl, RSC 1~6 Alkyl, RNHC 1~6 Alkyl, (R) 2 NC 1~6 Alkyl, RSO 2 C 1~6 Alkyl, RNHSO 2 C 1~6 Alkyl, R 2 NSO 2 C 1~6 Alkyl or RSO(NR)C 1~6 alkyl, where R is H, R a , R b or R c and R a is R b or R c C optionally substituted with 1~6 is alkyl, R b is C 3~7 cycloalkyl, heterocyclyl, heteroaryl or aryl, 3~7 Cycloalkyl, heterocyclyl, heteroaryl and aryl are unsubstituted or substituted with halogen or R c and optionally substituted with R c is C 1~6 Alkyl, haloC 1~6 Alkyl, C 2~6 Alkenyl, HaloC 2~6 Alkenyl, C 2~6 Alkynyl, HaloC 2~6Alkynyl, C 3~7 Cycloalkyl, HaloC 3~7 Cycloalkyl, Amino, C 1~6 Alkylamino, (C 1~6 Alkyl) 2 Amino, HaloC 1~6 Alkylamino, halo(C 1~6 Alkyl) 2 Amino, C 3~7 Cycloalkylamino, (C 3~7 Cycloalkyl) 2 Amino, HaloC 3~7 Cycloalkylamino, (HaloC 3~7 Cycloalkyl) 2 Amino, C 3~7 Cycloalkyl(C 1~6 Alkyl)amino, haloC 3~7 Cycloalkyl(C 1~6 Alkyl)amino, C 1~6 Alkoxy C 1~6 Alkyl, (HaloC 1~6 Alkoxy)C 1~6 Alkyl, C 1~6 Alkoxy(halo)C 1~6 Alkyl, C 3~7 Cycloalkyl C 1~6 Alkyl, C 3~7 Cycloalkyl Halo C 1~6 Alkyl, C 1~6 Alkylcarbonyl, HaloC 1~6 Alkyl carbonyl, C 3~7 Cycloalkylcarbonyl, HaloC 3~7 Cycloalkylcarbonyl, C 1~6 Alkoxycarbonyl, HaloC 1~6 Alkoxycarbonyl, C 3~7 Cycloalkoxycarbonyl, HaloC 3~7 Cycloalkoxycarbonyl, HaloC 1~6 Alkoxycarbonyl, C 1~6 Alkylaminocarbonyl, (C 1~6 Alkyl) 2 Aminocarbonyl, C 3~7 Cycloalkylaminocarbonyl, (C 3~7 Cycloalkyl) 2 Aminocarbonyl, C1~6 Alkyl C 3~7 Cycloalkylaminocarbonyl, haloC 1~6 Alkylaminocarbonyl, halo(C 1~6 Alkyl) 2 Aminocarbonyl, HaloC 3~7 Cycloalkylaminocarbonyl, halo(C 3~7 Cycloalkyl) 2 Aminocarbonyl, HaloC 1~6 Alkyl C 3~7 Cycloalkylaminocarbonyl, C 1~6 Alkyl Halo C 3~7 Cycloalkylaminocarbonyl, (C 1~6 Alkyl) 3 Ammonio, C 1~6 Alkylsulfanyl, C 1~6 Alkylsulfinyl, C 1~6 Alkylsulfonyl, C 3~7 Cycloalkylsulfanyl, C 3~7 Cycloalkylsulfinyl, C 3~7 Cycloalkylsulfonyl, HaloC 1~6 Alkylsulfanyl, HaloC 1~6 Alkylsulfinyl, HaloC 1~6 Alkylsulfonyl, HaloC 3~7 Cycloalkylsulfanyl, HaloC 3~7 Cycloalkylsulfinyl, HaloC 3~7 Cycloalkylsulfonyl, HaloC 1~6 Alkoxysulfonyl, C 1~6 Alkylaminosulfonyl, (HaloC 1~6 alkylamino)sulfonyl, (C 1~6 Alkyl) 2 Aminosulfonyl, (HaloC 1~6 Alkyl) 2 Aminosulfonyl, (C 1~6 Alkyl) 2 Phosphoryl, (C 1~6 Alkoxy) 2 Phosphoryl, hydroxy (C 1~6 Alkoxy)phosphoryl, C 1~6 Alkoxyphosphoryl, Hydroxy, HydroxyC 1~6Alkyl, hydroxyhaloC 1~6 Alkyl, Hydroxy C 1~6 Alkoxy, Hydroxy, HaloC 1~6 Alkoxy, Hydroxy C 3~7 Cycloalkyl, hydroxyhaloC 3~7 Cycloalkyl, as well as H, C 1~6 Alkyl, C 1~6 selected from sulfonimidoyl optionally substituted with alkoxy, aryl, heteroaryl, and heterocyclyl; M 2 is arylene, heterocyclylene, or heteroarylene, and the arylene, heterocyclylene, or heteroarylene is R 1 and optionally substituted with M 3 is unsubstituted or R 3 and R 2 ,Juterio,R,ROC 1~6 Alkyl, RSC 1~6 Alkyl, RSO 2 C 1~6 Alkyl, RNHC 1~6 Alkyl or (R) 2 NC 1~6 is alkyl, R 3 is heteroaryl, aryl, heteroarylcarbonyl or arylcarbonyl, and the heteroaryl and aryl are R 1 and optionally substituted with Q 1 is -M-, -MOM-, -MSM-, -MN(R)-M-, where M is unsubstituted or deuterio, halogen, cyano, carboxy, R, RO, RS, RNH, R 2 N, RSO 2 , R.O.C. 1~6 Alkyl, RSC 1~6 Alkyl, RNHC 1~6 Alkyl, (R) 2 NC 1~6 Alkyl, and RSO 2 C 1~6C, optionally substituted with substituents independently selected from alkyl 1~6 is alkylene, Q 2 is NH, O or S) The present invention relates to a compound, or a pharma- ceutically acceptable salt thereof.

[0072] Another embodiment of the present invention is a compound represented by the formula (ii') [ka] (In the formula, R 1 is deuterio, H, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C 1~6 Alkyl, (C 1~6 Alkylsulfonylpiperazinyl)C 1~6 Alkyl, Amino, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkoxycarbonyl, C 1~6 Alkyl, C 1~6 Alkylaminocarbonyl, C 1~6 Alkylcarbonylamino, C 3~7 Cycloalkyl, HaloC 1~6 Alkyl, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkyl, Hydroxy, Pyrazolyl C 1~6 Alkyl or triazolyl C 1~6 is alkyl, R 2 is H, ((C 1~6 Alkyl) 3 Ammonio)C 1~6 Alkyl, (C 1~6 Alkylsulfonylpiperazinyl)C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkyl, C 3~7 Cycloalkyl C 1~6Alkyl, haloC 1~6 Alkyl, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkyl, Phenyl C 1~6 Alkyl, pyrimidinyloxy C 1~6 Alkyl, Tetrazolyl C 1~6 Alkyl or trideuterio C 1~6 is alkyl, R 3 teeth, [ka] where: R 4 is H, (C 1~6 Alkyl) 2 Aminocarbonyl, (C 1~6 Alkyl) 2 Phosphoryl, amino, aminocarbonyl, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkylamino, C 1~6 Alkoxycarbonyl, C 1~6 Alkyl, C 1~6 Alkylamino, C 3-7 Cycloalkyl, carboxy, cyano, hydroxy, hydroxyC 1~6 Alkyl, morpholinyl, morpholinyl C 1~6 Alkoxy or morpholinyl C 1~6 is alkyl, R 5 is thienyl, Unsubstituted, or halogen or C 1~6 alkyl-substituted bicyclo[1.1.1]pentanyl, C 1~6 Alkyl) 2 Phosphoryl, (C 1~6 Alkylmorpholinyl)C 1~6 Alkoxy, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkoxy, C 1~6 Alkoxy C1~6 Alkyl, C 1~6 Alkyl, C 1~6 Alkylamino, C 1~6 Alkylsulfanyl, C 1~6 Alkylsulfinyl, C 1~6 Alkylsulfonyl, C 2~6 Alkenyl, C 3~7 Cycloalkoxy, C 3~7 Cycloalkyl, carboxy, cyano, haloC 1~6 Alkoxy, HaloC 1~6 Alkyl, halogen, hydroxy, morpholinyl C 1~6 Alkoxy, oxetanyl C 1~6 Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl and trideuterioC 1~6 phenyl substituted once or twice with substituents independently selected from alkoxy; Unsubstituted or halogen, hydroxy and C 1~6 pyridinyl substituted once or twice with substituents independently selected from alkoxy, or pyrimidinyl, unsubstituted or substituted by halogen; R 6 is H or C 1~6 is alkyl, R 7 is C 1~6 is alkyl, Q 1 is unsubstituted or C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkoxy, C 1~6 Alkyl, C 1~6 Alkylcarbonyloxy, carboxy, hydroxy, hydroxyC 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkoxy and trideuterioC 1~6 C substituted once or twice with substituents independently selected from alkoxy 1~6 is alkylene, or -MOM-, where M is C1~6 is alkylene, Q 2 is NH, O or S, A 1 is CH or N, A 2 is CH or N, A 3 CR 8 or N, where R 8 , H, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkoxy, , cyano, haloazetidinyl C 1~6 Alkyl, haloC 1~6 Alkoxy, morpholinyl C 1~6 alkyl or oxetanyl; A 4 is CR 9 or N, where R 9 is H, or R 8 and R 9 together with the atoms to which they are attached form a heterocyclyl, A 5 is CR 10 or N, where R 10 is H or a halogen, A 6 CR 11 or N, where R 11 is H, deuterio, halogen, C 1~6 Alkyl or C 1~6 is an alkoxy; A 7 is CR 12 or N, where R 12 is H or a halogen, However, A 1 , A 2 , A 3 and A 4 Two or less of the following are simultaneously N and A 5 , A 6 and A 7 (exactly one of is N) or a pharma- ceutically acceptable salt thereof.

[0073] Another embodiment of the present invention is a compound represented by the formula (iii') [ka] (In the formula, R 1 is deuterio, H, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C 1~6 Alkyl, (C 1~6 Alkylsulfonylpiperazinyl)C 1~6 Alkyl, Amino, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkoxycarbonyl, C 1~6 Alkyl, C 1~6 Alkylaminocarbonyl, C 1~6 Alkylcarbonylamino, C 3~7 Cycloalkyl, HaloC 1~6 Alkyl, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkyl, Hydroxy, Pyrazolyl C 1~6 Alkyl or triazolyl C 1~6 is alkyl, R 2 is H, ((C 1~6 Alkyl) 3 Ammonio)C 1~6 Alkyl, (C 1~6 Alkylsulfonylpiperazinyl)C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkyl, C 3~7 Cycloalkyl C 1~6 Alkyl, haloC 1~6 Alkyl, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkyl, Phenyl C 1~6Alkyl, pyrimidinyloxy C 1~6 Alkyl, Tetrazolyl C 1~6 Alkyl or trideuterio C 1~6 is alkyl, R 3 teeth, [ka] where: R 4 is H, (C 1~6 Alkyl) 2 Aminocarbonyl, (C 1~6 Alkyl) 2 Phosphoryl, amino, aminocarbonyl, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkylamino, C 1~6 Alkoxycarbonyl, C 1~6 Alkyl, C 1~6 Alkylamino, C 3-7 Cycloalkyl, carboxy, cyano, hydroxy, hydroxyC 1~6 Alkyl, morpholinyl, morpholinyl C 1~6 Alkoxy or morpholinyl C 1~6 is alkyl, R 5 is thienyl, Unsubstituted, or halogen or C 1~6 alkyl-substituted bicyclo[1.1.1]pentanyl, C 1~6 Alkyl) 2 Phosphoryl, (C 1~6 Alkylmorpholinyl)C 1~6 Alkoxy, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 1~6 Alkylamino, C 1~6 Alkylsulfanyl, C 1~6Alkylsulfinyl, C 1~6 Alkylsulfonyl, C 2~6 Alkenyl, C 3~7 Cycloalkoxy, C 3~7 Cycloalkyl, carboxy, cyano, haloC 1~6 Alkoxy, HaloC 1~6 Alkyl, halogen, hydroxy, morpholinyl C 1~6 Alkoxy, oxetanyl C 1~6 Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl and trideuterioC 1~6 phenyl substituted once or twice with substituents independently selected from alkoxy; Unsubstituted or halogen, hydroxy and C 1~6 pyridinyl substituted once or twice with substituents independently selected from alkoxy, or pyrimidinyl, unsubstituted or substituted by halogen; R 6 is H or C 1~6 is alkyl, R 7 is C 1~6 is alkyl, Q 1 is unsubstituted or C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkoxy, C 1~6 Alkyl, C 1~6 Alkylcarbonyloxy, carboxy, hydroxy, hydroxyC 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, morpholinyl C 1~6 Alkoxy and trideuterioC 1~6 C substituted once or twice with substituents independently selected from alkoxy 1~6 is alkylene, or -MOM-, where M is C 1~6 is alkylene, Q 2 is NH, O or S, A 1 is CH or N, A 2 is CH or N, A 3 CR 8 or N, where R 8 , H, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, C 3~7 Cycloalkoxy, , cyano, haloazetidinyl C 1~6 Alkyl, haloC 1~6 Alkoxy, morpholinyl C 1~6 alkyl or oxetanyl; A 4 is CR 9 or N, where R 9 is H, or R 8 and R 9 together with the atoms to which they are attached form a heterocyclyl, A 5 is CR 10 or N, where R 10 is H or a halogen, A 6 CR 11 or N, where R 11 is H, deuterio, halogen, C 1~6 Alkyl or C 1~6 is an alkoxy; A 7 is CR 12 or N, where R 12 is H or a halogen, However, A 1 , A 2 , A 3 and A 4 Two or less of the following are simultaneously N and A 5 , A 6 and A 7 (exactly one of is N) or a pharma- ceutically acceptable salt thereof.

[0074] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to (iv'), (i') or (iii'), or a pharma- ceutically acceptable salt thereof, wherein R 1 is H or C 1~6 It is an alkyl.

[0075] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (v')(i') to (iv'), or a pharma- ceutically acceptable salt thereof, wherein R 1 is H or methyl.

[0076] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (vi')(i') to (v'), wherein R 2 is H or C 1~6 It is an alkyl.

[0077] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (vi), or a pharma- ceutically acceptable salt thereof, wherein R 2 is H, methyl or ethyl. A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (vii), or a pharma- ceutically acceptable salt thereof, wherein R 3 teeth, [ka] where: R 4 is H, amino, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, Hydroxy C 1~6 Alkyl or morpholinyl C 1~6 is alkyl, R 5 is C 1~6 Alkoxy, C 3~7 Cycloalkoxy, HaloC 1~6Alkoxy, halogen, hydroxy and trideuterioC 1~6 phenyl substituted one, two or three times with substituents independently selected from alkoxy; R 6 is H.

[0078] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (ix)(i) to (viii), or a pharma- ceutically acceptable salt thereof, wherein R 3 teeth, [ka] where: R 4 is H, amino, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl or morpholinylmethyl, R 5 is phenyl substituted once, twice or three times with substituents independently selected from fluoro, methoxy, trideuteriomethoxy, difluoromethoxy, ethoxy, cyclopropoxy and hydroxy; R 6 is H.

[0079] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (x'), (i') to (ix'), or a pharma- ceutically acceptable salt thereof, wherein R 3 teeth, [ka] where: R 4 is H or C 1~6 Alkoxy C 1~6 is alkyl, R 5 is C 1~6 phenyl substituted two or three times with substituents independently selected from alkoxy and halogen; R 6 is H. A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (i) to (x), or a pharma- ceutically acceptable salt thereof, wherein R 3 teeth, [ka] where: R 4 is H or methoxymethyl, R 5 is phenyl substituted two or three times with substituents independently selected from methoxy and fluoro; R 6 is H.

[0080] A further embodiment of the present invention is (xii) a compound of formula (I) or (Ia) according to any one of (i) to (xi), or a pharma- ceutically acceptable salt thereof, wherein Q 1 is C 1~6 Alkoxy, C 1~6 Alkylcarbonyloxy, hydroxy, and C 1~6 substituted once or twice with substituents independently selected from alkyl 1~6 It is alkylene.

[0081] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xiii') (i') to (xii'), or a pharma- ceutically acceptable salt thereof, wherein Q 1 is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl and acetoxy.

[0082] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xiv')(i') to (xiii'), or a pharma- ceutically acceptable salt thereof, wherein Q 1 is C 1~6 Alkoxy-substituted C 1~6 It is alkylene.

[0083] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xv')(i') to (xiv'), or a pharma- ceutically acceptable salt thereof, wherein Q 1 is methoxy or ethoxy substituted propylene.

[0084] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xvi')(i') to (xv'), or a pharma- ceutically acceptable salt thereof, wherein Q 2 is NH or O.

[0085] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xvii')(i') to (xvi'), or a pharma- ceutically acceptable salt thereof, wherein A 1 is N.

[0086] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xviii')(i') to (xvii'), or a pharma- ceutically acceptable salt thereof, wherein A 3 is CR 8 and R 8 is H, C 1~6 Alkoxy, C 1~6 Alkyl, C 3~7 Cycloalkoxy or haloC 1~6 It is an alkoxy.

[0087] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xix')(i') to (xviii'), or a pharma- ceutically acceptable salt thereof, wherein A 3 is CR 8 and R 8 is H, methoxy, methyl, cyclopropoxy or difluoromethoxy.

[0088] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xx')(i') to (xix'), or a pharma- ceutically acceptable salt thereof, wherein A 3 is CR 8 and R 8 is H.

[0089] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxi')(i') to (xx'), or a pharma- ceutically acceptable salt thereof, wherein A 4 is CR 9 and R 9 is H.

[0090] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxii')(i') to (xxi'), or a pharma- ceutically acceptable salt thereof, wherein A 5 is CR 10 or N and R 10 is H or fluoro.

[0091] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxiii') (i') to (xxii'), or a pharma- ceutically acceptable salt thereof, wherein A 5 is CR 10 and R 10 is H.

[0092] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxiv')(i') to (xxiii'), or a pharma- ceutically acceptable salt thereof, wherein A 6 is CR 11 and R 11 is H or a halogen.

[0093] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxv')(i') to (xxiv'), or a pharma- ceutically acceptable salt thereof, wherein A 6 is CR 11and R 11 is H or fluoro.

[0094] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxvi')(i') to (xxv'), or a pharma- ceutically acceptable salt thereof, wherein A 6 is CR 11 and R 11 is a halogen.

[0095] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxvii')(i') to (xxvi'), or a pharma- ceutically acceptable salt thereof, wherein A 6 is CR 11 and R 11 is fluoro.

[0096] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxviii')(i') to (xxvii'), or a pharma- ceutically acceptable salt thereof, wherein A 7 is CR 12 and R 12 is H or a halogen.

[0097] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxix')(i') to (xxviii'), or a pharma- ceutically acceptable salt thereof, wherein A 7 is CR 12 and R 12 is H or fluoro.

[0098] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to any one of (xxx')(i') to (xxix'), or a pharma- ceutically acceptable salt thereof, wherein A 7 is CR 12 and R 12 is H. A further embodiment of the present invention is a compound of formula (I) or formula (Ia) according to any one of (xxxi') (i') or (ii') or (iii'), wherein R 1 is H or C 1~6 is alkyl, R 2 is H or C 1~6 is alkyl, R 3 teeth, [ka] where: R 4 is H, amino, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkyl, Hydroxy C 1~6 Alkyl or morpholinyl C 1~6 is alkyl, R 5 is C 1~6 Alkoxy, C 3~7 Cycloalkoxy, HaloC 1~6 Alkoxy, halogen, hydroxy and trideuterioC 1~6 phenyl substituted one, two or three times with substituents independently selected from alkoxy; R 6 is H, Q 1 is C 1~6 Alkoxy, C 1~6 Alkylcarbonyloxy, HydroxyC 1~6 C substituted once or twice with substituents independently selected from alkyl 1~6 is alkylene, Q 2 is NH or O, A 1 is CH or N, A 2 is CH or N, A 3 is CR 8 where R8 is H, C 1~6 Alkoxy, C 1~6 Alkyl, C 3~7 Cycloalkoxy or haloC 1~6 is an alkoxy; A 4 is CR 9 where R 9 is H, A 5 is CR 10 or N, where R 10 is H or a halogen, A 6 is CR 11 where R 11 is H or a halogen, A 7 is CR 12 where R 12 is H or a halogen; or a pharma- ceutically acceptable salt thereof. A further embodiment of the present invention is a compound of formula (I) or (Ia) according to (xxxii')(xxxi'), wherein R 1 is H or methyl, R 2 is H, methyl or ethyl, R 3 teeth, [ka] where: R 4 is H, amino, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl, R 5 is phenyl substituted once, twice or three times with substituents independently selected from fluoro, methoxy, trideuteriomethoxy, difluoromethoxy, ethoxy, cyclopropoxy and hydroxy; R 6 is H, Q 1is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl and acetoxy; Q 2 is NH or O, A 1 is CH or N, A 2 is CH or N, A 3 is CR 8 where R 8 is H, methoxy, methyl, cyclopropoxy or difluoromethoxy; A 4 is CR 9 where R 9 is H, A 5 is CR 10 or N, where R 10 is H or fluoro, A 6 is CR 11 where R 11 is H or fluoro, A 7 is CR 12 where R 12 is H or fluoro; or a pharma- ceutically acceptable salt thereof.

