Macrocycles for the treatment of autoimmune disease

Abstract

The present invention relates to compounds of formula (I) wherein Q1 to Q4 and M1 to M3 are as described herein, and pharmaceutically acceptable salts thereof; as well as compositions comprising the compounds and methods of using the compounds. (I)

Claims

1. A compound of formula (I), (I)， in M 1 It is an arylene, a heterocyclic, or a heteroarylene, each of which is optionally oxidized by R 1 Replace; among them R 1 For deuterated, halogenated, cyano, carboxyl, NO2, 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 optional location R b Or R c Replacement C 1-6 alkyl; R b C 3-7 Cycloalkyl, heterocyclic, heteroaryl, or aryl, wherein the C 3-7 Cycloalkyl, heterocyclic, heteroaryl, and aryl groups are unsubstituted or optionally deuterated, halogenated, or R-substituted. c replace; R c Selected from deuterium, 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, halogenated C 2-6 Alkyne group, deuterated C 2-6 alkynyl group, 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 Alkyl carbonyl amino, halogenated C 1-6 Alkylamino, halogenated C 1-6 Alkyl carbonyl amino, (halogenated C) 1-6 alkyl)2amino, C 3-7 Cycloalkylamino, C 3-7 Cycloalkylcarbonylamino, (C 3-7 Cycloalkyl)2-amino, halogenated C 3-7 Cycloalkylamino, (halogenated C) 3-7 cycloalkyl)2-amino, C 3-7 cycloalkyl (C 1-6 Alkyl)amino, halogenated C 3-7 cycloalkyl (C 1-6 Alkyl)amino, C 1-6 Alkylsulfonylamino, halogenated 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 halocarbon 1-6 Alkyl, C 1-6 Alkyl carbonyl, halogenated C 1-6 alkyl carbonyl, C 3-7 Cycloalkyl carbonyl, halogenated C 3-7 cycloalkyl carbonyl, C 1-6 alkoxy carbonyl, halogenated C 1-6 alkoxycarbonyl, C 3-7 Cycloalkoxycarbonyl, halogenated C 3-7 Cycloalkoxycarbonyl, C 1-6 Alkylaminocarbonyl, (C 1-6 alkyl)2-aminocarbonyl, C 3-7 Cycloalkylaminocarbonyl, (C 3-7 Cycloalkyl)2-aminocarbonyl, C 1-6 Alkyl C 3-7 Cycloalkylaminocarbonyl, halogenated C 1-6 Alkylaminocarbonyl, halogenated (C 1-6 alkyl)2-aminocarbonyl, halogenated C 3-7 Cycloalkylaminocarbonyl, halogenated (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)3-ammonium group, C 1-6 Alkyl thio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, C 3-7 cycloalkylthio, C 3-7 Cycloalkylsulfinyl, C 3-7 Cycloalkylsulfonyl, halogenated C 1-6 Alkyl thio, halogenated C 1-6 Alkyl sulfinyl, halogenated C 1-6 Alkyl sulfonyl, halogenated C 3-7 cycloalkylthio, halogenated C 3-7 Cycloalkyl sulfinyl, halogenated C 3-7 Cycloalkylsulfonyl, halogenated 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)2 phosphoryl, (C 1-6 Alkoxy)2 phosphoryl group, hydroxyl group (C 1-6 Alkoxy)phosphoryl, C 1-6 Alkoxyphosphoryl group, hydroxyl group, hydroxyl C 1-6 Alkyl, hydroxyl halide C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy, hydroxyl halide C 1-6 Alkoxy, hydroxy C 3-7 Cycloalkyl, hydroxyhalogenated C 3-7 Cycloalkyl and imine sulfonyl groups, each of which is optionally oxidized by H, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy, aryl, heteroaryl, or heterocyclic substitutions; M 2 C 2-6 alkenyl, arylene, heterocyclic, heteroarylene, C 3-7 Cycloalkylene, halogenated C 3-7 Cycloalkyl, cycloalkylene, bicycloalkylene[1.1.1]pentyl or adamantylene, each of which is optionally R-treated. 1 replace; M 3 For R 2 Replace and optionally via R 1 Substituted heterocyclic group; wherein R 2 It is a heterocyclic group, a heteroaryl group, an aryl group, a heterocyclic carbonyl group, a heteroaryl carbonyl group, or an aryl carbonyl group, each of which is optionally R-treated. b replace; Q 1 for , -W-, -WOW-, -WSW-, -W-SO2-W-, -W-SO(NR)-W-, -W-SiR2-W-, -C 1-6 Alkylene-WC 1-6 Alkylene-, -W-CONH-W-, -W-CON(R)-W-, -WN(R)CO-W-, or -WN(R)-W-; wherein each W is independently selected from CONH, carbonyl, SO2, SO(NR), P(O)R, PO(NR), Se, N(R), SiR2, C 1-6 Alkylene, -C 1-6 Alkylene -O-, -C 1-6 Alkylene-S-, C 3-7 Cycloalkylene, arylene, heteroarylene, and heterocyclic groups, each of which is unsubstituted or optionally independently selected from deuterated, halogenated, 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; Q 2 For key, C 1-6 Alkylene, O, S, SO, SO2, SO(NR), P(O)R, PO(NR), Se, N(R) or SiR2; Q 3 C 1-6 Alkylene, O, S, SO, SO2, SO(NR), P(O)R, PO(NR), Se, N(R), SiR2, optionally substituted heterocyclic group, optionally substituted heteroaryl group or optionally substituted aryl group; Q 4 For bonds, N(R), carbonyl, -CONR-, SO2, SO(NR), P(O)R, PO(NR), Se, N(R), SiR2, optionally substituted heterocyclic group, optionally substituted heteroaryl group or optionally substituted aryl group; Or its pharmaceutically acceptable salt.

