Imidazole macrocycles for treatment of autoimmune diseases

Abstract

The present invention relates to compounds of Formula (Ia) # imgabs0 # wherein R2, M1, M2, M3, Q1 and Q2 are as described herein, and pharmaceutically acceptable salts thereof, as well as compositions including the compounds and methods of using the compounds.

Description

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

[0002] Autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD), are diseases in which the immune system mistakenly attacks its own body, resulting in unrelieved and improperly activated inflammation that becomes pathogenic. Many autoimmune diseases are poorly managed by existing treatments, which only provide symptom relief. Steroids and a wide range of immunosuppressant drugs (e.g., mycophenolate mofetil and cyclophosphamide) constitute the standard of care, but are associated with significant treatment-related toxicities. Pathway-selective agents such as adalimumab (anti-TNF antibody, used for RA and IBD) occasionally lead to insufficient infection or tumor monitoring. And belimumab (anti-BAFF antibody, the only new drug approved by the FDA for SLE) shows slow relief and moderate efficacy in the clinic. In addition, the heterogeneity of many autoimmune diseases for which there is no treatment method illustrates the difficulty of finding efficacy by blocking an immune pathway. Therefore, currently available treatments cannot meet the greater unmet needs of autoimmune inflammatory diseases, which bring limited relief, serious side effects, opportunistic infections, and a poor quality of life with chronic inflammation.

[0003] Stimulator of interferon genes (STING) is a transmembrane protein located in the endoplasmic reticulum (ER) and 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 coupling cytoplasmic DNA recognition with the induction of type I interferons (IFNs) and a broader immune defense program. 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 secondary messenger molecule with agonistic activity for STING. Upon activation, STING translocates from the ER to the Golgi apparatus and recruits TANK-binding kinase 1 (TBK1), which phosphorylates interferon regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB) to initiate the expression of type I IFNs and numerous proinflammatory cytokines (e.g., IL-6 and TNFα), respectively. In addition to 2'3'-cGAMP, STING can also be activated by other types of cyclic dinucleotides (CDNs), such as c-di-AMP, c-di-GMP, and 3',3'-cGAMP from bacteria. After signaling, STING is rapidly degraded to prevent its constitutive signaling from transmitting inflammatory responses.

[0004] While triggering a robust host defense response, aberrant STING signaling contributes to dysregulated immune responses associated with many pathologies. Gain-of-function (GoF) human STING mutations are the root cause of STING-associated vasculopathy (SAVI) of infancy, a monogenic disease characterized by the onset of an autoinflammatory condition known as type I interferon disease. Mechanistically, pathogenic substitutions trigger ligand-independent, constitutive STING activation. In addition, STING is involved in DNA-driven inflammation, such as Aicardi-Goutières syndrome (AGS) and hereditary forms of lupus. Unlike SAVI, the continuous innate immune activation mediated by STING in AGS is caused by defects in self-DNA clearance and metabolism caused by mutations in the nuclease genes TREX1 and / or DNASE2. Consistently, genetic and pharmacological inhibition of STING improves systemic morbidity and mortality in Trex1- / - mouse models. In addition to genetic disorders, robust preclinical and clinical evidence supports a general pathogenic role for STING in a range of inflammatory-related diseases, such as SLE and RA. A direct link between the cGAS-STING pathway and SLE was established by the observation that PBMCs from a subset of SLE patients have elevated cytosolic cGAMP compared to healthy controls. Furthermore, membrane vesicles from apoptotic cells in SLE serum have high ISG-stimulating activity that is dependent on cGAS-STING. Furthermore, disruption of STING signaling in FcγrIIb- / - mice ameliorates the development of lupus-like phenotypes. Furthermore, multiple recent studies have linked STING to diverse neurodegenerative diseases. For example, in Parkinson's disease, missense mutations in PARKIN and PINK lead to accumulation of mitochondrial DNA, which triggers neuronal inflammation in a cGAS-STING-dependent manner. In mouse models of the disease, loss of STING rescues motor deficits and neuronal cell loss. Finally, STING mediates the tumorigenic DNA response driven by chromosomal instability during cancer metastasis, and STING deficiency confers protection against colorectal and skin cancers in mice. Summary of the Invention

[0005] The present invention relates to novel compounds of formula (Ia),

[0006]

[0007] in

[0008] M 1 Optionally, R 1 Substituted heteroarylene; wherein

[0009] R 1Deuterated, halogen, cyano, carboxyl, R, RO, RS, RNH, (R)2N, RCO, RSO2, RNHSO2, R2NSO2, RSO(NR), R3Si, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RNHC 1-6 Alkyl, (R)2NC 1-6 Alkyl, RSO2C 1-6 Alkyl, RNHSO2C 1-6 Alkyl, R2NSO2C 1-6 Alkyl, RSO(NR)C 1-6 Alkyl or R3SiC 1-6 Alkyl; wherein R is H, R a 、R b or R c ;

[0010] R a For optionally through R b or R c Substituted C 1-6 alkyl;

[0011] R b C 3-7 Cycloalkyl, heterocyclyl, heteroaryl or aryl, the C 3-7 Cycloalkyl, heterocyclyl, heteroaryl and aryl are unsubstituted or optionally substituted with deuterium, halogen or R c replace;

[0012] R c Selected from deuterated, C 1-6 Alkyl, (C 1-6 Alkyl)3Si, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, deuterated C 2-6 Alkenyl, C 2-6 Alkynyl, halo C 2-6 Alkynyl, deuterated C 2-6 Alkynyl, C 3-7 Cycloalkyl, halogenated C 3-7 Cycloalkyl, deuterated C 3-7 Cycloalkyl, amino, C 1-6 Alkylamino, (C 1-6 Alkyl)2amino, C 1-6 Alkylcarbonylamino, haloC 1-6 Alkylamino, halogenated C 1-6 Alkylcarbonylamino, (halogenated C1-6 Alkyl)2amino, C 3-7 Cycloalkylamino, C 3-7 Cycloalkylcarbonylamino, (C 3-7 Cycloalkyl)2amino, halogenated C 3-7 Cycloalkylamino, (halogenated C 3-7 Cycloalkyl)2amino, C 3-7 Cycloalkyl (C 1-6 Alkyl)amino, halo C 3-7 Cycloalkyl (C 1-6 Alkyl)amino, C 1-6 Alkylsulfonylamino, halo C 1-6 Alkylsulfonylamino, C 1-6 Alkoxy C 1-6 Alkyl, (halogenated C 1-6 Alkoxy) C 1-6 Alkyl, C 1-6 Alkoxy (halogenated) C 1-6 Alkyl, C 3-7 Cycloalkyl C 1-6 Alkyl, C 3-7 Cycloalkyl halide C 1-6 Alkyl, C 1-6 Alkylcarbonyl, haloC 1-6 Alkylcarbonyl, C 3-7 Cycloalkylcarbonyl, haloC 3-7 Cycloalkylcarbonyl, C 1-6 Alkoxycarbonyl, halocarbonyl 1-6 Alkoxycarbonyl, C 3-7 Cycloalkoxycarbonyl, halo 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, halogenated C 3-7 Cycloalkylaminocarbonyl, halo(C 3-7 Cycloalkyl)2-aminocarbonyl, halogenated C 1-6 Alkyl C 3-7 Cycloalkylaminocarbonyl, C 1-6 Alkyl halide C 3-7 Cycloalkylaminocarbonyl, (C 1-6 alkyl)3ammonium group, C 1-6 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C3-7 Cycloalkylthio, C 3-7 Cycloalkylsulfinyl, C 3-7 Cycloalkylsulfonyl, halo C 1-6 Alkylthio, halo C 1-6 Alkylsulfinyl, halo C 1-6 Alkylsulfonyl, halo C 3-7 Cycloalkylthio, halo C 3-7 Cycloalkylsulfinyl, halo C 3-7 Cycloalkylsulfonyl, halo C 1-6 Alkoxysulfonyl, C 1-6 Alkylaminosulfonyl, (halogenated C 1-6 alkylamino)sulfonyl, (C 1-6 Alkyl) 2-aminosulfonyl, (halogenated C 1-6 alkyl)2-aminosulfonyl, (C 1-6 alkyl)2phosphoryl, (C 1-6 Alkoxy) 2-phosphoryl, hydroxyl (C 1-6 Alkoxy)phosphoryl, C 1-6 Alkoxyphosphoryl, hydroxyl, hydroxyl C 1-6 Alkyl, hydroxy halide C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy, hydroxy halide C 1-6 Alkoxy, hydroxy C 3-7 Cycloalkyl, hydroxy halide C 3-7 Cycloalkyl and sulfoimide, which are optionally substituted by H, C 1-6 Alkyl, C 1-6 alkoxy, aryl, heteroaryl, and heterocyclyl substitution;

[0013] M 2 is an arylene group, a heterocyclyl group or a heteroarylene group, wherein the arylene group, the heterocyclyl group or the heteroarylene group is optionally substituted by R 1 replace;

[0014] M 3 is unsubstituted or optionally substituted with R 3 substituted heterocyclylene;

[0015] R 2 Deuterium, R, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RSO2C 1-6 Alkyl, RNHC 1-6 Alkyl or (R)2NC 1-6 alkyl;

[0016] R 3is a heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl or arylcarbonyl group, wherein the heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl and arylcarbonyl groups are unsubstituted or optionally substituted by R 1 replace;

[0017] Q 1 is -M-, -MOM-, -MSM-, -M-SO2-M-, -M-SO(NH)-M-, -M-SO(NR)-M-, -M-SiR2-M- or -MN(R)-M-; wherein M is unsubstituted or optionally independently selected from deuterated, halogen, cyano, carboxyl, R, RO, RS, RNH, R2N, RSO2, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RNHC 1-6 Alkyl, (R)2NC 1-6 Alkyl and RSO2C 1-6 Alkyl substituents substituted C 1-6 alkylene;

[0018] Q 2 is NH, O, S, SO, SO2, P(O)R, PO(NR), Se, N(R), SiR2, heterocyclyl, heteroaryl or aryl;

[0019] or a pharmaceutically acceptable salt thereof.

[0020] Another object of the present invention relates to novel compounds of formula (I) or (Ia). Their manufacture, medicaments based on the compounds according to the invention and their production, and the use of compounds of formula (I) or (Ia) as STING antagonists, and for the treatment or prevention of autoimmune diseases, inflammatory diseases, neurological disorders, metabolic diseases, cardiovascular diseases, or selective cancer types in which overexpression or activation of STING is implicated. The compounds of formula (I) or (Ia) exhibit excellent STING antagonistic activity. In addition, the compounds of formula (I) or (Ia) also exhibit good cytotoxicity, phototoxicity, solubility, hPBMC, human microsomal stability and SDPK characteristics, as well as low CYP inhibition. DETAILED DESCRIPTION

[0021] definition

[0022] The term "deuterated" or "heavy hydrogen" refers to an isotope of hydrogen with a single neutron and a single proton in the nucleus.

[0023] The term "C 1-6 "Alkyl" means a saturated, straight-chain or branched alkyl group containing 1 to 6, especially 1 to 4, carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, etc. In particular, "C1-6 "Alkyl" groups are methyl, ethyl and n-propyl.

[0024] The term "(C 1-6 ) Alkylene" means a linear or branched saturated divalent hydrocarbon group of 1 to 6 carbon atoms or a divalent branched saturated divalent hydrocarbon group of 3 to 6 carbon atoms. (C 1-6 ) Examples of the alkylene group include methylene, ethylene, propylene, 2-methylpropylene, butylene, 2-ethylbutylene, pentylene, and hexylene.

[0025] The term "C 1-6 "Alkoxy" means C 1-6 Alkyl-O-.

[0026] The term "trideuterated C 1-6 "Alkyl" means a C 1-6 Three of the hydrogen atoms in the alkyl group have been replaced by deuterium. 1-6 Alkyl group. Trideuterated C 1-6 Examples of the alkyl group include a trideuterated methyl group.

[0027] The term "C 2-6 "Alkenyl" means a monovalent straight or branched hydrocarbon group of 2 to 6 carbon atoms with at least one double bond. In certain embodiments, alkenyl has 2 to 4 carbon atoms and at least one double bond. 2-6 Examples of alkenyl groups include ethenyl (vinyl), propenyl, prop-2-enyl, isopropenyl, n-butenyl, and isobutenyl.

[0028] The term "C 2-6 "Alkynyl" refers to a monovalent straight or branched hydrocarbon group of 2 to 6 carbon atoms with at least one triple bond. In particular embodiments, the alkynyl group has 2 to 4 carbon atoms and at least one triple bond. 2-6 Examples of alkynyl groups include ethynyl (—C≡CH), prop-1-ynyl (—C≡CCH ), prop-2-ynyl (propargyl, —CH 2 C≡CH), but-1-ynyl, but-2-ynyl, and but-3-ynyl. The term “halogen” and “halo” are used interchangeably herein and refer to fluorine, chlorine, bromine, or iodine.

[0029] The term "halogenated C 1-6 "Alkyl" means C 1-6 Alkyl groups, where C 1-6 At least one hydrogen atom of the alkyl group has been replaced by identical or different halogen atoms, in particular fluorine atoms. Examples of haloalkyl groups include monofluoro-, difluoro- or trifluoro-methyl, -ethyl or -propyl, for example 3,3,3-trifluoropropyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, fluoromethyl or trifluoromethyl.

[0030] The term "halogenated C 1-6 "Alkoxy" means a halogenated C 1-6 Alkyl-O-.

[0031] The term "haloazetidinyl" denotes an azetidinyl group wherein at least one hydrogen atom of the azetidinyl group has been replaced by the same or different halogen atoms, in particular fluorine atoms. Examples of halopiperidinyl groups include fluoroazetidinyl and difluoroazetidinyl.

[0032] The term "pyrimidinyloxy" refers to pyrimidinyl-O-.

[0033] The term "trideuterated C 1-6 "Alkoxy" means trideuterated C 1-6 Alkyl-O-.

[0034] The term "carboxyl" refers to -COOH.

[0035] The term "C 3-7 "Cycloalkyl" means a monovalent saturated monocyclic or bicyclic hydrocarbon radical of 3 to 7 ring carbon atoms. Bicyclic means consisting of two saturated carbocyclic rings having one or two common carbon atoms. 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]heptyl, bicyclo[1.1.1]pentanyl or bicyclo[2.2.2]octyl.

[0036] The term "halogenated C 3-7 "Cycloalkyl" means C 3-7 Cycloalkyl groups, wherein C 3-7 At least one hydrogen atom of the cycloalkyl group has been replaced by identical or different halogen atoms, in particular fluorine atoms.

[0037] The term "halo-1,2,3,5,6,7-hexahydropyrrolizinyl" refers to a group wherein C 3-7 1,2,3,5,6,7-hexahydropyrrolazinyl radical in which at least one of the hydrogen atoms of the cycloalkyl radical has been replaced by the same or different halogen atoms, in particular a fluorine atom.

[0038] The term "C 3-7 "Cycloalkoxy" means C 3-7 Cycloalkyl-O-.

[0039] The term "oxetanyloxy" refers to oxetanyl-O-.

[0040] The term "azetidinyloxy" refers to azetidinyl-O-.

[0041] The term "C 1-6 "Alkylcarbonyloxy" means C 1-6Alkyl-C(O)-O-.

[0042] The terms "heterocyclic group," "heterocyclic," "heterocycle," "heterocyclyl," or "heterocyclyl" are used interchangeably and refer to any monocyclic, bicyclic, tricyclic, spirocyclic, or bridged, saturated, partially saturated, or unsaturated, non-aromatic ring system having from 3 to 20 ring atoms, wherein the ring atoms are carbon, and at least one atom in the ring or ring system is a heteroatom selected from nitrogen, sulfur, oxygen, or silicon. If any of the ring atoms of the ring system is a heteroatom, then the system is a heterocycle, regardless of the point of attachment of the ring system to the rest of the molecule. In one example, a heterocyclyl comprises 3-11 ring atoms ("members") and includes monocyclic, bicyclic, tricyclic, spirocyclic, and bridged ring systems, wherein the ring atoms are carbon, and wherein at least one atom in the ring or ring system is a heteroatom selected from nitrogen, sulfur, oxygen, or silicon. In other examples, a heterocyclyl comprises 4-10 or 5-10 ring atoms. In one example, a heterocyclyl comprises 1 to 4 heteroatoms. In one example, the heterocyclic group includes 1 to 3 heteroatoms. In another example, the heterocyclic group includes a 3- to 7-membered monocyclic ring having 1-2, 1-3, or 1-4 heteroatoms selected from nitrogen, sulfur, oxygen, or silicon. In another example, the heterocyclic group includes a 4- to 6-membered monocyclic ring having 1-2, 1-3, or 1-4 heteroatoms selected from nitrogen, sulfur, oxygen, or silicon. In another example, the heterocyclic group includes a 3-membered monocyclic ring. In another example, the heterocyclic group includes a 4-membered monocyclic ring. In another example, the heterocyclic group includes a 5-6-membered monocyclic ring. In some embodiments, the heterocycloalkyl group includes at least one nitrogen. In one example, the heterocyclic group includes 0 to 3 double bonds. Any nitrogen or sulfur heteroatom may be optionally oxidized (e.g., NO, SO, SO2), and any nitrogen heteroatom may be optionally quaternized (e.g., [NR4] + Cl - 、[NR4] + OH - Examples of heterocycles include oxiranyl, aziridinyl, thiopyranyl, azetidinyl, oxetanyl, thietanyl, 1,2-dithietanyl, 1,3-dithietanyl, pyrrolidinyl, dihydro-1H-pyrrolyl, dihydrofuranyl, tetrahydrofuranyl, dihydrothiophenyl, tetrahydrothiophenyl, imidazolidinyl, piperidinyl, piperazinyl, isoquinolinyl, tetrahydroisoquinolinyl, morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, dihydropyranyl, tetrahydropyranyl, hexahydrothiopyranyl, hexahydropyrimidinyl, oxazinyl, thiazinyl, thiooxanyl, homopiperazinyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepine 1,4-diazepanyl, diazepanyl, 1,4-diazepanyl, diazepanyl, thiazolinone yl, thiazepanyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolinyl, isothiazolidinyl, 1,1-isothiazolidinone, 1,1-dioxaisothiazolyl, oxazolidinone, imidazolinone, 4,5,6,7-tetrahydro[2H]indazolyl, tetrahydrobenzimidazolyl, 4,5,6,7-tetrahydrobenzo[d]imidazolyl, thiazinyl, oxazinyl, thiadiazinyl, oxadiazinyl, dithiazinyl, dioxazinyl, oxathiazinyl, thiatriazinyl, oxatriazinyl, dithiadiazinyl, imidazolinyl, dihydropyrimidinyl, tetrahydropyrimidinyl, 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, indolyl, thiopyranyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, pyrazolidinyl, dithienyl, dithiolanyl, pyrimidinone, pyrimidinedione, pyrimidine-2,4-diacyl, piperazinone, piperazinediacyl, pyrazolinylimidazolinyl, 3-azabis[3.1.0] hexyl, 3,6-diazabicyclo[3.1.1]heptyl, 6-azabicyclo[3.1.1]heptyl, 3-azabicyclo[3.1.1]heptyl, 3-azabicyclo[4.1.0]heptyl, azabicyclo[2.2.2]hexyl, 2-azabicyclo[3.2.1]octyl, 8-azabicyclo[3.2.1]octyl, 2-azabicyclo[2.2.2]octyl, 8-azabicyclo[2.2.2]octyl, 7-oxabicyclo[2.2.1]heptane, azaspiro[3.5]nonane, azaspiro[2.5]octanyl, azaspiro[4.5]decane, 1-azaspiro[4.5]decane-2-yl, azaspiro[5.5]undecyl, tetrahydroindolyl, octahydroindolyl, tetrahydroisoindolyl, tetrahydroindolyl, 1,1-dioxohexahydrothiopyranyl and 2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrolyl. In particular, the heterocyclic group herein may be

[0043] The term "heterocyclylene" refers to a divalent heterocyclyl group.

[0044] 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 aromatic group.

[0045] The term "heteroaryl" refers to any monocyclic, bicyclic or tricyclic aromatic ring system containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and in an exemplary embodiment, at least one heteroatom is nitrogen. See, 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 is fused to an aryl ring, wherein the aryl ring or the heteroaryl ring is attached to the remainder of the molecule. In one embodiment, heteroaryl includes 5-6 membered monocyclic aromatic groups in which one or more ring atoms are nitrogen, sulfur, or oxygen. In one embodiment, heteroaryl includes 7-12 membered bicyclic aromatic groups in which one or more ring atoms are nitrogen, sulfur, or oxygen. Example heteroaryl groups include thienyl, furanyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, thiatriazolyl, oxatriazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, tetrazinyl, tetrazolo[1,5-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1H-pyrazolo[3,4-d]pyrimidine, 1H-pyrazolo[3,4-d]pyridazine, imidazo[1,5-a]pyrazine, 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, benzofuranyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, benzimidazolyl, indazolyl and indolyl. In particular, the heteroaryl groups herein may be

[0046] The term "heteroarylene" refers to a divalent heteroaryl group.

[0047] In particular embodiments, the heterocyclyl group or heteroaryl group is attached to a carbon atom of the heterocyclyl group or heteroaryl group. By way of example, carbon-bonded heterocyclyl groups include the following bonding arrangements: at the 2, 3, 4, 5, or 6 position of a pyridine ring, at the 3, 4, 5, or 6 position of a pyridazine ring, at the 2, 4, 5, or 6 position of a pyrimidine ring, at the 2, 3, 5, or 6 position of a pyrazine ring, at the 2, 3, 4, or 5 position of a furan, tetrahydrofuran, thiofuran, thiophene, pyrrole, or tetrahydropyrrole ring, at the 2, 4, or 5 position of an oxazole, imidazole, or thiazole ring, at the 3, 4, or 5 position of an isoxazole, pyrazole, or isothiazole ring, at the 2 or 3 position of an aziridine ring, at the 2, 3, or 4 position of an azetidine ring, at the 2, 3, 4, 5, 6, 7, or 8 position of a quinoline ring, or at the 1, 3, 4, 5, 6, 7, or 8 position of an isoquinoline ring.

[0048] In certain embodiments, the heterocyclyl or heteroaryl group is N-linked. For example, nitrogen-linked heterocyclyl or heteroaryl groups include the following bonding arrangements: position 1 of 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; position 2 of isoindole or isoindolinone; position 4 of morpholine; and position 9 of carbazole or β-carboline.