[0099] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to (xxxiii')(xxxi'), wherein R 1 is C 1~6 is alkyl, R 2 is C 1~6 is alkyl, R 3 teeth, [ka] where: R 4 is H or C 1~6 Alkoxy C 1~6is alkyl, R 5 is C 1~6 phenyl substituted two or three times with substituents independently selected from alkoxy and halogen; R 6 is H, Q 1 is C 1~6 Alkoxy-substituted C 1~6 is alkylene, Q 2 is NH or O, A 1 is N, A 2 is CH or N, A 3 is CR 8 where R 8 is H, A 4 is CR 9 where R 9 is H, A 5 is CR 10 or N, where R 10 is H, A 6 is CR 11 where R 11 is a halogen, A 7 is CR 12 where R 12 is H, or a pharma- ceutically acceptable salt thereof.

[0100] A further embodiment of the present invention is a compound of formula (I) or (Ia) according to (xxxiv')(xxxiii'), wherein R 1 is methyl, R 2 is methyl, R 3 teeth, [ka] where: R 4 is H or methoxymethyl, R 5 is phenyl substituted two or three times with substituents independently selected from methoxy and fluoro; R 6 is H, Q 1 is methoxy or ethoxy substituted propylene; Q 2 is NH or O, A 1 is N, A 2 is CH or N, A 3 is CR 8 where R 8 is H, A 4 is CR 9 where R 9 is H, A 5 is CR 10 or N, where R 10 is H, A 6 is CR 11 where R 11 is fluoro, A 7 is CR 12 where R 12 is H, or a pharma- ceutically acceptable salt thereof.

[0101] Another embodiment (xxxv) of the present invention is a compound of formula (I) or (Ia) selected from: (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[2-(2,4-difluorophenyl)-3-methyl-imidazole-4-carbonyl]-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,16,18-tetrazapentacyclo[14.6.1.1 2,6 .1 8,11 .0 19,23 ]Pentacosa-1(22),2,4,6(25),17,19(23),20-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-hydroxyethyl)-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-Benzyl-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-methoxyethyl)-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-morpholinopropyl)-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 3-[(8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-13-yl]propyl-trimethyl-ammonium; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyridazin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-Methyl-10-[3-(3-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[7-(2,4-difluorophenyl)imidazo[5,1-f][1,2,4]triazin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-methoxyethoxy)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-methoxyethoxy)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-methoxyethoxy)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-4-(oxetan-3-yl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-22-fluoro-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(2-fluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(2-fluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,6-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(1-bicyclo[1.1.1]pentanyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[3-(2,4-difluorophenyl)-[1,2,4]triazolo[4,3-a]pyrazin-8-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(3,4-difluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-15-methoxy-13,18-dimethyl-10-[1-(3-methyl-1-bicyclo[1.1.1]pentanyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(3-fluoro-1-bicyclo[1.1.1]pentanyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 5-Fluoro-2-[4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile; [(8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate;

[0102] (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-4-carbonitrile;

[0103] (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-4-carbonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0104] (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0105] (8S,11S,15S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-4,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-4,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-4,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-4,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-4,5,10,13,17,19-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-4,5,10,13,17,19-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-4,5,10,13,17,19-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-4,5,10,13,17,19-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-(hydroxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-(hydroxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-(4-Fluoro-2-methoxy-phenyl)-4-[(8S,11S)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxamide; 1-(4-Fluoro-2-methoxy-phenyl)-N,N-dimethyl-4-[(8S,11S)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxamide; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(methylamino)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-methoxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-hydroxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 8S,11S)-10-[1-(2,4-difluorophenyl)-6-ethoxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(2-methoxyethylamino)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(2-morpholinoethoxy)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-10-[1-(4-fluoro-2-methylsulfanyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26 hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(6-fluoro-2-hydroxy-3-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,6-difluoro-3-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-13-Methyl-10-[3-(2-thienyl)imidazo[1,5-a]pyrazin-8-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(5-fluoro-3-methoxy-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(3-fluoro-5-methoxy-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(3,5-difluoro-2-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[2-(2-chloro-4-fluoro-phenyl)pyrimidin-5-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(methylamino)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,22,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-(cyclopropylmethyl)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,21,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(2-morpholinoethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(2-morpholinoethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(2-methoxyethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(2-methoxyethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(oxetan-3-ylmethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(oxetan-3-ylmethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(oxetan-3-yloxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(oxetan-3-yloxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-[(4-methylmorpholin-2-yl)methoxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-18-(2-methoxyethyl)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-18-(2-morpholinoethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-(2-hydroxyethyl)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-18-[2-[(4aR,7aS)-2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrol-6-yl]ethyl]-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-[2-(4-methylsulfonylpiperazin-1-yl)ethyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-[2-(1,2,4-triazol-1-yl)ethyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-(2-pyrazol-1-ylethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-23-fluoro-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,19,21,28-hexazapentacyclo[17.6.1.1 2,6 .1 8,11 .0 22,26 ]Octacosa-1(25),2(28),3,5,20,22(26),23-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-3-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(trifluoromethyl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 5-Fluoro-2-[4-[(8S,11S)-13-methyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile; 5-Fluoro-2-[4-[(8S,11S)-13-methyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]benzoic acid; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-ethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-13-Ethyl-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-methoxyethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .18,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-(2-morpholinoethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-hydroxypropyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-[3-(tetrazol-2-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-[3-(tetrazol-1-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-[3-(4-methylsulfonylpiperazin-1-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-hydroxyethoxy)-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-hydroxyethoxy)-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-15-(2-morpholinoethoxy)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-15-(2-morpholinoethoxy)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-18,22-dideuterio-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-15-hydroxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .18,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-hydroxy-13,15,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-hydroxy-13,15,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-hydroxy-13,15,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-hydroxy-13,15,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; [(8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-dimethylphosphoryl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxylic acid; 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carbonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-c]pyridazin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-c]pyridazin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-b]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-b]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-b]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-b]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-23-Chloro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(hydroxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-morpholino-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; Ethyl 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxylate; (8S,11S)-10-[1-(4-fluoro-2-methylsulfanyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methylsulfinyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methylsulfonyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-dimethylphosphoryl-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0106] (8S,11S)-4-[(3,3-difluoroazetidin-1-yl)methyl]-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-4-(morpholinomethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-4,15-dimethoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-4,15-dimethoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-4,13-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-4,13-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-amino-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[6-amino-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-(Cyclopropylmethyl)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-hydroxy-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-vinyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2-cyclopropyl-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2-bromo-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,22-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-4-(Difluoromethoxy)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-4-(Cyclopropoxy)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-13-Cyclopropyl-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(trideuteriomethoxy)-13-(trideuteriomethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-(difluoromethyl)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-ethyl-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-18-Ethyl-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(hydroxymethyl)-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[6-cyclobutyl-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4,5-difluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(trifluoromethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-15-Methoxy-10-[1-(2-methoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-chloro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11.0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(5-chloro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-4-(methoxymethyl)-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-4-carbonitrile; (8S,11S)-10-[1-[4-fluoro-2-(trifluoromethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-(trifluoromethyl)-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-4,13-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13-ethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13-ethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6.1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-4,13-dimethyl-3,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-3,5,7,10,13,17,19-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-thia-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)triazolo[4,5-c]pyridin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-[4-fluoro-2-(methoxymethyl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(5-fluoropyrimidin-2-yl)pyrazolo[4,3-c]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-3,10,13,17,19-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-3,10,13,17,19-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-3,10,13,17,19-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-4,10,13,17,19-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-4,10,13,17,19-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-4,10,13,17,19-pentaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(1-bicyclo[1.1.1]pentanyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6.1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(5-fluoropyrimidin-2-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-fluoro-4-phenyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(4,4,4-trifluorobutyl)-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-22-fluoro-13-(3-pyrimidin-2-yloxypropyl)-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-22-chloro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-21-chloro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(3,5-difluoro-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(3,5-difluoro-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6.1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-methoxypropyl)-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-16-oxa-7,10,13,19,21,28-hexazapentacyclo[17.6.1.1 2,6 .1 8,11 .0 22,26]Octacosa-1(25),2(28),3,5,20,22(26),23-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-15-methoxy-13,18-dimethyl-10-(1-pyrimidin-5-ylpyrazolo[3,4-d]pyrimidin-4-yl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (11S,14S,18R)-13-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-25-fluoro-18-methoxy-16,21-dimethyl-5-oxa-10,13,16,20,22,29-hexazahexacyclo[18.6.1.1 2,9 .1 11,14 .0 3,7 .0 23,27 ]Nonacosa-1(26),2(29),3(7),8,21,23(27),24-heptaen-15-one; (8S,11S,15R)-22-Fluoro-15-methoxy-13,18-dimethyl-10-[1-methyl-6-(3-thienyl)pyrazolo[4,3-c]pyridin-3-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(2,4-difluorophenyl)-1-methyl-pyrazolo[4,3-c]pyridin-3-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-21,23-difluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluoro-6-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[2-(2,4-difluorophenoxy)-4-pyridyl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-15-Ethoxy-10-[1-[4-fluoro-2-(2-oxopyrrolidin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,15,18-trimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,15,18-trimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6.1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,15,18-trimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,15,18-trimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,21,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,21,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-18-hydroxy-13-methyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaene-14-carboxylic acid; (8S,11S,15R)-10-[6-ethoxy-1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-methoxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-ethoxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(morpholinomethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-isopropyl-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; Methyl (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-18-carboxylate; (8S,11S)-18-(chloromethyl)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-hydroxy-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-18-Amino-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-N,13-dimethyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-18-carboxamide; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; N-[(8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-18-yl]acetamide; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-18-Cyclopropyl-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-fluoro-4-tetrahydrofuran-3-yl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22,23-difluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(2-oxopyrrolidin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-15-(trideuteriomethoxy)-13-(trideuteriomethyl)-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-tetrahydrofuran-3-yl-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-tetrahydropyran-4-yl-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-3-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-2-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-methylsulfonylazetidin-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(1-acetylazetidin-3-yl)methyl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[2-hydroxy-1-(hydroxymethyl)ethyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[1-(hydroxymethyl)-2-methoxy-ethyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-methylsulfonylazetidin-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(1-acetylazetidin-3-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-methylsulfonylpyrrolidin-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(1-acetylpyrrolidin-3-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-methylsulfonylpyrrolidin-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[[1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(1-acetylpyrrolidin-3-yl)methyl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-methyl-4-piperidyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-13-(3-morpholinopropyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-13-[3-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-13-[3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-[3-[(4aR,7aS)-2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrol-6-yl]propyl]-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11.0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-ethylsulfonylazetidin-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(1-cyclopropylsulfonylazetidin-3-yl)methyl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[[1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(pyrrolidine-1-carbonyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-(2,4-difluorophenyl)-4-[(8S,11S)-22-fluoro-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]-N-(2-hydroxyethyl)pyrazolo[3,4-d]pyrimidine-6-carboxamide; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(morpholine-4-carbonyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-(methoxymethyl)pyrazolo[4,3-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-5,13,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(1,3-dihydroisobenzofuran-4-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-methyl-6-oxo-pyrazolo[3,4-b]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2,2,2-trifluoro-1-hydroxy-ethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[7-cyclopropyl-1-(2,4-difluorophenyl)-6-oxo-pyrazolo[3,4-b]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-(2-methoxyethyl)-6-oxo-pyrazolo[3,4-b]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-methoxy-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-methoxy-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-methoxycyclopropyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-hydroxycyclopropyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(azetidin-1-yl)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-morpholino-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(2-fluoro-4-morpholino-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro-2-(3-methoxycyclobutoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro-2-[1-(methoxymethyl)cyclopropoxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(hydroxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-4,22-difluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2,2-dioxo-2λ 6 -Thia-6-azaspiro[3.3]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(hydroxymethyl)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxy-1-methyl-ethyl)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(3R,4R)-3-amino-4-fluoro-pyrrolidin-1-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-[(dimethylamino)methyl]azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-methylsulfonylazetidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(tetrahydrofuran-3-ylmethoxy)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(1-cyclopropylazetidin-3-yl)oxy-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[2-(4-methylpiperazin-1-yl)ethoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[[1-(2,2-difluoroacetyl)azetidin-3-yl]methoxy]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-methylpiperazin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-methylazetidin-3-yl)methoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-methylpyrrolidin-3-yl)methoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[1-(2-fluoroethyl)azetidin-3-yl]oxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-3-ylmethoxy)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(3S,4S)-3-amino-4-methoxy-pyrrolidin-1-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(dimethylamino)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .18,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(3-amino-3-methyl-azetidin-1-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[1-(2,2-difluoroethyl)azetidin-3-yl]oxy-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-morpholinoazetidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[[1-(2,2-difluoroethyl)azetidin-3-yl]methoxy]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[1-(2,2-difluoroethyl)azetidin-3-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]ethyl acetate; (8S,11S,15R)-22-Fluoro-10-[1-(5-fluoro-3-methylsulfanyl-2-pyridyl)-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R)-1-hydroxyethyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6.1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1S)-1-hydroxyethyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(morpholinomethyl)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 2-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]acetonitrile; (8S,11S,15R)-10-[6-(4,7-diazaspiro[2.5]octan-7-ylmethyl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[4-(oxetan-3-yl)piperazin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(4,7-diazaspiro[2.5]octan-7-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[4-(2H-tetrazol-5-yl)-1-piperidyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-methyl-4,7-diazaspiro[2.5]octan-7-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(3,5-difluoro-2-pyridyl)-6-(3-morpholinoazetidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolidin-8-yl]methoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(3aR,6aS)-2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-cyclopentyl-1-(3,5-difluoro-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(4aR,7aR)-4-methyl-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazin-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-Benzyl-4-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]piperazine-2-carboxylic acid; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-oxazol-5-yl-1-piperidyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-methylsulfonyl-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-15-methoxy-13,18-dimethyl-10-(3-prop-1-ynyl imidazo[1,5-a]pyrazin-8-yl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)-6-[[1-(2-methoxyacetyl)azetidin-3-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-[4-fluoro-2-(3-methoxy-3-methyl-but-1-ynyl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-[4-fluoro-2-(3-methoxypyrrolidin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-tetrahydrofuran-3-yloxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 2-[2-[4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]-3,5-difluoro-phenoxy]acetonitrile; (8S,11S,15S)-10-[1-[2,4-difluoro-6-[(1-methylsulfonylazetidin-3-yl)methoxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-4-(cyclopropylamino)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(6-fluoro-1H-indazol-5-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)indazol-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]-6-(oxetan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]-6-[3-oxa-6-azabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-methyl-7-oxo-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-methoxyethyl)-7-oxo-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[7-benzyloxy-1-(2,4-difluorophenyl)pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(cyclopropylmethyl)-1-(2,4-difluorophenyl)-7-oxo-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[(1,1-dioxothiethane-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 2-[3-[1-(2,4-difluorophenyl)-4-[(8S,11S,15S)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidin-1-yl]acetonitrile; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(1,1-dioxothian-4-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(methylsulfonylmethyl)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[6-(1-cyclopropylazetidin-3-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[(1,1-dioxothiethane-3-yl)methylsulfanyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(azetidin-1-yl)-1-[4-fluoro-2-(trideuteriomethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(azetidin-1-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(dimethylamino)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-imidazol-1-yl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2,2,2-trifluoroethoxy)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-(oxetan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (3S)-1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]pyrrolidine-3-carbonitrile; 8-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazin-4-one; (8S,11S,15R)-10-[6-(3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidine-3-carbonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-oxa-6-azabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-oxa-6-azabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidine-3-carbonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[8-(2-fluoroethyl)-5-oxa-2,8-diazaspiro[3.5]nonan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[8-(2-methoxyethyl)-5-oxa-2,8-diazaspiro[3.5]nonan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[5-(2-fluoroethyl)-8-oxa-2,5-diazaspiro[3.5]nonan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 4-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]morpholin-3-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-methyl-2-oxo-pyrrolidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-5-(3-phenylpropylamino)pyrazole-4-carbonyl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[(1S,5S)-3-cyclopropyl-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxopyrrolidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .18,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-[(3-fluorooxetan-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-[(3-fluorooxetan-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-hydroxy-6-(trifluoromethyl)-2-azaspiro[3.3]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6-oxa-1-azaspiro[3.3]heptan-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(2-fluoroethyl)-1,6-diazaspiro[3.3]heptan-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11.0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6.1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; 2-[3-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidin-1-yl]acetonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; 3-[6-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]propanenitrile; (8S,11S,15R)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-5-(2-morpholinoethylamino)pyrazole-4-carbonyl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[11-benzyl-3-(2,4-difluorophenyl)-3,4,8,11-tetrazatricyclo[7.3.0.0 2,6 ]dodeca-1(9),2(6),4,7-tetraen-7-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[3-(2,4-difluorophenyl)-11-methyl-3,4,8,11-tetrazatricyclo[7.3.0.0 2,6 ]dodeca-1(9),2(6),4,7-tetraen-7-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[5-amino-1-(2,4-difluorophenyl)pyrazole-4-carbonyl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; 2-[6-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]acetonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidine-3-carbonitrile; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[7-(2-fluoroethyl)-1,7-diazaspiro[3.5]nonan-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[7-(oxetan-3-yl)-1,7-diazaspiro[3.5]nonan-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(oxetan-3-yl)-1,6-diazaspiro[3.3]heptan-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6,6-dioxo-6λ 6 -Thia-1-azaspiro[3.3]heptan-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,7-diazabicyclo[4.2.0]octan-7-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[3-(2,4-difluorophenyl)-11-(oxetan-3-yl)-3,4,8,11-tetrazatricyclo[7.3.0.0 2,6 ]dodeca-1(9),2(6),4,7-tetraen-7-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6.1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,5S)-3-(oxetan-3-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-hydroxy-2-oxo-pyrrolidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxopyrrolidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; 3-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]oxazolidin-2-one; 3-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]oxazolidin-2-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-methyl-2-oxo-piperazin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[6-[3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxycyclobutanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; and (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(3-fluorocyclobutyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]Hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; or a pharma- ceutically acceptable salt thereof.

[0107] Another embodiment (xxxvi) of the present invention is a process for the preparation of a compound according to any one of (i) to (xxxv), comprising: a) in the presence of a base, a compound of formula (VIII) [ka] and R 3 via nucleophilic substitution between X and [ka] forming a compound of b) reacting a compound of formula (VIII) with R 3 forming a compound of formula (I) via a Buchwald-Hartwig reaction between X and c) reacting a compound of formula (VIII) with R 3 forming a compound of formula (I) via a condensation reaction between d) A compound of formula (XVIII) [ka] forming a compound of formula (I) via a cyclization reaction between e) in the presence of a base, a compound of formula (XX) [ka] and R 3 via nucleophilic substitution with X [ka] forming a compound of f) in the presence of a base, a compound of formula (Ic) [ka] and an alcohol or amine (R 4 -X) via a reaction between [ka] A process of forming g) A compound of formula (XXIV) [ka] reacting the amino group of with a halide via nucleophilic substitution or with a ketone via reductive amination to provide the final compound of formula (XXII), In this method, In steps a) and e), the base is DIEA, In step b), the catalyst is Pd 2 (dba) 3 and In step c) the coupling reagent is HATU, In step d), the reagent is CDI, BrCN or R 1 (OCH 3 ) 3 and In step e) the base is DIEA, In step f), the base is DIPEA, K 2 CO 3 or NaH, X is a halogen and R 13 is R a , R b or R c and M is C 1~6 alkylene, R e is a substituent having a primary or secondary amino group, and R 1 ~R 7 , Q 1 , Q 2 , A 1 ~A 7 is as described in any one of (i) to (xxxv) or (i') to (xxxiv').

[0108] Another embodiment (xxxvii) of the invention relates to a compound or a pharma- ceutically acceptable salt according to any one of (i) to (xxxv) or (i') to (xxxiv') for use as a therapeutically active substance.

[0109] Another embodiment (xxxviii) of the present invention relates to a pharmaceutical composition comprising a compound according to any one of (i)-(xxxv) or (i')-(xxxiv') and a therapeutically inert carrier.

[0110] Another embodiment (xxxix) of the invention relates to the use of a compound according to any one of (i)-(xxxv) or (i')-(xxxiv') for the treatment or prevention of an autoimmune disease, an inflammatory disease, a neuropathic disease, a metabolic disease, a cardiovascular disease, an eye disease, or select types of cancer in which overexpression or activation of STING is involved.