2. The compound according to claim 1, wherein M 1 It is an arylene, a heterocyclic, or a heteroarylene, each of which is subjected to R 1 Replace once, twice, or three times; where R 1 Independently selected from H, deuterated, halogenated, cyano, NO2, C 1-6 Alkyl, Halogenated C 1-6 Alkyl and C 1-6 Alkylaminocarbonyl.

3. The compound according to claim 1 or 2, wherein... M 1 It is [1,2,4]triazolo[4,3-a]pyridyl. 1H-pyrazolo[3,4-b]pyridyl, 2,3-Dihydropyrrolo[3,2-b]pyridyl, 2-oxo-1,3-benzothiazolyl, 2-oxo-1,4-dihydro-3,1-benzoxazinyl, Unsubstituted or halogenated 2-oxo-3H-benzimidazole group, 2-Oxoindololinyl, Unsubstituted or independently selected from halogens and C 1-6 The alkyl substituent replaces the 2-oxopyridyl group twice. 5,6,7,8-Tetrahydro-[1,2,4]triazolo[4,3-a]pyridyl, via C 1-6 Alkyl-substituted 5,6-dihydropyrrolo[3,2-c]pyrazolyl, via C 1-6 Alkyl-substituted 5-oxo-1,2,4-triazolyl, 5-oxo-2,3-dihydro-1H-indazine, Unsubstituted or independently selected from halogens and C 1-6 The alkyl substituent replaces the benzimidazole group once or twice. Benzotriazole, Imidazolo[1,2-a]pyridyl, via C 1-6 Alkyl-substituted imidazolyl, Unsubstituted or halogenated or C 1-6 Alkyl-substituted indazole group, Indolyl group Isoindoline group. Unsubstituted or cyano-, NO2-, C 1-6 Alkyl, Halogenated C 1-6 Alkyl and C 1-6 Alkylaminocarbonyl-substituted phenylene, pyrazolo[1,5-a]pyridyl, via C 1-6 Alkyl-substituted pyrazolyl group, pyridyl group, via C 1-6 Alkyl-substituted pyridine[2,3-b]pyridyl, Unsubstituted or halogenated pyrrolo[3,2-c]pyridyl, or Isothiazole group.