[0049] Unless otherwise indicated, the term "optionally substituted" means that a group may be unsubstituted or substituted with one or more (e.g., 0, 1, 2, 3, 4, or 5 or more, or any range derivatizable therein) substituents for the group, wherein the substituents may be the same or different. In an embodiment, the optionally substituted group has 1 substituent. In another embodiment, the optionally substituted group has 2 substituents. In another embodiment, the optionally substituted group has 3 substituents. In another embodiment, the optionally substituted group has 4 substituents. In another embodiment, the optionally substituted group has 5 substituents.

[0050] In one embodiment, one skilled in the art will appreciate that keto-enol tautomerism exists in certain structures shown below:

[0051]

[0052] The term "RSO(NR)" means

[0053] The term "SO2" or "sulfonyl" means

[0054] The term "sulfonimide" means

[0055] The term "pharmaceutically acceptable salts" refers to salts that are not biologically or otherwise undesirable."Pharmaceutically acceptable salts" include both acid addition salts and base addition salts.

[0056] "Pharmaceutically acceptable acid addition salts" refer to 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, formic 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, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, aspartic acid, ascorbic acid, glutamic acid, anthranilic acid, benzoic acid, cinnamic acid, mandelic acid, pamoic acid, phenylacetic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid, and the like.

[0057] The term "pharmaceutical base addition salt" refers to those pharmaceutical salts formed with organic or inorganic bases. Examples of acceptable inorganic bases include sodium, potassium, ammonium, calcium, magnesium, iron, zinc, copper, manganese and aluminum salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include primary, secondary and tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines and basic ion exchange resins (such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-diethylaminoethanol, tromethamine, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine and polyamine resins).

[0058] The term "pharmaceutically active metabolite" refers to a pharmacologically active product produced by the in vivo metabolism of a specific compound or its salt. Upon entering the human body, most drugs serve as substrates for chemical reactions that may alter their physical properties and biological effects. These metabolic transformations, which often affect the polarity of the compounds of this invention, alter the drug's distribution and excretion patterns in the body. However, in certain circumstances, drug metabolism is essential for therapeutic efficacy.

[0059] The term "therapeutically effective amount" refers to an amount of a compound or molecule of the present 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 as described herein. The therapeutically effective amount depends on the compound, the disease state 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 medical or veterinary doctor, and other factors.

[0060] The term "pharmaceutical composition" refers to a mixture or solution comprising a therapeutically effective amount of an active pharmaceutical ingredient together with a pharmaceutically acceptable excipient for administration to a mammal (eg, a human) in need thereof.

[0061] STING antagonists

[0062] The present invention relates to (i) a compound of formula (Ia),

[0063]

[0064] in

[0065] M 1 For optionally through R 1 Substituted heteroarylene; wherein

[0066] R 1Deuterated, halogen, cyano, carboxyl, R, RO, RS, RNH, (R)2N, RCO, RSO2, RNHSO2, R2NSO2, RSO(NR), R3Si, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RNHC 1-6 Alkyl, (R)2NC 1-6 Alkyl, RSO2C 1-6 Alkyl, RNHSO2C 1-6 Alkyl, R2NSO2C 1-6 Alkyl, RSO(NR)C 1-6 Alkyl or R3SiC 1-6 Alkyl; wherein R is H, R a 、R b or R c ;

[0067] R a Optionally, R b or R c Substituted C 1-6 alkyl;

[0068] R b C 3-7 Cycloalkyl, heterocyclyl, heteroaryl or aryl, the C 3-7 Cycloalkyl, heterocyclyl, heteroaryl and aryl are unsubstituted or optionally substituted with deuterium, halogen or R c replace;

[0069] R c Selected from deuterated, C 1-6 Alkyl, (C 1-6 Alkyl)3Si, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, deuterated C 2-6 Alkenyl, C 2-6 Alkynyl, halo C 2-6 Alkynyl, deuterated C 2-6 Alkynyl, C 3-7 Cycloalkyl, halogenated C 3-7 Cycloalkyl, deuterated C 3-7 Cycloalkyl, amino, C 1-6 Alkylamino, (C 1-6 Alkyl)2amino, C 1-6 Alkylcarbonylamino, haloC 1-6 Alkylamino, halogenated C 1-6 Alkylcarbonylamino, (halogenated C1-6 Alkyl)2amino, C 3-7 Cycloalkylamino, C 3-7 Cycloalkylcarbonylamino, (C 3-7 Cycloalkyl)2amino, halogenated C 3-7 Cycloalkylamino, (halogenated C 3-7 Cycloalkyl)2amino, C 3-7 Cycloalkyl (C 1-6 Alkyl)amino, halo C 3-7 Cycloalkyl (C 1-6 Alkyl)amino, C 1-6 Alkylsulfonylamino, halo C 1-6 Alkylsulfonylamino, C 1-6 Alkoxy C 1-6 Alkyl, (halogenated C 1-6 Alkoxy) C 1-6 Alkyl, C 1-6 Alkoxy (halogenated) C 1-6 Alkyl, C 3-7 Cycloalkyl C 1-6 Alkyl, C 3-7 Cycloalkyl halide C 1-6 Alkyl, C 1-6 Alkylcarbonyl, haloC 1-6 Alkylcarbonyl, C 3-7 Cycloalkylcarbonyl, haloC 3-7 Cycloalkylcarbonyl, C 1-6 Alkoxycarbonyl, halocarbonyl 1-6 Alkoxycarbonyl, C 3-7 Cycloalkoxycarbonyl, halo 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, halogenated C 3-7 Cycloalkylaminocarbonyl, halo(C 3-7 Cycloalkyl)2-aminocarbonyl, halogenated C 1-6 Alkyl C 3-7 Cycloalkylaminocarbonyl, C 1-6 Alkyl halide C 3-7 Cycloalkylaminocarbonyl, (C 1-6 alkyl)3ammonium group, C 1-6 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C3-7 Cycloalkylthio, C 3-7 Cycloalkylsulfinyl, C 3-7 Cycloalkylsulfonyl, halo C 1-6 Alkylthio, halo C 1-6 Alkylsulfinyl, halo C 1-6 Alkylsulfonyl, halo C 3-7 Cycloalkylthio, halo C 3-7 Cycloalkylsulfinyl, halo C 3-7 Cycloalkylsulfonyl, halo C 1-6 Alkoxysulfonyl, C 1-6 Alkylaminosulfonyl, (halogenated C 1-6 alkylamino)sulfonyl, (C 1-6 Alkyl) 2-aminosulfonyl, (halogenated C 1-6 alkyl)2-aminosulfonyl, (C 1-6 alkyl)2phosphoryl, (C 1-6 Alkoxy) 2-phosphoryl, hydroxyl (C 1-6 Alkoxy)phosphoryl, C 1-6 Alkoxyphosphoryl, hydroxyl, hydroxyl C 1-6 Alkyl, hydroxy halide C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy, hydroxy halide C 1-6 Alkoxy, hydroxy C 3-7 Cycloalkyl, hydroxy halide C 3-7 Cycloalkyl and sulfoimide, which are optionally substituted by H, C 1-6 Alkyl, C 1-6 alkoxy, aryl, heteroaryl, and heterocyclyl substitution;

[0070] M 2 is an arylene group, a heterocyclyl group or a heteroarylene group, wherein the arylene group, the heterocyclyl group or the heteroarylene group is optionally substituted by R 1 replace;

[0071] M 3 is unsubstituted or optionally substituted with R 3 substituted heterocyclylene;

[0072] R 2 Deuterium, R, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RSO2C 1-6 Alkyl, RNHC 1-6 Alkyl or (R)2NC 1-6 alkyl;

[0073] R 3is a heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl or arylcarbonyl group, wherein the heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl and arylcarbonyl groups are unsubstituted or optionally substituted by R 1 replace;

[0074] Q 1 is -M-, -MOM-, -MSM-, -M-SO2-M-, -M-SO(NH)-M-, -M-SO(NR)-M-, -M-SiR2-M- or -MN(R)-M-; wherein M is unsubstituted or optionally independently selected from deuterated, halogen, cyano, carboxyl, R, RO, RS, RNH, R2N, RSO2, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RNHC 1-6 Alkyl, (R)2NC 1-6 Alkyl and RSO2C 1-6 Alkyl substituents substituted C 1-6 alkylene;

[0075] Q 2 is NH, O, S, SO, SO2, P(O)R, PO(NR), Se, N(R), SiR2, heterocyclyl, heteroaryl or aryl;

[0076] or a pharmaceutically acceptable salt thereof.

[0077] Another embodiment of the present invention is (ii) a compound of formula (I),

[0078]

[0079] in

[0080] R 1 Deuterated, 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, halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, morpholinyl C 1-6 Alkyl, hydroxyl, pyrazolyl C 1-6 Alkyl or triazolyl C1-6 alkyl;

[0081] R 2 H, (2-oxa-5-azabicyclo[2.2.1]heptyl)C 1-6 Alkyl, (2-oxa-6-azaspiro[3.3]heptyl)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)3ammonium)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, halogenated C 1-6 Alkyl, hydroxyl 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 trideuterated C 1-6 alkyl;

[0082] R 3 for in

[0083] R 4 For H,

[0084] (C 1-6 Alkyl) 2 amino,

[0085] (C 1-6 alkyl)2-aminocarbonyl,

[0086] (C 1-6 alkyl)2phosphoryl,

[0087] 1,1-dioxothianilinyl,

[0088] C 1-6 Alkyl-substituted 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrolyl,

[0089] Halogenated C 1-6 1,6-diazaspiro[3.3]heptyl substituted by alkyl or oxetane,

[0090] Halogenated C 1-6 1,7-diazaspiro[3.5]nonyl substituted with alkyl or oxetane,

[0091] 2,2-Dioxo-2λ 6 -thia-6-azaspiro[3.3]heptyl,

[0092] C 1-6 Alkyl-substituted 2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazinyl,

[0093] C 1-6 Alkyl, halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl,

[0094] independently selected from halogenated C 1-6 2-azaspiro[3.3]heptyl substituted once or twice with alkyl and hydroxy substituents,

[0095] 2-oxa-5-azabicyclo[2.2.1]heptanyl,

[0096] 2-oxa-6-azaspiro[3.3]heptyl,

[0097] 3,4,6,7,8,8a-Hexahydro-1H-pyrrolo[1,2-a]pyrazinyl,

[0098] 3,4,6,7,9,9a-Hexahydro-1H-pyrazino[2,1-c][1,4]oxazinyl,

[0099] Hydroxyl(halogenated oxetane)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, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, haloC 3-7 Cycloalkyl, hydroxy C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl C 3-7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl,

[0100] 3,6-diazabicyclo[3.2.0]heptanyl substituted with oxetane,

[0101] 3,7-diazabicyclo[4.2.0]octanyl substituted with oxetane,

[0102] Halogenated C 1-6 Alkyl-substituted 3,8-diazabicyclo[3.2.1]octanyl,

[0103] 3-oxa-6-azabicyclo[3.1.1]heptanyl,

[0104] C 1-6 Alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonyl,

[0105] 3-oxa-8-azabicyclo[3.2.1]octanyl,

[0106] Unsubstituted or C 1-6 Alkyl-substituted 4,7-diazaspiro[2.5]octanyl,

[0107] 4-oxo-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazinyl,

[0108] Halogenated C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 Alkyl-substituted 5-oxa-2,8-diazaspiro[3.5]nonyl,

[0109] 6,6-dioxo-6λ 6 -thia-1-azaspiro[3.3]heptyl,

[0110] 6-oxa-1-azaspiro[3.3]heptyl,

[0111] 6-oxa-3-azabicyclo[3.1.1]heptanyl,

[0112] Halogenated C 1-6 Alkyl-substituted 8-oxa-2,5-diazaspiro[3.5]nonyl,

[0113] 8-oxa-3-azabicyclo[3.2.1]octanyl,

[0114] amino,

[0115] aminocarbonyl,

[0116] unsubstituted or independently selected from (C 1-6 alkyl)2amino, (C 1-6 Alkyl)2amino C 1-6 Alkyl, amino, C 1-6 Alkyl, C 1-6 Alkylcarbonyl, C 1-6 Alkylsulfonyl, C1-6 Alkylsulfonyl C 1-6 Alkyl, C 3-7 Cycloalkyl, cyano, cyano C 1-6 Alkyl, halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, morpholinyl and morpholinyl C 1-6 The substituent of the alkyl group is substituted once or twice with an azetidinyl group,

[0117] Halogenated C 1-6 Alkyl or C 3-7 cycloalkyl-substituted azetidinyloxy,

[0118] Unsubstituted or (halogenated C 1-6 alkylcarbonyl)azetidinyl, C 1-6 Alkylazetidinyl, C 1-6 Alkylpiperazinyl, C 1-6 Alkylpyrrolidinyl, halogenated-1,2,3,5,6,7-hexahydropyrrolizinyl, halogenated C 1-6 Alkyl azetidinyl, morpholinyl, oxetanyl or tetrahydrofuranyl substituted C 1-6 Alkoxy,

[0119] C 1-6 Alkoxy C 1-6 Alkylamino,

[0120] C 1-6 Alkoxycarbonyl,

[0121] unsubstituted or independently selected from (C 1-6 Alkoxy C 1-6 alkylcarbonyl)azetidinyl, (halogenated C 1-6 alkylcarbonyl)pyrrolidinyl, 1,1-dioxothietane, 2-oxa-6-azaspiro[3.3]heptyl, 3-oxa-6-azabicyclo[3.1.1]heptyl, 4,7-diazaspiro[2.5]octyl, 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, halo C 1-6 Alkylazetidinyl, hydroxy, hydroxy C 1-6 Alkyl, morpholinyl and oxetane substituents are substituted once or twice on the C 1-6 alkyl,

[0122] C 1-6 Alkylamino,

[0123] C unsubstituted or substituted with 1,1-dioxothietane 1-6 Alkylthio,

[0124] C 1-6 Alkylsulfonyl,

[0125] Unsubstituted or C 1-6 Alkoxy or hydroxy substituted C 3-7 Cycloalkyl,

[0126] carboxyl,

[0127] cyano group,

[0128] Halogenated C 1-6 Alkoxy,

[0129] Halogenated C substituted with hydroxyl 1-6 alkyl,

[0130] hydroxyl groups,

[0131] Hydroxyl C 1-6 Alkylcarbamoyl,

[0132] Imidazole,

[0133] Morpholinyl,

[0134] Morpholinylcarbonyl,

[0135] Oxetane,

[0136] Oxomorpholinyl,

[0137] Oxooxazolidinyl,

[0138] C 1-6 alkyl-substituted oxopiperazinyl,

[0139] Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group,

[0140] Independently selected from C 1-6 Alkyl, carboxyl, oxetane and phenyl C 1-6 a piperazinyl group substituted once or twice with an alkyl substituent,

[0141] C 1-6 alkyl, 2H-tetrazolyl or oxazolyl substituted piperidinyl,

[0142] are independently selected from amino, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, C1-6 Alkylcarbonyl, C 1-6 Alkylsulfonyl, cyano, halo C 1-6 alkylcarbonyl and halogen substituents substituted once or twice with pyrrolidinyl,

[0143] pyrrolidinylcarbonyl,

[0144] tetrahydrofuranyl, or

[0145] tetrahydropyranyl;

[0146] R 5 is 1,3-dihydroisobenzofuranyl,

[0147] 1H-indazolyl substituted by halogen,

[0148] C 2-6 Alkynyl,

[0149] Thiphenyl group,

[0150] Unsubstituted or halogen or C 1-6 Alkyl-substituted bicyclo[1.1.1]pentanyl,

[0151] Independently selected from (C 1-6 Alkoxy C 1-6 Alkyl)C 3-7 Cycloalkyloxy, (C 1-6 alkyl)2phosphoryl, (C 1-6 Alkylmorpholinyl)C 1-6 Alkoxy, (C 1-6 (alkylsulfonylazetidinyl)C 1-6 Alkoxy, 2-oxa-6-azaspiro[3.3]heptyl, 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 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C 2-6 Alkenyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyloxy, carboxyl, cyano, cyano C 1-6 Alkoxy, halogenated C 1-6Alkoxy, halogenated C 1-6 Alkyl, halogen, hydroxyl, morpholinyl, morpholinyl C 1-6 Alkoxy, oxetane C 1-6 Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl, tetrahydrofuranyloxy and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times,

[0152] unsubstituted or independently selected from halogen, hydroxy, C 1-6 Alkylthio and C 1-6 The alkoxy substituent is substituted once or twice with a pyridyl group, or

[0153] unsubstituted or halogen-substituted pyrimidinyl;

[0154] R 6 H or C 1-6 alkyl;

[0155] R 7 C 1-6 alkyl;

[0156] R 7a C 1-6 Alkyl, C 3-7 Cycloalkyl or C 1-6 Alkoxy C 1-6 alkyl;

[0157] R 7b H, C 1-6 Alkoxy or phenyl C 1-6 alkoxy;

[0158] R 7c H or C 1-6 alkoxy;

[0159] R 7d C 1-6 Alkyl, C 3-7 Cycloalkyl C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 alkyl;

[0160] R 7e H, amino, phenyl C 1-6 Alkylamino or morpholino C 1-6 Alkylamino;

[0161] R 7f C 1-6 Alkyl, phenyl C 1-6 Alkyl or oxetane;

[0162] R 7g H or C1-6 Alkoxy C 1-6 alkyl;

[0163] Q 1 is unsubstituted or independently selected from C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkoxy, C 1-6 Alkyl, C 1-6 Alkylcarbonyloxy, carboxyl, hydroxyl, hydroxyl C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, morpholinyl C 1-6 Alkoxy and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 Alkylene, or

[0164] -MOM-, where M is C 1-6 alkylene;

[0165] Q 2 is NH, O or S;

[0166] A 1 is CH or N;

[0167] A 2 CH, CR 7h or N; where R 7h C 1-6 alkyl;

[0168] 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, halogenated azetidinyl C 1-6 Alkyl, halogenated C 1-6 Alkoxy, halogen, morpholino C 1-6 Alkyl or oxetane;

[0169] A 4 CR 9 or N, where R 9 H; or R 8 and R 9 together with the atoms to which they are attached, form a heterocyclyl;

[0170] A 5 CR 10 or N, where R 10is H or halogen;

[0171] A 6 CR 11 or N, where R 11 H, deuterated, halogen, C 1-6 Alkyl or C 1-6 alkoxy;

[0172] A 7 CR 12 or N, where R 12 is H or halogen;

[0173] Condition A 1 、A 2 、A 3 and A 4 No more than two of them are N at the same time; and A 5 、A 6 and A 7 No more than one of them is N;

[0174] or a pharmaceutically acceptable salt thereof.

[0175] Another embodiment of the present invention is (iii) a compound having formula (Ib),

[0176]

[0177] in

[0178] R 1 Deuterated, 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, halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, morpholinyl C 1-6 Alkyl, hydroxyl, pyrazolyl C 1-6 Alkyl or triazolyl C 1-6 alkyl;

[0179] R 2 H, (2-oxa-5-azabicyclo[2.2.1]heptyl)C 1-6Alkyl, (2-oxa-6-azaspiro[3.3]heptyl)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)3ammonium)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, halogenated C 1-6 Alkyl, hydroxyl 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 trideuterated C 1-6 alkyl;

[0180] R 3 for in

[0181] R 4 For H,

[0182] (C 1-6 Alkyl) 2 amino,

[0183] (C 1-6 alkyl)2-aminocarbonyl,

[0184] (C 1-6 alkyl)2phosphoryl,

[0185] 1,1-dioxothianilinyl,

[0186] C 1-6 Alkyl-substituted 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrolyl,

[0187] Halogenated C 1-6 1,6-diazaspiro[3.3]heptyl substituted by alkyl or oxetane,

[0188] Halogenated C 1-6 1,7-diazaspiro[3.5]nonyl substituted with alkyl or oxetane,

[0189] 2,2-Dioxo-2λ6 -thia-6-azaspiro[3.3]heptyl,

[0190] C 1-6 Alkyl-substituted 2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazinyl,

[0191] C 1-6 Alkyl, halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl,

[0192] independently selected from halogenated C 1-6 2-azaspiro[3.3]heptyl substituted once or twice with alkyl and hydroxy substituents,

[0193] 2-oxa-5-azabicyclo[2.2.1]heptanyl,

[0194] 2-oxa-6-azaspiro[3.3]heptyl,

[0195] 3,4,6,7,8,8a-Hexahydro-1H-pyrrolo[1,2-a]pyrazinyl,

[0196] 3,4,6,7,9,9a-Hexahydro-1H-pyrazino[2,1-c][1,4]oxazinyl,

[0197] Hydroxyl(halogenated oxetane)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, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, haloC 3-7 Cycloalkyl, hydroxy C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl C 3-7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl,

[0198] 3,6-diazabicyclo[3.2.0]heptanyl substituted with oxetane,

[0199] 3,7-diazabicyclo[4.2.0]octanyl substituted with oxetane,

[0200] Halogenated C 1-6 Alkyl-substituted 3,8-diazabicyclo[3.2.1]octanyl,

[0201] 3-oxa-6-azabicyclo[3.1.1]heptanyl,

[0202] C 1-6 Alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonyl,

[0203] 3-oxa-8-azabicyclo[3.2.1]octanyl,

[0204] Unsubstituted or C 1-6 Alkyl-substituted 4,7-diazaspiro[2.5]octanyl,

[0205] 4-oxo-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazinyl,

[0206] Halogenated C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 Alkyl-substituted 5-oxa-2,8-diazaspiro[3.5]nonyl,

[0207] 6,6-dioxo-6λ 6 -thia-1-azaspiro[3.3]heptyl,

[0208] 6-oxa-1-azaspiro[3.3]heptyl,

[0209] 6-oxa-3-azabicyclo[3.1.1]heptanyl,

[0210] Halogenated C 1-6 Alkyl-substituted 8-oxa-2,5-diazaspiro[3.5]nonyl,

[0211] 8-oxa-3-azabicyclo[3.2.1]octanyl,

[0212] amino,

[0213] aminocarbonyl,

[0214] unsubstituted or independently selected from (C 1-6 alkyl)2amino, (C 1-6 Alkyl)2amino 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, halogenated C 1-6 Alkyl, hydroxyl C 1-6Alkyl, morpholinyl and morpholinyl C 1-6 The substituent of the alkyl group is substituted once or twice with an azetidinyl group,

[0215] Halogenated C 1-6 Alkyl or C 3-7 cycloalkyl-substituted azetidinyloxy,

[0216] Unsubstituted or (halogenated C 1-6 alkylcarbonyl)azetidinyl, C 1-6 Alkylazetidinyl, C 1-6 Alkylpiperazinyl, C 1-6 Alkylpyrrolidinyl, halogenated-1,2,3,5,6,7-hexahydropyrrolizinyl, halogenated C 1-6 Alkyl azetidinyl, morpholinyl, oxetanyl or tetrahydrofuranyl substituted C 1-6 Alkoxy,