[0111] Another embodiment (xl) of the present invention relates to the use of a compound according to any one of (i) to (xxxv) or (i') to (xxxiv') for the treatment of a subject suffering from an interferonopathy or autoinflammatory disease in which STING activation is an underlying cause of the disease pathology.

[0112] Another embodiment (xli) of the invention relates to the use of a compound according to any one of (i) to (xxxv) or (i') to (xxxiv') for the inhibition of STING.

[0113] Another embodiment (xlii) of the invention relates to the use of a compound according to any one of (i) to (xxxv) or (i') to (xxxiv') for the preparation of a medicament for inhibiting STING.

[0114] Another embodiment of the invention (xliii) relates to a compound or a pharma- ceutically acceptable salt according to any one of (i) to (xxxv) or (i') to (xxxiv') when prepared according to the process of (xxxvi).

[0115] Another embodiment (xliv) of the present invention relates to a method for treating or preventing an autoimmune disease, the method comprising administering a therapeutically effective amount of a compound defined in any one of (i)-(xxxv) or (i')-(xxxiv').

[0116] Pharmaceutical Compositions and Administration Another embodiment provides pharmaceutical compositions or medicaments containing the compounds of the invention and therapeutically inert carriers, diluents or excipients, as well as methods of using the compounds of the invention to prepare such compositions and medicaments. In one example, the compounds of formula (I) can be formulated into galenical dosage forms by mixing at ambient temperature, at an appropriate pH, and to the desired degree of purity with a physiologically acceptable carrier, i.e., a carrier that is non-toxic to the recipient at the dosage and concentration used. The pH of the formulation will depend primarily on the particular application and the concentration of the compound, but is preferably in the range of about 3 to about 8. In one example, the compounds of formula (I) are formulated in acetate buffer at pH 5. In another embodiment, the compounds of formula (I) are sterile. The compounds can be stored, for example, as solid or amorphous compositions, as lyophilized formulations, or as aqueous solutions.

[0117] The composition is formulated, dosed, and administered in a manner consistent with good medical practice. Factors to be considered in this regard include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the administration schedule, and other factors known to medical practitioners. The "effective amount" of the compound to be administered is governed by such considerations and is the minimum amount required to inhibit STING interaction with IRF3, NF-kB, NLRP3, etc., to block downstream type I IFN and proinflammatory cytokine (e.g., IL-6, TNFa, ISG) production, cellular responses / symptoms (e.g., autophagy, apoptosis, cellular senescence). For example, such an amount may be below an amount that is toxic to normal cells, or to the mammal as a whole.

[0118] In one example, a pharma- ceutical effective amount of a compound of the invention administered parenterally per dose will be in the range of about 0.1-1000 mg / kg of patient body weight per day, alternatively about 0.1-1000 mg / kg of patient body weight per day, with a typical initial range of the compound used being 0.1-1000 mg / kg / day. In another embodiment, oral unit dosage forms such as tablets and capsules preferably contain about 0.1 to about 1000 mg of a compound of the invention.

[0119] The compounds of the present invention may be administered by any suitable means, including oral, topical (including buccal and sublingual), rectal, vaginal, transdermal, parenteral, subcutaneous, intraperitoneal, intrapulmonary, intradermal, intrathecal and epidural, and intranasal, and, where localized treatment is desired, intralesional administration. Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration.

[0120] The compounds of the present invention may be administered in any convenient dosage form, such as tablets, powders, capsules, liquids, dispersions, suspensions, syrups, sprays, suppositories, gels, emulsions, patches, etc. Such compositions may contain conventional ingredients in pharmaceutical preparations, such as diluents, carriers, pH adjusters, sweeteners, fillers and additional active agents.

[0121] Typical preparation is prepared by mixing the compound of the present invention and carrier or excipient.Suitable carrier and excipient are well known to those skilled in the art, and are described in detail in, for example, Ansel, Howard C., et al., Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems.Philadelphia: Lippincott, Williams&Wilkins,2004;Gennaro, Alfonso R., et al.Remington: The Science and Practice of Pharmacy.Philadelphia: Lippincott, Williams&Wilkins,2000;and Rowe, Raymond C.Handbook of Pharmaceutical Excipients.Chicago, Pharmaceutical Press,2005. The formulation may also include one or more buffers, stabilizers, surfactants, wetting agents, lubricants, emulsifiers, suspending agents, preservatives, antioxidants, opacifiers, glidants, processing aids, colorants, sweeteners, fragrances, flavorings, diluents, and other known additives to provide for superior presentation of the drug (i.e., the compound of the present invention or a pharmaceutical composition thereof) or to aid in the manufacture of a pharmaceutical product (i.e., a medicament).

[0122] An example of a suitable oral dosage form is a tablet containing about 0.1-1000 mg of the compound of the present invention formulated with about 0.1-1000 mg of anhydrous lactose, about 0.1-1000 mg of croscarmellose sodium, about 0.1-1000 mg of polyvinylpyrrolidone (PVP) K30, and about 0.1-1000 mg of magnesium stearate. The powdered ingredients are first mixed together and then mixed with a solution of PVP. The resulting composition can be dried, granulated, mixed with magnesium stearate, and compressed into tablet form using conventional equipment. An example of an aerosol formulation can be prepared, for example, by dissolving 0.1-1000 mg of the compound of the present invention in a suitable buffer solution, for example, phosphate buffer, and adding, if desired, an isotonicity agent, for example, a salt such as sodium chloride. The solution may be filtered, for example, using a 0.2 micron filter, to remove impurities and contaminants.

[0123] Thus, one embodiment includes a pharmaceutical composition comprising a compound of formula (I), or a stereoisomer or pharma- ceutically acceptable salt thereof. A further embodiment includes a pharmaceutical composition comprising a compound of formula (I), or a stereoisomer or pharma- ceutically acceptable salt thereof, together with a pharma- ceutically acceptable carrier or excipient.

[0124] Another embodiment includes a pharmaceutical composition comprising a compound of formula (I) for use in the treatment of interferonopathies, autoimmune diseases and inflammatory diseases.Another embodiment includes a pharmaceutical composition comprising a compound of formula (I) for use in the treatment of infectious diseases or select types of cancer.

[0125] The following Compositions A and B illustrate typical compositions of the present invention and serve merely as representative thereof.

[0126] Composition A The compounds of the invention can be used, as active ingredient, in a manner known per se to produce tablets of the following composition: Per tablet Active ingredient: 200mg Microcrystalline cellulose 155mg Cornstarch 25mg Talc 25mg Hydroxypropyl methylcellulose 20mg 425mg

[0127] Composition B The compounds of the present invention can be used in a manner known per se to produce capsules of the following composition as an active ingredient: Per capsule Active ingredient 100.0mg Cornstarch 20.0mg Lactose 95.0mg Talc 4.5mg Magnesium stearate 0.5mg 220.0mg

[0128] Indications and Treatment Methods The compounds of the present invention inhibit STING, including its signal transduction and activity, and are therefore useful for treating infection, inflammation, autoimmunity, degenerative diseases and cancer.

[0129] In some embodiments, the compounds of the invention are useful for treating or preventing autoimmune diseases.

[0130] In some embodiments, the compounds of the invention are useful for treating or preventing inflammatory diseases.

[0131] In some embodiments, compounds of the invention are useful for the treatment or prevention of neuropathic diseases.

[0132] In some embodiments, compounds of the invention are useful for treating or preventing cardiovascular disease.

[0133] In some embodiments, the compounds of the invention are useful for treating or preventing ocular diseases.

[0134] In some embodiments, the compounds of the invention are useful for treating or preventing select types of cancer in which overexpression or activation of STING is implicated.

[0135] Alternatively, the compounds of the present invention are useful for treating subjects suffering from interferonopathies or autoinflammatory diseases in which STING activation is the underlying cause of the disease pathology.More broadly, the compounds can be used for treating any pathological cellular process that is STING-dependent.

[0136] Another embodiment includes a method of treating or preventing cancer in a mammal in need of such treatment or prevention, comprising administering to said mammal a therapeutically effective amount of a compound of formula (I), stereoisomer, tautomer, prodrug, or a pharma- ceutically acceptable salt thereof. synthesis

[0137] The compounds of the present invention can be prepared by any conventional means. Suitable processes for synthesizing these compounds and their starting materials are illustrated in the following schemes and examples. All substituents, particularly R 1 ~R 7 , Q 1 , Q 2 , A 1 ~A 7 are as defined above unless otherwise indicated. Further, unless expressly stated otherwise, all reactions, reaction conditions, abbreviations and symbols have the meanings well known to one of ordinary skill in the art of organic chemistry.

[0138] General synthetic routes for preparing compounds of the invention are depicted in the following schemes.

[0139] Scheme 1 [ka] In the formula, R d is H or PG, where PG may be, for example, BOC or Cbz, and X is a halogen.

[0140] As shown in Scheme 1, the synthesis of the compounds of the present invention began with the boronic ester compound of formula (II) or halide (III). Pd(dppf)Cl 2 Catalysts such as K 2 CO 3 Suzuki coupling of a compound of formula (II) with a compound of formula (IIb) using a base such as HCl or TFA in dioxane gives a compound of formula (V), which can also be obtained via Suzuki coupling of a boronic ester compound of formula (IIIb) with a halide (III). On the other hand, Suzuki coupling between a compound of formula (II) with a halide (IIa) or between a compound of formula (IIIa) with a halide (III) provides an intermediate of formula (IV), which can be reacted with a compound of formula (IVa) via Buchwald-Hartwig amination or nucleophilic substitution to give a compound of formula (V). Direct hydrolysis of a compound of formula (V) in the presence of LiOH followed by appropriate deprotection gives a compound of formula (VI) (BOC deprotection: HCl in dioxane or TFA in DCM; Cbz deprotection: H 2 Pd / C or Pd(OH) under 2 Compounds of formula (VI) can be cyclized in the presence of a coupling reagent, such as HATU, and a base, such as DIPEA, to give compounds of formula (VII). BOC deprotection under acidic conditions (HCl in dioxane or TFA in DCM) or catalytic hydrogenation (H 2 Pd / C or Pd(OH) below 2 Deprotection of Cbz under acidic conditions (TFA) or with DIEA afforded compounds of formula (VIII). Compounds of formula (I) can be prepared by nucleophilic substitution in the presence of a base such as DIEA or by Pd 2 (dba) 3 or the like. 3 On the other hand, the compound of formula (IX) can be obtained by reacting a compound of formula (VIII) with R in the presence of a coupling reagent such as HATU. 3 It can also be obtained by condensation reaction between OH.

[0141] Scheme 2 [ka]

[0142] As shown in Scheme 2, Suzuki coupling between a halide (IIb) and a boronic ester compound of formula X) provides a compound of formula (XI), which can be easily reacted with a base, such as DIPEA, K 2 CO 3 The compound of formula (XII) reacts with the compound of formula (XII) via nucleophilic substitution in the presence of R to give the compound of formula (XIII). The preparation of the compounds of formula (XIV), (XV), (XVI), (XVII) is similar to the preparation of the compounds of formula (VI), (VII), (VIII), (IX) as described above in Scheme 1. The compound of formula (XVII) is hydrogenated in the presence of zinc and ammonium chloride to give the compound of formula (XVIII), which can be reacted with CDI, BrCN or R 1 (OCH 3 ) 3 to give the compound of formula (I).

[0143] A general synthetic route for preparing compounds of formula (XXI) is given below.

[0144] Scheme 3 [ka] In the formula, R 13 is R a , R b or R c It is.

[0145] As shown in Scheme 3, the compound of formula (VIIa) can be prepared by reacting R 1 Hydroxy C 1~6The compound of formula (VIIa) is reacted with methanesulfonic anhydride or methanesulfonyl chloride in the presence of a base such as DIPEA or TEA to give a methanesulfonate intermediate, which is treated with an amine to give a compound of formula (XIX). The preparation of a compound of formula (XX) is similar to the preparation of a compound of formula (VIII) in Scheme 1. A compound of formula (XXI) can be prepared by reacting a compound of formula (XX) with R in the presence of a base such as DIEA. 3 X can be obtained via nucleophilic substitution between

[0146] A general synthetic route for preparing compounds of formula (XXII) is shown below. Scheme 4 [ka] wherein X is OH, NH, SH or halogen; e is a substituent having a primary or secondary amino group.

[0147] As shown in Scheme 4, compounds of formula (Ic) can be prepared by reacting R 3 but, [ka] The compound of formula (Ic) is reacted with DIPEA, K 2 CO 3 or in the presence of a base such as NaH, an alcohol or an amine (R 4 -X) to give a compound of formula (XXII) directly or to give an intermediate compound of formula (XXIII) which is then deprotected under acidic conditions to give a compound of formula (XXIV). The amino group of the compound of formula (XXIV) can be reacted with a halide via nucleophilic substitution or with a ketone via reductive amination to give the final compound of formula (XXII). On the other hand, Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 Reaction of a compound of formula (Ic) with an alkyl halide (R4 Photoredox coupling between Pd and the BOC-protected compound of formula (XXIII) can directly give the compound of formula XXII) or can give the BOC-protected compound of formula (XXIII) which can then be deprotected under acidic conditions to give the compound of formula (XXIV). Nucleophilic substitution with a halide or reductive amination of the compound of formula XXIV) with a ketone provides the final compound of formula (XXII). Third, Pd 2 dba 3 Buchwald coupling between compounds of formula (Ic) and lactams (eg, pyrrolidin-2-one, morpholin-3-one) in the presence of a catalyst such as provides compounds of formula (XXII).

[0148] The compounds of the invention may be obtained as mixtures of diastereomers or enantiomers, which may be separated by methods well known in the art, for example (chiral) HPLC or SFC.

[0149] The present invention also relates to a process for the preparation of a compound of formula (I) or formula (I), comprising: a) in the presence of a base, a compound of formula (VIII) [ka] and R 3 via nucleophilic substitution between X and [ka] forming a compound of b) reacting a compound of formula (VIII) with R 3 forming a compound of formula (I) via a Buchwald-Hartwig reaction between X and c) reacting a compound of formula (VIII) with R 3 forming a compound of formula (I) via a condensation reaction between d) A compound of formula (XVIII) [ka] forming a compound of formula (I) via a cyclization reaction between e) in the presence of a base, a compound of formula (XX) [ka] and R 3 via nucleophilic substitution with X [ka] forming a compound of f) in the presence of a base, a compound of formula (Ic) [ka] and an alcohol or amine (R 4 -X) via a reaction between [ka] A process of forming g) A compound of formula (XXIV) [ka] reacting the amino group of with a halide via nucleophilic substitution or with a ketone via reductive amination to provide the final compound of formula (XXII), In this method, In steps a) and e), the base may be, for example, DIEA, In step b), the catalyst is, for example, Pd 2 (dba) 3 may be In step c) the coupling reagent may be, for example, HATU, In step d), the reagent is, for example, CDI, BrCN or R 1 (OCH3 ) 3 may be In step e) the base may be, for example, DIEA, In step f), the base is, for example, DIPEA, K 2 CO 3 or NaH, X is a halogen and R 13 is R a , R b or R c and M is C 1~6 alkylene, R e is a substituent having a primary or secondary amino group.

[0150] Compounds of formula (I) or (Ia) when prepared according to the above process are also an object of the present invention. EXAMPLES

[0151] The present invention will be more fully understood by reference to the following examples, which should not, however, be construed as limiting the scope of the invention.

[0152] Abbreviation The present invention will be more fully understood by reference to the following examples, which should not, however, be construed as limiting the scope of the invention.

[0153] The abbreviations used herein are as follows: ACN: Acetonitrile BOC 2 O: Di-tert-butyl dicarbonate BINAP: 2,2'-bis(diphenylphosphino)-1,1'-dinaphthalene DCM: dichloromethane DCE: Dichloroethane DIPEA or DIEA: N,N-Diisopropylethylamine DIBAL-H: Diisobutylaluminum hydride DIAD: Diisopropyl azodicarboxylate DMA: N,N-Dimethylacetylamine DMAP: 4-dimethylaminopyridine DMF: N,N-dimethylformamide DMSO: Dimethyl sulfoxide DPPP: 1,3-bis(diphenylphosphino)propane EA or EtOAc: Ethyl acetate FA: Formic acid HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate h(s) or hr(s): hours hPBMC: human peripheral blood mononuclear cells I C 50 :50% inhibitory concentration Ir[dF(CF 3 )ppy] 2 (dtbpy)(PF 6 ):[4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine-N1,N1']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate IPA: Isopropanol LCMS: Liquid Chromatography Mass Spectrometry mCPBA metachloroperoxybenzoic acid min(s) MS: Mass spectrometry MsCl: methanesulfonyl chloride Ms 2 O: Methanesulfonic anhydride NBS: N-bromosuccinimide NIS: N-iodosuccinimide NMP: N-methylpyrrolidone NiCl 2 .dtbbpy: [4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine]nickel(II) dichloride PE: Petroleum ether Preparative HPLC; Preparative High Performance Liquid Chromatography Preparative TLC: Preparative thin layer chromatography PyBOP / BOP: (1-hydroxy-1H-benzotriazolato-o)tri-1-pyrrolidinylphosphorus hexafluorophosphate PPh 3 : Triphenylphosphine Pd 2 (dba) 3 : Tris(dibenzylideneacetone)dipalladium(0) (R)-binap: (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene Rf: Retention factor rt, rt: room temperature RT: retention time RuPhos Pd G2: Second generation chloro(2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) Selectfluor 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) SFC: Supercritical Fluid Chromatography S-Phos: 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl TBSCl: tert-butyldimethylsilyl chloride t-BuXPhos: 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl tBuXPhos Pd G3: Methanesulfonato(2-di-t-butylphosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) tBu 3 P-Pd-G2 Chloro[(tri-tert-butylphosphine)(2-aminobiphenyl-2-yl)palladium(II) T 3 P: Propylphosphonic anhydride TEA: Trimethylamine TFA: Trifluoroacetic acid TFAA: Trifluoroacetic anhydride THF: tetrahydrofuran TLC: Thin Layer Chromatography Xantphos: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene XPhos: 2-dicyclohexylphosphino-2',4',6-triisopropylbiphenyl XPhos Pd G2: Chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) v / v volume ratio

[0154] General experimental conditions Intermediates and final compounds were purified by flash chromatography using one of the following instruments: i) Biotage SP1 system and Quad 12 / 25 cartridge module, ii) ISCO combi-flash chromatography instrument. Brand and pore size of silica gel: i) KP-SIL 60 Å, particle size: 40-60 μm; ii) CAS registration number: silica gel: 63231-67-4, particle size: 47-60 micron silica gel; iii) ZCX from Qingdao Haiyang Chemical Co.,Ltd, pore size: 200-300 or 300-400.

[0155] Intermediates and final compounds were purified by preparative HPLC on reversed-phase columns using XBridge™ Prep-C18 (5 μm, OBD™ 30×100 mm) columns, SunFire™ Prep-C18 (5 μm, OBD™ 30×100 mm) columns, Phenomenex Synergi-C18 (10 μm, 25×150 mm) or Phenomenex Gemini-C18 (10 μm, 25×150 mm) Waters AutoP purification system (sample manager 2767, pump 2525, detectors: Micromass ZQ and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water; acetonitrile and 0.1% FA in water or acetonitrile and 0.1% TFA in water). or Gilson-281 purification system (Pump 322, Detector: UV 156, Solvent system: acetonitrile and 0.05% ammonium hydroxide in water; acetonitrile and 0.225% FA in water; acetonitrile and 0.05% HCl in water; acetonitrile and 0.075% TFA in water; or acetonitrile and water).

[0156] For SFC chiral separation, the intermediates were purified by chiral column (Daicel chiralpak IC, 5 μm, 30 × 250 mm), AS (10 μm, 30 × 250 mm) or AD (10 μm, 30 × 250 mm) on a Mettler Toledo Multigram III system SFC, Waters 80Q preparative SFC or Thar80 preparative SFC, solvent system: CO 2 and IPA (0.5% TEA in IPA) or CO 2 and MeOH (0.1% NH in MeOH 3 H 2 O), 100 bar back pressure, UV detection at 254 or 220 nm.

[0157] LC / MS spectra of the compounds were obtained using an LC / MS (Waters™ Alliance 2795-Micromass ZQ, Shimadzu Alliance 2020-Micromass ZQ, or Agilent Alliance 6110-Micromass ZQ). The LC / MS conditions were as follows (run time 3 or 1.5 min): Acidic conditions I:A:H 2 B: 0.1% TFA in acetonitrile; C: 0.1% TFA in acetonitrile; Acidic condition II:A:H 2 B: 0.0375% TFA in O; C: 0.01875% TFA in acetonitrile; Basic conditions I:A:H 2 0.1%NH in O 3 H 2 O;B: acetonitrile; Basic conditions II:A:H 2 0.025%NH in O 3 H 2 O;B: acetonitrile; Neutral condition: A:H 2 O;B: acetonitrile.