4. The compound according to any one of claims 1 to 3, wherein... M 1 For being independently selected from halogens and C 1-6 The alkyl substituent replaces the benzimidazole group once or twice. Benzotriazole, Unreplaced or C 1-6 Alkyl-substituted indazole group, or via C 1-6 Alkyl-substituted pyridine[2,3-b]pyridyl.

5. The compound according to any one of claims 1 to 4, wherein... M 1 The benzimidazole group is substituted once or twice with substituents independently selected from fluorine and methyl. Benzotriazole, Unsubstituted or methyl-substituted indazole group, or Methyl-substituted pyridine[2,3-b]pyridyl.

6. The compound according to any one of claims 1 to 5, wherein M 2 C 2-6 Alkenyl, phenylene, pyridyl, pyrimidinyl, or thiazolyl.

7. The compound according to any one of claims 1 to 6, wherein M 2 It is phenylene, pyridinyl, pyrimidinyl, or thiazolyl.

8. The compound according to any one of claims 1 to 7, Where M 3 For R 2 Replacement or via R 2 and C 1-6 Alkyl-substituted twice pyridine alkyl; Where R 2 for , , , , , or ;in R 3 C 1-6 alkyl; R 4 It is phenyl or phenyl C 1-6 Alkyl groups, each of which is independently selected from halogens and C. 1-6 The alkoxy group is substituted once or twice; R 5 For H, Oxycyclic butyl, C 1-6 Alkoxy C 1-6 alkyl, Cyano or cyano C 1-6 Alkyl-substituted nitrogen-containing heterocyclic butyl groups, or via C 1-6 Alkyl, Halogenated C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 Alkyl-substituted 3,6-diazabicyclo[3.1.1]heptyl.

9. The compound according to any one of claims 1 to 8, Where M 3 For R 2 Replacement or via R 2 and C 1-6 Alkyl-substituted twice pyridine alkyl; Where R 2 for , or ; in R 4 It is a phenyl group that has undergone two halogen substitutions; R 5 For H, Oxycyclic butyl, C 1-6 Alkoxy C 1-6 alkyl, Cyano or cyano C 1-6 Alkyl-substituted nitrogen-containing heterocyclic butyl groups, or via C 1-6 Alkyl, Halogenated C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 Alkyl-substituted 3,6-diazabicyclo[3.1.1]heptyl.

10. The compound according to any one of claims 1 to 9, Where M 3 For R 2 Replacement or via R 2 And pyridine alkyl groups that are substituted twice with methyl groups; Where R 2 for , or ; in R 4 It is 2,4-difluorophenyl; R 5 It is H, 2-(cyanomethyl)azacyclobutane-1-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-cyanoazacyclobutane-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptane-6-yl, methoxymethyl, or oxacyclobutane-3-yl.

11. The compound according to any one of claims 1 to 9, wherein Q 1 for ,in L 1 For key, C 1-6 Alkylene, hydroxyl C 1-6 Alkylene or (C 1-6 Alkoxy)C 1-6 Alkylene; L 2 For key, (C 1-6 Alkyl)piperazinyl, 3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxazinyl, carbonyl, halopyrrolidinyl, morpholinyl, NR 6 , O, oxypyrrolidinyl or piperazineyl; wherein R 6 For H, (C 1-6 alkyl)2-aminocarbonyl C 1-6 Alkyl, amino carbonyl C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Alkylaminocarbonyl, C 1-6 Alkylaminocarbonyl C 1-6 Alkyl, C 1-6 Alkyl carbonyl, carboxyl C 1-6 Alkyl, imidazole carbonyl, morpholinyl carbonyl C 1-6 Alkyl, phenyl C 1-6 alkyl carbonyl, piperazine carbonyl C 1-6 Alkyl, pyrazolyl C 1-6 alkyl carbonyl, pyridyl C 1-6 alkyl carbonyl or pyrimidinyl; L 3 For bond, NH, carbonyl, pyridine alkyl, CONH or (C 1-6 alkyl)amino; L 4 For key, (C 1-6 alkoxycarbonyl)C 1-6 Alkylene, (C 1-6 (alkylimidazolium)C 1-6 Alkylene, (C 1-6 (alkylpiperazinylcarbonyl)C 1-6 Alkylene, (phenyl C) 1-6 (alkylaminocarbonyl)C 1-6 alkylene, (pyridylpiperazinylcarbonyl)C 1-6 Alkylene, C 1-6 Alkylene, C 1-6 alkylidenepiperazine group C 1-6 Alkylene or C 2-6 alkenyl; L 5 For bond, O, NR 7 Or unsubstituted or via phenyl C 1-6 Alkyl or phenyl C 1-6 Alkoxycarbonyl-substituted piperazine group; wherein R 7 H, (carboxymorpholino)C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl, morpholino C 1-6 Alkyl, phenyl C 1-6 Alkyl or thiazolyl C 1-6 alkyl; The condition is L 1 L 2 L 3 L 4 and L 5 They are not keys at the same time.