[0217] C 1-6 Alkoxy C 1-6 Alkylamino,

[0218] C 1-6 Alkoxycarbonyl,

[0219] unsubstituted or independently selected from (C 1-6 Alkoxy C 1-6 alkylcarbonyl)azetidinyl, (halogenated C 1-6 alkylcarbonyl)pyrrolidinyl, 1,1-dioxothietane, 2-oxa-6-azaspiro[3.3]heptyl, 3-oxa-6-azabicyclo[3.1.1]heptyl, 4,7-diazaspiro[2.5]octyl, 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, halo C 1-6 Alkylazetidinyl, hydroxy, hydroxy C 1-6 Alkyl, morpholinyl and oxetane substituents are substituted once or twice on the C 1-6 alkyl,

[0220] C 1-6 Alkylamino,

[0221] C unsubstituted or substituted with 1,1-dioxothietane 1-6 Alkylthio,

[0222] C 1-6 Alkylsulfonyl,

[0223] Unsubstituted or C 1-6 Alkoxy or hydroxy substituted C 3-7 Cycloalkyl,

[0224] carboxyl,

[0225] cyano group,

[0226] Halogenated C 1-6 Alkoxy,

[0227] Halogenated C substituted with hydroxyl 1-6 alkyl,

[0228] hydroxyl groups,

[0229] Hydroxyl C 1-6 Alkylcarbamoyl,

[0230] Imidazole,

[0231] Morpholinyl,

[0232] Morpholinylcarbonyl,

[0233] Oxetane,

[0234] Oxomorpholinyl,

[0235] Oxooxazolidinyl,

[0236] C 1-6 alkyl-substituted oxopiperazinyl,

[0237] Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group,

[0238] Independently selected from C 1-6 Alkyl, carboxyl, oxetane and phenyl C 1-6 a piperazinyl group substituted once or twice with an alkyl substituent,

[0239] C 1-6 alkyl, 2H-tetrazolyl or oxazolyl substituted piperidinyl,

[0240] are independently selected from amino, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkylcarbonyl, C 1-6 Alkylsulfonyl, cyano, halo C 1-6 alkylcarbonyl and halogen substituents substituted once or twice with pyrrolidinyl,

[0241] pyrrolidinylcarbonyl,

[0242] tetrahydrofuranyl, or

[0243] tetrahydropyranyl;

[0244] R 5 is 1,3-dihydroisobenzofuranyl,

[0245] 1H-indazolyl substituted by halogen,

[0246] C 2-6 Alkynyl,

[0247] Thiphenyl group,

[0248] Unsubstituted or halogen or C 1-6 Alkyl-substituted bicyclo[1.1.1]pentanyl,

[0249] Independently selected from (C 1-6 Alkoxy C 1-6 Alkyl)C 3-7 Cycloalkyloxy, (C 1-6 alkyl)2phosphoryl, (C 1-6 Alkylmorpholinyl)C 1-6 Alkoxy, (C 1-6 (alkylsulfonylazetidinyl)C 1-6 Alkoxy, 2-oxa-6-azaspiro[3.3]heptyl, 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 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C 2-6 Alkenyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyloxy, carboxyl, cyano, cyano C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogen, hydroxyl, morpholinyl, morpholinyl C 1-6 Alkoxy, oxetane C 1-6Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl, tetrahydrofuranyloxy and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times,

[0250] unsubstituted or independently selected from halogen, hydroxy, C 1-6 Alkylthio and C 1-6 The alkoxy substituent is substituted once or twice with a pyridyl group, or

[0251] unsubstituted or halogen-substituted pyrimidinyl;

[0252] R 6 H or C 1-6 alkyl;

[0253] R 7 C 1-6 alkyl;

[0254] R 7a C 1-6 Alkyl, C 3-7 Cycloalkyl or C 1-6 Alkoxy C 1-6 alkyl;

[0255] R 7b H, C 1-6 Alkoxy or phenyl C 1-6 alkoxy;

[0256] R 7c H or C 1-6 alkoxy;

[0257] R 7d C 1-6 Alkyl, C 3-7 Cycloalkyl C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 alkyl;

[0258] R 7e H, amino, phenyl C 1-6 Alkylamino or morpholino C 1-6 Alkylamino;

[0259] R 7f C 1-6 Alkyl, phenyl C 1-6 Alkyl or oxetane;

[0260] R 7g H or C 1-6 Alkoxy C 1-6 alkyl;

[0261] Q 1is unsubstituted or independently selected from C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkoxy, C 1-6 Alkyl, C 1-6 Alkylcarbonyloxy, carboxyl, hydroxyl, hydroxyl C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, morpholinyl C 1-6 Alkoxy and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 Alkylene, or

[0262] -MOM-, where M is C 1-6 alkylene;

[0263] Q 2 is NH, O or S;

[0264] A 1 is CH or N;

[0265] A 2 CH, CR 7h or N; where R 7h C 1-6 alkyl;

[0266] 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, halogenated azetidinyl C 1-6 Alkyl, halogenated C 1-6 Alkoxy, halogen, morpholino C 1-6 Alkyl or oxetane;

[0267] A 4 CR 9 or N, where R 9 H; or R 8 and R 9 together with the atoms to which they are attached, form a heterocyclyl;

[0268] A 5 CR 10 or N, where R 10 is H or halogen;

[0269] A 6 CR 11 or N, where R11 H, deuterated, halogen, C 1-6 Alkyl or C 1-6 alkoxy;

[0270] A 7 CR 12 or N, where R 12 is H or halogen;

[0271] Condition A 1 、A 2 、A 3 and A 4 No more than two of them are N at the same time; and A 5 、A 6 and A 7 No more than one of them is N;

[0272] or a pharmaceutically acceptable salt thereof.

[0273] Another embodiment of the present invention is (iv) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to (i) or (iii), wherein R 1 H or C 1-6 alkyl.

[0274] Another embodiment of the present invention is (v) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (iv), wherein R 1 is H or methyl.

[0275] Another embodiment of the present invention is (vi) a compound of formula (I) or (Ia) according to any one of (i) to (v), wherein R 2 C 1-6 Alkyl or trideuterated C 1-6 alkyl.

[0276] Another embodiment of the present invention is (vii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (vi), wherein R 2 It is methyl, ethyl or trideuterated methyl.

[0277] Another embodiment of the present invention is (viii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (vii), wherein R 3 for

[0278] in

[0279] R 4 For H,

[0280] Halogenated C 1-6alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl,

[0281] C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, C 3-7 Cycloalkylcarbonyl, haloC 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, hydroxyl C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl C 3-7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl,

[0282] 3-oxa-6-azabicyclo[3.1.1]heptanyl,

[0283] C 1-6 Alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonyl,

[0284] amino,

[0285] C 1-6 Alkylcarbonyl, C 1-6 an azetidinyl group substituted with an alkylsulfonyl group or a cyano group,

[0286] C 1-6 Alkoxy,

[0287] Unsubstituted or C 1-6 Alkoxy, C 1-6 Alkylcarbonylazetidinyl, C 1-6 Alkylsulfonylazetidinyl, C 3-7 Cycloalkylsulfonylazetidinyl, halo C 1-6 Alkylazetidinyl, hydroxy, morpholinyl or oxetanyl substituted C 1-6 alkyl,

[0288] Oxetane,

[0289] Oxooxazolidinyl, or

[0290] Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group;

[0291] R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkyloxy, cyano, haloC 1-6 Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times,

[0292] pyridyl substituted twice with halogen, or

[0293] halogen-substituted pyrimidinyl;

[0294] R 6 is H;

[0295] R 7a C 1-6 alkyl;

[0296] R 7e It is amino;

[0297] R 7f C 1-6 alkyl;

[0298] R 7g H or C 1-6 Alkoxy C 1-6 alkyl.

[0299] Another embodiment of the present invention is (ix) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (viii), wherein R 3 for in

[0300] R 4 For H,

[0301] R 4H, (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, 1.1]heptane-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 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-aza-1 ... heterobicyclo[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;

[0302] R 5 is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropyloxy, cyano, difluoromethoxy, fluorine, hydroxyl and trideuteromethoxy,

[0303] pyridyl substituted twice with fluorine, or

[0304] fluorine-substituted pyrimidinyl;

[0305] R 6 is H;

[0306] R 7a is methyl;

[0307] R 7e It is amino;

[0308] R 7f is methyl;

[0309] R 7g is H or methoxymethyl.

[0310] Another embodiment of the present invention is (x) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (ix), wherein R 3 is H; in

[0311] R 4 For H,

[0312] Halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl,

[0313] C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, C 3-7 Cycloalkylcarbonyl, haloC 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, hydroxyl C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl C 3-7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl,

[0314] 3-oxa-6-azabicyclo[3.1.1]heptanyl,

[0315] C 1-6 Alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonyl,

[0316] amino,

[0317] C 1-6 Alkylcarbonyl, C 1-6 an azetidinyl group substituted with an alkylsulfonyl group or a cyano group,

[0318] C 1-6 Alkoxy,

[0319] Unsubstituted or C 1-6 Alkoxy, C 1-6 Alkylcarbonylazetidinyl, C 1-6 Alkylsulfonylazetidinyl, C 3-7 Cycloalkylsulfonylazetidinyl, halo C 1-6 Alkylazetidinyl, hydroxy, morpholinyl or oxetanyl substituted C 1-6 alkyl,

[0320] Oxetane,

[0321] Oxooxazolidinyl, or

[0322] Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group;

[0323] R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkyloxy, cyano, haloC 1-6 Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times,

[0324] pyridyl substituted twice with halogen, or

[0325] halogen-substituted pyrimidinyl;

[0326] R 6 For H.

[0327] Another embodiment of the present invention is (xi) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (x), wherein R 3 for in

[0328] R 4H, (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, 1.1]heptane-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 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-aza-1 ... heterobicyclo[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;

[0329] R 5 is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropyloxy, cyano, difluoromethoxy, fluorine, hydroxyl and trideuteromethoxy,

[0330] pyridyl substituted twice with fluorine, or

[0331] fluorine-substituted pyrimidinyl;

[0332] R 6 For H.

[0333] Another embodiment of the present invention is (xii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xi), wherein Q 1 are independently selected from C 1-6 Alkoxy, C 1-6 Alkylcarbonyloxy, hydroxyl, C 1-6 Alkyl and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 Alkylene.

[0334] Another embodiment of the present invention is (xiii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xii), wherein Q 1 is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl, acetoxy and trideuteromethoxy.

[0335] Another embodiment of the present invention is (xiv) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xiii), wherein Q 1 For C 1-6 Alkoxy-substituted C 1-6 Alkylene.

[0336] Another embodiment of the present invention is (xv) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xiv), wherein Q 1 It is a propylene group substituted by a methoxy group or an ethoxy group.

[0337] Another embodiment of the present invention is (xvi) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xv), wherein Q 2 is NH or O.

[0338] Another embodiment of the present invention is (xvii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xvi), wherein A 1 is N.

[0339] Another embodiment of the present invention is (xviii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xvii), wherein A 3 CR 8 , where R 8 H, C1-6 Alkoxy, C 1-6 Alkyl, C 3-7 Cycloalkoxy, halogenated C 1-6 Alkoxy or halogen.

[0340] Another embodiment of the present invention is (xix) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xviii), wherein A 3 CR 8 , where R 8 is H, methoxy, methyl, cyclopropyloxy, difluoromethoxy or fluorine.

[0341] Another embodiment of the present invention is (xx) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xix), wherein A 3 CR 8 , where R 8 For H.

[0342] Another embodiment of the present invention is (xxi) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xx), wherein A 4 CR 9 , where R 9 For H.

[0343] Another embodiment of the present invention is (xxii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xxi), wherein A 5 CR 10 or N, where R 10 is H or fluorine.

[0344] Another embodiment of the present invention is (xxiii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xxii), wherein A 5 CR 10 , where R 10 For H.

[0345] Another embodiment of the present invention is (xxiv) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xxiii), wherein A 6 CR 11 , where R 11 is H or halogen.

[0346] Another embodiment of the present invention is (xxv) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xxiv), wherein A 6 CR 11 , where R 11 is H or fluorine.

[0347] Another embodiment of the present invention is (xxvi) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xxv), wherein A 6 CR 11 , where R 11 It is a halogen.

[0348] Another embodiment of the present invention is (xxvii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xxvi), wherein A 6 CR 11 , where R 11 For fluorine.

[0349] Another embodiment of the present invention is (xxviii) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xxvii), wherein A 7 CR 12 , where R 12 is H or halogen.

[0350] Another embodiment of the present invention is (xxix) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xxviii), wherein A 7 CR 12 , where R 12 is H or fluorine.

[0351] Another embodiment of the present invention is (xxx) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (xxix), wherein A 7 CR 12 , where R 12 For H.

[0352] Another embodiment of the present invention is (xxxi) a compound of formula (I) or (Ia) according to any one of (i) or (ii) or (iii), wherein

[0353] R 1 H or C 1-6 alkyl;

[0354] R 2 C 1-6 Alkyl or trideuterated C 1-6 alkyl;

[0355] R 3 for in

[0356] R 4 For H,

[0357] Halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl,

[0358] C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, C 3-7 Cycloalkylcarbonyl, haloC 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, hydroxyl C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl C 3-7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl,

[0359] 3-oxa-6-azabicyclo[3.1.1]heptanyl,

[0360] C 1-6 Alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonyl,

[0361] amino,

[0362] C 1-6 Alkylcarbonyl, C 1-6 an azetidinyl group substituted with an alkylsulfonyl group or a cyano group,

[0363] C 1-6 Alkoxy,

[0364] Unsubstituted or C 1-6 Alkoxy, C 1-6 Alkylcarbonylazetidinyl, C 1-6 Alkylsulfonylazetidinyl, C 3-7 Cycloalkylsulfonylazetidinyl, halo C 1-6 Alkylazetidinyl, hydroxy, morpholinyl or oxetanyl substituted C 1-6 alkyl,

[0365] Oxetane,

[0366] Oxooxazolidinyl,

[0367] Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group;

[0368] R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkyloxy, cyano, haloC 1-6Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times,

[0369] pyridyl substituted twice with halogen, or

[0370] halogen-substituted pyrimidinyl;

[0371] R 6 is H;

[0372] R 7a C 1-6 alkyl;

[0373] R 7e It is amino;

[0374] R 7f C 1-6 alkyl;

[0375] R 7g H or C 1-6 Alkoxy C 1-6 alkyl;

[0376] Q 1 are independently selected from C 1-6 Alkoxy, C 1-6 Alkylcarbonyloxy, hydroxyl, C 1-6 Alkyl and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 alkylene;

[0377] Q 2 is NH or O;

[0378] A 1 is N;

[0379] A 2 CH, CR 7h or N; where R 7h C 1-6 alkyl;

[0380] A 3 CR 8 , where R 8 H, C 1-6 Alkoxy, C 1-6 Alkyl, C 3-7 Cycloalkoxy, halogenated C 1-6 Alkoxy or halogen;

[0381] A 4 CR 9 , where R 9 is H;

[0382] A5 CR 10 or N, where R 10 is H or halogen;

[0383] A 6 CR 11 , where R 11 is H or halogen;

[0384] A 7 CR 12 , where R 12 is H or halogen;

[0385] or a pharmaceutically acceptable salt thereof.

[0386] Another embodiment of the present invention is (xxxii) a compound of formula (I) or (Ia) according to (xxxi), wherein

[0387] R 1 is H or methyl;

[0388] R 2 is methyl, ethyl or trideuterated methyl;

[0389] R 3 for in

[0390] R 4 For H,

[0391] R 4H, (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, 1.1]heptane-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 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-aza-1 ... heterobicyclo[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;

[0392] R 5 is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropyloxy, cyano, difluoromethoxy, fluorine, hydroxyl and trideuteromethoxy,

[0393] pyridyl substituted twice with fluorine, or

[0394] fluorine-substituted pyrimidinyl;

[0395] R 6 is H;

[0396] R 7a is methyl;

[0397] R 7e It is amino;

[0398] R 7f is methyl;

[0399] R 7g is H or methoxymethyl;

[0400] Q 1 is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl, acetoxy and trideuteromethoxy;

[0401] Q 2 is NH or O;

[0402] A 1 is N;

[0403] A 2 CH, CR 7h or N; where R 7h is methyl;

[0404] A 3 CR 8 , where R 8 is H, methoxy, methyl, cyclopropyloxy, difluoromethoxy or fluorine;

[0405] A 4 CR 9 , where R 9 is H;

[0406] A 5 CR 10 or N, where R 10 is H or fluorine;

[0407] A 6 CR 11 , where R 11 is H or fluorine;

[0408] A 7 CR 12 , where R 12 is H or fluorine;

[0409] or a pharmaceutically acceptable salt thereof.

[0410] Another embodiment of the present invention is (xxxiii) a compound of formula (I) or (Ia) according to (xxxii), wherein

[0411] R 1 C 1-6 alkyl;

[0412] R 2 C 1-6 alkyl;

[0413] R 3 for in

[0414] R 4 For H,

[0415] Halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl,

[0416] C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, C 3-7 Cycloalkylcarbonyl, haloC 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, hydroxyl C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl C 3-7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl,

[0417] 3-oxa-6-azabicyclo[3.1.1]heptanyl,

[0418] C 1-6 Alkyl-substituted 3-oxa-7,9-diazabicyclo[3.3.1]nonyl,

[0419] amino,

[0420] C 1-6 Alkylcarbonyl, C 1-6 an azetidinyl group substituted with an alkylsulfonyl group or a cyano group,

[0421] C 1-6 Alkoxy,

[0422] Unsubstituted or C 1-6 Alkoxy, C 1-6 Alkylcarbonylazetidinyl, C 1-6 Alkylsulfonylazetidinyl, C 3-7 Cycloalkylsulfonylazetidinyl, halo C 1-6Alkylazetidinyl, hydroxy, morpholinyl or oxetanyl substituted C 1-6 alkyl,

[0423] Oxetane,

[0424] Oxooxazolidinyl,

[0425] Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group;

[0426] R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkyloxy, cyano, haloC 1-6 Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times,

[0427] pyridyl substituted twice with halogen, or

[0428] halogen-substituted pyrimidinyl;

[0429] R 6 is H;

[0430] Q 1 For C 1-6 Alkoxy-substituted C 1-6 alkylene;

[0431] Q 2 is NH or O;

[0432] A 1 is N;

[0433] A 2 is CH or N;

[0434] A 3 CR 8 , where R 8 is H;

[0435] A 4 CR 9 , where R 9 is H;

[0436] A 5 CR 10 or N, where R 10 is H;

[0437] A 6 CR 11 , where R 11 is a halogen;

[0438] A 7CR 12 , where R 12 is H;

[0439] or a pharmaceutically acceptable salt thereof.

[0440] Another embodiment of the present invention is (xxxiv) a compound of formula (I) or (Ia) according to (xxxiii), wherein

[0441] R 1 is methyl;

[0442] R 2 is methyl;

[0443] R 3 for in

[0444] R 4H, (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, 1.1]heptane-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 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-aza-1 ... heterobicyclo[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;

[0445] R 5 is phenyl substituted once, twice or three times with substituents independently selected from ethoxy, methoxy, cyclopropyloxy, cyano, difluoromethoxy, fluorine, hydroxyl and trideuteromethoxy,

[0446] pyridyl substituted twice with fluorine, or

[0447] fluorine-substituted pyrimidinyl;

[0448] R 6 is H;

[0449] Q 1 is a propylene group substituted by a methoxy group or an ethoxy group;

[0450] Q 2 is NH or O;

[0451] A 1 is N;

[0452] A 2 is CH or N;

[0453] A 3 CR 8 , where R 8 is H;

[0454] A 4 CR 9 , where R 9 is H;

[0455] A 5 CR 10 or N, where R 10 is H;

[0456] A 6 CR 11 , where R 11 For fluorine;

[0457] A 7 CR 12 , where R 12 is H;

[0458] or a pharmaceutically acceptable salt thereof.

[0459] The present invention relates to (i') compounds of formula (Ia),

[0460]

[0461] in

[0462] M 1 Optionally, R 1 Substituted heteroarylene; wherein

[0463] R 1 Deuterated, halogen, cyano, carboxyl, R, RO, RS, RNH, (R)2N, RCO, RSO2, RNHSO2, R2NSO2, RSO(NR), ROC 1-6 Alkyl, RSC1-6 Alkyl, RNHC 1-6 Alkyl, (R)2NC 1-6 Alkyl, RSO2C 1-6 Alkyl, RNHSO2C 1-6 Alkyl, R2NSO2C 1-6 Alkyl or RSO(NR)C 1-6 Alkyl; wherein R is H, R a 、R b or R c ;

[0464] R a Optionally, R b or R c Substituted C 1-6 alkyl;

[0465] R b C 3-7 Cycloalkyl, heterocyclyl, heteroaryl or aryl, the C 3-7 Cycloalkyl, heterocyclyl, heteroaryl and aryl are unsubstituted or optionally substituted with halogen or R c replace;

[0466] R c Selected from optionally H, C 1-6 Alkyl, C 1-6 Alkoxy, aryl, heteroaryl and heterocyclic substituted C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, halo C 2-6 Alkynyl, C 3-7 Cycloalkyl, halogenated C 3-7 Cycloalkyl, amino, C 1-6 Alkylamino, (C 1-6 Alkyl)2amino, halogenated C 1-6 Alkylamino, halo (C 1-6 Alkyl)2amino, C 3-7 Cycloalkylamino, (C 3-7 Cycloalkyl)2amino, halogenated C 3-7 Cycloalkylamino, (halogenated C 3-7 Cycloalkyl)2amino, C 3-7 Cycloalkyl (C 1-6 Alkyl)amino, halo C 3-7 Cycloalkyl (C 1-6 Alkyl)amino, C 1-6 Alkoxy C 1-6 Alkyl, (halogenated C 1-6 Alkoxy) C 1-6 Alkyl, C1-6 Alkoxy (halogenated) C 1-6 Alkyl, C 3-7 Cycloalkyl C 1-6 Alkyl, C 3-7 Cycloalkyl halide C 1-6 Alkyl, C 1-6 Alkylcarbonyl, haloC 1-6 Alkylcarbonyl, C 3-7 Cycloalkylcarbonyl, haloC 3-7 Cycloalkylcarbonyl, C 1-6 Alkoxycarbonyl, halocarbonyl 1-6 Alkoxycarbonyl, C 3-7 Cycloalkoxycarbonyl, halo 3-7 Cycloalkoxycarbonyl, halo 1-6 Alkoxycarbonyl, 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, halogenated C 3-7 Cycloalkylaminocarbonyl, halo(C 3-7 Cycloalkyl)2-aminocarbonyl, halogenated C 1-6 Alkyl C 3-7 Cycloalkylaminocarbonyl, C 1-6 Alkyl halide C 3-7 Cycloalkylaminocarbonyl, (C 1-6 alkyl)3ammonium group, C 1-6 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C 3-7 Cycloalkylthio, C 3-7 Cycloalkylsulfinyl, C 3-7 Cycloalkylsulfonyl, halo C 1-6 Alkylthio, halo C 1-6 Alkylsulfinyl, halo C 1-6 Alkylsulfonyl, halo C 3-7 Cycloalkylthio, halo C 3-7 Cycloalkylsulfinyl, halo C 3-7 Cycloalkylsulfonyl, halo C 1-6 Alkoxysulfonyl, C 1-6 Alkylaminosulfonyl, (halogenated C 1-6 alkylamino)sulfonyl, (C 1-6 Alkyl) 2-aminosulfonyl, (halogenated C 1-6alkyl)2-aminosulfonyl, (C 1-6 alkyl)2phosphoryl, (C 1-6 Alkoxy) 2-phosphoryl, hydroxyl (C 1-6 Alkoxy)phosphoryl, C 1-6 Alkoxyphosphoryl, hydroxyl, hydroxyl C 1-6 Alkyl, hydroxy halide C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy, hydroxy halide C 1-6 Alkoxy, hydroxy C 3-7 Cycloalkyl, hydroxy halide C 3-7 cycloalkyl and sulfonimide groups;

[0467] M 2 is an arylene group, a heterocyclyl group or a heteroarylene group, wherein the arylene group, the heterocyclyl group or the heteroarylene group is optionally substituted by R 1 replace;

[0468] M 3 is unsubstituted or optionally substituted with R 3 substituted heterocyclylene;

[0469] R 2 Deuterium, R, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RSO2C 1-6 Alkyl, RNHC 1-6 Alkyl or (R)2NC 1-6 alkyl;

[0470] R 3 is heteroaryl, aryl, heteroarylcarbonyl or arylcarbonyl, wherein the heteroaryl and aryl are optionally substituted by R 1 replace;

[0471] Q 1 -M-, -MOM-, -MSM-, -MN(R)-M-; wherein M is unsubstituted or optionally independently selected from deuterated, halogen, cyano, carboxyl, R, RO, RS, RNH, R2N, RSO2, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RNHC 1-6 Alkyl, (R)2NC 1-6 Alkyl and RSO2C 1-6 Alkyl substituents substituted C 1-6 alkylene;

[0472] Q 2 is NH, O or S;

[0473] or a pharmaceutically acceptable salt thereof.