[0158] Mass spectra (MS): Generally, only the ions representing the parent mass are reported; unless otherwise stated, the mass ions quoted are positive mass ions (MH). + It is.

[0159] NMR spectra were obtained using a Bruker Avance 400 MHz, 500 MHz.

[0160] Microwave-assisted reactions were performed on a Biotage Initiator Sixty microwave synthesizer. All reactions involving air-sensitive reagents were carried out under an argon or nitrogen atmosphere. Reagents were used as received and without further purification unless otherwise noted.

[0161] Preparation Example The following examples are intended to illustrate the meaning of the invention but do not in any way represent a limitation within the scope of the meaning of the invention.

[0162] Intermediate A1 tert-Butyl N-[2-methoxy-3-[2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0163] Step 1: Preparation of tert-butyl N-[3-(2-bromo-6-nitro-anilino)-2-hydroxy-propyl]carbamate (compound A1-b) To a solution of 1,3-diamino-2-propanol (35.64 g, 395.45 mmol, as "amine" in Table 1) in ACN, 3-bromo-2-fluoronitrobenzene (compound A1-a, 43.5 g, 197.73 mmol, as "aryl fluoride" in Table 1) was slowly added at 25° C. After stirring for 0.5 h at 20° C., the mixture was filtered, the filter cake was collected and dissolved in methanol. Then, tert-butyl (2-methylpropan-2-yl)oxycarbonyl carbonate (106.8 g, 489.47 mmol) and DIPEA (63.26 g, 489.47 mmol) were added. After stirring for 1 h at 20° C., the mixture was concentrated and the residue was purified by preparative HPLC to give compound A1-b (51.5 g). LCMS (M-56+H) + :336.

[0164] Step 2: Preparation of tert-butyl N-[3-(2-amino-6-bromo-anilino)-2-hydroxy-propyl]carbamate (compound A1-c) To a solution of tert-butyl N-[3-(2-bromo-6-nitro-anilino)-2-hydroxy-propyl]carbamate (compound A1-b, 50.5 g, 129.41 mmol) in methanol (846 mL) was added Raney Ni (30.38 g, 517.64 mmol) and hydrazine hydrate (34.79 g, 694.97 mmol). After stirring at 25° C. for 1 h, the mixture was filtered and concentrated. The crude product was dissolved in DCM (500 mL) and washed with water (300 mL). The organic layer was dried and concentrated to give compound A1-c (43 g). LCMS (M+H) + :360.

[0165] Step 3: Preparation of tert-butyl N-[3-(7-bromo-2-methyl-benzimidazol-1-yl)-2-hydroxy-propyl]carbamate (compound A1-d) To a solution of tert-butyl N-[3-(2-amino-6-bromo-anilino)-2-hydroxy-propyl]carbamate (compound A1-c, 37.5 g, 104.09 mmol) in anhydrous THF (496 mL) was added trimethyl orthoacetate (45 mL, as "solvent" in Table 1) and pyridinium p-toluenesulfonate (3.75 g, 14.92 mmol). After stirring at 20° C. for 1 h, the mixture was concentrated and the residue was triturated with PE / EA (1 / 1, 150 mL) to give compound A1-d (39 g). LCMS (M+H) + :384.

[0166] Step 4: Preparation of tert-butyl N-[3-(7-bromo-2-methyl-benzimidazol-1-yl)-2-methoxypropyl]-N-methyl-carbamate (compound A1-e) To a solution of tert-butyl N-[3-(7-bromo-2-methyl-benzimidazol-1-yl)-2-hydroxy-propyl]carbamate (compound A1-d, 10.0 g, 26.02 mmol) in DMF (200 mL) was added CH 3 I (11.08 g, 78.07 mmol, as “alkyl iodide” in Table 1) was added to N 2The mixture was stirred at -10°C for 5 h. Then the mixture was stirred at 20°C for an additional 12 h. The reaction was cooled to -10°C and then NaH (2.6 g, 65.06 mmol) was added slowly in portions. The mixture was stirred at -10°C for 5 h. Then the mixture was stirred at 20°C for an additional 12 h. The reaction was cooled to -10°C and then cooled to -10°C. 4 Quenched with Cl solution and extracted twice with EA, the organic layer was dried and concentrated to give compound A1-e (11.7 g). LCMS (M+H) + :412.

[0167] Step 5: Preparation of tert-butyl N-[2-methoxy-3-[2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate (Intermediate A1) To a mixture of tert-butyl N-[3-(7-bromo-2-methyl-benzimidazol-1-yl)-2-methoxy-propyl]-N-methyl-carbamate (compound A1-e, 10.5 g, 25.47 mmol) in DMSO (150 mL) was added potassium acetate (5.0 g, 50.93 mmol), bis(triphenylphosphine)palladium(II) chloride (2.68 g, 3.82 mmol) and butyldi-1-adamantylphosphine (2.74 g, 7.64 mmol). The mixture was cooled to 5° C. for 1 hour and then cooled to 5° C. 2 The mixture was degassed three times at rt and stirred at 130° C. for 2 h. The reaction mixture was poured into water (1000 mL) and extracted twice with EA (300 mL). The organic phase was washed with brine (300 mL), dried, concentrated and the residue was purified by silica gel to give intermediate A1 (8.8 g). LCMS (M+H) + :460.

[0168] The following intermediates in Table 1 can be prepared by replacing compound A1-a with "aryl fluoride" in step 1, replacing 1,3-diamino-2-propanol with "amine", replacing trimethyl orthoacetate with "solvent" in step 3, and replacing 1,3-diamino-2-propanol with "CH 3 Prepared similarly to intermediate A1 by replacing I with "alkyl iodide". [Table 1] TIFF2025506393000059.tif120170

[0169] Intermediate A6 tert-Butyl N-[(2R)-3-[5-fluoro-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]-2-methoxypropyl]-N-methyl-carbamate [ka] The title compound was prepared according to the following scheme. [ka] The title compound was prepared similarly to the preparation of intermediate A1 by using compound A7-d instead of compound A1-d. LCMS (M+H) + :478.

[0170] Intermediate A7 tert-Butyl N-[(2R)-2-ethoxy-3-[5-fluoro-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0171] Step 1: Preparation of tert-butyl N-[(2R)-3-(2-bromo-4-fluoro-6-nitro-anilino)-2-hydroxy-propyl]carbamate (compound A7-b) To a mixture of tert-butyl N-[(2R)-3-amino-2-hydroxy-propyl]carbamate (59.59 g, 313.25 mmol) and 1-bromo-2,5-difluoro-3-nitro-benzene (71.0 g, 298.33 mmol) in ACN (710 mL) was added potassium carbonate (82.46 g, 596.66 mmol). After stirring at 50° C. for 2 h, the mixture was filtered and the filtrate was concentrated to give compound A7-b (131 g). LCMS (M+H) + :352.

[0172] Step 2: Preparation of tert-butyl N-[(2R)-3-(2-amino-6-bromo-4-fluoro-anilino)-2-hydroxy-propyl]carbamate (compound A7-c) To a solution of compound A7-b (63.0 g, 154.33 mmol) in methanol (1000 mL) was added Raney Ni (36.23 g, 617.31 mmol) and hydrazine hydrate (29.19 g, 583.1 mmol). After stirring at 25° C. for 1 h, the mixture was filtered and the filtrate was concentrated. The residue was dissolved in DCM and washed with water and brine. The organic layer was dried and concentrated to give compound A7-c (128 g). LCMS (M+H) + :378.

[0173] Step 3: Preparation of tert-butyl N-[(2S)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-hydroxy-propyl]carbamate (compound A7-d) To a solution of compound A7-c (123.0 g, 325.19 mmol) in anhydrous THF (1500 mL) was added trimethyl orthoacetate (136.74 mL, 1104 mmol) and pyridinium p-toluenesulfonate (11.71 g, 46.62 mmol). The reaction was stirred at 20° C. for 1 h. The mixture was concentrated under reduced pressure to give compound A7-d (160 g). LCMS (M+H) + :400.

[0174] Step 4: Preparation of tert-butyl N-[(2S)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-[tert-butyl(dimethyl)silyl]oxy-propyl]carbamate (compound A7-e) To a solution of compound A7-d (80.0 g, 198.88 mmol) and imidazole (40.62 g, 596.63 mmol) in DMF (765 mL) was added tert-butyldimethylchlorosilane (59.95 g, 397.75 mmol), and the mixture was then stirred at 30° C. for 18 h. The mixture was cooled to ice-NH 4 Poured into aqueous Cl (2000 mL) and extracted twice with EtOAc (800 mL). The organic layer was dried and concentrated to give compound A7-e (94 g). LCMS (M+H) + :518.

[0175] Step 5: Preparation of tert-butyl N-[(2R)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-[tert-butyl(dimethyl)silyl]oxy-propyl]-N-methyl-carbamate (compound A7-f) To a solution of compound A7-e (82.0 g, 158.75 mmol) in DMF (800 mL) was added sodium hydride (60% in oil, 15.87 g, 396.89 mmol) at 0° C. and then stirred at 0° C. for 1 h. Then iodomethane (90.13 g, 635.02 mmol) was added at 0° C. and the mixture was stirred at 0° C. for 1 h. The reaction was quenched with water and extracted with EA. The organic layer was dried and concentrated and the crude product was purified by column chromatography to give compound A7-f (44.4 g). LCMS (M+H-56) + :530.

[0176] Step 6: Preparation of tert-butyl N-[(2R)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-hydroxy-propyl]-N-methyl-carbamate (compound A7-g) A mixture of compound A7-f (39.8 g, 75.02 mmol) and TBAF / THF (1 M, 150.0 mL, 150 mmol) was stirred at 20° C. for 2 h. The mixture was then concentrated and the crude product was diluted with EtOAc (600 mL) and washed with water and brine. The organic layer was dried and concentrated to give compound A7-g (39.4 g). LCMS (M+H) + :416.

[0177] Step 7: Preparation of tert-butyl N-[(2R)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-ethoxy-propyl]-N-methyl-carbamate (compound A7-h) To a solution of compound A7-g (17.4 g, 41.8 mmol) and iodoethane (5.01 mL, 62.7 mmol) in DMF (174 mL) was added sodium hydride (2.17 g, 54.34 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 3 h. The reaction was then quenched with water and the mixture was extracted with EA. The organic layer was dried and concentrated to give compound A7-h (20.4 g). LCMS (M+H) + :444.

[0178] Step 8: Preparation of tert-butyl N-[(2R)-2-ethoxy-3-[5-fluoro-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate (Intermediate A7) To a mixture of compound A7-h (19.4 g, 43.66 mmol) and bis(pinacolato)diboron (27.72 g, 109.15 mmol) in DMSO (194 mL) was added potassium acetate (8.57 g, 87.32 mmol), bis(triphenylphosphine)palladium(II) chloride (4.6 g, 6.55 mmol) and butyldi-1-adamantylphosphine (4.7 g, 13.1 mmol). The mixture was cooled to 5° C. for 2 hours and then cooled to 5° C. 2The mixture was degassed three times at rt and then stirred at 130° C. for 2 h. The reaction mixture was then poured into water (1000 mL) and extracted with EA (500 mL). The organic layer was dried, concentrated and the crude product was purified by column chromatography to give intermediate A7 (15 g). LCMS (M+H) + :478.

[0179] Intermediate A8 tert-Butyl N-[(2R)-2-ethoxy-3-[2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate [ka] The title compound was prepared similarly to the preparation of intermediate A7 by using 3-bromo-2-fluoronitrobenzene instead of 1-bromo-2,5-difluoro-3-nitro-benzene. LCMS (M+H) + :474.

[0180] Intermediate A9 tert-Butyl N-[2-ethoxy-3-[5-fluoro-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate [ka] The title compound was prepared similarly to the preparation of intermediate A7 by using tert-butyl N-[(3-amino-2-hydroxy-propyl]carbamate instead of tert-butyl N-[(2R)-3-amino-2-hydroxy-propyl]carbamate. LCMS (M+H) + :492.

[0181] Intermediate A10 tert-Butyl N-[2-ethoxy-3-[2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate [ka] The title compound was prepared similarly to the preparation of intermediate A7 by using tert-butyl N-[(3-amino-2-hydroxy-propyl]carbamate instead of tert-butyl N-[(2R)-3-amino-2-hydroxy-propyl]carbamate and 3-bromo-2-fluoronitrobenzene instead of 1-bromo-2,5-difluoro-3-nitro-benzene. LCMS (M+H) + :474.

[0182] Intermediate A15 tert-Butyl N-[3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0183] Step 1: Preparation of tert-butyl N-[3-(2-bromo-6-nitro-anilino)propyl]carbamate (Intermediate A15-a) A microwave tube was charged with 1-bromo-2-fluoro-3-nitro-benzene (2.7 g, 12.3 mmol, referred to as "aryl fluoride" in Table 2), tert-butyl N-(3-aminopropyl)carbamate (2.14 g, 12.3 mmol, referred to as "amine" in Table 2), K 2 CO 3(1.7 g, 12.3 mmol) and acetonitrile (15 mL) were added. The tube was sealed and heated to 90° C. for 3 h. The mixture was cooled, filtered, the filtrate was concentrated, and the residue was purified by silica gel to give intermediate A15-a (4.8 g). LCMS (M+H + ):374.

[0184] Step 2: Preparation of tert-butyl N-[3-(2-amino-6-bromo-anilino)propyl]carbamate (Intermediate A15-b) A flask was charged with nickel (2.9 g, 49.4 mmol), MeOH (100 mL) and tert-butyl N-[3-(2-bromo-6-nitro-anilino)propyl]carbamate (Intermediate A15-a, 5 g, 13.4 mmol), the suspension was stirred vigorously, and then hydrazine (8.56 g, 8.32 mL, 134 mmol) was added. After stirring at room temperature for 1 h, the mixture was filtered and the filtrate was concentrated. The residue was dissolved in DCM and washed with water and brine. The organic layer was dried and concentrated to give Intermediate A15-b (4.6 g). LCMS (M+H + ):344.

[0185] Step 3: Preparation of tert-butyl N-[3-(7-bromobenzimidazol-1-yl)propyl]carbamate (Intermediate A15-c) To a flask containing tert-butyl N-[3-(2-amino-6-bromo-anilino)propyl]carbamate (Intermediate A15-b, 3.5 g, 10.2 mmol), trimethyl orthoformate (9.7 g, 10 mL, 91.4 mmol, as "Solvent" in Table 2) and p-toluenesulfonic acid monohydrate (387 mg, 2.03 mmol) were added to form a pale yellow solution. The mixture was stirred at room temperature for 5 hours. The mixture was concentrated and the residue was purified by silica gel to give Intermediate A15-c (3.2 g). LCMS (M+H + ):354.

[0186] Step 4: Preparation of tert-butyl N-[3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate (Intermediate A15) To the tube was added tert-butyl N-[3-(7-bromobenzimidazol-1-yl)propyl]carbamate (Intermediate A15-c, 2.7 g, 7.62 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (4.84 g, 19.1 mmol), potassium acetate (1.5 g, 15.2 mmol) and DMSO (12 mL). The solution was diluted with N 2 The mixture was bubbled with 500 mg of ethyl acetate for 5 min, then butyldi-1-adamantylphosphine (820 mg, 2.29 mmol) and bis(triphenylphosphine)palladium(II) dichloride (802 mg, 1.14 mmol) were added. The tube was sealed and heated to 130° C. for 4 h. The mixture was diluted with water, then it was extracted with EA. The organic layer was dried and concentrated, and the residue was purified by silica gel to give intermediate A15 (2.1 g). LCMS (M+H + ):402.

[0187] The following intermediates in Table 2 were prepared similarly to Intermediate A15 with the reagents shown in Table 2, by replacing 1-bromo-2-fluoro-3-nitro-benzene with "aryl fluoride", tert-butyl N-(3-aminopropyl)carbamate with "amine" in step 1, and trimethyl orthoformate with "solvent" in step 3. [Table 2] TIFF2025506393000070.tif69170

[0188] Intermediate A17 tert-Butyl N-[2-ethoxy-3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate [ka] The title compound was prepared similarly to the preparation of intermediate A7 by using tert-butyl N-[(3-amino-2-hydroxy-propyl]carbamate instead of tert-butyl N-[(2R)-3-amino-2-hydroxy-propyl]carbamate, trimethoxymethane instead of 1,1,1-trimethoxyethane, and 3-bromo-2-fluoronitrobenzene instead of 1-bromo-2,5-difluoro-3-nitro-benzene. LCMS (M+H) + :474.

[0189] Intermediate A18 tert-Butyl N-[3-[2-(2-morpholinoethyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0190] Step 1: Preparation of 3-[7-bromo-2-(2-morpholinoethyl)benzimidazol-1-yl]propan-1-amine (Intermediate A18-a) A mixture of tert-butyl N-[3-(2-amino-6-bromo-anilino)propyl]carbamate (compound A15-b 4.5 g, 13.07 mmol) and 3-morpholinopropanoic acid (2.08 g, 13.07 mmol) in concentrated aqueous HCl (45.0 mL, 13.07 mmol) and water (45 mL) was stirred at 100 °C for 40 h. After adjusting the pH of the reaction mixture to 8-10 with NaOH (20%), the reaction mixture was extracted with DCM, and the organic layer was dried and concentrated to give compound A18-a (3.7 g). LCMS (M+H) + ):367.

[0191] Step 2: Preparation of tert-butyl N-[3-[7-bromo-2-(2-morpholinoethyl)benzimidazol-1-yl]propyl]carbamate (Intermediate A18-b) A mixture of compound A18-a (3.7 g, 10.21 mmol) and di-t-butyl dicarbonate (3.34 g, 15.32 mmol) in methanol was stirred at 20° C. for 16 h. The reaction mixture was concentrated and the residue was purified by preparative HPLC to give intermediate A18-b (1 g). LCMS (M+H + ):467.

[0192] Step 3: Preparation of tert-butyl N-[3-[2-(2-morpholinoethyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate (Intermediate A18) To the tube was added tert-butyl N-[3-[7-bromo-2-(2-morpholinoethyl)benzimidazol-1-yl]propyl]carbamate (Intermediate A18-b, 560 mg, 1.2 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (700 mg, 2.76 mmol), potassium acetate (235 mg, 2.4 mmol) and DMSO (6 mL). The solution was diluted with N 2 The mixture was bubbled with 500 ml of ethyl acetate for 5 min, then butyldi-1-adamantylphosphine (85.9 mg, 240 μmol) and bis(triphenylphosphine)palladium(II) dichloride (84.1 mg, 120 μmol) were added. The tube was heated to 130° C. for about 6 h. The mixture was diluted with water, then extracted with EA, and the organic layer was dried and concentrated. The residue was purified by silica gel to give intermediate A18 (180 mg). LCMS (M+H + ):515.

[0193] Intermediate A19 tert-Butyl N-methyl-N-[3-[5-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0194] Step 1: Preparation of tert-butyl N-methyl-N-[3-(4-methyl-2-nitro-anilino)propyl]carbamate (compound A19-a) To a mixture of 4-fluoro-3-nitrotoluene (5.0 g, 32 mmol) and potassium carbonate (8.9 g, 64 mmol) in ACN (100 mL) was added N-(3-aminopropyl)-N-methylcarbamic acid tert-butyl ester (6.7 g, 35.5 mmol) slowly at 25° C. After stirring at 85° C. for 2 h, the mixture was filtered and concentrated to give compound A19-a (11.6 g). LCMS (M+H) + :324. Step 2: Preparation of tert-butyl N-[3-(2-bromo-4-methyl-6-nitro-anilino)propyl]-N-methyl-carbamate (compound A19-b) A mixture of compound A19-a (10.0 g, 31 mmol) and NBS (6.73 g, 37.82 mmol) in ACN (100 mL) was stirred at 85° C. for 12 h. The reaction was then concentrated and the residue was purified by flash chromatography to give compound A19-b (4.75 g). LCMS (M+H) + :402.