12. The compound according to any one of claims 1 to 11, wherein Q 1 for ,in L 1 For key, C 1-6 Alkylene or (C 1-6 Alkoxy)C 1-6 Alkylene; L 2 It is a bond, carbonyl, NH, imiderinyl or halopyrroleyl group; L 3 For bond, carbonyl, NH, CONH or (C 1-6 alkyl)amino; L 4 For key, (C 1-6 alkoxycarbonyl)C 1-6 Alkylene, (phenyl C) 1-6 (alkylaminocarbonyl)C 1-6 Alkylene or C 1-6 Alkylene; L 5 For bond, O, NR 7 Or via phenyl C 1-6 Alkyl or phenyl C 1-6 Alkoxycarbonyl-substituted piperazine group; wherein R 7 For H, C 1-6 Alkyl or phenyl C 1-6 alkyl; The condition is L 1 L 2 L 3 L 4 and L 5 They are not keys at the same time.

13. The compound according to any one of claims 1 to 12, wherein Q 1 for ,in L 1 For bonds, (ethoxy)ethylidene, (methoxy)ethylidene, ethylidene, methylene, or propylidene; L 2 The group is a bond, carbonyl, NH, morpholino, or difluoropyrroleyl; L 3 For bonds, carbonyl, NH, CONH or (methyl)amino; L 4 For bonds, (benzylaminocarbonyl)ethylene, (methoxycarbonyl)ethylene, ethylene, methylene or propylene; L 5 For bond, O, NR 7 Or a piperazine group substituted with benzyl or benzyloxycarbonyl; wherein R 7 It can be H, methyl, benzyl, or phenylpropyl; The condition is L 1 L 2 L 3 L 4 and L 5 They are not keys at the same time.