[0474] Another embodiment of the present invention is a compound of formula (ii'),

[0475]

[0476] in

[0477] R 1 Deuterated, 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, halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, morpholinyl C 1-6 Alkyl, hydroxyl, pyrazolyl C 1-6 Alkyl or triazolyl C 1-6 alkyl;

[0478] R 2 H、((C 1-6 alkyl)3ammonium)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, halogenated C 1-6 Alkyl, hydroxyl 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 trideuterated C 1-6 alkyl;

[0479] R 3 for in

[0480] R 4 H, (C 1-6alkyl)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, carboxyl, cyano, hydroxyl, hydroxyl C 1-6 Alkyl, morpholinyl, morpholinyl C 1-6 Alkoxy or morpholino C 1-6 alkyl;

[0481] R 5 is a thienyl group,

[0482] Unsubstituted or halogen or C 1-6 Alkyl-substituted bicyclo[1.1.1]pentanyl,

[0483] Independently selected from (C 1-6 alkyl)2phosphoryl, (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 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C 2-6 Alkenyl, C 3-7 Cycloalkoxy, C 3-7 Cycloalkyl, carboxyl, cyano, halo C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogen, hydroxyl, morpholinyl C 1-6 Alkoxy, oxetane C 1-6 Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times,

[0484] unsubstituted or independently selected from halogen, hydroxyl and C 1-6 The alkoxy substituent is substituted once or twice with a pyridyl group, or

[0485] unsubstituted or halogen-substituted pyrimidinyl;

[0486] R 6 H or C 1-6 alkyl;

[0487] R 7 C 1-6 alkyl;

[0488] Q 1 is unsubstituted or independently selected from C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkoxy, C 1-6 Alkyl, C 1-6 Alkylcarbonyloxy, carboxyl, hydroxyl, hydroxyl C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, morpholinyl C 1-6 Alkoxy and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 Alkylene, or

[0489] -MOM-, where M is C 1-6 alkylene;

[0490] Q 2 is NH, O or S;

[0491] A 1 is CH or N;

[0492] A 2 is CH or N;

[0493] 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, halogenated azetidinyl C 1-6 Alkyl, halogenated C 1-6 Alkoxy, morpholinyl C 1-6 Alkyl or oxetane;

[0494] A 4 CR 9 or N, where R 9 H; or R 8 and R 9 together with the atoms to which they are attached, form a heterocyclyl;

[0495] A 5 CR 10 or N, where R10 is H or halogen;

[0496] A 6 CR 11 or N, where R 11 H, deuterated, halogen, C 1-6 Alkyl or C 1-6 alkoxy;

[0497] A 7 CR 12 or N, where R 12 is H or halogen;

[0498] Condition A 1 、A 2 、A 3 and A 4 No more than two of them are N at the same time; and A 5 、A 6 and A 7 No more than one of them is N;

[0499] or a pharmaceutically acceptable salt thereof.

[0500] Another embodiment of the present invention is (iii') a compound having formula (Ib),

[0501]

[0502] in

[0503] R 1 Deuterated, 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, halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, morpholinyl C 1-6 Alkyl, hydroxyl, pyrazolyl C 1-6 Alkyl or triazolyl C 1-6 alkyl;

[0504] R 2 H、((C 1-6 alkyl)3ammonium)C 1-6Alkyl, (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, halogenated C 1-6 Alkyl, hydroxyl 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 trideuterated C 1-6 alkyl;

[0505] R 3 for in

[0506] R 4 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, carboxyl, cyano, hydroxyl, hydroxyl C 1-6 Alkyl, morpholinyl, morpholinyl C 1-6 Alkoxy or morpholino C 1-6 alkyl;

[0507] R 5 is a thienyl group,

[0508] Unsubstituted or halogen or C 1-6 Alkyl-substituted bicyclo[1.1.1]pentanyl,

[0509] Independently selected from (C 1-6 alkyl)2phosphoryl, (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, C1-6 Alkyl, C 1-6 Alkylamino, C 1-6 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C 2-6 Alkenyl, C 3-7 Cycloalkoxy, C 3-7 Cycloalkyl, carboxyl, cyano, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogen, hydroxyl, morpholinyl C 1-6 Alkoxy, oxetane C 1-6 Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times,

[0510] unsubstituted or independently selected from halogen, hydroxyl and C 1-6 The alkoxy substituent is substituted once or twice with a pyridyl group, or

[0511] unsubstituted or halogen-substituted pyrimidinyl;

[0512] R 6 H or C 1-6 alkyl;

[0513] R 7 C 1-6 alkyl;

[0514] Q 1 is unsubstituted or independently selected from C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkoxy, C 1-6 Alkyl, C 1-6 Alkylcarbonyloxy, carboxyl, hydroxyl, hydroxyl C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, morpholinyl C 1-6 Alkoxy and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 Alkylene, or

[0515] -MOM-, where M is C 1-6 alkylene;

[0516] Q 2 is NH, O or S;

[0517] A 1 is CH or N;

[0518] A 2 is CH or N;

[0519] 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, halogenated azetidinyl C 1-6 Alkyl, halogenated C 1-6 Alkoxy, morpholinyl C 1-6 Alkyl or oxetane;

[0520] A 4 CR 9 or N, where R 9 H; or R 8 and R 9 together with the atoms to which they are attached, form a heterocyclyl;

[0521] A 5 CR 10 or N, where R 10 is H or halogen;

[0522] A 6 CR 11 or N, where R 11 H, deuterated, halogen, C 1-6 Alkyl or C 1-6 alkoxy;

[0523] A 7 CR 12 or N, where R 12 is H or halogen;

[0524] Condition A 1 、A 2 、A 3 and A 4 No more than two of them are N at the same time; and A 5 、A 6 and A 7 No more than one of them is N;

[0525] or a pharmaceutically acceptable salt thereof.

[0526] Another embodiment of the present invention is (iv') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to (i') or (iii'), wherein R 1 H or C 1-6 alkyl.

[0527] Another embodiment of the present invention is (v') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i) to (iv'), wherein R 1 is H or methyl.

[0528] Another embodiment of the present invention is (vi') a compound of formula (I) or (Ia) according to any one of (i') to (v'), wherein R 2 H or C 1-6 alkyl.

[0529] Another embodiment of the present invention is (vii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (vi'), wherein R 2 is H, methyl or ethyl.

[0530] Another embodiment of the present invention is (viii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (vii'), wherein R 3 for in

[0531] R 4 H, amino, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl or morpholinyl C 1-6 alkyl;

[0532] R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkoxy, halogenated C 1-6 Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituents are phenyl groups substituted once, twice or three times;

[0533] R 6 For H.

[0534] Another embodiment of the present invention is (ix) a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (viii'), wherein R 3 for in

[0535] R 4 is H, amino, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl or morpholinylmethyl;

[0536] R 5is phenyl substituted once, twice or three times with substituents independently selected from fluoro, methoxy, trideuteromethoxy, difluoromethoxy, ethoxy, cyclopropyloxy and hydroxy;

[0537] R 6 For H.

[0538] Another embodiment of the present invention is (x') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (ix'), wherein R 3 for in

[0539] R 4 H or C 1-6 Alkoxy C 1-6 alkyl;

[0540] R 5 are independently selected from C 1-6 phenyl substituted once, twice or three times with alkoxy and halogen substituents;

[0541] R 6 For H.

[0542] Another embodiment of the present invention is (xi') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (x'), wherein R 3 for in

[0543] R 4 is H or methoxymethyl;

[0544] R 5 is phenyl substituted once, twice or three times with substituents independently selected from methoxy and fluorine;

[0545] R 6 For H.

[0546] Another embodiment of the present invention is (xii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xi'), wherein Q 1 are independently selected from C 1-6 Alkoxy, C 1-6 Alkylcarbonyloxy, hydroxyl and C 1-6 The alkyl substituents replace once or twice the C 1-6 Alkylene.

[0547] Another embodiment of the present invention is (xiii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xii'), wherein Q 1is a propylene group substituted once or twice with a substituent independently selected from ethoxy, methoxy, hydroxy, methyl and acetoxy.

[0548] Another embodiment of the present invention is (xiv') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xiii'), wherein Q 1 For C 1-6 Alkoxy-substituted C 1-6 Alkylene.

[0549] Another embodiment of the present invention is (xv') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xiv'), wherein Q 1 It is a propylene group substituted by a methoxy group or an ethoxy group.

[0550] Another embodiment of the present invention is (xvi') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xv'), wherein Q 2 is NH or O.

[0551] Another embodiment of the present invention is (xvii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xvi'), wherein A 1 is N.

[0552] Another embodiment of the present invention is (xviii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xvii'), wherein A 3 CR 8 , where R 8 H, C 1-6 Alkoxy, C 1-6 Alkyl, C 3-7 Cycloalkoxy or halogenated C 1-6 Alkoxy.

[0553] Another embodiment of the present invention is (xix') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xviii'), wherein A 3 CR 8 , where R 8 is H, methoxy, methyl, cyclopropyloxy or difluoromethoxy.

[0554] Another embodiment of the present invention is (xx') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xix'), wherein A 3 CR 8 , where R 8 For H.

[0555] Another embodiment of the present invention is (xxi') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xx'), wherein A 4 CR 9 , where R 9 For H.

[0556] Another embodiment of the present invention is (xxii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xxi'), wherein A 5 CR 10 or N, where R 10 is H or fluorine.

[0557] Another embodiment of the present invention is (xxiii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xxii'), wherein A 5 CR 10 , where R 10 For H.

[0558] Another embodiment of the present invention is (xxiv') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xxiii'), wherein A 6 CR 11 , where R 11 is H or halogen.

[0559] Another embodiment of the present invention is (xxv') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xxiv'), wherein A 6 CR 11 , where R 11 is H or fluorine.

[0560] Another embodiment of the present invention is (xxvi') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xxv'), wherein A 6 CR 11 , where R 11 It is a halogen.

[0561] Another embodiment of the present invention is (xxvii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xxvi'), wherein A 6 CR 11 , where R 11 For fluorine.

[0562] Another embodiment of the present invention is (xxviii') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xxvii'), wherein A7 CR 12 , where R 12 is H or halogen.

[0563] Another embodiment of the present invention is (xxix') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xxviii'), wherein A 7 CR 12 , where R 12 is H or fluorine.

[0564] Another embodiment of the present invention is (xxx') a compound of formula (I) or (Ia) or a pharmaceutically acceptable salt thereof according to any one of (i') to (xxix'), wherein A 7 CR 12 , where R 12 For H.

[0565] Another embodiment of the present invention is (xxxi') a compound of formula (I) or (Ia) according to any one of (i') or (ii') or (iii'), wherein

[0566] R 1 H or C 1-6 alkyl;

[0567] R 2 H or C 1-6 alkyl;

[0568] R 3 for in

[0569] R 4 H, amino, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl or morpholinyl C 1-6 alkyl;

[0570] R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkoxy, halogenated C 1-6 Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituents are phenyl groups substituted once, twice or three times;

[0571] R 6 is H;

[0572] Q 1 are independently selected from C 1-6 Alkoxy, C 1-6Alkylcarbonyloxy, hydroxyl and C 1-6 The alkyl substituents replace once or twice the C 1-6 alkylene;

[0573] Q 2 is NH or O;

[0574] A 1 is CH or N;

[0575] A 2 is CH or N;

[0576] A 3 CR 8 , where R 8 H, C 1-6 Alkoxy, C 1-6 Alkyl, C 3-7 Cycloalkoxy or halogenated C 1-6 alkoxy;

[0577] A 4 CR 9 , where R 9 is H;

[0578] A 5 CR 10 or N, where R 10 is H or halogen;

[0579] A 6 CR 11 , where R 11 is H or halogen;

[0580] A 7 CR 12 , where R 12 is H or halogen;

[0581] or a pharmaceutically acceptable salt thereof.

[0582] Another embodiment of the present invention is (xxxii') a compound of formula (I) or (Ia) according to (xxxi'), wherein

[0583] R 1 is H or methyl;

[0584] R 2 is H, methyl or ethyl;

[0585] R 3 for in

[0586] R 4 is H, amino, ethoxy, hydroxymethyl, methoxy, methoxymethyl, methyl, morpholinylmethyl;

[0587] R 5 is phenyl substituted once, twice or three times with substituents independently selected from fluoro, methoxy, trideuteromethoxy, difluoromethoxy, ethoxy, cyclopropyloxy and hydroxy;

[0588] R 6 is H;

[0589] Q 1 is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl and acetoxy;

[0590] Q 2 is NH or O;

[0591] A 1 is CH or N;

[0592] A 2 is CH or N;

[0593] A 3 CR 8 , where R 8 is H, methoxy, methyl, cyclopropyloxy or difluoromethoxy;

[0594] A 4 CR 9 , where R 9 is H;

[0595] A 5 CR 10 or N, where R 10 is H or fluorine;

[0596] A 6 CR 11 , where R 11 is H or fluorine;

[0597] A 7 CR 12 , where R 12 is H or fluorine;

[0598] or a pharmaceutically acceptable salt thereof.

[0599] Another embodiment of the present invention is (xxxiii') a compound of formula (I) or (Ia) according to (xxxi'), wherein

[0600] R 1 C 1-6 alkyl;

[0601] R 2 C 1-6 alkyl;

[0602] R3 for in

[0603] R 4 H or C 1-6 Alkoxy C 1-6 alkyl;

[0604] R 5 are independently selected from C 1-6 phenyl substituted once, twice or three times with alkoxy and halogen substituents;

[0605] R 6 is H;

[0606] Q 1 For C 1-6 Alkoxy-substituted C 1-6 alkylene;

[0607] Q 2 is NH or O;

[0608] A 1 is N;

[0609] A 2 is CH or N;

[0610] A 3 CR 8 , where R 8 is H;

[0611] A 4 CR 9 , where R 9 is H;

[0612] A 5 CR 10 or N, where R 10 is H;

[0613] A 6 CR 11 , where R 11 is a halogen;

[0614] A 7 CR 12 , where R 12 is H;

[0615] or a pharmaceutically acceptable salt thereof.

[0616] Another embodiment of the present invention is (xxxiv') a compound of formula (I) or (Ia) according to (xxxiii'),

[0617] in

[0618] R 1is methyl;

[0619] R 2 is methyl;

[0620] R 3 for in

[0621] R 4 is H or methoxymethyl;

[0622] R 5 is phenyl substituted once, twice or three times with substituents independently selected from methoxy and fluorine;

[0623] R 6 is H;

[0624] Q 1 is a propylene group substituted by a methoxy group or an ethoxy group;

[0625] Q 2 is NH or O;

[0626] A 1 is N;

[0627] A 2 is CH or N;

[0628] A 3 CR 8 , where R 8 is H;

[0629] A 4 CR 9 , where R 9 is H;

[0630] A 5 CR 10 or N, where R 10 is H;

[0631] A 6 CR 11 , where R 11 For fluorine;

[0632] A 7 CR 12 , where R 12 is H;

[0633] or a pharmaceutically acceptable salt thereof.

[0634] Another embodiment of the present invention is (xxxv) a compound of formula (I) or formula (Ia) selected from the following:

[0635] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0636] (8S,11S)-10-[2-(2,4-difluorophenyl)-3-methyl-imidazole-4-carbonyl]-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0637] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,16,18-tetraazapentacyclo[14.6.1.1 2,6 .1 8,11 .0 19,23 ]pentacosa-1(22),2,4,6(25),17,19(23),20-hepten-12-one;

[0638] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-hydroxyethyl)-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0639] (8S,11S)-13-Benzyl-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0640] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-methoxyethyl)-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0641] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-morpholinopropyl)-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0642] 3-[(8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-oxo-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-13-yl]propyl-trimethyl-ammonium;

[0643] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0644] (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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0645] (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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0646] (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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0647] (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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0648] (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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0649] (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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0650] (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0651] (8S,11S)-10-[1-(4-fluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0652] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyridazin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0653] (8S,11S)-13-methyl-10-[3-(3-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0654] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0655] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0656] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0657] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0658] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0659] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11.0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0660] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0661] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0662] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0663] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0664] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0665] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0666] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0667] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0668] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0669] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0670] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0671] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0672] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0673] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0674] (8S,11S)-10-[1-[2-(cyclopropyloxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0675] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0676] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0677] (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-hexaazapentacyclo[15.6.1.12,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0678] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0679] (8S,11S,15R)-22-fluoro-10-[1-[4-fluoro-2-(trideuteromethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0680] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0681] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0682] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0683] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0684] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0685] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0686] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0687] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0688] 5-Fluoro-2-[4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile;

[0689] [(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-tetraazapentacyclo[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;

[0690] [(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-tetraazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-heptaen-15-yl]acetate;

[0691] [(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-tetraazapentacyclo[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;

[0692] [(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-tetraazapentacyclo[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;

[0693] (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-tetraazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecene-1(23),2(26),3,5,18,20(24),21-heptaene-4-carbonitrile;

[0694] (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-tetraazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecene-1(23),2(26),3,5,18,20(24),21-heptadecene-4-carbonitrile;

[0695] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0696] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0697] (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0698] (8S,11S,15S)-10-[1-[2-(cyclopropyloxy)-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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0699] (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 .18,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0700] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0701] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0702] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0703] (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0704] (8S,11S,15S)-10-[1-[2-(cyclopropyloxy)-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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0705] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0706] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0707] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0708] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0709] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0710] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0711] (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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0712] (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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0713] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0714] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0715] 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-hepten-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxamide;

[0716] 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-hepten-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxamide;

[0717] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0718] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0719] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0720] 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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0721] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0722] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0723] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0724] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0725] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0726] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0727] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0728] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0729] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0730] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0731] (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0732] (8S,11S,15S)-10-[1-[2-(cyclopropyloxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0733] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0734] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0735] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0736] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0737] (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-hexaazapentacyclo[15.6.1.1 2,6.1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0738] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0739] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0740] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0741] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0742] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0743] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0744] (8S,11S,15S)-10-[1-[2-(cyclopropyloxy)-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0745] (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0746] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0747] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0748] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0749] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0750] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0751] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0752] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0753] (8S,11S)-10-[3-(2,6-difluoro-3-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0754] (8S,11S)-13-methyl-10-[3-(2-thienyl)imidazo[1,5-a]pyrazin-8-yl]-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0755] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0756] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0757] (8S,11S)-10-[3-(3,5-difluoro-2-pyridyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0758] (8S,11S)-10-[2-(2-chloro-4-fluoro-phenyl)pyrimidin-5-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0759] (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0760] (8S,11S)-10-[1-[4-fluoro-2-(methylamino)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0761] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0762] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,23,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0763] (8S,11S)-13-(cyclopropylmethyl)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,23,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0764] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,21,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0765] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0766] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0767] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0768] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0769] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0770] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0771] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0772] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0773] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0774] (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-hexaazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0775] (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-18-(2-morpholinoethyl)-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0776] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0777] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0778] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0779] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0780] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0781] (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-23-fluoro-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0782] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,19,21,28-hexaazapentacyclo[17.6.1.1 2,6 .1 8,11 .0 22,26 ]octacosyl-1(25),2(28),3,5,20,22(26),23-heptaen-12-one;

[0783] (8S,11S)-10-[1-(2,4-difluorophenyl)-3-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0784] (8S,11S)-10-[1-[4-fluoro-2-(trifluoromethyl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0785] 5-Fluoro-2-[4-[(8S,11S)-13-methyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2,4,6(26),18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile;

[0786] 5-Fluoro-2-[4-[(8S,11S)-13-methyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2,4,6(26),18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]benzoic acid;

[0787] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-ethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0788] (8S,11S)-13-Ethyl-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0789] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-methoxyethyl)-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0790] (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-(2-morpholinoethyl)-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0791] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-hydroxypropyl)-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0792] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0793] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0794] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0795] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0796] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0797] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0798] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0799] (8S,11S)-18,22-dideutero-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0800] (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-15-hydroxy-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0801] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0802] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0803] (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-hexaazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0804] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0805] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0806] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0807] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0808] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0809] [(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-hexaazapentacyclo[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;

[0810] [(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-hexaazapentacyclo[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;

[0811] [(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-hexaazapentacyclo[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;