[0195] Steps 3-5: Preparation of N-methyl-N-[3-[5-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate tert-butyl (Intermediate A19) The title compound was prepared similarly to the preparation of intermediate A15 by using compound A19-b instead of compound A15-a. LCMS (M+H) + :430. Intermediate A20 tert-Butyl N-cyclopropyl-N-[3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0196] Steps 1 to 3: Preparation of 3-(7-bromobenzimidazol-1-yl)propan-1-ol (compound A20-c) Compound A20-c was prepared similarly to the preparation of intermediate A15-c by using 3-aminopropan-1-ol instead of tert-butyl N-(3-aminopropyl)carbamate. LCMS (M+H) + :255. Step 4: Preparation of 7-bromo-1-(3-chloropropyl)benzimidazole (compound A20-d) SOCl 2 A mixture of compound A20-c (10 g, 39 mmol) in (40 mL) was stirred at 80° C. for 1 h. The mixture was then concentrated and the residue was dissolved in EtOAc and 5% NaHCO 3 and brine (50.0 mL). The organic layer was dried and concentrated to give compound A20-d (7.0 g). LCMS (M+H) + :273. Step 5: Preparation of N-[3-(7-bromobenzimidazol-1-yl)propyl]cyclopropanamine (compound A20-e) A mixture of compound A20-d (1.6 g, 5.85 mmol), cyclopropylamine (1.6 g, 28.03 mmol), DIPEA (1.6 g, 12.38 mmol) in NMP (10.0 mL) was stirred at 110° C. for 12 h. The mixture was then diluted with DCM and washed with water and brine. The organic layer was dried and concentrated to give crude compound A20-e (560 mg). LCMS (M+H) + :295. Step 6: Preparation of tert-butyl N-[3-(7-bromobenzimidazol-1-yl)propyl]-N-cyclopropyl-carbamate (compound A20-f) A mixture of compound A20-e (500 mg, 1.7 mmol) and di-t-butyl dicarbonate (500 mg, 2.29 mmol) in DCM (10 mL) was stirred at 20° C. for 1 h. The mixture was concentrated and the residue was purified by preparative TLC to give compound A20-f (560 mg), which was used directly in the next step. LCMS (M+H) + :396.

[0197] Step 7: Preparation of tert-butyl N-cyclopropyl-N-[3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate (Intermediate A20) The title compound was prepared similarly to the preparation of intermediate A15 by using compound A20-f instead of compound A15-c. LCMS (M+H) + :442.

[0198] Intermediate A22 tert-Butyl N-[3-[2-ethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]-2-methoxypropyl]-N-methyl-carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0199] Step 1: Preparation of tert-butyl N-[3-(7-bromo-2-ethyl-benzimidazol-1-yl)-2-hydroxy-propyl]carbamate (compound A22-a) To a solution of compound A1-c (7.3 g, 20 mmol) in water (8 mL) and DMF (80 mL), oxone (3.41 g, 20.26 mmol), propionaldehyde (1.35 g, 23.3 mmol) were added in sequence at 0° C., then stirred at 20° C. for 12 h. The reaction was quenched with saturated ammonium chloride solution (500 mL) and extracted with EA (1000 mL). The organic layer was dried and concentrated, and the residue was purified by column chromatography to give compound A22-a (2.5 g). LCMS (M+H) + :398.

[0200] Steps 2-3: tert-Butyl N-[3-[2-ethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]-2-methoxypropyl]-N-methyl-carbamate (Intermediate A22) The title compound was prepared similarly to the preparation of intermediate A1 by using compound A22-a instead of compound A1-d. LCMS (M+H) + :474.

[0201] Intermediate A23 tert-Butyl N-[2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-[2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0202] Step 1: Preparation of ethyl 3-(benzylamino)-2-[(benzylamino)methyl]propanoate (compound A23-a) To a mixture of benzylamine (7.97 mL, 73.01 mmol) and DIPEA (12.72 mL, 73.01 mmol) in ACN (80 mL) was slowly added ethyl-3-bromo-2-(bromomethyl)propionate (10 g, 36.5 mmol) in ACN (20 mL) at 80° C. for 1 h. The mixture was then stirred at 80° C. for 6 h. The reaction was concentrated and the residue was purified by flash chromatography to give compound A23-a (5.9 g). LCMS (M+H + ):327.

[0203] Step 2: Preparation of 3-(benzylamino)-2-[(benzylamino)methyl]propan-1-ol (compound A23-b) A solution of compound A23-a (8.7 g, 26.65 mmol) in THF (120 mL) was added with LiAlH 4 (1.2 g, 32 mmol) was added at 0° C., and the mixture was then stirred at 0° C. for 2 h. The reaction was cooled to 5° C. 2 The mixture was then diluted with EA (100 mL) and dried over anhydrous magnesium sulfate. The organic layer was concentrated to give compound A23-b (6.1 g). LCMS (M+H) + :285.

[0204] Step 3: Preparation of 3-amino-2-(aminomethyl)propan-1-ol (compound A23-c) A solution of compound A23-b (11 g, 38.68 mmol) in methanol (80 mL) and acetic acid (10 mL) was treated with Pd(OH) 2 / C(2.2g) 2 The mixture was stirred under hydrogen at 60° C. for 48 hours. The reaction mixture was filtered and concentrated to give compound A23-c (5 g). LCMS (M+H) + :105.

[0205] Steps 4-7: Preparation of tert-butyl N-[2-[(7-bromo-2-methyl-benzimidazol-1-yl)methyl]-3-hydroxy-propyl]carbamate (compound A23-g) Compound A23-g was prepared similarly to the preparation of intermediate A1-d by using compound A23-c instead of 1,3-diamino-2-propanol, LCMS (M+H) + :398.

[0206] Steps 8-9: Preparation of tert-butyl N-[2-[(7-bromo-2-methyl-benzimidazol-1-yl)methyl]-3-[tert-butyl(dimethyl)silyl]oxy-propyl]carbamate (compound A23-i) Compound A23-i was prepared similarly to the preparation of intermediate A7-f by using compound A23-g instead of compound A7-d. LCMS (M+H + ):526.

[0207] Step 10: Preparation of tert-butyl N-[2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-[2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate (Intermediate A23) The title compound was prepared similarly to the preparation of intermediate A1 by using compound A23-i instead of compound A1-e. LCMS (M+H + ):574.

[0208] Intermediate A24 tert-Butyl N-[2-(2-methoxyethoxy)-3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate [ka] The title compound was prepared similarly to the preparation of intermediate A7 by using tert-butyl N-[(3-amino-2-hydroxy-propyl]carbamate instead of tert-butyl N-[(2R)-3-amino-2-hydroxy-propyl]carbamate, 3-bromo-2-fluoronitrobenzene instead of 1-bromo-2,5-difluoro-3-nitro-benzene, trimethoxymethane instead of trimethoxymethane, and 1-bromo-2-methoxy-ethane instead of ethyl iodide. LCMS (M+H) + :490.

[0209] Intermediate A25 tert-Butyl N-methyl-N-[3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)benzimidazol-1-yl]propyl]carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0210] Step 1: Preparation of 3-[7-bromo-2-(trifluoromethyl)benzimidazol-1-yl]-N-methyl-propan-1-amine (Compound A25-b) A mixture of compound A26-a (7.65 g, 21.35 mmol) and concentrated HCl (1 mL) in TFA (70.0 mL) was stirred at 70° C. for 12 hours. The mixture was concentrated to give compound A25-b (6.6 g). LCMS (M+H) + :336

[0211] Step 2: Preparation of 3-[7-bromo-2-(trifluoromethyl)benzimidazol-1-yl]-N-methyl-propan-1-amine (compound A25-c) Compound A25-b (3.25 g, 9.67 mmol) in methanol (30 mL), BOC2 A mixture of O (4.36 g, 20 mmol) and DIPEA (3.37 mL, 19.34 mmol) was stirred at 20° C. for 1 h. The mixture was then concentrated and the residue was purified by silica gel to give compound A25-c (3.25 g). LCMS (M+H) + :436.

[0212] Step 3: Preparation of tert-butyl N-methyl-N-[3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)benzimidazol-1-yl]propyl]carbamate (Intermediate A25) To a mixture of compound A25-c (3.2 g, 7.33 mmol) and bis(pinacolato)diboron (4.66 g, 18.34 mmol) in DMSO (44.73 mL) was added potassium acetate (1.44 g, 14.67 mmol), bis(triphenylphosphine)palladium(II) chloride (0.77 g, 1.1 mmol) and butyldi-1-adamantylphosphine (0.79 g, 2.2 mmol). The mixture was cooled to 37° C. for 1 hour and cooled to 37° C. for 1 hour. 2 The mixture was degassed three times at 40° C. and stirred at 130° C. for 2 h. The reaction mixture was poured into water and extracted with EA. The organic layer was dried and concentrated, and the residue was purified by silica gel to give intermediate A25 (1.46 g). LCMS (M+H) + :484.

[0213] Intermediate A26 tert-Butyl N-[3-[2-methoxy-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0214] Step 1: Preparation of tert-butyl N-[3-(7-bromo-2-methoxy-benzimidazol-1-yl)propyl]-N-methyl-carbamate (compound A26-b) To a solution of compound A26-a (9.0 g, 26.1 mmol, synthesis see A15-b) in methanol (50 mL) was added tetramethoxymethane (7.1 g, 52.2 mmol) and TsOH·pyridine (1.3 g, 5.2 mmol). After stirring at 60 °C for 12 h, the mixture was concentrated and then purified by preparative HPLC to give compound A26-b (4.0 g). LCMS (M+H + ):454.

[0215] Step 2: Preparation of tert-butyl N-[3-[2-methoxy-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methyl-carbamate (Intermediate A26) To a mixture of compound A26-b (2.0 g, 5.0 mmol) and bis(pinacolato)diboron (1.9 g, 7.5 mmol) in 1,4-dioxane (20 mL) was added potassium acetate (1.0 g, 10.04 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.6 g, 0.7 mmol). 2 After stirring at 100° C. for 2 hours under atmospheric pressure, the mixture was poured into water (20.0 mL) and extracted with EtOAc. The organic layer was dried and concentrated, and the residue was purified by preparative HPLC to give intermediate A26 (0.5 g). LCMS (M+H + ):446.

[0216] Intermediate A27 tert-Butyl N-methyl-N-[5-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]pentyl]carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0217] Step 1: Preparation of tert-butyl N-[5-(2-bromo-6-nitro-anilino)pentyl]carbamate (compound A27-a) 1-Bromo-2-fluoro-3-nitro-benzene (660 mg, 3 mmol), tert-butyl N-(5-aminopentyl)carbamate (667 mg, 3.3 mmol), K 2 CO 3 A mixture of (622 mg, 4.5 mmol) was heated to 85° C. for 2 h. After cooling to room temperature, the reaction mixture was partitioned between water and DCM. The separated aqueous layer was extracted with DCM and the combined organic layers were washed with brine, dried and concentrated to give crude compound A27-a (1.43 g), which was used directly in the next step without purification. LCMS (M+H + ):302.

[0218] Step 2 Preparation of tert-butyl N-[5-(2-amino-6-bromo-anilino)pentyl]carbamate (compound A27-b) Hydrazine hydrate (698 mg, 9.0 mmol) was added dropwise to a mixture of tert-butyl N-[5-(2-bromo-6-nitro-anilino)pentyl]carbamate (compound A27-a, 1.43 g, 3.0 mmol) and Raney nickel (197 mg, 3.0 mmol) in methanol (10 mL), and after 30 min (no more bubbles), the reaction mixture was carefully filtered. The filtrate was concentrated, the residue was dissolved in EtOAc, then washed with water and brine, the organic layer was dried and concentrated to give crude compound A27-b (1.54 g), which was used directly in the next step without purification. LCMS (M+H) + ):372.

[0219] Step 3: Preparation of tert-butyl N-[5-(7-bromobenzimidazol-1-yl)pentyl]carbamate (compound A27-c) A mixture of tert-butyl N-[5-(7-bromobenzimidazol-1-yl)pentyl]carbamate (A27-b, 1.54 g, 2.9 mmol), trimethyl orthoformate (922 mg, 8.7 mmol) and p-toluenesulfonic acid monohydrate (55 mg, 0.29 mmol) in anhydrous THF was stirred at room temperature for 16 h. The reaction mixture was concentrated to give some oil, which was dissolved in DCM and then saturated NaHCO 3 The organic layer was dried and concentrated to give crude compound A27-c (1.59 g), which was used directly in the next step without purification. LCMS (M+H + ):382.

[0220] Step 4: Preparation of tert-butyl N-[5-(7-bromobenzimidazol-1-yl)pentyl]-N-methyl-carbamate (compound A27-d) To a mixture of tert-butyl N-[5-(7-bromobenzimidazol-1-yl)pentyl]-N-methyl-carbamate (A27-c, 1.59 g, 2.08 mmol) and iodomethane (886 mg, 6.24 mmol) in anhydrous DMF (8 mL), NaH (333 mg, 8.32 mmol) was added in one portion and the resulting mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with water and then extracted with EtOAc. The separated organic layer was washed with water and brine, the organic layer was dried and concentrated, and the residue was purified by flash column to give compound A27-d (595 mg). LCMS (M+H + ):396.

[0221] Step 5: Preparation of tert-butyl N-methyl-N-[5-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]pentyl]carbamate (Intermediate A27) A mixture of tert-butyl N-[5-(7-bromobenzimidazol-1-yl)pentyl]-N-methyl-carbamate (compound A27-d, 595 mg, 1.13 mmol), bis(pinacolato)diboron (572 mg, 2.25 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (47 mg, 0.056 mmol) and potassium acetate (332 mg, 3.38 mmol) in anhydrous 1,4-dioxane (10 mL) was heated at 110° C. for 16 h under nitrogen using conventional heating. After cooling to room temperature, the reaction mixture was partitioned between water and DCM. The separated aqueous layer was extracted with DCM and the combined organic layers were washed with brine and anhydrous Na 2 SO 4 The mixture was dried at 40° C. and then concentrated. The residue was purified by flash chromatography to give crude intermediate A27 (429 mg). LCMS (M+H + ):444.

[0222] Intermediate A28 tert-Butyl N-methyl-N-[2-[2-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]ethoxy]ethyl]carbamate [ka] The title intermediate A28 was prepared similarly to the preparation of intermediate A27 by replacing tert-butyl N-(5-aminopentyl)carbamate with tert-butyl N-[2-(2-aminoethoxy)ethyl]carbamate. LCMS (M+H + ):446.

[0223] Intermediate A30 tert-Butyl N-[(2S)-3-[5-fluoro-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]-2-methoxypropyl]-N-methyl-carbamate [ka] The title compound was prepared according to the following scheme. [ka]

[0224] Steps 1-3: Preparation of tert-butyl N-[(2S)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-hydroxy-propyl]carbamate (compound A30-d) The title compound was prepared similarly to the preparation of compound A7-d by using tert-butyl N-[(2S)-3-amino-2-hydroxy-propyl]carbamate instead of tert-butyl N-[(2R)-3-amino-2-hydroxy-propyl]carbamate. LCMS (M+H) + :400.

[0225] Steps 4-5: Preparation of tert-butyl N-[(2S)-3-[5-fluoro-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]-2-methoxy-propyl]-N-methyl-carbamate (Intermediate A30) The title compound was prepared similarly to the preparation of intermediate A1 by using compound A30-d instead of compound A1-d. LCMS (M+H) + :478.

[0226] Intermediates B1 and B2 O1-tert-butyl O2-methyl(2S,4S)-4-[(4-chloropyrimidin-2-yl)amino]pyrrolidine-1,2-dicarboxylate (Intermediate B1) and O1-tert-butyl O2-methyl(2S,4S)-4-[(2-chloropyrimidin-4-yl)amino]pyrrolidine-1,2-dicarboxylate (Intermediate B2) [ka] The title compound was prepared according to the following scheme. [ka] 2,4-Dichloropyrimidine (19.21 g, 128.94 mmol), 1-(tert-butyl) 2-methyl(2S,4S)-4-aminopyrrolidine-1,2-dicarboxylate (21 g, 85.96 mmol) and K in DMF (100 mL). 2 CO 3 A mixture of (35.64 g, 257.89 mmol) was stirred at 80° C. for 16 h. The reaction was then diluted with EtOAc, washed with water and brine, the organic layer was concentrated, and the residue was purified by silica gel (eluting with 10%-30% PE in EtOAc) to give Intermediate B1 (faster eluting, 5 g) LCMS (M+H + ): 357, and intermediate B2 (slower eluting, 25 g), LCMS (M+H + ):357 was obtained.

[0227] Intermediates B3 and B4 O1-tert-butyl O2-methyl (2S,4S)-4-[(4-chloro-6-methyl-pyrimidin-2-yl)amino]pyrrolidine-1,2-dicarboxylate (Intermediate B3) and O1-tert-butyl O2-methyl (2S,4S)-4-[(2-chloro-6-methyl-pyrimidin-4-yl)amino]pyrrolidine-1,2-dicarboxylate (Intermediate B4) [ka] The title compound was prepared according to the following scheme. [ka] 2,4-Dichloro-6-methyl-pyrimidine (1.2 g, 7.37 mmol), 1-(tert-butyl) 2-methyl (2S,4S)-4-aminopyrrolidine-1,2-dicarboxylate (1.2 g, 4.91 mmol), DIPEA (634.85 mg, 4.91 mmol) and K in acetonitrile (24 mL). 2 CO 3 A mixture of (2.04 g, 14.74 mmol) was stirred at 80° C. for 16 h. The reaction was then filtered, concentrated, and the residue was purified by silica gel (eluting with 10% to 30% PE in EtOAc) to give Intermediate B3 (faster eluting, 300 mg), LCMS (M+H + ):371, and intermediate B4 (slower eluting, 700 mg). + ):371

[0228] Intermediate B5 O1-tert-butyl O2-methyl(2S,4S)-4-[(6-chloropyrimidin-4-yl)amino]pyrrolidine-1,2-dicarboxylate [ka] The title compound was prepared according to the following scheme. [ka] 4,6-Dichloropyrimidine (2.29 g, 15.35 mmol), 1-(tert-butyl) 2-methyl(2S,4S)-4-aminopyrrolidine-1,2-dicarboxylate (2.5 g, 10.23 mmol, 1 equiv.) and K in acetonitrile (50 mL). 2 CO 3 (4.24 g, 30.7 mmol) was stirred at 80° C. for 16 h. The reaction was then filtered, concentrated, and the residue was purified by silica gel to give Intermediate B5 (3.5 g). LCMS (M+H + ):357.

[0229] Intermediates B6 and B7 O1-benzyl O2-methyl (2S,4S)-4-[(4-chloropyrimidin-2-yl)amino]pyrrolidine-1,2-dicarboxylate (Intermediate B6) and O1-benzyl O2-methyl (2S,4S)-4-[(2-chloropyrimidin-4-yl)amino]pyrrolidine-1,2-dicarboxylate (Intermediate B7) [ka] The title compound was synthesized according to the following scheme: [ka] It was prepared according to

[0230] 2,4-Dichloropyrimidine (5.35 g, 35.9 mmol), 1-benzyl 2-methyl(2S,4S)-4-aminopyrrolidine-1,2-dicarboxylate (5 g, 18 mmol), K 2 CO 3 A mixture of (4.97 g, 35.9 mmol) and DIPEA (4.64 g, 35.9 mmol) was stirred at room temperature for 48 h. The reaction was then filtered, concentrated, and the residue was purified by silica gel (eluting with 10%-30% PE in EtOAc) to give intermediate B6 (faste...