14. The compound according to any one of claims 1 to 13, wherein Q 2 For bond, O, NH or (C 1-6 Alkyl)amino.

15. The compound according to any one of claims 1 to 14, wherein Q 2 For key.

16. The compound according to any one of claims 1 to 15, wherein Q 3 It can be O or NH.

17. The compound according to any one of claims 1 to 16, wherein Q 4 It is a bond, carbonyl or tetrazolium group.

18. The compound according to any one of claims 1 to 17, wherein Q 4 It is a carbonyl or tetrazolium group.

19. The compound according to any one of claims 1 to 18, wherein M 1 For being independently selected from halogens and C 1-6 The alkyl substituent replaces the benzimidazole group once or twice. Benzotriazole, Unreplaced or C 1-6 Alkyl-substituted indazole group, or via C 1-6 Alkyl-substituted pyridine[2,3-b]pyridyl; M 2 It is phenylene, pyridinyl, pyrimidinyl, or thiazolyl; M 3 For R 2 Replacement or via R 2 and C 1-6 Alkyl-substituted twice pyridine alkyl; Where R 2 for , or ; in R 4 It is a phenyl group that has undergone two halogen substitutions; R 5 For H, Oxycyclic butyl, C 1-6 Alkoxy C 1-6 alkyl, Cyano or cyano C 1-6 Alkyl-substituted nitrogen-containing heterocyclic butyl groups, or via C 1-6 Alkyl, Halogenated C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 Alkyl-substituted 3,6-diazabicyclo[3.1.1]heptyl; Q 1 for ,in L 1 For key, C 1-6 Alkylene or (C 1-6 Alkoxy)C 1-6 Alkylene; L 2 It is a bond, carbonyl, NH, imiderinyl or halopyrroleyl group; L 3 For bond, carbonyl, NH, CONH or (C 1-6 alkyl)amino; L 4 For key, (C 1-6 alkoxycarbonyl)C 1-6 Alkylene, (phenyl C) 1-6 (alkylaminocarbonyl)C 1-6 Alkylene or C 1-6 Alkylene; L 5 For bond, O, NR 7 Or via phenyl C 1-6 Alkyl or phenyl C 1-6 Alkoxycarbonyl-substituted piperazine group; wherein R 7 For H, C 1-6 Alkyl or phenyl C 1-6 alkyl; The condition is L 1 L 2 L 3 L 4 and L 5 Not both are keys; Q 2 For key; Q 3 For O or NH; Q 4 It is a carbonyl or tetrazolium group; Or its pharmaceutically acceptable salt.

20. The compound according to any one of claims 1 to 19, wherein... M 1 The benzimidazole group is substituted once or twice with substituents independently selected from fluorine and methyl. Benzotriazole, Unsubstituted or methyl-substituted indazole group, or Methyl-substituted pyridine[2,3-b]pyridyl; M 2 It is phenylene, pyridinyl, pyrimidinyl, or thiazolyl; M 3 For R 2 Replacement or via R 2 And pyridine alkyl groups that are substituted twice with methyl groups; Where R 2 for , or ; in R 4 It is 2,4-difluorophenyl; R 5 The derivatives are H, 2-(cyanomethyl)azacyclobutane-1-yl, 3-(2-fluoroethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-(2-methoxyethyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl, 3-cyanoazacyclobutane-1-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptane-6-yl, methoxymethyl, or oxacyclobutane-3-yl; Q 1 for ,in L 1 For bonds, (ethoxy)ethylidene, (methoxy)ethylidene, ethylidene, methylene, or propylidene; L 2 The group is a bond, carbonyl, NH, morpholino, or difluoropyrroleyl; L 3 For bonds, carbonyl, NH, CONH or (methyl)amino; L 4 For bonds, (benzylaminocarbonyl)ethylene, (methoxycarbonyl)ethylene, ethylene, methylene or propylene; L 5 For bond, O, NR 7 Or a piperazine group substituted with benzyl or benzyloxycarbonyl; wherein R 7 It can be H, methyl, benzyl, or phenylpropyl; The condition is L 1 L 2 L 3 L 4 and L 5 Not both are keys; Q 2 For key; Q 3 For O or NH; Q 4 It is a carbonyl or tetrazolium group; Or its pharmaceutically acceptable salt.