[0812] [(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-hexaazapentacyclo[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;

[0813] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2,4,6(26),18,20(24),21-hepten-12-one;

[0814] 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxylic acid;

[0815] 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2,4,6(26),18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidine-6-carbonitrile;

[0816] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0817] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0818] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0819] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0820] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0821] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0822] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0823] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-12-one;

[0824] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0825] 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxylic acid ethyl ester;

[0826] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-12-one;

[0827] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-12-one;

[0828] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-12-one;

[0829] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-12-one;

[0830] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0831] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0832] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0833] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0834] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0835] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0836] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0837] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0838] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0839] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0840] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0841] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0842] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0843] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0844] (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] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0845] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0846] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-methoxy-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[0847] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0848] (8S,11S)-10-[1-(2,4-difluorophenyl)-6-methyl-pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0849] (8S,11S)-4-(difluoromethoxy)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0850] (8S,11S)-4-(cyclopropyloxy)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0851] (8S,11S)-13-cyclopropyl-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0852] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-(trideuteriomethoxy)-13-(trideuteriomethyl)-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0853] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0854] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11.0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0855] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0856] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0857] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0858] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0859] (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-hexaazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0860] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0861] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0862] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0863] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0864] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0865] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0866] (8S,11S)-15-methoxy-10-[1-(2-methoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0867] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0868] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0869] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0870] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecene-1(23),2(26),3,5,18,20(24),21-heptadecene-4-carbonitrile;

[0871] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0872] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0873] (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-heptaazapentacyclo[15.6.1.1 2,6 .18,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0874] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-4,13-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0875] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0876] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0877] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0878] (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-heptaazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0879] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]26-carbon-1(23),2(26),3,5,;

[0880] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0881] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0882] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0883] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0884] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0885] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0886] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0887] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0888] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0889] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0890] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0891] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0892] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0893] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0894] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0895] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0896] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0897] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0898] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0899] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0900] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0901] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0902] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0903] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0904] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0905] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .020 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0906] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0907] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0908] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0909] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0910] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0911] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0912] (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-3,5,7,10,13,17,19-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0913] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0914] (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-[4-fluoro-2-(trideuteromethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0915] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0916] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0917] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0918] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0919] (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0920] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0921] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0922] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0923] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0924] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0925] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0926] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0927] (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] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0928] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0929] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0930] 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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0931] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0932] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0933] (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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0934] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0935] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0936] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0937] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0938] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0939] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2,4,6(26),18,20(24),21-hepten-12-one;

[0940] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0941] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .020,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0942] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0943] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0944] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0945] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0946] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0947] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0948] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0949] (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-4,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0950] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-methoxypropyl)-4,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0951] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0952] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0953] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-16-oxa-7,10,13,19,21,28-hexaazapentacyclo[17.6.1.1 2,6 .1 8,11 .0 22,26 ]octacosyl-1(25),2(28),3,5,20,22(26),23-heptaen-12-one;

[0954] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0955] (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-hexaazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0956] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0957] (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-hexaazahexacyclo[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-hepten-15-one;

[0958] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0959] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0960] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0961] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0962] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0963] (8S,11S)-10-[2-(2,4-difluorophenoxy)-4-pyridyl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0964] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .020,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0965] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0966] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0967] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0968] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0969] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0970] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0971] (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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[0972] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0973] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecene-1(24),2(26),3,5,18,20,22-heptadecene-14-carboxylic acid;

[0974] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0975] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0976] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0977] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0978] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0979] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Methyl hexadecene-1(23),2(26),3,5,18,20(24),21-heptadecene-18-carboxylate;

[0980] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0981] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0982] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0983] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexacosyl-1(23),2(26),3,5,18,20(24),21-heptaene-18-carboxamide;

[0984] (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0985] 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-hexaazapentacyclo[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;

[0986] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0987] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0988] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0989] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[0990] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2,4,6(26),18,20(24),21-heptaen-12-one;

[0991] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0992] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0993] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[0994] (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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0995] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0996] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0997] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0998] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[0999] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1000] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1001] (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-heptaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1002] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1003] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1004] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1005] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1006] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1007] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1008] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1009] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1010] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1011] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1012] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(1-methyl-4-piperidinyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1013] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1014] (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]heptane-5-yl)propyl]-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1015] (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]heptane-6-yl)propyl]-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1016] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1017] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1018] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1019] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1020] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1021] 1-(2,4-difluorophenyl)-4-[(8S,11S)-22-fluoro-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]-N-(2-hydroxyethyl)pyrazolo[3,4-d]pyrimidine-6-carboxamide;

[1022] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1023] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1024] (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-hexaazapentacyclo[15.6.1.1 2,6.1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1025] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1026] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1027] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1028] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1029] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1030] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1031] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1032] (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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1033] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1034] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1035] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1036] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1037] (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro(fluor)-2-(2-oxa-6-azaspiro[3.3]heptane-6-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1038] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1039] (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro-2-(3-methoxycyclobutyloxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1040] (8S,11S,15R)-22-fluoro-10-[1-[4-fluoro-2-[1-(methoxymethyl)cyclopropyloxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1041] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1042] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1043] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2,2-dioxo-2λ 6 -thia-6-azaspiro[3.3]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1044] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1045] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxa-6-azaspiro[3.3]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1046] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1047] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1048] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1049] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1050] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1051] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1052] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1053] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1054] (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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1055] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1056] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1057] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1058] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1059] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1060] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1061] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1062] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1063] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1064] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1065] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1066] 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]ethyl acetate;

[1067] (8S,11S,15R)-22-Fluoro-10-[1-(5-fluoro-3-methylsulfanyl-2-pyridinyl)-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1068] (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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1069] (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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1070] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxa-6-azaspiro[3.3]heptane-6-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1071] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1072] 2-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]acetonitrile;

[1073] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1074] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1075] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1076] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[4-(2H-tetrazol-5-yl)-1-piperidinyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1077] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1078] (8S,11S,15R)-10-[1-(3,5-difluoro-2-pyridinyl)-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1079] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-methyl-3,6-diazabicyclo[3.1.1]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1080] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1081] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1082] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1083] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1084] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptane-6-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1085] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1086] 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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]piperazine-2-carboxylic acid;

[1087] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1088] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-oxazol-5-yl-1-piperidinyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1089] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1090] (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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1091] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1092] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1093] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1094] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1095] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1096] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1097] 2-[2-[4-[(8S,11S,15R)-15-ethoxy-22-fluoro-13,18-dimethyl-12-oxo-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-1-yl]-3,5-difluoro-phenoxy]acetonitrile;

[1098] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1099] (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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1100] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1101] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1102] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1103] (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-[4-fluoro-2-(trideuteromethoxy)phenyl]-6-[3-oxa-6-azabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1104] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1105] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1106] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1107] (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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1108] (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[(1,1-dioxothietane-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1109] 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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidin-1-yl]acetonitrile;

[1110] (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(1,1-dioxothianilan-4-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1111] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1112] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1113] (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[(1,1-dioxothietane-3-yl)methylsulfanyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1114] (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro-2-(trideuteromethoxy)phenyl]-6-(3-oxa-6-azabicyclo[3.1.1]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1115] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1116] (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-heptaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1117] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1118] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1119] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1120] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(2-oxa-5-azabicyclo[2.2.1]heptane-5-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1121] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1122] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1123] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1124] (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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1125] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1126] (8S,11S,15R)-15-ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-(oxetane-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1127] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]pyrrolidine-3-carbonitrile;

[1128] 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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazin-4-one;

[1129] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1130] 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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidine-3-carbonitrile;

[1131] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-oxa-6-azabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1132] (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-oxa-6-azabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1133] (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-methyl-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1134] 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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidine-3-carbonitrile;

[1135] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1136] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1137] (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1138] (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1139] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1140] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1141] (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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1142] 4-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]morpholin-3-one;

[1143] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1144] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1145] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1146] (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1147] (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1148] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1149] (8S,11S,15R)-10-[6-[(1S,5S)-3-cyclopropyl-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1150] (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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1151] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6-oxa-3-azabicyclo[3.1.1]heptane-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1152] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-3-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1153] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-[(3-fluorooxetan-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1154] (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-[(3-fluorooxetane-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1155] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-hydroxy-6-(trifluoromethyl)-2-azaspiro[3.3]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1156] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6-oxa-1-azaspiro[3.3]heptane-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1157] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1158] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1159] (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1160] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1161] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1162] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1163] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1164] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1165] (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1166] (8S,11S)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1167] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1168] (8S,11S,15R)-10-[6-[3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1169] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1170] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1171] (8S,11S)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1172] 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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidin-1-yl]acetonitrile;

[1173] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1174] 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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2(26),3,5,18,20,22-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]propionitrile;

[1175] (8S,11S,15R)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1176] (8S,11S,15R)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1177] (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1178] (8S,11S,15S)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1179] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1180] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1181] (8S,11S,15R)-10-[11-benzyl-3-(2,4-difluorophenyl)-3,4,8,11-tetraazatricyclo[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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1182] (8S,11S,15R)-10-[3-(2,4-difluorophenyl)-11-methyl-3,4,8,11-tetraazatricyclo[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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1183] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1184] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1185] (8S,11S,15S)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1186] (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1187] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1188] 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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]acetonitrile;

[1189] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1190] (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1191] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1192] (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1193] 1-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidine-3-carbonitrile;

[1194] (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-methyl-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1195] (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxyphenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1196] (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1197] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1198] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1199] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(oxetan-3-yl)-1,6-diazaspiro[3.3]heptane-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1200] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6,6-dioxo-6λ 6 -thia-1-azaspiro[3.3]heptane-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1201] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1202] (8S,11S,15R)-10-[3-(2,4-difluorophenyl)-11-(oxetane-3-yl)-3,4,8,11-tetraazatricyclo[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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1203] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,5S)-3-(oxetan-3-yl)-3,6-diazabicyclo[3.2.0]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1204] (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1205] (8S,11S,15S)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1206] (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1207] (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1208] (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.12,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1209] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1210] (8S,11S,15R)-15-Ethoxy-22-fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(oxetane-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1211] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1212] (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-heptaazapentacyclo[15.6.1.1 2,6 .18,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1213] 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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]oxazolidin-2-one;

[1214] 3-[1-(2,4-difluorophenyl)-4-[(8S,11S,15R)-22-fluoro-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]oxazolidin-2-one;

[1215] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one;

[1216] (8S,11S,15S)-22-Fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1217] (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1218] (8S,11S,15S)-10-[6-[3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one;

[1219] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1220] (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1221] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1222] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1223] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxycyclobutanecarbonyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1224] (8S,11S,15R)-10-[6-[3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24] Hexacosyl-1(24),2(26),3,5,18,20,22-hepten-12-one; and

[1225] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(3-fluorocyclobutyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one;

[1226] or a pharmaceutically acceptable salt thereof.

[1227] Another embodiment (xxxvi) of the present invention is a method for preparing a compound according to any one of (i) to (xxxv), comprising any one of the following steps:

[1228] a) in the presence of a base, via a compound of formula (VIII), With R 3 Nucleophilic substitution between X to form a compound of formula (I)

[1229] b) in the presence of a catalyst, reacting a compound of formula (VIII) with R 3 Buchwald-Hartwig reaction between X to form a compound of formula (I);

[1230] c) in the presence of a coupling reagent, via the compound of formula (VIII) and R 3 The condensation reaction between OH forms a compound of formula (I);

[1231] d) via a compound of formula (XVIII), A cyclization reaction with a reagent to form a compound of formula (I);

[1232] e) in the presence of a base via a compound of formula (XX), With R 3 Nucleophilic substitution between X forms a compound of formula (XXI),

[1233] f) in the presence of a base, via a compound of formula (Ic), With alcohols or amines (R 4 -X) to form a compound of formula (XXII),

[1234]

[1235] g) a compound of formula (XXIV), The amino group of is reacted with a halide via nucleophilic substitution or with a ketone via reductive amination to provide the final compound of formula (XXII);

[1236] in

[1237] In steps a) and e), the base is DIEA;

[1238] In step b), the catalyst is Pd2(dba)3;

[1239] In step c), the coupling reagent is HATU;

[1240] In step d), the reagent is CDI, BrCN or R 1 (OCH3)3;

[1241] In step e), the base is DIEA;

[1242] In step f), the base is DIPEA, K2CO3 or NaH;

[1243] X is halogen; R 13 R a 、R b or R c ; M is C 1-6 Alkylene; R e is a substituent having a primary amino group or a di-secondary amino group; R 1 to R 7 , Q 1 , Q 2 、A 1 To A 7 As defined in any one of (i) to (xxxv) or (i') to (xxxiv').

[1244] Another embodiment (xxxvii) of the present invention relates to a compound or a pharmaceutically acceptable salt according to any one of (i) to (xxxv) or (i') to (xxxiv') for use as therapeutically active substance.

[1245] Another embodiment (xxxviii) of the present invention relates to a pharmaceutical composition comprising a compound according to any one of (i) to (xxxv) or (i') to (xxxiv') and a therapeutically inert carrier.

[1246] Another embodiment (xxxix) 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 or prevention of autoimmune diseases, inflammatory diseases, neurological disorders, metabolic diseases, cardiovascular diseases or selected cancer types in which overexpression or activation of STING is involved.

[1247] 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 treating a subject suffering from an interferonopathy or an autoinflammatory disease in which STING activation is the underlying cause of the disease pathology.

[1248] Another embodiment (xli) of the present invention relates to the use of a compound according to any one of (i) to (xxxv) or (i') to (xxxiv') for inhibiting STING.

[1249] Another embodiment (xlii) 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 preparation of a medicament for inhibiting STING.

[1250] Another embodiment (xliii) of the present invention relates to a compound or pharmaceutically acceptable salt according to any one of (i) to (xxxv) or (i') to (xxxiv'), which is manufactured according to the process of (xxxvi).

[1251] Another embodiment (xliv) of the present invention relates to a method for treating or preventing an autoimmune disease, comprising administering a therapeutically effective amount of a compound as defined in any one of (i) to (xxxv) or (i') to (xxxiv').

[1252] Pharmaceutical compositions and administration

[1253] Another embodiment provides a pharmaceutical composition or medicine containing the compounds of this invention and a treatment inert carrier, a diluent or an excipient, and methods for preparing such compositions and medicines using the compounds of this invention. In one example, the compound of formula (I) can be formulated as a galenical administration form by mixing with a physiologically acceptable carrier (i.e., a carrier that is nontoxic to the recipient under the dosage and concentration used) at ambient temperature under suitable pH and the purity of the expectation. The pH of the preparation depends primarily on the specific use and concentration of the compound, but is preferably in the range of about 3 to about 8. In one example, the compound of formula (I) is prepared in an acetate buffer at pH 5. In another embodiment, the compound of formula (I) is sterile. The compound can be, for example, stored as a solid or amorphous composition, as a lyophilized formulation, or as an aqueous solution.

[1254] The composition is formulated, metered, and administered in a manner consistent with good medical practice. Factors to be considered in this case include the specific disorder being treated, the specific mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the delivery site of the agent, the method of administration, the timing of administration, and other factors known to practitioners. The "effective amount" of the compound to be administered will be determined by such considerations and is to inhibit the interaction of STING with IRF3, NF-kB, NLRP3, etc. to block downstream type I IFN and pro-inflammatory cytokines (e.g., IL-6, TNFa, ISG) production, cellular responses / conditions (e.g., autophagy, apoptosis, cellular senescence). For example, the amount may be lower than an amount that is toxic to normal cells or mammals as a whole.

[1255] In one example, the pharmaceutically effective amount of the compound of the invention administered parenterally per dose will be in the range of about 0.1 to 1000 mg / kg of patient body weight per day, alternatively about 0.1 to 1000 mg / kg of patient body weight, typically with an initial range of 0.1 to 1000 mg / kg / day of the compound used. In another embodiment, oral unit dosage forms such as tablets and capsules preferably contain about 0.1 to about 1000 mg of the compound of the invention.

[1256] The compounds of the present invention can 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 (if necessary for local treatment) intralesional administration. Parenteral infusion includes intramuscular, intravenous, intraarterial, intraperitoneal or subcutaneous administration.

[1257] The compounds of the present invention can be administered in any convenient administration form, for example, tablets, powders, capsules, solutions, dispersions, suspensions, syrups, sprays, suppositories, gels, emulsions, patches, etc. Such compositions may contain conventional components of pharmaceutical preparations, for example, diluents, carriers, pH adjusters, sweeteners, fillers and other active agents.

[1258] Typical formulations are prepared by mixing the compound of the invention with a carrier or excipient. Suitable carriers and excipients are well known to those skilled in the art and are described, for example, in 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 contain one or more buffers, stabilizers, surfactants, wetting agents, lubricants, emulsifiers, suspending agents, preservatives, antioxidants, opacifying agents, glidants, processing aids, colorants, sweeteners, flavorings, flavorings, diluents and other known additives to provide an aesthetically pleasing display of a drug (e.g., a compound of the present invention or a pharmaceutical composition thereof) or to facilitate the preparation of a pharmaceutical product (e.g., a drug).

[1259] An example of a suitable oral dosage form is a tablet containing about 0.1 to 1000 mg of a compound of the present invention compounded with about 0.1 to 1000 mg of anhydrous lactose, about 0.1 to 1000 mg of croscarmellose sodium, about 0.1 to 1000 mg of polyvinylpyrrolidone (PVP) K30, and about 0.1 to 1000 mg of magnesium stearate. The powdered ingredients are first mixed together and then mixed with the PVP solution. 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 by dissolving a compound of the present invention (e.g., 0.1 mg to 1000 mg) in a suitable buffer solution (e.g., phosphate buffer) and, if necessary, adding a penetration enhancer (e.g., a salt such as sodium chloride). The solution can be filtered, for example, using a 0.2 micron filter to remove impurities and contaminants.

[1260] Thus, embodiments include a pharmaceutical composition comprising a compound of formula (I) or a stereoisomer or pharmaceutically acceptable salt thereof. Further embodiments include a pharmaceutical composition comprising a compound of formula (I) or a stereoisomer or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient.

[1261] Another embodiment includes a pharmaceutical composition comprising a compound of formula (I) for use in treating interferonopathies, autoimmune diseases, and inflammatory diseases. Another embodiment includes a pharmaceutical composition comprising a compound of formula (I) for use in treating infections or selected cancer types.

[1262] The following compositions A and B illustrate typical compositions of the present invention but are intended to be representative only.

[1263] Composition A

[1264] The compounds of the invention can be used as active ingredients in a manner known per se to produce tablets of the following composition:

[1265]

[1266] Composition B

[1267] The compounds of the invention can be used as active ingredients in a manner known per se to produce capsules of the following composition:

[1268]

[1269] Indications and treatments

[1270] The compounds of the present invention inhibit STING (including its signaling and activity). Therefore, the compounds of the present invention are useful in the treatment of infections, inflammation, autoimmunity, degenerative diseases and cancer.

[1271] In some embodiments, the compounds of the invention are used to treat or prevent autoimmune diseases.

[1272] In some embodiments, the compounds of the present invention are used to treat or prevent inflammatory diseases.

[1273] In some embodiments, the compounds of the present invention are used to treat or prevent neurological disorders.

[1274] In some embodiments, the compounds of the present invention are used to treat or prevent cardiovascular disease.

[1275] In some embodiments, the compounds of the present invention are used to treat or prevent ocular diseases.

[1276] In some embodiments, compounds of the invention are used to treat or prevent select cancer types in which overexpression or activation of STING is implicated.

[1277] Alternatively, the compounds of the invention are useful in treating subjects suffering from interferonopathies or autoinflammatory diseases in which STING activation is the underlying cause of the disease pathology. More broadly, the compounds are useful in treating all pathological cellular processes that are STING-dependent.

[1278] Another embodiment includes a method of treating or preventing cancer in a mammal in need of such treatment, wherein the method comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof.

[1279] synthesis

[1280] The compounds of the present invention may be prepared by any conventional method. Suitable methods for synthesizing these compounds and their starting materials are provided in the following schemes and examples. Unless otherwise indicated, all substituents, particularly R 1 to R 7 , Q 1 , Q2 、A 1 To A 7 As defined above. Furthermore, unless otherwise specifically indicated, all reactions, reaction conditions, abbreviations and symbols have the meanings well known to one of ordinary skill in the art of organic chemistry.

[1281] General synthetic routes for preparing compounds of the present invention are shown in the following schemes.

[1282] Solution 1

[1283]

[1284] where R d is H or PG, wherein PG may be, for example, Boc or Cbz; and X is halogen.

[1285] As depicted in Scheme 1, the synthesis of the compounds of the present invention begins with an organoboron ester compound of formula (II) or a halide (III). Suzuki coupling between a compound of formula (II) and a compound of formula (IIb) using a catalyst such as Pd(dppf)Cl2 and a base such as K2CO3 provides a compound of formula (V), which can be obtained via Suzuki coupling between an organoboron ester compound of formula (IIIb) and a halide (III). On the other hand, Suzuki coupling between a compound of formula (II) and a halide (IIa) or between a compound of formula (IIIa) and a halide (III) provides an intermediate of formula (IV), which reacts with a compound of formula (IVa) via Buchwald-Hartwig amination or nucleophilic substitution to obtain a compound of formula (V). The compound of formula (V) is hydrolyzed directly in the presence of LiOH or after appropriate deprotection to obtain the compound of formula (VI) (Boc deprotection: dioxane containing HCl or DCM containing TFA; Cbz deprotection: Pd / C or Pd(OH)2 / C under H2). The compound of formula (VI) can be cyclized in the presence of a coupling reagent such as HATU and a base such as DIPEA to obtain the compound of formula (VII). The following Boc deprotection is carried out under acidic conditions (dioxane containing HCl or DCM containing TFA), or Cbz deprotection is carried out by catalytic hydrogenation (Pd / C or Pd(OH)2 / C under H2) or under acidic conditions (TFA) to obtain the compound of formula (VIII). The compound of formula (I) can be prepared by reacting the compound of formula (VIII) with R 3 X can be obtained by reacting a nucleophilic substitution reaction in the presence of a base such as DIEA, or by reacting a Buchwald-Hartwig reaction in the presence of a catalyst such as Pd2(dba)3. On the other hand, the compound of formula (IX) can also be obtained by reacting a compound of formula (VIII) with R 3 It is obtained by the condensation reaction between OH groups in the presence of a coupling agent such as HATU.