Claims

1. Formula (Ia) 【Chemical 1】 (In the formula, M １ is R １ and heteroarylene optionally substituted with R １ is deuterio, halogen, cyano, carboxy, R, RO, RS, RNH, (R) ２ N, RCO, RSO ２ , RNHSO ２ , R ２ NSO ２ , RSO(NR), R ３ Si, ROC １～６ Alkyl, RSC １～６ Alkyl, RNHC １～６ alkyl, (R) ２ NC １～６ Alkyl, RSO ２ C １～６ Alkyl, RNHSO ２ C １～６ Alkyl, R ２ NSO ２ C １～６ Alkyl, RSO(NR)C １～６ Alkyl or R ３ SiC １～６ alkyl, R is H, R ａ , R ｂ or R ｃ and R ａ is R ｂ or R ｃ C optionally substituted with １～６ is alkyl, R ｂ is C ３～７ cycloalkyl, heterocyclyl, heteroaryl or aryl, ３～７ Cycloalkyl, heterocyclyl, heteroaryl and aryl are unsubstituted or substituted with deuterio, halogen or R ｃ optionally substituted with R ｃ , Deuterio, C １～６ Alkyl, (C １～６ alkyl) ３ Si, HaloC １～６ Alkyl, deuterio C １～６ Alkyl, C １～６ Alkoxy, HaloC １～６ Alkoxy, Deuterio C １～６ Alkoxy, C ２～６ Alkenyl, HaloC ２～６ Alkenyl, deuterio C ２～６ Alkenyl, C ２～６ Alkynyl, HaloC ２～６ Alkynyl, deuterio C ２～６ Alkynyl, C ３～７ Cycloalkyl, haloC ３～７ Cycloalkyl, deuterio C ３～７ Cycloalkyl, amino, C １～６ alkylamino, (C １～６ alkyl) ２ Amino, C １～６ Alkylcarbonylamino, HaloC １～６ Alkylamino, HaloC １～６ Alkylcarbonylamino, (haloC １～６ alkyl) ２ Amino, C ３～７ Cycloalkylamino, C ３～７ cycloalkylcarbonylamino, (C ３～７ cycloalkyl) ２ Amino, Halo C ３～７ cycloalkylamino, (haloC ３～７ cycloalkyl) ２ Amino, C ３～７ Cycloalkyl (C １～６ Alkyl)amino, haloC ３～７ Cycloalkyl (C １～６ alkyl)amino, C １～６ Alkyl sulfonyl amino, halo C １～６ Alkylsulfonylamino, C １～６ Alkoxy C １～６ Alkyl, (haloC １～６ Alkoxy)C １～６ Alkyl, C １～６ Alkoxy (halo) C １～６ Alkyl, C ３～７ Cycloalkyl C １～６ Alkyl, C ３～７ Cycloalkylhalo C １～６ Alkyl, C １～６ Alkylcarbonyl, HaloC １～６ Alkylcarbonyl, C ３～７ Cycloalkylcarbonyl, haloC ３～７ Cycloalkylcarbonyl, C １～６ Alkoxycarbonyl, HaloC １～６ Alkoxycarbonyl, C ３～７ Cycloalkoxycarbonyl, halo C ３～７ Cycloalkoxycarbonyl, C １～６ alkylaminocarbonyl, (C １～６ alkyl) ２ Aminocarbonyl, C ３～７ cycloalkylaminocarbonyl, (C ３～７ cycloalkyl) ２ Aminocarbonyl, C １～６ Alkyl C ３～７ Cycloalkylaminocarbonyl, haloC １～６ alkylaminocarbonyl, halo(C １～６ alkyl) ２ Aminocarbonyl, HaloC ３～７ cycloalkylaminocarbonyl, halo(C ３～７ cycloalkyl) ２ Aminocarbonyl, HaloC １～６ Alkyl C ３～７ cycloalkylaminocarbonyl, C １～６ Alkyl halo C ３～７ cycloalkylaminocarbonyl, (C １～６ alkyl) ３ Ammonio, C. １～６ Alkylsulfanyl, C １～６ Alkylsulfinyl, C １～６ Alkylsulfonyl, C ３～７ Cycloalkylsulfanyl, C ３～７ Cycloalkylsulfinyl, C ３～７ Cycloalkylsulfonyl, haloC １～６ Alkylsulfanyl, HaloC １～６ Alkylsulfinyl, HaloC １～６ Alkyl sulfonyl, halo C ３～７ Cycloalkylsulfanyl, haloC ３～７ Cycloalkylsulfinyl, haloC ３～７ Cycloalkylsulfonyl, haloC １～６ Alkoxysulfonyl, C １～６ Alkylaminosulfonyl, (haloC １～６ alkylamino)sulfonyl, (C １～６ alkyl) ２ Aminosulfonyl, (haloC １～６ alkyl) ２ aminosulfonyl, (C １～６ alkyl) ２ phosphoryl, (C １～６ alkoxy) ２ Phosphoryl, hydroxy (C １～６ Alkoxy)phosphoryl, C １～６ Alkoxyphosphoryl, hydroxy, hydroxy C １～６ Alkyl, hydroxyhalo C １～６ Alkyl, hydroxy C １～６ Alkoxy, hydroxyl halo C １～６ Alkoxy, hydroxy C ３～７ Cycloalkyl, hydroxyhaloC ３～７ Cycloalkyl, as well as H, C １～６ Alkyl, C １～６ selected from sulfonimidoyl optionally substituted with alkoxy, aryl, heteroaryl, and heterocyclyl; M ２ is an arylene, heterocyclylene, or heteroarylene, and the arylene, heterocyclylene, or heteroarylene is R １ optionally substituted with M ３ is unsubstituted or R ３ is a heterocyclylene optionally substituted by R ２ is Deuterio, R, ROC １～６ Alkyl, RSC １～６ Alkyl, RSO ２ C １～６ Alkyl, RNHC １～６ Alkyl or (R) ２ NC １～６ is alkyl, R ３ is heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl, or arylcarbonyl, wherein the heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl, and arylcarbonyl are unsubstituted or １ optionally substituted with Q １ -M-, -M-O-M-, -M-SM-, -M-SO ２ -M-, -M-SO(NH)-M-, -M-SO(NR)-M-, -M-SiR ２ -M- or -M-N(R)-M-, where M is unsubstituted or deuterio, halogen, cyano, carboxy, R, RO, RS, RNH, R ２ N, RSO ２ , R.O.C. １～６ Alkyl, RSC １～６ Alkyl, RNHC １～６ alkyl, (R) ２ NC １～６ Alkyl and RSO ２ C １～６ C optionally substituted with substituents independently selected from alkyl １～６ is alkylene, Q ２ NH, O, S, SO, SO ２ , P(O)R, PO(NR), Se, N(R), SiR ２ , heterocyclyl, heteroaryl, or aryl) or a pharmaceutically acceptable salt thereof.

2. 10. A compound of formula (I) according to claim 1, 【Chemistry 2】 (In the formula, R １ is deuterio, H, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C １～６ Alkyl, (C １～６ Alkylsulfonylpiperazinyl)C １～６ Alkyl, amino, C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkoxycarbonyl, C １～６ Alkyl, C １～６ Alkylaminocarbonyl, C １～６ Alkylcarbonylamino, C ３～７ Cycloalkyl, haloC １～６ Alkyl, hydroxy C １～６ Alkyl, morpholinyl C １～６ Alkyl, hydroxy, pyrazolyl C １～６ Alkyl or triazolyl C １～６ is alkyl, R ２ is H, (2-oxa-5-azabicyclo[2.2.1]heptanyl)C １～６ alkyl, (2-oxa-6-azaspiro[3.3]heptanyl)C １～６ alkyl, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C １～６ Alkyl, ((C １～６ alkyl) ３ Ammonio) C １～６ Alkyl, (C １～６ Alkylsulfonylpiperazinyl)C １～６ Alkyl, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkyl, C ３～７ Cycloalkyl C １～６ Alkyl, haloC １～６ Alkyl, hydroxy C １～６ Alkyl, morpholinyl C １～６ Alkyl, phenyl C １～６ Alkyl, pyrimidinyloxy C １～６ Alkyl, tetrazolyl C １～６ Alkyl or trideuterio C １～６ is alkyl, R ３ teeth, 【Chemistry 3】 wherein: R ４ H, (C １～６ alkyl) ２ amino, (C １～６ alkyl) ２ aminocarbonyl, (C １～６ alkyl) ２ phosphoryl, 1,1-dioxotianil, C １～６ alkyl-substituted 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrolyl; Haro C １～６ 1,6-diazaspiro[3.3]heptanyl substituted with alkyl or oxetanyl, Haro C １～６ 1,7-diazaspiro[3.5]nonanyl substituted with alkyl or oxetanyl, 2,2-dioxo-2λ ６ -thia-6-azaspiro[3.3]heptanyl, C １～６ alkyl-substituted 2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazinyl; C １～６ Alkyl, haloC １～６ 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, Haro C １～６ 2-azaspiro[3.3]heptanyl substituted once or twice with substituents independently selected from alkyl and hydroxy; 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazinyl, 3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazinyl, (haloxetanyl) C １～６ Alkyl, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkyl, C ３～７ Cycloalkylcarbonyl, cyano C １～６ Alkyl, haloC １～６ Alkyl, haloC １～６ Alkylcarbonyl, HaloC ３～７ Cycloalkyl, hydroxy C １～６ Alkyl, hydroxy C １～６ Alkylcarbonyl, hydroxy C ３～７ 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3,6-diazabicyclo[3.2.0]heptanyl substituted with oxetanyl, 3,7-diazabicyclo[4.2.0]octanyl substituted with oxetanyl, Haro C １～６ alkyl-substituted 3,8-diazabicyclo[3.2.1]octanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C １～６ alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl, 3-oxa-8-azabicyclo[3.2.1]octanyl, Unsubstituted or C １～６ alkyl-substituted 4,7-diazaspiro[2.5]octanyl, 4-oxo-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazinyl, Haro C １～６ Alkyl or C １～６ Alkoxy C １～６ alkyl-substituted 5-oxa-2,8-diazaspiro[3.5]nonanyl, 6,6-dioxo-6λ ６ -thia-1-azaspiro[3.3]heptanyl, 6-oxa-1-azaspiro[3.3]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, Haro C １～６ alkyl-substituted 8-oxa-2,5-diazaspiro[3.5]nonanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, amino, aminocarbonyl, unsubstituted, or (C １～６ alkyl) ２ Amino, (C １～６ alkyl) ２ Amino C １～６ Alkyl, amino, C １～６ Alkyl, C １～６ Alkylcarbonyl, C １～６ Alkylsulfonyl, C １～６ Alkylsulfonyl C １～６ Alkyl, C ３～７ Cycloalkyl, cyano, cyano C １～６ Alkyl, haloC １～６ Alkyl, hydroxy C １～６ Alkyl, morpholinyl and morpholinyl C １～６ azetidinyl substituted once or twice with substituents independently selected from alkyl; Haro C １～６ Alkyl or C ３～７ cycloalkyl-substituted azetidinyloxy, Unsubstituted or (haloC １～６ alkylcarbonyl)azetidinyl, C １～６ Alkylazetidinyl, C １～６ Alkylpiperazinyl, C １～６ Alkylpyrrolidinyl, halo-1,2,3,5,6,7-hexahydropyrrolidinyl, halo C １～６ C substituted with alkylazetidinyl, morpholinyl, oxetanyl or tetrahydrofuranyl １～６ Alkoxy, C １～６ Alkoxy C １～６ alkylamino, C １～６ alkoxycarbonyl, unsubstituted, or (C １～６ Alkoxy C １～６ alkylcarbonyl)azetidinyl, (haloC １～６ alkylcarbonyl)pyrrolidinyl, 1,1-dioxothietanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, 4,7-diazaspiro[2.5]octanyl, C １～６ Alkoxy, C １～６ Alkylcarbonylazetidinyl, C １～６ Alkylcarbonyloxy, C １～６ Alkylcarbonylpyrrolidinyl, C １～６ Alkylsulfonylazetidinyl, C １～６ Alkylsulfonylpyrrolidinyl, C ３～７ Cycloalkylsulfonylazetidinyl, cyano, haloC １～６ Alkylazetidinyl, hydroxy, hydroxy C １～６ C substituted once or twice with substituents independently selected from alkyl, morpholinyl and oxetanyl １～６ Alkyl, C １～６ alkylamino, Unsubstituted or substituted with 1,1-dioxothietanyl C １～６ alkylsulfanyl, C １～６ alkylsulfonyl, Unsubstituted, or C １～６ C substituted with alkoxy or hydroxy ３～７ cycloalkyl, Carboxy, Cyano, Haro C １～６ Alkoxy, Hydroxy-substituted halo C １～６ Alkyl, Hydroxy, Hydroxy C １～６ alkylcarbamoyl, imidazolyl, morpholinyl, morpholinylcarbonyl, oxetanyl, oxomorpholinyl, oxooxazolidinyl, C １～６ alkyl-substituted oxopiperazinyl, Unsubstituted, or C １～６ alkyl- or hydroxy-substituted oxopyrrolidinyl; C １～６ Alkyl, carboxy, oxetanyl and phenyl C １～６ piperazinyl substituted once or twice with substituents independently selected from alkyl; C １～６ piperidinyl substituted with alkyl, 2H-tetrazolyl or oxazolyl; Amino, C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkylcarbonyl, C １～６ Alkyl sulfonyl, cyano, halo C １～６ pyrrolidinyl substituted once or twice with substituents independently selected from alkylcarbonyl and halogen; pyrrolidinyl carbonyl, tetrahydrofuranyl, or is tetrahydropyranyl, R ５ is 1,3-dihydroisobenzofuranyl, 1H-indazolyl substituted with halogen, C ２～６ Alkynyl, Thienyl, Unsubstituted, or halogen or C １～６ alkyl-substituted bicyclo[1.1.1]pentanyl, (C １～６ Alkoxy C １～６ alkyl) C ３～７ cycloalkyloxy, (C １～６ alkyl) ２ phosphoryl, (C １～６ alkylmorpholinyl)C １～６ Alkoxy, (C １～６ Alkylsulfonylazetidinyl)C １～６ Alkoxy, 2-oxa-6-azaspiro[3.3]heptanyl, azetidinyl, C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkoxy C ２～６ Alkynyl, C １～６ Alkoxy C ３～７ Cycloalkyloxy, C １～６ Alkoxypyrrolidinyl, C １～６ Alkyl, C １～６ Alkylamino, C １～６ Alkylsulfanyl, C １～６ Alkylsulfinyl, C １～６ Alkylsulfonyl, C ２～６ Alkenyl, C ３～７ Cycloalkyl, C ３～７ Cycloalkyloxy, carboxy, cyano, cyano C １～６ Alkoxy, HaloC １～６ Alkoxy, HaloC １～６ Alkyl, halogen, hydroxy, morpholinyl, morpholinyl C １～６ Alkoxy, oxetanyl C １～６ Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl, tetrahydrofuranyloxy and trideuterioC １～６ phenyl substituted once, twice or three times with substituents independently selected from alkoxy; Unsubstituted or halogen, hydroxy, C １～６ Alkylsulfanyl and C １～６ pyridinyl substituted once or twice with substituents independently selected from alkoxy, or pyrimidinyl, unsubstituted or substituted with halogen; R ６ is H or C １～６ is alkyl, R ７ is C １～６ is alkyl, R ７ａ is C １～６ Alkyl, C ３～７ Cycloalkyl or C １～６ Alkoxy C １～６ is alkyl, R ７ｂ is H, C １～６ Alkoxy or phenyl C １～６ is an alkoxy; R ７ｃ is H or C １～６ is an alkoxy; R ７ｄ is C １～６ Alkyl, C ３～７ Cycloalkyl C １～６ Alkyl or C １～６ Alkoxy C １～６ is alkyl, R ７ｅ is H, amino, phenyl C １～６ Alkylamino or morpholinyl C １～６ alkylamino, R ７ｆ is C １～６ Alkyl, phenyl C １～６ alkyl or oxetanyl, R ７ｇ is H or C １～６ Alkoxy C １～６ is alkyl, Q １ is unsubstituted or C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkoxy, C １～６ Alkyl, C １～６ Alkylcarbonyloxy, carboxy, hydroxy, hydroxy C １～６ Alkoxy, hydroxy C １～６ Alkyl, morpholinyl C １～６ Alkoxy and trideuterio C １～６ C substituted once or twice with substituents independently selected from alkoxy １～６ is alkylene, or -MOM-, where M is C １～６ is alkylene, Q ２ is NH, O or S, A １ is CH or N, A ２ , CH, CR ７ｈ or N, wherein R ７ｈ is C １～６ is alkyl, A ３ is CR ８ or N, wherein R ８ is H, C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkoxy, C ３～７ Cycloalkoxyamino, cyano, haloazetidinyl C １～６ Alkyl, haloC １～６ Alkoxy, halogen, morpholinyl C １～６ alkyl or oxetanyl, A ４ is CR ９ or N, wherein R ９ is H, or R ８ and R ９ together with the atoms to which they are attached form a heterocyclyl, A ５ is CR １０ or N, wherein R １０ is H or a halogen, A ６ is CR １１ or N, wherein R １１ is H, deuterio, halogen, C １～６ Alkyl or C １～６ is an alkoxy; A ７ is CR １２ or N, wherein R １２ is H or a halogen, However, A １ , A ２ , A ３ and A ４ At most two of the ５ , A ６ and A ７ and only one of them is N) or a pharmaceutically acceptable salt thereof.

3. A compound of formula (Ib) according to claim 1, 【Chemistry 4】 (In the formula, R １ is deuterio, H, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C １～６ Alkyl, (C １～６ Alkylsulfonylpiperazinyl)C １～６ Alkyl, amino, C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkoxycarbonyl, C １～６ Alkyl, C １～６ Alkylaminocarbonyl, C １～６ Alkylcarbonylamino, C ３～７ Cycloalkyl, haloC １～６ Alkyl, hydroxy C １～６ Alkyl, morpholinyl C １～６ Alkyl, hydroxy, pyrazolyl C １～６ Alkyl or triazolyl C １～６ is alkyl, R ２ is H, (2-oxa-5-azabicyclo[2.2.1]heptanyl)C １～６ alkyl, (2-oxa-6-azaspiro[3.3]heptanyl)C １～６ Alkyl, (2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl)C １～６ Alkyl, ((C １～６ alkyl) ３ Ammonio) C １～６ Alkyl, (C １～６ Alkylsulfonylpiperazinyl)C １～６ Alkyl, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkyl, C ３～７ Cycloalkyl C １～６ Alkyl, haloC １～６ Alkyl, hydroxy C １～６ Alkyl, morpholinyl C １～６ Alkyl, phenyl C １～６ Alkyl, pyrimidinyloxy C １～６ Alkyl, tetrazolyl C １～６ Alkyl or trideuterio C １～６ is alkyl, R ３ teeth, 【Chemistry 5】 wherein: R ４ H, (C １～６ alkyl) ２ amino, (C １～６ alkyl) ２ aminocarbonyl, (C １～６ alkyl) ２ phosphoryl, 1,1-dioxotianil, C １～６ alkyl-substituted 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrolyl; Haro C １～６ 1,6-diazaspiro[3.3]heptanyl substituted with alkyl or oxetanyl, Haro C １～６ 1,7-diazaspiro[3.5]nonanyl substituted with alkyl or oxetanyl, 2,2-dioxo-2λ ６ -thia-6-azaspiro[3.3]heptanyl, C １～６ alkyl-substituted 2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazinyl; C １～６ Alkyl, haloC １～６ 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, Haro C １～６ 2-azaspiro[3.3]heptanyl substituted once or twice with substituents independently selected from alkyl and hydroxy; 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazinyl, 3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazinyl, (haloxetanyl) C １～６ Alkyl, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkyl, C ３～７ Cycloalkylcarbonyl, cyano C １～６ Alkyl, haloC １～６ Alkyl, haloC １～６ Alkylcarbonyl, HaloC ３～７ Cycloalkyl, hydroxy C １～６ Alkyl, hydroxy C １～６ Alkylcarbonyl, hydroxy C ３～７ 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3,6-diazabicyclo[3.2.0]heptanyl substituted with oxetanyl, 3,7-diazabicyclo[4.2.0]octanyl substituted with oxetanyl, Haro C １～６ alkyl-substituted 3,8-diazabicyclo[3.2.1]octanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C １～６ alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl, 3-oxa-8-azabicyclo[3.2.1]octanyl, Unsubstituted or C １～６ alkyl-substituted 4,7-diazaspiro[2.5]octanyl, 4-oxo-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazinyl, Haro C １～６ Alkyl or C １～６ Alkoxy C １～６ alkyl-substituted 5-oxa-2,8-diazaspiro[3.5]nonanyl, 6,6-dioxo-6λ ６ -thia-1-azaspiro[3.3]heptanyl, 6-oxa-1-azaspiro[3.3]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, Haro C １～６ alkyl-substituted 8-oxa-2,5-diazaspiro[3.5]nonanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, amino, aminocarbonyl, unsubstituted, or (C １～６ alkyl) ２ Amino, (C １～６ alkyl) ２ Amino C １～６ Alkyl, amino, C １～６ Alkyl, C １～６ Alkylcarbonyl, C １～６ Alkylsulfonyl, C １～６ Alkylsulfonyl C １～６ Alkyl, C ３～７ Cycloalkyl, cyano, cyano C １～６ Alkyl, haloC １～６ Alkyl, hydroxy C １～６ Alkyl, morpholinyl and morpholinyl C １～６ azetidinyl substituted once or twice with substituents independently selected from alkyl; Haro C １～６ Alkyl or C ３～７ cycloalkyl-substituted azetidinyloxy, Unsubstituted or (haloC １～６ alkylcarbonyl)azetidinyl, C １～６ Alkylazetidinyl, C １～６ Alkylpiperazinyl, C １～６ Alkylpyrrolidinyl, halo-1,2,3,5,6,7-hexahydropyrrolidinyl, halo C １～６ C substituted with alkylazetidinyl, morpholinyl, oxetanyl or tetrahydrofuranyl １～６ Alkoxy, C １～６ Alkoxy C １～６ alkylamino, C １～６ alkoxycarbonyl, unsubstituted, or (C １～６ Alkoxy C １～６ alkylcarbonyl)azetidinyl, (haloC １～６ alkylcarbonyl)pyrrolidinyl, 1,1-dioxothietanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, 4,7-diazaspiro[2.5]octanyl, C １～６ Alkoxy, C １～６ Alkylcarbonylazetidinyl, C １～６ Alkylcarbonyloxy, C １～６ Alkylcarbonylpyrrolidinyl, C １～６ Alkylsulfonylazetidinyl, C １～６ Alkylsulfonylpyrrolidinyl, C ３～７ Cycloalkylsulfonylazetidinyl, cyano, haloC １～６ Alkylazetidinyl, hydroxy, hydroxy C １～６ C substituted once or twice with substituents independently selected from alkyl, morpholinyl and oxetanyl １～６ Alkyl, C １～６ alkylamino, Unsubstituted or substituted with 1,1-dioxothietanyl C １～６ alkylsulfanyl, C １～６ alkylsulfonyl, Unsubstituted, or C １～６ C substituted with alkoxy or hydroxy ３～７ cycloalkyl, Carboxy, Cyano, Haro C １～６ Alkoxy, Hydroxy-substituted halo C １～６ Alkyl, Hydroxy, Hydroxy C １～６ alkylcarbamoyl, imidazolyl, morpholinyl, morpholinylcarbonyl, oxetanyl, oxomorpholinyl, oxooxazolidinyl, C １～６ alkyl-substituted oxopiperazinyl, Unsubstituted, or C １～６ alkyl- or hydroxy-substituted oxopyrrolidinyl; C １～６ Alkyl, carboxy, oxetanyl and phenyl C １～６ piperazinyl substituted once or twice with substituents independently selected from alkyl; C １～６ piperidinyl substituted with alkyl, 2H-tetrazolyl or oxazolyl; Amino, C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkylcarbonyl, C １～６ Alkyl sulfonyl, cyano, halo C １～６ pyrrolidinyl substituted once or twice with substituents independently selected from alkylcarbonyl and halogen; pyrrolidinyl carbonyl, tetrahydrofuranyl, or is tetrahydropyranyl, R ５ is 1,3-dihydroisobenzofuranyl, 1H-indazolyl substituted with halogen, C ２～６ Alkynyl, Thienyl, Unsubstituted, or halogen or C １～６ alkyl-substituted bicyclo[1.1.1]pentanyl, (C １～６ Alkoxy C １～６ alkyl) C ３～７ cycloalkyloxy, (C １～６ alkyl) ２ phosphoryl, (C １～６ alkylmorpholinyl)C １～６ Alkoxy, (C １～６ Alkylsulfonylazetidinyl)C １～６ Alkoxy, 2-oxa-6-azaspiro[3.3]heptanyl, azetidinyl, C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkoxy C ２～６ Alkynyl, C １～６ Alkoxy C ３～７ Cycloalkyloxy, C １～６ Alkoxypyrrolidinyl, C １～６ Alkyl, C １～６ Alkylamino, C １～６ Alkylsulfanyl, C １～６ Alkylsulfinyl, C １～６ Alkylsulfonyl, C ２～６ Alkenyl, C ３～７ Cycloalkyl, C ３～７ Cycloalkyloxy, carboxy, cyano, cyano C １～６ Alkoxy, HaloC １～６ Alkoxy, HaloC １～６ Alkyl, halogen, hydroxy, morpholinyl, morpholinyl C １～６ Alkoxy, oxetanyl C １～６ Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl, tetrahydrofuranyloxy and trideuterioC １～６ phenyl substituted once, twice or three times with substituents independently selected from alkoxy; Unsubstituted or halogen, hydroxy, C １～６ Alkylsulfanyl and C １～６ pyridinyl substituted once or twice with substituents independently selected from alkoxy, or pyrimidinyl, unsubstituted or substituted with halogen; R ６ is H or C １～６ is alkyl, R ７ is C １～６ is alkyl, R ７ａ is C １～６ Alkyl, C ３～７ Cycloalkyl or C １～６ Alkoxy C １～６ is alkyl, R ７ｂ is H, C １～６ Alkoxy or phenyl C １～６ is an alkoxy; R ７ｃ is H or C １～６ is an alkoxy; R ７ｄ is C １～６ Alkyl, C ３～７ Cycloalkyl C １～６ Alkyl or C １～６ Alkoxy C １～６ is alkyl, R ７ｅ is H, amino, phenyl C １～６ Alkylamino or morpholinyl C １～６ alkylamino, R ７ｆ is C １～６ Alkyl, phenyl C １～６ alkyl or oxetanyl, R ７ｇ is H or C １～６ Alkoxy C １～６ is alkyl, Q １ is unsubstituted or C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkoxy, C １～６ Alkyl, C １～６ Alkylcarbonyloxy, carboxy, hydroxy, hydroxy C １～６ Alkoxy, hydroxy C １～６ Alkyl, morpholinyl C １～６ Alkoxy and trideuterio C １～６ C substituted once or twice with substituents independently selected from alkoxy １～６ alkylene, or -MOM-, where M is C １～６ is alkylene, Q ２ is NH, O or S, A １ is CH or N, A ２ , CH, CR ７ｈ or N, wherein R ７ｈ is C １～６ is alkyl, A ３ is CR ８ or N, wherein R ８ is H, C １～６ Alkoxy, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkoxy, C ３～７ Cycloalkoxyamino, cyano, haloazetidinyl C １～６ Alkyl, haloC １～６ Alkoxy, halogen, morpholinyl C １～６ alkyl or oxetanyl, A ４ is CR ９ or N, wherein R ９ is H, or R ８ and R ９ together with the atoms to which they are attached form a heterocyclyl, A ５ is CR １０ or N, wherein R １０ is H or a halogen, A ６ is CR １１ or N, wherein R １１ is H, deuterio, halogen, C １～６ Alkyl or C １～６ is an alkoxy; A ７ is CR １２ or N, wherein R １２ is H or a halogen, However, A １ , A ２ , A ３ and A ４ At most two of the ５ , A ６ and A ７ and only one of them is N) or a pharmaceutically acceptable salt thereof.