[1286] Option 2

[1287]

[1288] As depicted in Scheme 2, Suzuki coupling between halide (IIb) and organoboron ester compound of formula (X) provides compound of formula (XI), which reacts with compound of formula (XII) in the presence of base such as DIPEA, K2CO3 via nucleophilic substitution to give compound of formula (XIII). The preparation of compounds of formula (XIV), (XV), (XVI), (XVII) is similar to the preparation of compounds of formula (VI), (VII), (VIII), (IX) described in Scheme 1 above. Compound of formula (XVII) is hydrogenated in the presence of zinc and ammonium chloride to give compound of formula (XVIII), which is reacted with CDI, BrCN or R 1 (OCH3)3 reaction to obtain the compound of formula (I).

[1289] The general synthetic route for preparing compounds of formula (XXI) is shown below.

[1290] Option 3

[1291]

[1292] where R 13 R a 、R b or R c .

[1293] As depicted in Scheme 3, when R in Formula (VII) 1 Hydroxyl C 1-6 When alkyl is present, a compound of formula (VIIa) is shown. The 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 methanesulfonic acid intermediate, which is treated with an amine to provide a compound of formula (XIX). The preparation of the compound of formula (XX) is similar to the preparation of the compound of formula (VIII) in Scheme 1. The compound of formula (XXI) can be prepared by reacting the compound of formula (XX) with R 3 X is obtained by nucleophilic substitution between X in the presence of a base such as DIEA.

[1294] The general synthetic route for preparing compounds of formula (XXII) is shown below.

[1295] Option 4

[1296]

[1297] Wherein X is OH, NH, SH or halogen; R eis a substituent having a primary or secondary amino group.

[1298] As depicted in Scheme 4, when R 3 for When , the compound of formula (Ic) is displayed. The compound of formula (Ic) is reacted with alcohol or amine (R 4 -X) in the presence of a base such as DIPEA, K2CO3 or NaH to directly obtain a compound of formula (XXII) or to obtain an intermediate compound of formula (XXIII), which is then deprotected under acidic conditions to obtain a compound of formula (XXIV). The amino group of the compound of formula (XXIV) reacts with a halide via nucleophilic substitution or with a ketone via reductive amination to provide the final compound of formula (XXII). On the other hand, the compound of formula (Ic) reacts with an alkyl halide (R 4 The photoredox coupling between the compound of formula (X) and the lactam (such as pyrrolidone, morpholin-3-one) in the presence of a catalyst such as Ir[dF(CF3)ppy]2(dtbbpy)PF6 gives the compound of formula (XXII) or the Boc-protected compound of formula (XXIII), which is then deprotected under acidic conditions to give the compound of formula (XXIV). The compound of formula (XXIV) is nucleophilically substituted with a halide or reductively aminized with a ketone to provide the final compound of formula (XXII). Third, the Buchwald coupling between the compound of formula (Ic) and a lactam (such as pyrrolidone, morpholin-3-one) in the presence of a catalyst such as Pd2dba3 gives the compound of formula (XXII).

[1299] The compounds of the present invention may be obtained as diastereomers or mixtures of enantiomers, which may be separated by methods well known in the art, for example, (chiral) HPLC or SFC.

[1300] The present invention also relates to a process for preparing a compound of formula (I) or (I), which comprises any of the following steps:

[1301] a) in the presence of a base, via a compound of formula (VIII), With R 3 Nucleophilic substitution between X forms a compound of formula (I),

[1302] b) in the presence of a catalyst, via a compound of formula (VIII) and R 3 Buchwald-Hartwig reaction between X to form a compound of formula (I);

[1303] c) in the presence of a coupling reagent, via the compound of formula (VIII) and R 3 The condensation reaction between OH forms a compound of formula (I);

[1304] d) via a compound of formula (XVIII), A cyclization reaction with a reagent to form a compound of formula (I);

[1305] e) in the presence of a base via a compound of formula (XX), With R 3 Nucleophilic substitution between X forms a compound of formula (XXI),

[1306] f) in the presence of a base, via a compound of formula (Ic), With alcohols or amines (R 4 -X) to form a compound of formula (XXII),

[1307] g) a compound of formula (XXIV), The amino group of is reacted with a halide via nucleophilic substitution or with a ketone via reductive amination to provide the final compound of formula (XXII);

[1308] in

[1309] In steps a) and e), the base may be, for example, DIEA;

[1310] In step b), the catalyst may be, for example, Pd2(dba)3;

[1311] In step c), the coupling reagent may be, for example, HATU;

[1312] In step d), the reagent may be, for example, CDI, BrCN or R 1 (OCH3)3;

[1313] In step e), the base may be, for example, DIEA;

[1314] In step f), the base may be, for example, DIPEA, K2CO3 or NaH;

[1315] X is halogen; R 13 R a 、R b or R c ; M is C 1-6 Alkylene; R e is a substituent having a primary or secondary amino group.

[1316] The compounds of formula (I) or (Ia) produced according to the above-described process are also an object of the present invention.

[1317] Example

[1318] The present invention will be more fully understood by reference to the following examples, which, however, should not be construed as limiting the scope of the invention.

[1319] abbreviation

[1320] The present invention will be more fully understood by reference to the following examples, which, however, should not be construed as limiting the scope of the invention.

[1321] The abbreviations used in this article are as follows:

[1322] ACN: Acetonitrile

[1323] Boc2O: di-tert-butyl dicarbonate

[1324] BINAP: 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl

[1325] DCM: dichloromethane

[1326] DCE: dichloroethane

[1327] DIPEA or DIEA: N,N-diisopropylethylamine

[1328] DIBAL-H: Diisobutylaluminum hydride

[1329] DIAD: Diisopropyl azodicarboxylate

[1330] DMA: N,N-dimethylacetamide

[1331] DMAP: 4-dimethylaminopyridine

[1332] DMF: N,N-dimethylformamide

[1333] DMSO: dimethyl sulfoxide

[1334] DPPP: 1,3-bis(diphenylphosphino)propane

[1335] EA or EtOAc: Ethyl acetate

[1336] FA: Formic acid

[1337] HATU: 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate

[1338] h or hr: hours

[1339] hPBMC: human peripheral blood mononuclear cells

[1340] IC 50 : Half inhibitory concentration

[1341] Ir[dF(CF3)ppy]2(dtbpy)(PF6): [4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridyl-N1,N1']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl-N]phenyl-C]iridium(III) hexafluorophosphate

[1342] IPA: Isopropyl alcohol

[1343] LCMS: Liquid chromatography-mass spectrometry

[1344] mCPBA: meta-chloroperbenzoic acid

[1345] min: minutes

[1346] MS: mass spectrometry

[1347] MsCl: methanesulfonyl chloride

[1348] Ms2O: Methanesulfonic anhydride

[1349] NBS: N-bromosuccinamide

[1350] NIS: N-iodosuccinimide

[1351] NMP: N-methylpyrrolidone

[1352] NiCl2.dtbbpy: [4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridyl] nickel(II) dichloride

[1353] PE: Petroleum ether

[1354] prep-HPLC: Preparative High Performance Liquid Chromatography

[1355] prep-TLC: Preparative Thin Layer Chromatography

[1356] PyBOP / BOP: (1-Hydroxy-1H-benzotriazol-o)tris-1-pyrrolidinylphosphonium hexafluorophosphate

[1357] PPh3: triphenylphosphine

[1358] Pd2(dba)3: Tris(dibenzylideneacetone)dipalladium(0)

[1359] (R)-binap: (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl

[1360] Rf: retention factor

[1361] rt, rt: room temperature

[1362] RT: retention time

[1363] RuPhos Pd G2: Chloro(2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) 2nd generation

[1364] Selective fluorine reagent 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane bis(tetrafluoroborate)

[1365] SFC: Supercritical fluid chromatography

[1366] S-Phos: 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl

[1367] TBSCl: tert-Butyldimethylsilyl chloride

[1368] t-BuXPhos: 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl

[1369] tBuXPhos Pd G3: Mesylate (2-di-tert-butylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl) palladium(II)

[1370] tBu3P-Pd-G2 Chloro[(tri-tert-butylphosphino)(2-aminobiphenyl-2-yl)palladium(II)

[1371] T3P: Propylphosphonic anhydride

[1372] TEA: Trimethylamine

[1373] TFA: trifluoroacetic acid

[1374] TFAA: trifluoroacetic anhydride

[1375] THF: Tetrahydrofuran

[1376] TLC: Thin layer chromatography

[1377] XantPhos: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene

[1378] XPhos: 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl

[1379] XPhos Pd G2: Chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II)

[1380] v / v volume ratio

[1381] General experimental conditions

[1382] 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 chromatograph. Silica gel brand and pore size: i) KP-SIL Particle size: 40-60 μm; ii) CAS registration number: silica gel: 63231-67-4, particle size: 47-60 μm silica gel; iii) ZCX from Qingdao Ocean Chemical Co., Ltd., pore size: 200-300 or 300-400.

[1383] Intermediates and final compounds were purified by preparative HPLC on a reversed-phase column using an XBridge TM Prep-C18 (5 μm, OBDTM 30 × 100 mm) column, SunFire TM Prep-C18(5μm,OBD TM 30 × 100 mm) chromatographic 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 systems: 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 systems: 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).

[1384] For SFC chiral separation, the intermediates were separated by chiral columns (Daicel chiralpak IC, 5 μm, 30×250 mm), AS (10 μm, 30×250 mm) or AD (10 μm, 30×250 mm) using a Mettler Toledo Multigram III system SFC, Waters 80Q preparative SFC or Thar 80 preparative SFC, solvent systems: CO2 and IPA (0.5% TEA in IPA) or CO2 and MeOH (0.1% NH3·H2O in MeOH), back pressure 100 bar, and UV detection at 254 or 220 nm.

[1385] LC / MS (Waters TM LC / MS spectra of the compounds were obtained using an Agilent Alliance 2795-Micromass ZQ, a Shimadzu Alliance 2020-Micromass ZQ, or an Agilent Alliance 6110-Micromass ZQ. The LC / MS conditions were as follows (run time 3 or 1.5 minutes):

[1386] Acidic conditions I: A: 0.1% TFA in H2O; B: 0.1% TFA in acetonitrile;

[1387] Acidic conditions II: A: 0.0375% TFA solution in H2O; B: 0.01875% TFA solution in acetonitrile;

[1388] Basic conditions I: A: 0.1% NH3·H2O solution in H2O; B: acetonitrile;

[1389] Basic conditions II: A: 0.025% NH3·H2O solution in H2O; B: acetonitrile;

[1390] Neutral conditions: A: H2O; B: acetonitrile.

[1391] Mass spectrometry (MS): Usually only ions representing the parent mass are reported. Unless otherwise stated, the mass ion quoted is the positive mass ion (MH). + .

[1392] NMR spectra were obtained using a Bruker Avance 400 MHz, 500 MHz.

[1393] Microwave-assisted reactions were performed in a Biotage Initiator Sixty microwave synthesizer. All reactions involving air-sensitive reagents were performed under argon or nitrogen atmosphere. Unless otherwise stated, reagents were purchased from commercial suppliers as received without further purification.

[1394] Preparation Example

[1395] The following examples are intended to illustrate the meaning of the present invention, but are by no means intended to limit the meaning of the present invention:

[1396] Intermediate A1

[1397] 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-methylcarbamate

[1398]

[1399] The title compound was prepared according to the following scheme:

[1400]

[1401] Step 1: Preparation of tert-butyl N-[3-(2-bromo-6-nitro-anilino)-2-hydroxy-propyl]carbamate (Compound A1-b)

[1402] To a solution of 1,3-diamino-2-propanol (35.64 g, 395.45 mmol, as "amine" in Table 1) in ACN was slowly added 3-bromo-2-fluoronitrobenzene (compound A1-a, 43.5 g, 197.73 mmol, as "aryl fluoride" in Table 1) at 25 ° C. After stirring at 20 ° C. for 0.5 hours, the mixture was filtered, and the filter cake was collected and dissolved in methanol. Tert-butyl (2-methylpropane-2-yl) oxycarbonyl carbonate (106.8 g, 489.47 mmol) and DIPEA (63.26 g, 489.47 mmol) were then added. After stirring at 20 ° C. for 1 hour, 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.

[1403] Step 2: Preparation of tert-butyl N-[3-(2-amino-6-bromo-anilino)-2-hydroxy-propyl]carbamate (Compound A1-c)

[1404] 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 hour, 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.

[1405] Step 3: Preparation of tert-butyl N-[3-(7-bromo-2-methyl-benzoimidazol-1-yl)-2-hydroxy-propyl]carbamate (Compound A1-d)

[1406] 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 hour, 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.

[1407] Step 4: Preparation of N-[3-(7-bromo-2-methyl-benzoimidazol-1-yl)-2-methoxy-propyl]-N-methyl-carbamic acid tert-butyl ester (Compound A1-e)

[1408] Under N2, to a solution of tert-butyl N-[3-(7-bromo-2-methyl-benzoimidazol-1-yl)-2-hydroxy-propyl]carbamate (compound A1-d, 10.0 g, 26.02 mmol) in DMF (200 mL) was added CH3I (11.08 g, 78.07 mmol, as "alkyl iodide" in Table 1) at -10°C, and then NaH (2.6 g, 65.06 mmol) was slowly added in portions. The mixture was stirred at -10°C for 5 hours. The mixture was then stirred at 20°C for another 12 hours. The reaction was quenched with ice-cold NH4Cl solution and extracted twice with EA, and the organic layer was dried and concentrated to give compound A1-e (11.7 g). LCMS (M+H) + :412.

[1409] 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-methylcarbamate (Intermediate A1)

[1410] To a mixture of N-[3-(7-bromo-2-methyl-benzoimidazol-1-yl)-2-methoxy-propyl]-N-methyl-tert-butyl 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(triphenylphosphino)palladium chloride (II) (2.68 g, 3.82 mmol) and butyldi-1-adamantylphosphine (2.74 g, 7.64 mmol). The mixture was degassed three times with N2 and stirred at 130 ° C for 2 hours. 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 and concentrated, and the residue was purified by silica gel to obtain intermediate A1 (8.8 g). LCMS (M+H) + :460.

[1411] Similar to Intermediate A1, the following intermediates in Table 1 were prepared by replacing Compound A1-a with “aryl fluoride” and 1,3-diamino-2-propanol with “amine” in Step 1, replacing trimethyl orthoacetate with “solvent” in Step 3, and replacing CH3I with “alkyl iodide” in Step 4 with the reagents shown in Table 1.

[1412] Table 1. Compound synthesis and characterization

[1413]

[1414]

[1415]

[1416] Intermediate A6

[1417] 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-carbamic acid tert-butyl ester

[1418]

[1419] The title compound was prepared according to the following scheme:

[1420]

[1421] The title compound was prepared in analogy to the preparation of intermediate A1 by using compound A7-d instead of compound A1-d. LCMS (M+H) + :478.

[1422] Intermediate A7

[1423] 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-methylcarbamate

[1424]

[1425] The title compound was prepared according to the following scheme:

[1426]

[1427] Step 1: Preparation of tert-butyl N-[(2R)-3-(2-bromo-4-fluoro-6-nitro-anilino)-2-hydroxy-propyl]carbamate (Compound A7-b)

[1428] 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 hours, the mixture was filtered and the filtrate was concentrated to give compound A7-b (131 g). LCMS (M+H) + :352.

[1429] Step 2: Preparation of tert-butyl N-[(2R)-3-(2-amino-6-bromo-4-fluoro-anilino)-2-hydroxy-propyl]carbamate (Compound A7-c)

[1430] 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 hour, 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.

[1431] 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)

[1432] 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 hour. The mixture was concentrated under reduced pressure to give compound A7-d (160 g). LCMS (M+H) + :400.

[1433] Step 4: Preparation of tert-butyl N-[(2S)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-[tert-butyl(dimethyl)silanyl]oxy-propyl]carbamate (Compound A7-e)

[1434] 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-butyldimethylsilyl chloride (59.95 g, 397.75 mmol), and the mixture was stirred at 30 ° C for 18 hours. The mixture was poured into ice-NH4Cl aqueous solution (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.

[1435] Step 5: Preparation of N-[(2R)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-[tert-butyl(dimethyl)silanyl]oxy-propyl]-N-methyl-carbamic acid tert-butyl ester (Compound A7-f)

[1436] To 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, followed by stirring at 0°C for 1 hour. Iodomethane (90.13 g, 635.02 mmol) was then added at 0°C, and the mixture was stirred at 0°C for 1 hour. 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.

[1437] Step 6: Preparation of N-[(2R)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-hydroxy-propyl]-N-methyl-carbamic acid tert-butyl ester (Compound A7-g)

[1438] 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 hours. The mixture was then concentrated, and the crude product was diluted with EtOAc (600 mL), washed with water and brine. The organic layer was dried and concentrated to give compound A7-g (39.4 g). LCMS (M+H) + :416.

[1439] Step 7: Preparation of N-[(2R)-3-(7-bromo-5-fluoro-2-methyl-benzimidazol-1-yl)-2-ethoxy-propyl]-N-methyl-carbamic acid tert-butyl ester (Compound A7-h)

[1440] 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 hours. 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.

[1441] 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-methylcarbamate (Intermediate A7)

[1442] 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) were added potassium acetate (8.57 g, 87.32 mmol), bis(triphenylphosphino)palladium(II) chloride (4.6 g, 6.55 mmol) and butyldi-1-adamantylphosphine (4.7 g, 13.1 mmol). The mixture was degassed three times with N2 and then stirred at 130 °C for 2 hours. The reaction mixture was then poured into water (1000 mL) and extracted with EA (500 mL). The organic layer was dried and concentrated, and the crude product was purified by column chromatography to obtain intermediate A7 (15 g). LCMS (M+H) + :478.

[1443] Intermediate A8

[1444] 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-methylcarbamate

[1445]

[1446] The title compound was prepared in analogy 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.

[1447] Intermediate A9

[1448] 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-methylcarbamate

[1449]

[1450] The title compound was prepared in analogy 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.

[1451] Intermediate A10

[1452] 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-methylcarbamate

[1453]

[1454] The title compound was prepared analogously 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.

[1455] Intermediate A15

[1456] tert-Butyl N-[3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate

[1457]

[1458] The title compound was prepared according to the following scheme:

[1459]

[1460] Step 1: Preparation of tert-butyl N-[3-(2-bromo-6-nitro-anilino)propyl]carbamate (Intermediate A15-a)

[1461] To a microwave tube was added 1-bromo-2-fluoro-3-nitro-benzene (2.7 g, 12.3 mmol, as "aryl fluoride" in Table 2), tert-butyl N-(3-aminopropyl)carbamate (2.14 g, 12.3 mmol, as "amine" in Table 2), K2CO3 (1.7 g, 12.3 mmol) and acetonitrile (15 mL). The tube was sealed and heated to 90 ° C for 3 hours. The mixture was cooled and 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.

[1462] Step 2: Preparation of tert-butyl N-[3-(2-amino-6-bromo-anilino)propyl]carbamate (Intermediate A15-b)

[1463] 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) were added to the flask and the suspension was stirred vigorously before adding hydrazine (8.56 g, 8.32 mL, 134 mmol). After stirring at room temperature for 1 hour, 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.

[1464] Step 3: Preparation of tert-butyl N-[3-(7-bromobenzimidazol-1-yl)propyl]carbamate (Intermediate A15-c)

[1465] To the flask containing N-[3-(2-amino-6-bromo-anilino)propyl]carbamic acid tert-butyl ester (intermediate A15-b, 3.5g, 10.2mmol), trimethyl orthoformate (9.7g, 10mL, 91.4mmol, as "solvent" in Table 2) and p-toluenesulfonic acid monohydrate (387mg, 2.03mmol) were added to form a light 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 obtain intermediate A15-c (3.2g). LCMS (M+H + ):354.

[1466] 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)

[1467] To the tube was added tert-butyl N-[3-(7-bromobenzimidazole-1-yl)propyl]carbamate (intermediate A15-c, 2.7 g, 7.62 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(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 bubbled with N2 for 5 minutes, followed by addition of butyldi-1-adamantylphosphine (820 mg, 2.29 mmol) and bis(triphenylphosphino)palladium(II) chloride (802 mg, 1.14 mmol). The tube was sealed and heated to 130 ° C for 4 hours. The mixture was diluted with water and then extracted with EA. The organic layer was dried and concentrated, and the residue was purified by silica gel to obtain intermediate A15 (2.1 g). LCMS (M+H + ):402.

[1468] Analogously to Intermediate A15, the following intermediates in Table 2 were prepared by replacing 1-bromo-2-fluoro-3-nitro-benzene with “aryl fluoride” and tert-butyl N-(3-aminopropyl)carbamate with “amine” in Step 1 with the reagents shown in Table 2, and replacing trimethyl orthoformate with “solvent” in Step 3.

[1469] Table 2. Compound synthesis and characterization

[1470]

[1471]

[1472] Intermediate A17

[1473] tert-Butyl N-[2-ethoxy-3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]-N-methylcarbamate

[1474]

[1475] The title compound was prepared analogously 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.

[1476] Intermediate A18

[1477] tert-Butyl N-[3-[2-(2-morpholinoethyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate

[1478]

[1479] The title compound was prepared according to the following scheme:

[1480]

[1481] Step 1: Preparation of 3-[7-bromo-2-(2-morpholinoethyl)benzimidazol-1-yl]propan-1-amine (Intermediate A18-a)

[1482] 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-morpholinopropionic acid (2.08 g, 13.07 mmol) in concentrated hydrochloric acid (45.0 mL, 13.07 mmol) and water (45 mL) was stirred at 100 ° C for 40 hours. After the pH of the reaction mixture was adjusted to 8 to 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.

[1483] Step 2: Preparation of tert-butyl N-[3-[7-bromo-2-(2-morpholinoethyl)benzimidazol-1-yl]propyl]carbamate (Intermediate A18-b)

[1484] A mixture of compound A18-a (3.7 g, 10.21 mmol) and di-tert-butyl dicarbonate (3.34 g, 15.32 mmol) in methanol was stirred at 20° C. for 16 hours. The reaction mixture was concentrated and the residue was purified by preparative HPLC to give intermediate A18-b (1 g). LCMS (M+H + ):467.

[1485] 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)

[1486] 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'-bis(1,3,2-dioxaborolane) (700 mg, 2.76 mmol), potassium acetate (235 mg, 2.4 mmol) and DMSO (6 mL). The solution was bubbled with N2 for 5 minutes, followed by addition of butyldi-1-adamantylphosphine (85.9 mg, 240 μmol) and bis(triphenylphosphine)palladium(II) dichloride (84.1 mg, 120 μmol). The tube was heated to 130 ° C for approximately 6 hours. 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 obtain intermediate A18 (180 mg). LCMS (M+H + ):515.

[1487] Intermediate A19

[1488] 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

[1489]

[1490] The title compound was prepared according to the following scheme:

[1491]

[1492] Step 1: Preparation of tert-butyl N-methyl-N-[3-(4-methyl-2-nitro-anilino)propyl]carbamate (Compound A19-a)

[1493] 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 slowly added tert-butyl N-(3-aminopropyl)-N-methylcarbamate (6.7 g, 35.5 mmol) at 25°C. After stirring at 85°C for 2 hours, the mixture was filtered and concentrated to give compound A19-a (11.6 g). LCMS (M+H) + :324.

[1494] Step 2: Preparation of N-[3-(2-bromo-4-methyl-6-nitro-anilino)propyl]-N-methyl-carbamic acid tert-butyl ester (Compound A19-b)

[1495] 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 hours. 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.

[1496] Steps 3 to 5: Preparation of 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 (Intermediate A19)

[1497] The title compound was prepared in analogy to the preparation of intermediate A15 by using compound A19-b instead of compound A15-c. LCMS (M+H) + :430.

[1498] Intermediate A20

[1499] tert-Butyl N-cyclopropyl-N-[3-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]propyl]carbamate

[1500]

[1501] The title compound was prepared according to the following scheme:

[1502]

[1503] Steps 1 to 3: Preparation of 3-(7-bromobenzimidazol-1-yl)propan-1-ol (Compound A20-c)

[1504] Similar to the preparation of intermediate A15-c, compound A20-c was prepared by using 3-aminopropane-1-ol instead of tert-butyl N-(3-aminopropyl)carbamate, LCMS (M+H) + :255.

[1505] Step 4: Preparation of 7-bromo-1-(3-chloropropyl)benzimidazole (Compound A20-d)

[1506] A mixture of compound A20-c (10 g, 39 mmol) in SOCl2 (40 mL) was stirred at 80°C for 1 hour. The mixture was then concentrated, and the residue was dissolved in EtOAc and washed with 5% NaHCO3 and brine (50.0 mL). The organic layer was dried and concentrated to give compound A20-d (7.0 g). LCMS (M+H) + :273.

[1507] Step 5: Preparation of N-[3-(7-bromobenzimidazol-1-yl)propyl]cyclopropylamine (Compound A20-e)

[1508] A mixture of compound A20-d (1.6 g, 5.85 mmol), cyclopropylamine (1.6 g, 28.03 mmol), and DIPEA (1.6 g, 12.38 mmol) in NMP (10.0 mL) was stirred at 110° C. for 12 hours. 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.

[1509] Step 6: Preparation of N-[3-(7-bromobenzimidazol-1-yl)propyl]-N-cyclopropyl-carbamic acid tert-butyl ester (Compound A20-f)

[1510] A mixture of compound A20-e (500 mg, 1.7 mmol) and di-tert-butyl dicarbonate (500 mg, 2.29 mmol) in DCM (10 mL) was stirred at 20° C. for 1 hour. 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.

[1511] Step 7: 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)

[1512] The title compound was prepared in analogy to the preparation of intermediate A15 by using compound A20-f instead of compound A15-c. LCMS (M+H) + :442.

[1513] Intermediate A22

[1514] N-[3-[2-ethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]-2-methoxy-propyl]-N-methyl-carbamic acid tert-butyl ester

[1515]

[1516] The title compound was prepared according to the following scheme:

[1517]

[1518] Step 1: Preparation of N-[3-(7-bromo-2-ethyl-benzoimidazol-1-yl)-2-hydroxy-propyl]carbamic acid tert-butyl ester (Compound A22-a)

[1519] To a solution of compound A1-c (7.3 g, 20 mmol) in water (8 mL) and DMF (80 mL) was added potassium persulfate (oxone) (3.41 g, 20.26 mmol) and propionaldehyde (1.35 g, 23.3 mmol) in sequence at 0°C, and then stirred at 20°C for 12 hours. The reaction was quenched with saturated ammonium chloride solution (500 mL) and extracted with EA (1000 mL). The organic layer was dried and concentrated; the residue was purified by column chromatography to obtain compound A22-a (2.5 g). LCMS (M+H) + :398.

[1520] Steps 2 to 3: N-[3-[2-Ethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazol-1-yl]-2-methoxy-propyl]-N-methyl-carbamic acid tert-butyl ester (Intermediate A22)

[1521] The title compound was prepared in analogy to the preparation of intermediate A1 by using compound A22-a instead of compound A1-d. LCMS (M+H) + :474.

[1522] Intermediate A23

[1523] 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-methylcarbamate

[1524]

[1525] The title compound was prepared according to the following scheme:

[1526]

[1527] Step 1: Preparation of ethyl 3-(benzylamino)-2-[(benzylamino)methyl]propanoate (Compound A23-a)

[1528] 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)propanoate (10 g, 36.5 mmol) in ACN (20 mL) at 80 ° C over 1 hour. The mixture was then stirred at 80 ° C for 6 hours. The reaction was concentrated and the residue was purified by flash chromatography to give compound A23-a (5.9 g). LCMS (M+H + ):327.

[1529] Step 2: Preparation of 3-(benzylamino)-2-[(benzylamino)methyl]propan-1-ol (Compound A23-b)

[1530] To a solution of compound A23-a (8.7 g, 26.65 mmol) in THF (120 mL) was added LiAlH4 (1.2 g, 32 mmol) at 0°C, and the mixture was stirred at 0°C for 2 hours. The reaction was quenched with H2O (1.2 mL) and 10% aqueous NaOH solution (3.6 mL). 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.

[1531] Step 3: Preparation of 3-amino-2-(aminomethyl)propan-1-ol (Compound A23-c)

[1532] To a solution of compound A23-b (11 g, 38.68 mmol) in methanol (80 mL) and acetic acid (10 mL) was added Pd(OH) / C (2.2 g) under N2. The mixture was stirred at 60°C under hydrogen for 48 hours. The reaction mixture was filtered and concentrated to give compound A23-c (5 g). LCMS (M+H) + :105.

[1533] Steps 4 to 7: Preparation of tert-butyl N-[2-[(7-bromo-2-methyl-benzoimidazol-1-yl)methyl]-3-hydroxy-propyl]carbamate (Compound A23-g)

[1534] Similar to the preparation of intermediate A1-d, compound A23-g was prepared by using compound A23-c instead of 1,3-diamino-2-propanol, LCMS (M+H) + :398.

[1535] Steps 8 to 9: Preparation of tert-butyl N-[2-[(7-bromo-2-methyl-benzimidazol-1-yl)methy...

Claims

1. A compound of formula (Ia), in M 1 For optionally through R 1 Substituted heteroarylene; wherein R 1 Deuterated, halogen, cyano, carboxyl, R, RO, RS, RNH, (R)2N, RCO, RSO2, RNHSO2, R2NSO2, RSO(NR), R3Si, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RNHC 1-6 Alkyl, (R)2NC 1-6 Alkyl, RSO2C 1-6 Alkyl, RNHSO2C 1-6 Alkyl, R2NSO2C 1-6 Alkyl, RSO(NR)C 1-6 Alkyl or R3SiC 1-6 Alkyl; wherein R is H, R a 、R b or R c ; R a For optionally through R b or R c Substituted C 1-6 alkyl; R b C 3-7 Cycloalkyl, heterocyclyl, heteroaryl or aryl, the C 3-7 Cycloalkyl, heterocyclyl, heteroaryl and aryl are unsubstituted or optionally substituted with deuterium, halogen or R c replace; R c Selected from deuterated, C 1-6 Alkyl, (C 1-6 Alkyl)3Si, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, deuterated C 2-6 Alkenyl, C 2-6 Alkynyl, halo C 2-6 Alkynyl, deuterated C 2-6 Alkynyl, C 3-7 Cycloalkyl, halogenated C 3-7 Cycloalkyl, deuterated C 3-7 Cycloalkyl, amino, C 1-6 Alkylamino, (C 1-6 Alkyl)2amino, C 1-6 Alkylcarbonylamino, haloC 1-6 Alkylamino, halogenated C 1-6 Alkylcarbonylamino, (halogenated C 1-6 Alkyl)2amino, C 3-7 Cycloalkylamino, C 3-7 Cycloalkylcarbonylamino, (C 3-7 Cycloalkyl)2amino, halogenated C 3-7 Cycloalkylamino, (halogenated C 3-7 Cycloalkyl)2amino, C 3-7 Cycloalkyl (C 1-6 Alkyl)amino, halogenated C 3-7 Cycloalkyl (C 1-6 Alkyl)amino, C 1-6 Alkylsulfonylamino, halo C 1-6 Alkylsulfonylamino, C 1-6 Alkoxy C 1-6 Alkyl, (halogenated C 1-6 Alkoxy) C 1-6 Alkyl, C 1-6 Alkoxy (halogenated) C 1-6 Alkyl, C 3-7 Cycloalkyl C 1-6 Alkyl, C 3-7 Cycloalkyl halide C 1-6 Alkyl, C 1-6 Alkylcarbonyl, haloC 1-6 Alkylcarbonyl, C 3-7 Cycloalkylcarbonyl, haloC 3-7 Cycloalkylcarbonyl, C 1-6 Alkoxycarbonyl, halocarbonyl 1-6 Alkoxycarbonyl, C 3-7 Cycloalkoxycarbonyl, halo 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, halogenated C 3-7 Cycloalkylaminocarbonyl, halo(C 3-7 Cycloalkyl)2-aminocarbonyl, halogenated C 1-6 Alkyl C 3-7 Cycloalkylaminocarbonyl, C 1-6 Alkyl halide C 3-7 Cycloalkylaminocarbonyl, (C 1-6 alkyl)3ammonium group, C 1-6 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C 3-7 Cycloalkylthio, C 3-7 Cycloalkylsulfinyl, C 3-7 Cycloalkylsulfonyl, halo C 1-6 Alkylthio, halo C 1-6 Alkylsulfinyl, halo C 1-6 Alkylsulfonyl, halo C 3-7 Cycloalkylthio, halo C 3-7 Cycloalkylsulfinyl, halo C 3-7 Cycloalkylsulfonyl, halo C 1-6 Alkoxysulfonyl, C 1-6 Alkylaminosulfonyl, (halogenated C 1-6 alkylamino)sulfonyl, (C 1-6 Alkyl) 2-aminosulfonyl, (halogenated C 1-6 alkyl)2-aminosulfonyl, (C 1-6 alkyl)2phosphoryl, (C 1-6 Alkoxy) 2-phosphoryl, hydroxyl (C 1-6 Alkoxy)phosphoryl, C 1-6 Alkoxyphosphoryl, hydroxyl, hydroxyl C 1-6 Alkyl, hydroxy halide C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy, hydroxy halide C 1-6 Alkoxy, hydroxy C 3-7 Cycloalkyl, hydroxy halide C 3-7 Cycloalkyl and sulfimidoyl, which are optionally substituted by H, C 1-6 Alkyl, C 1-6 alkoxy, aryl, heteroaryl, and heterocyclyl substitution; M 2 is an arylene group, a heterocyclylene group or a heteroarylene group, wherein the arylene group, the heterocyclylene group or the heteroarylene group is optionally substituted by R 1 replace; M 3 is unsubstituted or optionally substituted with R 3 substituted heterocyclylene; R 2 Deuterium, R, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RSO2C 1-6 Alkyl, RNHC 1-6 Alkyl or (R)2NC 1-6 alkyl; R 3 is a heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl or arylcarbonyl group, wherein the heterocyclyl, heteroaryl, aryl, heterocyclylcarbonyl, heteroarylcarbonyl and arylcarbonyl groups are unsubstituted or optionally substituted by R 1 replace; Q 1 is -M-, -MOM-, -MSM-, -M-SO2-M-, -M-SO(NH)-M-, -M-SO(NR)-M-, -M-SiR2-M- or -MN(R)-M-; wherein M is unsubstituted or optionally independently selected from deuterated, halogen, cyano, carboxyl, R, RO, RS, RNH, R2N, RSO2, ROC 1-6 Alkyl, RSC 1-6 Alkyl, RNHC 1-6 Alkyl, (R)2NC 1-6 Alkyl and RSO2C 1-6 Alkyl substituents substituted C 1-6 alkylene; Q 2 is NH, O, S, SO, SO2, P(O)R, PO(NR), Se, N(R), SiR2, heterocyclyl, heteroaryl or aryl; or a pharmaceutically acceptable salt thereof.

2. The compound of formula (I) according to claim 1, in R 1 Deuterated, 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, halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, morpholinyl C 1-6 Alkyl, hydroxyl, pyrazolyl C 1-6 Alkyl or triazolyl C 1-6 alkyl; R 2 H, (2-oxa-5-azabicyclo[2.2.1]heptyl)C 1-6 Alkyl, (2-oxa-6-azaspiro[3.3]heptyl)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)3ammonium)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, halogenated C 1-6 Alkyl, hydroxyl 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 trideuterated C 1-6 alkyl; R 3 for in R 4 For H, (C 1-6 Alkyl) 2 amino, (C 1-6 alkyl)2-aminocarbonyl, (C 1-6 alkyl)2phosphoryl, 1,1-dioxothianilinyl, C 1-6 Alkyl-substituted 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrolyl, Halogenated C 1-6 1,6-diazaspiro[3.3]heptyl substituted by alkyl or oxetane, Halogenated C 1-6 1,7-diazaspiro[3.5]nonyl substituted with alkyl or oxetane, 2,2-Dioxo-2λ 6 -thia-6-azaspiro[3.3]heptyl, C 1-6 Alkyl-substituted 2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazinyl, C 1-6 Alkyl, halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl, independently selected from halogenated C 1-6 2-azaspiro[3.3]heptyl substituted once or twice with alkyl and hydroxy substituents, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptyl, 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, Hydroxyl(halogenated oxetane)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, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, haloC 3-7 Cycloalkyl, hydroxy C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl C 3-7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3,6-diazabicyclo[3.2.0]heptanyl substituted with oxetane, 3,7-diazabicyclo[4.2.0]octanyl substituted with oxetane, Halogenated 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]nonyl, 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, Halogenated C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 Alkyl-substituted 5-oxa-2,8-diazaspiro[3.5]nonyl, 6,6-dioxo-6λ 6 -thia-1-azaspiro[3.3]heptyl, 6-oxa-1-azaspiro[3.3]heptyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, Halogenated C 1-6 Alkyl-substituted 8-oxa-2,5-diazaspiro[3.5]nonyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, amino, aminocarbonyl, unsubstituted or independently selected from (C 1-6 alkyl)2amino, (C 1-6 Alkyl)2amino 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, halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, morpholinyl and morpholinyl C 1-6 The substituent of the alkyl group is substituted once or twice with an azetidinyl group, Halogenated C 1-6 Alkyl or C 3-7 cycloalkyl-substituted azetidinyloxy, Unsubstituted or (halogenated C 1-6 alkylcarbonyl)azetidinyl, C 1-6 Alkylazetidinyl, C 1-6 Alkylpiperazinyl, C 1-6 Alkylpyrrolidinyl, halogenated-1,2,3,5,6,7-hexahydropyrrolizinyl, halogenated C 1-6 Alkyl azetidinyl, morpholinyl, oxetanyl or tetrahydrofuranyl substituted C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkylamino, C 1-6 Alkoxycarbonyl, unsubstituted or independently selected from (C 1-6 Alkoxy C 1-6 alkylcarbonyl)azetidinyl, (halogenated C 1-6 alkylcarbonyl)pyrrolidinyl, 1,1-dioxothietane, 2-oxa-6-azaspiro[3.3]heptyl, 3-oxa-6-azabicyclo[3.1.1]heptyl, 4,7-diazaspiro[2.5]octyl, 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, halo C 1-6 Alkylazetidinyl, hydroxy, hydroxy C 1-6 Alkyl, morpholinyl and oxetane substituents are substituted once or twice on the C 1-6 alkyl, C 1-6 Alkylamino, C unsubstituted or substituted with 1,1-dioxothietane 1-6 Alkylthio, C 1-6 Alkylsulfonyl, Unsubstituted or C 1-6 Alkoxy or hydroxy substituted C 3-7 Cycloalkyl, carboxyl, cyano group, Halogenated C 1-6 Alkoxy, Halogenated C substituted with hydroxyl 1-6 alkyl, hydroxyl groups, Hydroxyl C 1-6 Alkylcarbamoyl, Imidazole, Morpholinyl, Morpholinylcarbonyl, Oxetane, Oxomorpholinyl, Oxooxazolidinyl, C 1-6 alkyl-substituted oxopiperazinyl, Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group, Independently selected from C 1-6 Alkyl, carboxyl, oxetane and phenyl C 1-6 a piperazinyl group substituted once or twice with an alkyl substituent, C 1-6 alkyl, 2H-tetrazolyl or oxazolyl substituted piperidinyl, are independently selected from amino, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkylcarbonyl, C 1-6 Alkylsulfonyl, cyano, halo C 1-6 alkylcarbonyl and halogen substituents substituted once or twice with pyrrolidinyl, pyrrolidinylcarbonyl, tetrahydrofuranyl, or tetrahydropyranyl; R 5 is 1,3-dihydroisobenzofuranyl, 1H-indazolyl substituted by halogen, C 2-6 Alkynyl, Thiphenyl group, Unsubstituted or halogen or C 1-6 Alkyl-substituted bicyclo[1.1.1]pentanyl, Independently selected from (C 1-6 Alkoxy C 1-6 Alkyl)C 3-7 Cycloalkyloxy, (C 1-6 alkyl)2phosphoryl, (C 1-6 Alkylmorpholinyl)C 1-6 Alkoxy, (C 1-6 (alkylsulfonylazetidinyl)C 1-6 Alkoxy, 2-oxa-6-azaspiro[3.3]heptyl, 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 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C 2-6 Alkenyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyloxy, carboxyl, cyano, cyano C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogen, hydroxyl, morpholinyl, morpholinyl C 1-6 Alkoxy, oxetane C 1-6 Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl, tetrahydrofuranyloxy and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times, unsubstituted or independently selected from halogen, hydroxy, C 1-6 Alkylthio and C 1-6 The alkoxy substituent is substituted once or twice with a pyridyl group, or unsubstituted or halogen-substituted pyrimidinyl; R 6 H or C 1-6 alkyl; R 7 C 1-6 alkyl; R 7a C 1-6 Alkyl, C 3-7 Cycloalkyl or C 1-6 Alkoxy C 1-6 alkyl; R 7b H, C 1-6 Alkoxy or phenyl C 1-6 alkoxy; R 7c H or C 1-6 alkoxy; R 7d C 1-6 Alkyl, C 3-7 Cycloalkyl C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 alkyl; R 7e H, amino, phenyl C 1-6 Alkylamino or morpholino C 1-6 Alkylamino; R 7f C 1-6 Alkyl, phenyl C 1-6 Alkyl or oxetane; R 7g H or C 1-6 Alkoxy C 1-6 alkyl; Q 1 is unsubstituted or independently selected from C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkoxy, C 1-6 Alkyl, C 1-6 Alkylcarbonyloxy, carboxyl, hydroxyl, hydroxyl C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, morpholinyl C 1-6 Alkoxy and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 Alkylene, or -MOM-, where M is C 1-6 alkylene; Q 2 is NH, O or S; A 1 is CH or N; A 2 CH, CR 7h or N; where R 7h C 1-6 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, halogenated azetidinyl C 1-6 Alkyl, halogenated C 1-6 Alkoxy, halogen, morpholino C 1-6 Alkyl or oxetane; A 4 CR 9 or N, where R 9 H; or R 8 and R 9 together with the atoms to which they are attached, form a heterocyclyl; A 5 CR 10 or N, where R 10 is H or halogen; A 6 CR 11 or N, where R 11 H, deuterated, halogen, C 1-6 Alkyl or C 1-6 alkoxy; A 7 CR 12 or N, where R 12 is H or halogen; Condition A 1 、A 2 、A 3 and A 4 No more than two of them are N at the same time; and A 5 、A 6 and A 7 No more than one of them is N; or a pharmaceutically acceptable salt thereof.