4. R １ is H or C １～６ 4. The compound of claim 2 or 3, wherein the compound is alkyl.

5. R １ The compound of any one of claims 1 to 4, wherein is H or methyl.

6. R ２ But C １～６ Alkyl or trideuterio C １～６ The compound of any one of claims 1 to 5, which is alkyl.

7. R ２ The compound according to any one of claims 1 to 6, wherein is methyl, ethyl or trideuteriomethyl.

8. R ３ but, 【Chemistry 6】 where: R ４ H, Haro C １～６ 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkylcarbonyl, haloC １～６ Alkyl, haloC １～６ Alkylcarbonyl, hydroxy C １～６ Alkyl, hydroxy C １～６ Alkylcarbonyl, hydroxy C ３～７ 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C １～６ alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl, amino, C １～６ Alkylcarbonyl, C １～６ alkylsulfonyl or cyano-substituted azetidinyl; C １～６ Alkoxy, Unsubstituted, or C １～６ Alkoxy, C １～６ Alkylcarbonylazetidinyl, C １～６ Alkylsulfonylazetidinyl, C ３～７ Cycloalkylsulfonylazetidinyl, halo C １～６ C substituted with alkylazetidinyl, hydroxy, morpholinyl or oxetanyl １～６ Alkyl, oxetanyl, oxooxazolidinyl, or Unsubstituted, or C １～６ alkyl- or hydroxy-substituted oxopyrrolidinyl; R ５ is C １～６ Alkoxy, C ３～７ Cycloalkyloxy, cyano, haloC １～６ Alkoxy, halogen, hydroxy and trideuterio C １～６ phenyl substituted once, twice or three times with substituents independently selected from alkoxy; pyridinyl substituted twice with halogen, or pyrimidinyl substituted with halogen; R ６ is H, R ７ａ is C １～６ is alkyl, R ７ｅ is an amino, R ７ｆ is C １～６ is alkyl, R ７ｇ is H or C １～６ Alkoxy C １～６ The compound of any one of claims 1 to 7, which is alkyl.

9. R ３ but, 【Chemistry 7】 where: R ４ H, R ４ is H, (1-acetylazetidin-3-yl)methyl, (1-cyclopropylsulfonylazetidin-3-yl)methyl, (1-ethylsulfonylazetidin-3-yl)methyl, (1-methylsulfonylazetidin-3-yl)methyl, [1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl, 1-acetylazetidin-3-yl, 1-methylsulfonylazetidin-3-yl, 2-oxooxazolidin-3-yl, 2-oxopyrrolidin-1-yl, 3-(1-hydroxycyclobutanecarbonyl)-3,6-diazabicyclo [3.1.1]heptan-6-yl, 3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl , 3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-cyanoazetidin-1-yl, 3-hydroxy -2-oxo-pyrrolidin-1-yl, 3-methyl-2-oxo-pyrrolidin-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, 5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl, amino, azetidin-1-yl, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl, oxetan-2-ylmethyl or oxetan-3-yl, R ５ is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropoxy, cyano, difluoromethoxy, fluoro, hydroxy and trideuteriomethoxy; pyridinyl substituted twice with fluoro, or pyrimidinyl substituted with fluoro; R ６ is H, R ７ａ is methyl, R ７ｅ is an amino, R ７ｆ is methyl, R ７ｇ The compound of any one of claims 1 to 8, wherein is H or methoxymethyl.

10. R ３ but, 【Chemistry 8】 where: R ４ H, Haro C １～６ 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkylcarbonyl, haloC １～６ Alkyl, haloC １～６ Alkylcarbonyl, hydroxy C １～６ Alkyl, hydroxy C １～６ Alkylcarbonyl, hydroxy C ３～７ 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C １～６ alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl, amino, C １～６ Alkylcarbonyl, C １～６ alkylsulfonyl or cyano-substituted azetidinyl; C １～６ Alkoxy, Unsubstituted, or C １～６ Alkoxy, C １～６ Alkylcarbonylazetidinyl, C １～６ Alkylsulfonylazetidinyl, C ３～７ Cycloalkylsulfonylazetidinyl, halo C １～６ C substituted with alkylazetidinyl, hydroxy, morpholinyl or oxetanyl １～６ Alkyl, oxetanyl, oxooxazolidinyl, or Unsubstituted, or C １～６ alkyl- or hydroxy-substituted oxopyrrolidinyl; R ５ is C １～６ Alkoxy, C ３～７ Cycloalkyloxy, cyano, haloC １～６ Alkoxy, halogen, hydroxy and trideuterio C １～６ phenyl substituted once, twice or three times with substituents independently selected from alkoxy; pyridinyl substituted twice with halogen, or pyrimidinyl substituted with halogen; R ６ The compound of any one of claims 1 to 8, wherein is H.

11. R ３ but, 【Chemistry 9】 where: R ４ is H, (1-acetylazetidin-3-yl)methyl, (1-cyclopropylsulfonylazetidin-3-yl)methyl, (1-ethylsulfonylazetidin-3-yl)methyl, (1-methylsulfonylazetidin-3-yl)methyl, [1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl, 1-acetylazetidin-3-yl, 1-methylsulfonylazetidin-3-yl, 2-oxooxazolidin-3-yl, 2-oxopyrrolidin-1-yl, 3-(1-hydroxycyclobutanecarbonyl)-3,6-diazabicyclo [3.1.1]heptan-6-yl, 3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl , 3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-cyanoazetidin-1-yl, 3-hydroxy -2-oxo-pyrrolidin-1-yl, 3-methyl-2-oxo-pyrrolidin-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, 5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl, amino, azetidin-1-yl, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl, oxetan-2-ylmethyl or oxetan-3-yl, R ５ is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropoxy, cyano, difluoromethoxy, fluoro, hydroxy and trideuteriomethoxy; pyridinyl substituted twice with fluoro, or pyrimidinyl substituted with fluoro; R ６ The compound of any one of claims 1 to 10, wherein is H.

12. Q １ But C １～６ Alkoxy, C １～６ Alkylcarbonyloxy, hydroxy, C １～６ Alkyl and trideuterio C １～６ C substituted once or twice with substituents independently selected from alkoxy １～６ The compound of any one of claims 1 to 11, which is alkylene.

13. Q １ is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl, acetoxy and trideuteriomethoxy.

14. Q １ But C １～６ Alkoxy-substituted C １～６ The compound of any one of claims 1 to 13, which is alkylene.

15. Q １ The compound of any one of claims 1 to 14, wherein is propylene substituted with methoxy or ethoxy.

16. Q ２ The compound according to any one of claims 1 to 15, wherein is NH or O.

17. A １ The compound of any one of claims 1 to 16, wherein is N.

18. A ３ is CR ８ and R ８ H, C １～６ Alkoxy, C １～６ Alkyl, C ３～７ Cycloalkoxy, halo C １～６ The compound of any one of claims 1 to 17, which is alkoxy or halogen.

19. A ３ is CR ８ and R ８ 19. The compound of claim 18, wherein is H, methoxy, methyl, cyclopropoxy, difluoromethoxy, or fluoro.

20. A ３ is CR ８ and R ８ The compound of any one of claims 1 to 19, wherein is H.

21. A ４ is CR ９ and R ９ The compound of any one of claims 1 to 20, wherein is H.

22. A ５ is CR １０ or N, and R １０ The compound of any one of claims 1 to 21, wherein is H or fluoro.

23. A ５ is CR １０ and R １０ The compound of any one of claims 1 to 22, wherein is H.

24. A ６ is CR １１ and R １１ The compound of any one of claims 1 to 22, wherein is H or halogen.

25. A ６ is CR １１ and R １１ The compound of any one of claims 1 to 24, wherein is H or fluoro.

26. A ６ is CR １１ and R １１ The compound of any one of claims 1 to 25, wherein is halogen.

27. A ６ is CR １１ and R １１ The compound of any one of claims 1 to 26, wherein is fluoro.

28. A ７ is CR １２ and R １２ The compound of any one of claims 1 to 27, wherein is H or halogen.

29. A ７ is CR １２ and R １２ The compound of any one of claims 1 to 28, wherein is H or fluoro.

30. A ７ is CR １２ and R １２ The compound of any one of claims 1 to 29, wherein is H.

31. 4. A compound according to claim 2 or 3, wherein: R １ is H or C １～６ is alkyl, R ２ is C １～６ Alkyl or trideuterio C １～６ is alkyl, R ３ teeth, 【Chemistry 10】 where: R ４ H, Haro C １～６ 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkylcarbonyl, haloC １～６ Alkyl, haloC １～６ Alkylcarbonyl, hydroxy C １～６ Alkyl, hydroxy C １～６ Alkylcarbonyl, hydroxy C ３～７ 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C １～６ alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl, amino, C １～６ Alkylcarbonyl, C １～６ alkylsulfonyl or cyano-substituted azetidinyl; C １～６ Alkoxy, Unsubstituted, or C １～６ Alkoxy, C １～６ Alkylcarbonylazetidinyl, C １～６ Alkylsulfonylazetidinyl, C ３～７ Cycloalkylsulfonylazetidinyl, halo C １～６ C substituted with alkylazetidinyl, hydroxy, morpholinyl or oxetanyl １～６ Alkyl, oxetanyl, oxooxazolidinyl, Unsubstituted, or C １～６ alkyl- or hydroxy-substituted oxopyrrolidinyl; R ５ is C １～６ Alkoxy, C ３～７ Cycloalkyloxy, cyano, haloC １～６ Alkoxy, halogen, hydroxy and trideuterio C １～６ phenyl substituted once, twice or three times with substituents independently selected from alkoxy; pyridinyl substituted twice with halogen, or pyrimidinyl substituted with halogen; R ６ is H, R ７ａ is C １～６ is alkyl, R ７ｅ is an amino, R ７ｆ is C １～６ is alkyl, R ７ｇ is H or C １～６ Alkoxy C １～６ is alkyl, Q １ is C １～６ Alkoxy, C １～６ Alkylcarbonyloxy, hydroxy, C １～６ Alkyl and trideuterio C １～６ C substituted once or twice with substituents independently selected from alkoxy １～６ is alkylene, Q ２ is NH or O, A １ is N, A ２ , CH, CR ７ｈ or N, wherein R ７ｈ is C １～６ is alkyl, A ３ is CR ８ wherein R ８ is H, C １～６ Alkoxy, C １～６ Alkyl, C ３～７ Cycloalkoxy, halo C １～６ alkoxy or halogen; A ４ is CR ９ wherein R ９ is H, A ５ is CR １０ or N, wherein R １０ is H or a halogen, A ６ is CR １１ wherein R １１ is H or a halogen, A ７ is CR １２ wherein R １２ is H or a halogen; or a pharmaceutically acceptable salt thereof.

32. 32. The compound of claim 31 , R １ is H or methyl, R ２ is methyl, ethyl or trideuteriomethyl, R ３ teeth, 【Chemistry 11】 where: R ４ H, R ４ is H, (1-acetylazetidin-3-yl)methyl, (1-cyclopropylsulfonylazetidin-3-yl)methyl, (1-ethylsulfonylazetidin-3-yl)methyl, (1-methylsulfonylazetidin-3-yl)methyl, [1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl, 1-acetylazetidin-3-yl, 1-methylsulfonylazetidin-3-yl, 2-oxooxazolidin-3-yl, 2-oxopyrrolidin-1-yl, 3-(1-hydroxycyclobutanecarbonyl)-3,6-diazabicyclo [3.1.1]heptan-6-yl, 3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl , 3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-cyanoazetidin-1-yl, 3-hydroxy -2-oxo-pyrrolidin-1-yl, 3-methyl-2-oxo-pyrrolidin-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, 5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl, amino, azetidin-1-yl, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl, oxetan-2-ylmethyl or oxetan-3-yl, R ５ is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropoxy, cyano, difluoromethoxy, fluoro, hydroxy and trideuteriomethoxy; pyridinyl substituted twice with fluoro, or pyrimidinyl substituted with fluoro; R ６ is H, R ７ａ is methyl, R ７ｅ is an amino, R ７ｆ is methyl, R ７ｇ is H or methoxymethyl, Q １ is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl, acetoxy and trideuteriomethoxy; Q ２ is NH or O, A １ is N, A ２ , CH, CR ７ｈ or N, wherein R ７ｈ is methyl, A ３ is CR ８ wherein R ８ is H, methoxy, methyl, cyclopropoxy, difluoromethoxy or fluoro; A ４ is CR ９ wherein R ９ is H, A ５ is CR １０ or N, wherein R １０ is H or fluoro; A ６ is CR １１ wherein R １１ is H or fluoro; A ７ is CR １２ wherein R １２ is H or fluoro; or a pharmaceutically acceptable salt thereof.

33. 32. The compound of claim 31 , R １ But C １～６ is alkyl, R ２ is C １～６ is alkyl, R ３ but, 【Chemistry 12】 where: R ４ H, Haro C １～６ 2,5-diazabicyclo[2.2.1]heptanyl substituted with alkyl or oxetanyl, C １～６ Alkoxy C １～６ Alkyl, C １～６ Alkyl, C ３～７ Cycloalkylcarbonyl, haloC １～６ Alkyl, haloC １～６ Alkylcarbonyl, hydroxy C １～６ Alkyl, hydroxy C １～６ Alkylcarbonyl, hydroxy C ３～７ 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, C １～６ alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl, amino, C １～６ Alkylcarbonyl, C １～６ alkylsulfonyl or cyano-substituted azetidinyl; C １～６ Alkoxy, Unsubstituted, or C １～６ Alkoxy, C １～６ Alkylcarbonylazetidinyl, C １～６ Alkylsulfonylazetidinyl, C ３～７ Cycloalkylsulfonylazetidinyl, halo C １～６ C substituted with alkylazetidinyl, hydroxy, morpholinyl or oxetanyl １～６ Alkyl, oxetanyl, oxooxazolidinyl, Unsubstituted, or C １～６ alkyl- or hydroxy-substituted oxopyrrolidinyl; R ５ is C １～６ Alkoxy, C ３～７ Cycloalkyloxy, cyano, haloC １～６ Alkoxy, halogen, hydroxy and trideuterio C １～６ phenyl substituted once, twice or three times with substituents independently selected from alkoxy; pyridinyl substituted twice with halogen, or pyrimidinyl substituted with halogen; R ６ is H, Q １ is C １～６ Alkoxy-substituted C １～６ is alkylene, Q ２ is NH or O, A １ is N, A ２ is CH or N, A ３ is CR ８ wherein R ８ is H, A ４ is CR ９ wherein R ９ is H, A ５ is CR １０ or N, wherein R １０ is H, A ６ is CR １１ wherein R １１ is a halogen, A ７ is CR １２ wherein R １２ is H, or a pharmaceutically acceptable salt thereof.

34. 34. The compound of claim 33, R １ is methyl, R ２ is methyl, R ３ teeth, 【Chemistry 13】 where: R ４ is H, (1-acetylazetidin-3-yl)methyl, (1-cyclopropylsulfonylazetidin-3-yl)methyl, (1-ethylsulfonylazetidin-3-yl)methyl, (1-methylsulfonylazetidin-3-yl)methyl, [1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl, 1-acetylazetidin-3-yl, 1-methylsulfonylazetidin-3-yl, 2-oxooxazolidin-3-yl, 2-oxopyrrolidin-1-yl, 3-(1-hydroxycyclobutanecarbonyl)-3,6-diazabicyclo [3.1.1]heptan-6-yl, 3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl , 3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-cyanoazetidin-1-yl, 3-hydroxy -2-oxo-pyrrolidin-1-yl, 3-methyl-2-oxo-pyrrolidin-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, 5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl, 9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl, amino, azetidin-1-yl, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl, oxetan-2-ylmethyl or oxetan-3-yl, R ５ is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropoxy, cyano, difluoromethoxy, fluoro, hydroxy and trideuteriomethoxy; pyridinyl substituted twice with fluoro, or pyrimidinyl substituted with fluoro; R ６ is H, Q １ is methoxy or ethoxy substituted propylene, Q ２ is NH or O, A １ is N, A ２ is CH or N, A ３ is CR ８ wherein R ８ is H, A ４ is CR ９ wherein R ９ is H, A ５ is CR １０ or N, wherein R １０ is H, A ６ is CR １１ wherein R １１ is fluoro, A ７ is CR １２ wherein R １２ is H, or a pharmaceutically acceptable salt thereof.