3. The compound of formula (Ib) according to claim 1, in R 1 Deuterated, 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, halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, morpholinyl C 1-6 Alkyl, hydroxyl, pyrazolyl C 1-6 Alkyl or triazolyl C 1-6 alkyl; R 2 H, (2-oxa-5-azabicyclo[2.2.1]heptyl)C 1-6 Alkyl, (2-oxa-6-azaspiro[3.3]heptyl)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)3ammonium)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, halogenated C 1-6 Alkyl, hydroxyl 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 trideuterated C 1-6 alkyl; R 3 for in R 4 For H, (C 1-6 Alkyl) 2 amino, (C 1-6 alkyl)2-aminocarbonyl, (C 1-6 alkyl)2phosphoryl, 1,1-dioxothianilinyl, C 1-6 Alkyl-substituted 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrolyl, Halogenated C 1-6 1,6-diazaspiro[3.3]heptyl substituted by alkyl or oxetane, Halogenated C 1-6 1,7-diazaspiro[3.5]nonyl substituted with alkyl or oxetane, 2,2-Dioxo-2λ 6 -thia-6-azaspiro[3.3]heptyl, C 1-6 Alkyl-substituted 2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazinyl, C 1-6 Alkyl, halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl, independently selected from halogenated C 1-6 2-azaspiro[3.3]heptyl substituted once or twice with alkyl and hydroxy substituents, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptyl, 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, Hydroxyl(halogenated oxetane)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, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, haloC 3-7 Cycloalkyl, hydroxy C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl C 3-7 3,6-diazabicyclo[3.1.1]heptanyl substituted with cycloalkylcarbonyl or oxetanyl, 3,6-diazabicyclo[3.2.0]heptanyl substituted with oxetane, 3,7-diazabicyclo[4.2.0]octanyl substituted with oxetane, Halogenated 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]nonyl, 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, Halogenated C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 Alkyl-substituted 5-oxa-2,8-diazaspiro[3.5]nonyl, 6,6-dioxo-6λ 6 -thia-1-azaspiro[3.3]heptyl, 6-oxa-1-azaspiro[3.3]heptyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, Halogenated C 1-6 Alkyl-substituted 8-oxa-2,5-diazaspiro[3.5]nonyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, amino, aminocarbonyl, unsubstituted or independently selected from (C 1-6 alkyl)2amino, (C 1-6 Alkyl)2amino 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, halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, morpholinyl and morpholinyl C 1-6 The substituent of the alkyl group is substituted once or twice with an azetidinyl group, Halogenated C 1-6 Alkyl or C 3-7 cycloalkyl-substituted azetidinyloxy, Unsubstituted or (halogenated C 1-6 alkylcarbonyl)azetidinyl, C 1-6 Alkylazetidinyl, C 1-6 Alkylpiperazinyl, C 1-6 Alkylpyrrolidinyl, halogenated-1,2,3,5,6,7-hexahydropyrrolizinyl, halogenated C 1-6 Alkyl azetidinyl, morpholinyl, oxetanyl or tetrahydrofuranyl substituted C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkylamino, C 1-6 Alkoxycarbonyl, unsubstituted or independently selected from (C 1-6 Alkoxy C 1-6 alkylcarbonyl)azetidinyl, (halogenated C 1-6 alkylcarbonyl)pyrrolidinyl, 1,1-dioxothietane, 2-oxa-6-azaspiro[3.3]heptyl, 3-oxa-6-azabicyclo[3.1.1]heptyl, 4,7-diazaspiro[2.5]octyl, 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, halo C 1-6 Alkylazetidinyl, hydroxy, hydroxy C 1-6 Alkyl, morpholinyl and oxetane substituents are substituted once or twice on the C 1-6 alkyl, C 1-6 Alkylamino, C unsubstituted or substituted with 1,1-dioxothietane 1-6 Alkylthio, C 1-6 Alkylsulfonyl, Unsubstituted or C 1-6 Alkoxy or hydroxy substituted C 3-7 Cycloalkyl, carboxyl, cyano group, Halogenated C 1-6 Alkoxy, Halogenated C substituted with hydroxyl 1-6 alkyl, hydroxyl groups, Hydroxyl C 1-6 Alkylcarbamoyl, Imidazole, Morpholinyl, Morpholinylcarbonyl, Oxetane, Oxomorpholinyl, Oxooxazolidinyl, C 1-6 alkyl-substituted oxopiperazinyl, Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group, Independently selected from C 1-6 Alkyl, carboxyl, oxetane and phenyl C 1-6 a piperazinyl group substituted once or twice with an alkyl substituent, C 1-6 alkyl, 2H-tetrazolyl or oxazolyl substituted piperidinyl, are independently selected from amino, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkylcarbonyl, C 1-6 Alkylsulfonyl, cyano, halo C 1-6 alkylcarbonyl and halogen substituents substituted once or twice with pyrrolidinyl, pyrrolidinylcarbonyl, tetrahydrofuranyl, or tetrahydropyranyl; R 5 is 1,3-dihydroisobenzofuranyl, 1H-indazolyl substituted by halogen, C 2-6 Alkynyl, Thiphenyl group, Unsubstituted or halogen or C 1-6 Alkyl-substituted bicyclo[1.1.1]pentanyl, Independently selected from (C 1-6 Alkoxy C 1-6 Alkyl)C 3-7 Cycloalkyloxy, (C 1-6 alkyl)2phosphoryl, (C 1-6 Alkylmorpholinyl)C 1-6 Alkoxy, (C 1-6 (alkylsulfonylazetidinyl)C 1-6 Alkoxy, 2-oxa-6-azaspiro[3.3]heptyl, 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 Alkylthio, C 1-6 Alkylsulfinyl, C 1-6 Alkylsulfonyl, C 2-6 Alkenyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyloxy, carboxyl, cyano, cyano C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogen, hydroxyl, morpholinyl, morpholinyl C 1-6 Alkoxy, oxetane C 1-6 Alkoxy, oxetanyloxy, oxopyrrolidinyl, phenyl, tetrahydrofuranyl, tetrahydrofuranyloxy and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times, unsubstituted or independently selected from halogen, hydroxy, C 1-6 Alkylthio and C 1-6 The alkoxy substituent is substituted once or twice with a pyridyl group, or unsubstituted or halogen-substituted pyrimidinyl; R 6 H or C 1-6 alkyl; R 7 C 1-6 alkyl; R 7a C 1-6 Alkyl, C 3-7 Cycloalkyl or C 1-6 Alkoxy C 1-6 alkyl; R 7b H, C 1-6 Alkoxy or phenyl C 1-6 alkoxy; R 7c H or C 1-6 alkoxy; R 7d C 1-6 Alkyl, C 3-7 Cycloalkyl C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 alkyl; R 7e H, amino, phenyl C 1-6 Alkylamino or morpholino C 1-6 Alkylamino; R 7f C 1-6 Alkyl, phenyl C 1-6 Alkyl or oxetane; R 7g H or C 1-6 Alkoxy C 1-6 alkyl; Q 1 is unsubstituted or independently selected from C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkoxy, C 1-6 Alkyl, C 1-6 Alkylcarbonyloxy, carboxyl, hydroxyl, hydroxyl C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, morpholinyl C 1-6 Alkoxy and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 Alkylene, or -MOM-, where M is C 1-6 alkylene; Q 2 is NH, O or S; A 1 is CH or N; A 2 CH, CR 7h or N; where R 7h C 1-6 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, halogenated azetidinyl C 1-6 Alkyl, halogenated C 1-6 Alkoxy, halogen, morpholino C 1-6 Alkyl or oxetane; A 4 CR 9 or N, where R 9 H; or R 8 and R 9 together with the atoms to which they are attached, form a heterocyclyl; A 5 CR 10 or N, where R 10 is H or halogen; A 6 CR 11 or N, where R 11 H, deuterated, halogen, C 1-6 Alkyl or C 1-6 alkoxy; A 7 CR 12 or N, where R 12 is H or halogen; Condition A 1 、A 2 、A 3 and A 4 No more than two of them are N at the same time; and A 5 、A 6 and A 7 No more than one of them is N; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 2 or 3, wherein R 1 H or C 1-6 alkyl.

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

6. The compound according to any one of claims 1 to 5, wherein R 2 C 1-6 Alkyl or trideuterated C 1-6 alkyl.

7. A compound according to any one of claims 1 to 6, wherein R 2 It is methyl, ethyl or trideuterated methyl.

8. A compound according to any one of claims 1 to 7, wherein R 3 for in R 4 For H, Halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, C 3-7 Cycloalkylcarbonyl, haloC 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, hydroxyl C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl 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]nonyl, amino, C 1-6 Alkylcarbonyl, C 1-6 an azetidinyl group substituted with an alkylsulfonyl group or a cyano group, 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 Alkylazetidinyl, hydroxy, morpholinyl or oxetanyl substituted C 1-6 alkyl, Oxetane, Oxooxazolidinyl, or Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group; R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkyloxy, cyano, haloC 1-6 Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times, pyridyl substituted twice with halogen, or halogen-substituted pyrimidinyl; R 6 is H; R 7a C 1-6 alkyl; R 7e It is amino; R 7f C 1-6 alkyl; R 7g H or C 1-6 Alkoxy C 1-6 alkyl.

9. The compound according to any one of claims 1 to 8, wherein R 3 for where R 4 For H, R 4 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, 1.1]heptane-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 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-aza-1 ... heterobicyclo[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, cyclopropyloxy, cyano, difluoromethoxy, fluorine, hydroxyl and trideuteromethoxy, pyridyl substituted twice with fluorine, or fluorine-substituted pyrimidinyl; R 6 is H; R 7a is methyl; R 7e It is amino; R 7f is methyl; R 7g is H or methoxymethyl.

10. The compound according to any one of claims 1 to 8, wherein R 3 for in R 4 For H, Halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, C 3-7 Cycloalkylcarbonyl, haloC 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, hydroxyl C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl 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]nonyl, amino, C 1-6 Alkylcarbonyl, C 1-6 an azetidinyl group substituted with an alkylsulfonyl group or a cyano group, 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 Alkylazetidinyl, hydroxy, morpholinyl or oxetanyl substituted C 1-6 alkyl, Oxetane, Oxooxazolidinyl, or Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group; R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkyloxy, cyano, haloC 1-6 Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times, pyridyl substituted twice with halogen, or halogen-substituted pyrimidinyl; R 6 For H.

11. The compound according to any one of claims 1 to 10, wherein R 3 for in R 4 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, 1.1]heptane-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 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-aza-1 ... heterobicyclo[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, cyclopropyloxy, cyano, difluoromethoxy, fluorine, hydroxyl and trideuteromethoxy, pyridyl substituted twice with fluorine, or fluorine-substituted pyrimidinyl; R 6 For H.

12. A compound according to any one of claims 1 to 11, wherein Q 1 are independently selected from C 1-6 Alkoxy, C 1-6 Alkylcarbonyloxy, hydroxyl, C 1-6 Alkyl and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 Alkylene.

13. A compound according to any one of claims 1 to 12, wherein Q 1 is propylene substituted once or twice with substituents independently selected from ethoxy, methoxy, hydroxy, methyl, acetoxy and trideuteromethoxy.

14. A compound according to any one of claims 1 to 13, wherein Q 1 For C 1-6 Alkoxy-substituted C 1-6 Alkylene.

15. A compound according to any one of claims 1 to 14, wherein Q 1 It is a propylene group substituted by a methoxy group or an ethoxy group.

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

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

18. A compound according to any one of claims 1 to 17, wherein A 3 CR 8 , where R 8 H, C 1-6 Alkoxy, C 1-6 Alkyl, C 3-7 Cycloalkoxy, halogenated C 1-6 Alkoxy or halogen.

19. The compound according to any one of claims 18, wherein A 3 CR 8 , where R 8 is H, methoxy, methyl, cyclopropyloxy, difluoromethoxy or fluorine.

20. A compound according to any one of claims 1 to 19, wherein A 3 CR 8 , where R 8 For H.

21. A compound according to any one of claims 1 to 20, wherein A 4 CR 9 , where R 9 For H.

22. A compound according to any one of claims 1 to 21, wherein A 5 CR 10 or N, where R 10 is H or fluorine.

23. A compound according to any one of claims 1 to 22, wherein A 5 CR 10 , where R 10 For H.

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

25. A compound according to any one of claims 1 to 24, wherein A 6 CR 11 , where R 11 is H or fluorine.

26. A compound according to any one of claims 1 to 25, wherein A 6 CR 11 , where R 11 It is a halogen.

27. A compound according to any one of claims 1 to 26, wherein A 6 CR 11 , where R 11 For fluorine.

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

29. A compound according to any one of claims 1 to 28, wherein A 7 CR 12 , where R 12 is H or fluorine.

30. A compound according to any one of claims 1 to 29, wherein A 7 CR 12 , where R 12 For H.

31. The compound according to claim 2 or 3, wherein R 1 H or C 1-6 alkyl; R 2 C 1-6 Alkyl or trideuterated C 1-6 alkyl; R 3 for in R 4 For H, Halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, C 3-7 Cycloalkylcarbonyl, haloC 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, hydroxyl C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl 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]nonyl, amino, C 1-6 Alkylcarbonyl, C 1-6 an azetidinyl group substituted with an alkylsulfonyl group or a cyano group, 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 Alkylazetidinyl, hydroxy, morpholinyl or oxetanyl substituted C 1-6 alkyl, Oxetane, Oxooxazolidinyl, Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group; R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkyloxy, cyano, haloC 1-6 Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times, pyridyl substituted twice with halogen, or halogen-substituted pyrimidinyl; R 6 is H; R 7a C 1-6 alkyl; R 7e It is amino; R 7f C 1-6 alkyl; R 7g H or C 1-6 Alkoxy C 1-6 alkyl; Q 1 are independently selected from C 1-6 Alkoxy, C 1-6 Alkylcarbonyloxy, hydroxyl, C 1-6 Alkyl and trideuterated C 1-6 The alkoxy substituents replace once or twice the C 1-6 alkylene; Q 2 is NH or O; A 1 is N; A 2 CH, CR 7h or N; where R 7h C 1-6 alkyl; A 3 CR 8 , where R 8 H, C 1-6 Alkoxy, C 1-6 Alkyl, C 3-7 Cycloalkoxy, halogenated C 1-6 Alkoxy or halogen; A 4 CR 9 , where R 9 is H; A 5 CR 10 or N, where R 10 is H or halogen; A 6 CR 11 , where R 11 is H or halogen; A 7 CR 12 , where R 12 is H or halogen; or a pharmaceutically acceptable salt thereof.

32. The compound according to claim 31, wherein R 1 is H or methyl; R 2 is methyl, ethyl or trideuterated methyl; R 3 for in R 4 For H, R 4 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, 1.1]heptane-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 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-aza-1 ... heterobicyclo[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, cyclopropyloxy, cyano, difluoromethoxy, fluorine, hydroxyl and trideuteromethoxy, pyridyl substituted twice with fluorine, or fluorine-substituted pyrimidinyl; R 6 is H; R 7a is methyl; R 7e It 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 trideuteromethoxy; Q 2 is NH or O; A 1 is N; A 2 CH, CR 7h or N; where R 7h is methyl; A 3 CR 8 , where R 8 is H, methoxy, methyl, cyclopropyloxy, difluoromethoxy or fluorine; A 4 CR 9 , where R 9 is H; A 5 CR 10 or N, where R 10 is H or fluorine; A 6 CR 11 , where R 11 is H or fluorine; A 7 CR 12 , where R 12 is H or fluorine; or a pharmaceutically acceptable salt thereof.

33. The compound according to claim 31, wherein R 1 C 1-6 alkyl; R 2 C 1-6 alkyl; R 3 for in R 4 For H, Halogenated C 1-6 alkyl or oxetanyl substituted 2,5-diazabicyclo[2.2.1]heptanyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, C 3-7 Cycloalkylcarbonyl, haloC 1-6 Alkyl, halogenated C 1-6 Alkylcarbonyl, hydroxyl C 1-6 Alkyl, hydroxyl C 1-6 Alkylcarbonyl, hydroxyl 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]nonyl, amino, C 1-6 Alkylcarbonyl, C 1-6 an azetidinyl group substituted with an alkylsulfonyl group or a cyano group, 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 Alkylazetidinyl, hydroxy, morpholinyl or oxetanyl substituted C 1-6 alkyl, Oxetane, Oxooxazolidinyl, Unsubstituted or C 1-6 an alkyl- or hydroxy-substituted oxopyrrolidinyl group; R 5 are independently selected from C 1-6 Alkoxy, C 3-7 Cycloalkyloxy, cyano, haloC 1-6 Alkoxy, halogen, hydroxyl and trideuterated C 1-6 The alkoxy substituent is a phenyl group substituted once, twice or three times, pyridyl substituted twice with halogen, or halogen-substituted pyrimidinyl; R 6 is H; Q 1 For C 1-6 Alkoxy-substituted C 1-6 alkylene; Q 2 is NH or O; A 1 is N; A 2 is CH or N; A 3 CR 8 , where R 8 is H; A 4 CR 9 , where R 9 is H; A 5 CR 10 or N, where R 10 is H; A 6 CR 11 , where R 11 is a halogen; A 7 CR 12 , where R 12 is H; or a pharmaceutically acceptable salt thereof.

34. The compound according to claim 33, wherein R 1 is methyl; R 2 is methyl; R 3 for in R 4 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, 1.1]heptane-6-yl, 3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 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-aza-1 ... heterobicyclo[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, cyclopropyloxy, cyano, difluoromethoxy, fluorine, hydroxyl and trideuteromethoxy, pyridyl substituted twice with fluorine, or fluorine-substituted pyrimidinyl; R 6 is H; Q 1 is a propylene group substituted by a methoxy group or an ethoxy group; Q 2 is NH or O; A 1 is N; A 2 is CH or N; A 3 CR 8 , where R 8 is H; A 4 CR 9 , where R 9 is H; A 5 CR 10 or N, where R 10 is H; A 6 CR 11 , where R 11 For fluorine; A 7 CR 12 , where 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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[14.6.1.1 2,6 .1 8,11 .0 19,23 ]pentacosa-1(22),2,4,6(25),17,19(23),20-hepten-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-10-[1-[2-(cyclopropyloxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-fluoro-10-[1-[4-fluoro-2-(trideuteromethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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-tetraazapentacyclo[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-tetraazapentacyclo[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-tetraazapentacyclo[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-tetraazapentacyclo[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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecene-1(23),2(26),3,5,18,20(24),21-heptadecene-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecene-1(23),2(26),3,5,18,20(24),21-heptadecene-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 ] Hexadecane-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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropyloxy)-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-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 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropyloxy)-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 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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-hepten-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-hepten-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropyloxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-[2-(cyclopropyloxy)-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[17.6.1.1 2,6 .1 8,11 .0 22,26 ]octacosyl-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2,4,6(26),18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2,4,6(26),18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-18,22-dideutero-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[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-hexaazapentacyclo[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-hexaazapentacyclo[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-hexaazapentacyclo[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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2,4,6(26),18,20(24),21-hepten-12-one; 1-(2,4-difluorophenyl)-4-[(8S,11S)-15-methoxy-13,18-dimethyl-12-oxo-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2,4,6(26),18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-10-yl]pyrazolo[3,4-d]pyrimidine-6-carboxylic acid ethyl ester; (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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S)-4-(cyclopropyloxy)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecene-1(23),2(26),3,5,18,20(24),21-heptadecene-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]26-carbon-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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 ] Hexadecane-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-(trideuteromethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-4-fluoro-phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]-hexacosyl-1(23),2,4,6(26),18,20(24),21-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[17.6.1.1 2,6 .1 8,11 .0 22,26 ]octacosyl-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazahexacyclo[18.6.1.1 2,9 .1 11,14 .0 3,7 .0 23 ,27 ]Nicosanoid-1(26),2(29),3(7),8,21,23(27),24-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecene-1(24),2(26),3,5,18,20,22-heptadecene-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-12-oxo-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Methyl hexadecene-1(23),2(26),3,5,18,20(24),21-heptadecene-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexacosyl-1(23),2(26),3,5,18,20(24),21-heptaene-18-carboxamide; (8S,11S,15R)-10-[1-[2-(cyclopropyloxy)-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-piperidinyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-5-yl)propyl]-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl)propyl]-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro-2-(3-methoxycyclobutyloxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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)cyclopropyloxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[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-pyridinyl)-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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]heptane-6-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-piperidinyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-10-[1-(3,5-difluoro-2-pyridinyl)-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexahydropyrrolizin-8-yl]methoxy]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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]heptane-6-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosyl-1(23),2(26),3,5,18,20(24),21-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(4-oxazol-5-yl-1-piperidinyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-(trideuteromethoxy)phenyl]-6-[3-oxa-6-azabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[(1,1-dioxothietane-3-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azetidin-1-yl]acetonitrile; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-(1,1-dioxothianilan-4-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[(1,1-dioxothietane-3-yl)methylsulfanyl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-[4-fluoro-2-(trideuteromethoxy)phenyl]-6-(3-oxa-6-azabicyclo[3.1.1]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-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]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20 ,24 ] Hexadecane-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]heptane-5-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8, 11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-(oxetane-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2 ,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[6-[(1S,5S)-3-cyclopropyl-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8 ,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6-oxa-3-azabicyclo[3.1.1]heptane-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-3-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-[(3-fluorooxetan-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-[(3-fluorooxetane-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-hydroxy-6-(trifluoromethyl)-2-azaspiro[3.3]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-(3-oxa-6-azabicyclo[3.1.1]heptane-6-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[6-[3-(2,2-difluoroacetyl)-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-hydroxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2(26),3,5,18,20,22-hepten-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]propionitrile; (8S,11S,15R)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2,2,2-trifluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15S)-10-[6-[(1R,4R)-5-(2,2-difluoroethyl)-2,5-diazabicyclo[2.2.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[(1R,4R)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[11-benzyl-3-(2,4-difluorophenyl)-3,4,8,11-tetraazatricyclo[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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-tetraazatricyclo[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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15S)-10-[6-[3-(2,2-difluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15S)-10-[1-(2,4-difluorophenyl)-6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(23),2(26),3,5,18,20(24),21-hepten-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (8S,11S,15R)-22-Fluoro-10-[1-(4-fluoro-2-hydroxyphenyl)-6-[3-(oxetan-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[6-(oxetan-3-yl)-1,6-diazaspiro[3.3]heptane-1-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(6,6-dioxo-6λ 6 -thia-1-azaspiro[3.3]heptane-1-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[3-(2,4-difluorophenyl)-11-(oxetane-3-yl)-3,4,8,11-tetraazatricyclo[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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15S)-22-Fluoro-10-[1-(4-fluoro-2-hydroxy-phenyl)-6-[3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-2-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-(oxetane-3-yl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,17,19,26-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2, 6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-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-heptaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ]hexacosa-1(24),2,4,6(26),18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2,4,6(26),18,20,22-hepten-12-one; (8S,11S,15S)-22-Fluoro-10-[6-[3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]-1-(4-fluoro-2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-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]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(2-hydroxy-2-methyl-propionyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxycyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(1-hydroxycyclobutanecarbonyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; (8S,11S,15R)-10-[6-[3-(cyclopropanecarbonyl)-3,6-diazabicyclo[3.1.1]heptane-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-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexacosyl-1(24),2(26),3,5,18,20,22-hepten-12-one; and (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-[3-(3-fluorocyclobutyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-22-fluoro-15-methoxy-13,18-dimethyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1 2,6 .1 8,11 .0 20,24 ] Hexadecane-1(24),2(26),3,5,18,20,22-hepten-12-one; or a pharmaceutically acceptable salt thereof.

36. A method for preparing a compound according to any one of claims 1 to 35, comprising any one of the following steps: a) in the presence of a base, via a compound of formula (VIII), With R 3 Nucleophilic substitution between X forms a compound of formula (I), b) in the presence of a catalyst, reacting a compound of formula (VIII) with R 3 Buchwald-Hartwig reaction between X to form a compound of formula (I); c) in the presence of a coupling reagent, via the compound of formula (VIII) and R 3 The condensation reaction between OH forms a compound of formula (I); d) via a compound of formula (XVIII), A cyclization reaction with a reagent to form a compound of formula (I); e) in the presence of a base via a compound of formula (XX), With R 3 Nucleophilic substitution between X forms a compound of formula (XXI), f) in the presence of a base, via a compound of formula (Ic), With alcohols or amines (R 4 -X) to form a compound of formula (XXII), g) a compound of formula (XXIV), The amino group of is reacted with a halide via nucleophilic substitution or with a ketone via reductive amination to provide the final compound of formula (XXII); in In steps a) and e), the base is DIEA; In step b), the catalyst is Pd2(dba)3; In step c), the coupling reagent is HATU; In step d), the reagent is CDI, BrCN or R 1 (OCH3)3; In step e), the base is DIEA; In step f), the base is DIPEA, K2CO3 or NaH; X is halogen; R 13 R a 、R b or R c ; M is C 1-6 Alkylene; R e is a substituent having a primary amino group or a secondary amino group; R 1 to R 7 , Q 1 , Q 2 、A 1 To A 7 As defined in any one of claims 1 to 34.

37. A compound or pharmaceutically acceptable salt according to any one of claims 1 to 35 for use as 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 autoimmune diseases, inflammatory diseases, neurological disorders, metabolic diseases, cardiovascular diseases, eye diseases or selected cancer types in which overexpression or activation of STING is implicated.

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

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

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

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

44. A method for treating or preventing an autoimmune disease, said method comprising administering a therapeutically effective amount of a compound as defined in any one of claims 1 to 35.

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