35. A compound selected from: (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[2-(2,4-difluorophenyl)-3-methyl-imidazole-4-carbonyl]-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,16,18-tetrazapentacyclo[14.6.1.1 ２，６ .1 ８，１１ .0 １９，２３ ]pentacosa-1(22),2,4,6(25),17,19(23),20-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-hydroxyethyl)-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-Benzyl-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-methoxyethyl)-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-morpholinopropyl)-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 3-[(8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-13-yl]propyl-trimethyl-ammonium; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyridazin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-Methyl-10-[3-(3-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[7-(2,4-difluorophenyl)imidazo[5,1-f][1,2,4]triazin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-methoxyethoxy)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-methoxyethoxy)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-methoxyethoxy)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-4-(oxetan-3-yl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-22-fluoro-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(2-fluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-fluoro-10-[1-(2-fluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,6-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(1-bicyclo[1.1.1]pentanyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[3-(2,4-difluorophenyl)-[1,2,4]triazolo[4,3-a]pyrazin-8-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(3,4-difluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-10-[1-(3-methyl-1-bicyclo[1.1.1]pentanyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(3-fluoro-1-bicyclo[1.1.1]pentanyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 5-fluoro-2-[4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile; [(8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; (8S,11S,15S)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-4-carbonitrile; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-4-carbonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-4,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-4,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-4,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-4,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-4,5,10,13,17,19-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-4,5,10,13,17,19-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-4,5,10,13,17,19-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-4,5,10,13,17,19-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-(hydroxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-(hydroxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-(4-fluoro-2-methoxy-phenyl)-4-[(8S,11S)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxamide; 1-(4-fluoro-2-methoxy-phenyl)-N,N-dimethyl-4-[(8S,11S)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]-hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxamide; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(methylamino)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-methoxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-hydroxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 8S,11S)-10-[1-(2,4-difluorophenyl)-6-ethoxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(2-methoxyethylamino)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(2-morpholinoethoxy)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-10,13,17,19,26-pentaazapentacyclo-[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-10-[1-(4-fluoro-2-methylsulfanyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26 hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(6-fluoro-2-hydroxy-3-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,6-difluoro-3-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-13-methyl-10-[3-(2-thienyl)imidazo[1,5-a]pyrazin-8-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(5-fluoro-3-methoxy-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(3-fluoro-5-methoxy-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(3,5-difluoro-2-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[2-(2-chloro-4-fluoro-phenyl)pyrimidin-5-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(methylamino)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,22,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-(cyclopropylmethyl)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,21,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(2-morpholinoethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(2-morpholinoethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(2-methoxyethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(2-methoxyethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(oxetan-3-ylmethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(oxetan-3-ylmethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(oxetan-3-yloxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(oxetan-3-yloxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-[(4-methylmorpholin-2-yl)methoxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-18-(2-methoxyethyl)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-18-(2-morpholinoethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-(2-hydroxyethyl)-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-18-[2-[(4aR,7aS)-2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrol-6-yl]ethyl]-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-[2-(4-methylsulfonylpiperazin-1-yl)ethyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-[2-(1,2,4-triazol-1-yl)ethyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-(2-pyrazol-1-ylethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-23-fluoro-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,19,21,28-hexazapentacyclo[17.6.1.1 ２，６ .1 ８，１１ .0 ２２，２６ ]octacosa-1(25),2(28),3,5,20,22(26),23-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-3-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[4-fluoro-2-(trifluoromethyl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 5-fluoro-2-[4-[(8S,11S)-13-methyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile; 5-fluoro-2-[4-[(8S,11S)-13-methyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]benzoic acid; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-ethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-13-Ethyl-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-methoxyethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-(2-morpholinoethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-hydroxypropyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-[3-(tetrazol-2-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-[3-(tetrazol-1-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-[3-(4-methylsulfonylpiperazin-1-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-hydroxyethoxy)-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(2-hydroxyethoxy)-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-15-(2-morpholinoethoxy)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-15-(2-morpholinoethoxy)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-18,22-dideuterio-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-15-hydroxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-hydroxy-13,15,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-hydroxy-13,15,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-hydroxy-13,15,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-hydroxy-13,15,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; [(8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; [(8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-dimethylphosphoryl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]-hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxylic acid; 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carbonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-c]pyridazin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-c]pyridazin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-b]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-b]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-b]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-b]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-23-chloro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(hydroxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]-hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-morpholino-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; Ethyl 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxylate; (8S,11S)-10-[1-(4-fluoro-2-methylsulfanyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]-hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methylsulfinyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]-hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methylsulfonyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]-hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-dimethylphosphoryl-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]-hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-4-[(3,3-difluoroazetidin-1-yl)methyl]-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-4-(morpholinomethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-4,15-dimethoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-4,15-dimethoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-4,13-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-4,13-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-amino-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]-hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[6-amino-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-(cyclopropylmethyl)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-hydroxy-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-vinyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2-cyclopropyl-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2-bromo-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,22-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-4-(difluoromethoxy)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-4-(cyclopropoxy)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-13-Cyclopropyl-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(trideuteriomethoxy)-13-(trideuteriomethyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-(difluoromethyl)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-ethyl-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-18-Ethyl-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(hydroxymethyl)-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[6-cyclobutyl-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4,5-difluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-[2-(difluoromethoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(trifluoromethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-15-Methoxy-10-[1-(2-methoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-chloro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(5-chloro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-4-(methoxymethyl)-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-4-carbonitrile; (8S,11S)-10-[1-[4-fluoro-2-(trifluoromethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-(trifluoromethyl)-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-4,13-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]Hexacosa-1(23),2(26),3,5,; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13-ethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13-ethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-22-Fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2-ethoxy-4-fluoro-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-4,13-dimethyl-3,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-3,5,7,10,13,17,19-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-thia-10,13,17,19,26-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)triazolo[4,5-c]pyridin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-[4-fluoro-2-(methoxymethyl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(5-fluoropyrimidin-2-yl)pyrazolo[4,3-c]pyridin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-3,10,13,17,19-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-3,10,13,17,19-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-3,10,13,17,19-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-4,10,13,17,19-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-4,10,13,17,19-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-4,10,13,17,19-pentaazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(1-bicyclo[1.1.1]pentanyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(5-fluoropyrimidin-2-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-fluoro-4-phenyl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(4,4,4-trifluorobutyl)-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-22-fluoro-13-(3-pyrimidin-2-yloxypropyl)-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]-hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-22-chloro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-21-chloro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-15-methoxy-13-methyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(3,5-difluoro-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(3,5-difluoro-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-methoxypropyl)-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-4,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-16-oxa-7,10,13,19,21,28-hexazapentacyclo[17.6.1.1 ２，６ .1 ８，１１ .0 ２２，２６ ]octacosa-1(25),2(28),3,5,20,22(26),23-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-10-(1-pyrimidin-5-ylpyrazolo[3,4-d]pyrimidin-4-yl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (11S,14S,18R)-13-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-25-fluoro-18-methoxy-16,21-dimethyl-5-oxa-10,13,16,20,22,29-hexazahexacyclo[18.6.1.1 ２，９ .1 １１，１４ .0 ３，７ .0 ２３，２７ ]nonacosa-1(26),2(29),3(7),8,21,23(27),24-heptaen-15-one; (8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-10-[1-methyl-6-(3-thienyl)pyrazolo[4,3-c]pyridin-3-yl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(2,4-difluorophenyl)-1-methyl-pyrazolo[4,3-c]pyridin-3-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-21,23-difluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluoro-6-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-10-[2-(2,4-difluorophenoxy)-4-pyridyl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S)-15-Ethoxy-10-[1-[4-fluoro-2-(2-oxopyrrolidin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,15,18-trimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,15,18-trimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,15,18-trimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,15,18-trimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,21,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,21,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-18-hydroxy-13-methyl-7-oxa-10,13,17,19-tetrazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaene-14-carboxylic acid; (8S,11S,15R)-10-[6-ethoxy-1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-methoxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-ethoxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(morpholinomethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-isopropyl-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; Methyl(8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-18-carboxylate; (8S,11S)-18-(chloromethyl)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-hydroxy-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-18-amino-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-N,13-dimethyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaene-18-carboxamide; (8S,11S,15R)-10-[1-[2-(cyclopropoxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; N-[(8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-18-yl]acetamide; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-18-Cyclopropyl-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2-fluoro-4-tetrahydrofuran-3-yl-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22,23-difluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-[2-fluoro-4-(2-oxopyrrolidin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-15-(trideuteriomethoxy)-13-(trideuteriomethyl)-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-tetrahydrofuran-3-yl-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-tetrahydropyran-4-yl-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-3-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-2-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-methylsulfonylazetidin-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(1-acetylazetidin-3-yl)methyl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[2-hydroxy-1-(hydroxymethyl)ethyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[1-(hydroxymethyl)-2-methoxy-ethyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-methylsulfonylazetidin-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(1-acetylazetidin-3-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-methylsulfonylpyrrolidin-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(1-acetylpyrrolidin-3-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-methylsulfonylpyrrolidin-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[[1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(1-acetylpyrrolidin-3-yl)methyl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-methyl-4-piperidyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-13-(3-morpholinopropyl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-13-[3-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-13-[3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)propyl]-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-13-[3-[(4aR,7aS)-2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrol-6-yl]propyl]-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-18-methyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-ethylsulfonylazetidin-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(1-cyclopropylsulfonylazetidin-3-yl)methyl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[[1-(2,2,2-trifluoroethyl)azetidin-3-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7,10,13,17,19,23,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(pyrrolidine-1-carbonyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-(2,4-difluorophenyl)-4-[(8S,11S)-22-fluoro-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]-N-(2-hydroxyethyl)pyrazolo[3,4-d]pyrimidine-6-carboxamide; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-(morpholine-4-carbonyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-(methoxymethyl)pyrazolo[4,3-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-5,13,18-trimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(1,3-dihydroisobenzofuran-4-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-methyl-6-oxo-pyrazolo[3,4-b]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2,2,2-trifluoro-1-hydroxy-ethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[7-cyclopropyl-1-(2,4-difluorophenyl)-6-oxo-pyrazolo[3,4-b]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-(2-methoxyethyl)-6-oxo-pyrazolo[3,4-b]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-methoxy-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-7-methoxy-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-methoxycyclopropyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-hydroxycyclopropyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(azetidin-1-yl)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-morpholino-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(2-fluoro-4-morpholino-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-[4-fluoro-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)-6-(methoxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-[4-fluoro-2-(3-methoxycyclobutoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-[4-fluoro-2-[1-(methoxymethyl)cyclopropoxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(hydroxymethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-4,22-difluoro-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2,2-dioxo-2λ ６ -thia-6-azaspiro[3.3]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(hydroxymethyl)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxy-1-methyl-ethyl)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(3R,4R)-3-amino-4-fluoro-pyrrolidin-1-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-[(dimethylamino)methyl]azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-methylsulfonylazetidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(tetrahydrofuran-3-ylmethoxy)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(1-cyclopropylazetidin-3-yl)oxy-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[2-(4-methylpiperazin-1-yl)ethoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[[1-(2,2-difluoroacetyl)azetidin-3-yl]methoxy]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-methylpiperazin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-methylazetidin-3-yl)methoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1-methylpyrrolidin-3-yl)methoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[1-(2-fluoroethyl)azetidin-3-yl]oxy-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxetan-3-ylmethoxy)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(3S,4S)-3-amino-4-methoxy-pyrrolidin-1-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(dimethylamino)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(3-amino-3-methyl-azetidin-1-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[1-(2,2-difluoroethyl)azetidin-3-yl]oxy-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-morpholinoazetidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[[1-(2,2-difluoroethyl)azetidin-3-yl]methoxy]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[1-(2,2-difluoroethyl)azetidin-3-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]ethyl acetate; (8S,11S,15R)-22-fluoro-10-[1-(5-fluoro-3-methylsulfanyl-2-pyridyl)-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R)-1-hydroxyethyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1S)-1-hydroxyethyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(morpholinomethyl)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 2-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]acetonitrile; (8S,11S,15R)-10-[6-(4,7-diazaspiro[2.5]octan-7-ylmethyl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[4-(oxetan-3-yl)piperazin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(4,7-diazaspiro[2.5]octan-7-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[4-(2H-tetrazol-5-yl)-1-piperidyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-methyl-4,7-diazaspiro[2.5]octan-7-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(3,5-difluoro-2-pyridyl)-6-(3-morpholinoazetidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolidin-8-yl]methoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[(3aR,6aS)-2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-cyclopentyl-1-(3,5-difluoro-2-pyridyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(4aR,7aR)-4-methyl-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazin-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-benzyl-4-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]piperazine-2-carboxylic acid; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-oxazol-5-yl-1-piperidyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-methylsulfonyl-pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-10-(3-prop-1-ynylimidazo[1,5-a]pyrazin-8-yl)-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-methoxy-phenyl)-6-[[1-(2-methoxyacetyl)azetidin-3-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-[4-fluoro-2-(3-methoxy-3-methyl-but-1-ynyl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-[4-fluoro-2-(3-methoxypyrrolidin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluoro-6-tetrahydrofuran-3-yloxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 2-[2-[4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]-3,5-difluoro-phenoxy]acetonitrile; (8S,11S,15S)-10-[1-[2,4-difluoro-6-[(1-methylsulfonylazetidin-3-yl)methoxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-4-(cyclopropylamino)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(6-fluoro-1H-indazol-5-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)indazol-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]-6-(oxetan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]-6-[3-oxa-6-azabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-methyl-7-oxo-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-methoxyethyl)-7-oxo-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[7-benzyloxy-1-(2,4-difluorophenyl)pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(cyclopropylmethyl)-1-(2,4-difluorophenyl)-7-oxo-pyrazolo[3,4-c]pyridin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[(1,1-dioxothietan-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 2-[3-[1-(2,4-difluorophenyl)-4-[(8S,11S,15S)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidin-1-yl]acetonitrile; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(1,1-dioxothian-4-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(methylsulfonylmethyl)azetidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[6-(1-cyclopropylazetidin-3-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[(1,1-dioxothietan-3-yl)methylsulfanyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-[4-fluoro-2-(trideuteriomethoxy)phenyl]-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(azetidin-1-yl)-1-[4-fluoro-2-(trideuteriomethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-(azetidin-1-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(dimethylamino)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-imidazol-1-yl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2,2,2-trifluoroethoxy)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-(oxetan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (3S)-1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]pyrrolidine-3-carbonitrile; 8-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazin-4-one; (8S,11S,15R)-10-[6-(3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl)-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidine-3-carbonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-oxa-6-azabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-oxa-6-azabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidine-3-carbonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[8-(2-fluoroethyl)-5-oxa-2,8-diazaspiro[3.5]nonan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[8-(2-methoxyethyl)-5-oxa-2,8-diazaspiro[3.5]nonan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[5-(2-fluoroethyl)-8-oxa-2,5-diazaspiro[3.5]nonan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 4-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]morpholin-3-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-methyl-2-oxo-pyrrolidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-5-(3-phenylpropylamino)pyrazole-4-carbonyl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[(1S,5S)-3-cyclopropyl-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxopyrrolidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-[(3-fluorooxetan-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-[(3-fluorooxetan-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-hydroxy-6-(trifluoromethyl)-2-azaspiro[3.3]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6-oxa-1-azaspiro[3.3]heptan-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(2-fluoroethyl)-1,6-diazaspiro[3.3]heptan-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; 2-[3-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidin-1-yl]acetonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; 3-[6-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]propanenitrile; (8S,11S,15R)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-5-(2-morpholinoethylamino)pyrazole-4-carbonyl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[11-benzyl-3-(2,4-difluorophenyl)-3,4,8,11-tetrazatricyclo[7.3.0.0 ２，６ ]dodeca-1(9),2(6),4,7-tetraen-7-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[3-(2,4-difluorophenyl)-11-methyl-3,4,8,11-tetrazatricyclo[7.3.0.0 ２，６ ]dodeca-1(9),2(6),4,7-tetraen-7-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[5-amino-1-(2,4-difluorophenyl)pyrazole-4-carbonyl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; 2-[6-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]acetonitrile; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidine-3-carbonitrile; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[7-(2-fluoroethyl)-1,7-diazaspiro[3.5]nonan-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[7-(oxetan-3-yl)-1,7-diazaspiro[3.5]nonan-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(oxetan-3-yl)-1,6-diazaspiro[3.3]heptan-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6,6-dioxo-6λ ６ -thia-1-azaspiro[3.3]heptan-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,7-diazabicyclo[4.2.0]octan-7-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[3-(2,4-difluorophenyl)-11-(oxetan-3-yl)-3,4,8,11-tetrazatricyclo[7.3.0.0 ２，６ ]dodeca-1(9),2(6),4,7-tetraen-7-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,5S)-3-(oxetan-3-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-hydroxy-2-oxo-pyrrolidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxopyrrolidin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; 3-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-5,7,10,13,17,19,26-heptazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]oxazolidin-2-one; 3-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]oxazolidin-2-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-methyl-2-oxo-piperazin-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2,4,6(26),18,20,22-heptaen-12-one; (8S,11S,15S)-22-Fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(4-fluoro-2-hydroxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[6-[3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-hydroxy-2-methyl-propanoyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxycyclobutanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; (8S,11S,15R)-10-[6-[3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]-1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; and (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(3-fluorocyclobutyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexazapentacyclo[15.6.1.1 ２，６ .1 ８，１１ .0 ２０，２４ ]hexacosa-1(24),2(26),3,5,18,20,22-heptaen-12-one; or a pharmaceutically acceptable salt thereof.

36. A process for preparing a compound according to any one of claims 1 to 35, comprising: a) a compound of formula (VIII) in the presence of a base 【Chemistry 14】 and R ３ via nucleophilic substitution between X and 【Chemistry 15】 forming a compound of b) reacting a compound of formula (VIII) with R ３ forming a compound of formula (I) via a Buchwald-Hartwig reaction between X and c) reacting a compound of formula (VIII) with R ３ forming a compound of formula (I) via a condensation reaction between OH, d) a compound of formula (XVIII) 【Chemistry 16】 forming a compound of formula (I) via a cyclization reaction between e) a compound of formula (XX) in the presence of a base 【Chemistry 17】 and R ３ via nucleophilic substitution between X and 【Chemistry 18】 forming a compound of f) a compound of formula (Ic) in the presence of a base 【Chemistry 19】 and an alcohol or amine (R ４ -X) to give a compound of formula (XXII) 【Chemistry 20】 The formation process of g) A compound of formula (XXIV) 【Chemical 21】 reacting the amino group of with a halide via nucleophilic substitution or with a ketone via reductive amination to provide the final compound of formula (XXII), In this method, In steps a) and e), the base is DIEA, In step b), the catalyst is Pd ２ (dba) ３ and In step c), the coupling reagent is HATU; In step d), the reagent is CDI, BrCN or R １ (OCH ３ ) ３ and In step e), the base is DIEA, In step f), the base is DIPEA, K ２ CO ３ or NaH, X is a halogen and R １３ is R ａ , R ｂ or R ｃ and M is C １～６ alkylene, and R ｅ is a substituent having a primary or secondary amino group, and R １ ~R ７ , Q １ , Q ２ , A １ ~A ７ is as claimed in any one of claims 1 to 34.

37. 36. A compound or a pharmaceutically acceptable salt according to any one of claims 1 to 35 for use as a therapeutically active substance.

38. A pharmaceutical composition comprising a compound according to any one of claims 1 to 35 and a therapeutically inert carrier.

39. Use of a compound according to any one of claims 1 to 35 for the treatment or prevention of an autoimmune disease, an inflammatory disease, a neuropathic disease, a metabolic disease, a cardiovascular disease, an eye disease, or a selective type of cancer in which overexpression or activation of STING is involved.

40. 36. Use of a compound according to any one of claims 1 to 35 for the treatment of a subject suffering from an interferonopathy or autoinflammatory disease in which STING activation is an underlying cause of the disease pathology.

41. Use of a compound according to any one of claims 1 to 35 for the inhibition of STING.

42. Use of a compound according to any one of claims 1 to 35 for the preparation of a medicament for the inhibition of STING.

43. 37. A compound or a pharmaceutically acceptable salt according to any one of claims 1 to 35 when produced according to the process of claim 36.

44. 36. A method for the treatment or prevention of autoimmune diseases, comprising administering a therapeutically effective amount of a compound according to any one of claims 1 to 35.

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