21. A compound selected from: (16S,19S)-17-[2-(2,4-difluorophenyl)-3-methyl-imidazol-4-carbonyl]-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] (16S,19S)-17-[2-(2,4-difluorophenyl)-3-methyl-imidazol-4-carbonyl]-14-(2-methoxyethyl)-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] (16S,19S)-17-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-14-methyl-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] (18S,21S)-19-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-22-oxa-9,12,16,19,29-pentazapentacyclo[21.3.1.1] 6,9 .1 18,21 .0 2,7 ] 29-carbon-1(27),2,4,6(29),7,23,25-heptaene-11,17-dione; (15S,22S,25S)-17-benzyl-23-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-26-oxa-9,13,17,20,23,33-hexaazahexane[25.3.1.1] 6,9 .1 22,25 .0 2,7 .0 15,20 [Trin-1(30),2,4,6(33),7,27(31),28-heptaene-14,21-dione;] (16S,23S,26S)-18-benzyl-24-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-27-oxa-9,14,18,21,24,34-hexaazahexane[26.3.1.1] 6,9 .1 23,26 .0 2,7 .0 16,21 [34-carbocarbon-1(32),2,4,6(34),7,28,30-heptaene-15,22-dione;] (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-21-oxa-9,15,18,28-tetraazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] (18S,21S)-19-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-22-oxa-9,16,19,29-tetraazapentacyclo[21.3.1.1] 6,9 .1 18,21 .0 2,7 ] 29-carbon-1(27),2,4,6(29),7,23,25-heptaen-17-one; (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-21-oxa-9,12,15,18,28-pentaazapentane[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaene-11,16-dione;] (18S,21S)-19-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-22-oxa-9,12,16,19,30-pentaazahexacyclo[21.3.1.1] 6,9 .1 12,15 .1 18,21 .0 2,7 [Tridecano-1(27),2,4,6(30),7,23,25-heptaene-11,17-dione;] (18S,21S)-20-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-17-oxa-1,4,20,23,26,33-hexaazahexane[24.2.2.1] 4,7 .1 12,16 .1 18,21 .0 6,11 [Trin-5,7(33),8,10,12(32),13,15-heptaen-22-one;] (15S,22S,25S)-23-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-14,21-dioxo-26-oxa-9,13,17,20,23,33-hexaazahexacyclic[25.3.1.1] 6,9 .1 22,25 .0 2,7 .0 15,20 ] Tridecano-1(30),2,4,6(33),7,27(31),28-heptaene-17-carboxylic acid benzyl ester; (15S,22S,25S)-23-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-26-oxa-9,13,17,20,23,33-hexaazahexacyclic[25.3.1.1] 6,9 .1 22,25 .0 2,7 .0 15,20 [Trin-1(30),2,4,6(33),7,27(31),28-heptaene-14,21-dione;] (11E,16S,19S)-17-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [27-octadec-1(25),2,4,6(27),7,11,21,23-octaen-15-one;] (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-12,21-dioxa-9,15,18,28-tetraazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] (15S,18S)-16-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-19-oxa-9,13,16,26-tetraazapentacyclo[18.3.1.1] 6,9 .1 15,18 .0 2,7 ] Twenty-hexacarbon-1(24),2,4,6(26),7,20,22-heptaen-14-one; (19S,22S)-20-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-23-oxa-9,17,20,30-tetraazapentacyclo[22.3.1.1] 6,9 .1 19,22 .0 2,7 [Tridecano-1(28),2,4,6(30),7,24,26-heptaen-18-one;] (11S,16S,19S)-17-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-11-hydroxy-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] (11R,16S,19S)-17-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-11-hydroxy-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-21-oxa-9,12,15,18,28-pentaazapentane[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-12-methyl-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] (17S,20S)-12-acetyl-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-12-(2-morpholino-2-oxo-ethyl)-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] 2-[(17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-16-oxo-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecacarbon-1(26),2,4,6(28),7,22,24-heptaen-12-yl]-N-methylacetamide; (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-12-(2-oxo-2-piperazin-1-yl-ethyl)-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] 2-[(17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-16-oxo-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-12-yl]acetamide; (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-12-(2-pyrazole-1-ylacetyl)-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] 2-[(17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-16-oxo-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-12-yl]acetic acid; (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-12-(2-phenylacetyl)-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] (17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-12-(3-phenylpropionyl)-21-oxa-9,12,15,18,28-pentaazapentane[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-16-one;] (16S,19S)-17-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-14-methyl-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] 2-[(17S,20S)-18-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-16-oxo-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaen-12-yl]-N,N-dimethylacetamide; (18S,21S)-20-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-17-oxa-1,4,20,23,27,34-hexaazahexane[25.2.2.1] 4,7 .1 12,16 .1 18,21 .0 6,11 [34-carbocarbon-5,7(34),8,10,12(33),13,15-heptaene-22,26-dione;] (18S,21S)-20-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-17-oxa-1,4,20,23,26,33-hexaazahexane[24.2.2.1] 4,7 .1 12,16 .1 18,21 .0 6,11 [Trin-5,7(33),8,10,12(32),13,15-heptaene-22,25-dione;] (18S,21S)-19-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-22-oxa-9,12,16,19,29-pentazapentacyclo[21.3.1.1] 6,9 .1 18,21 .0 2,7 ] 29-carbon-1(27),2,4,6(29),7,23,25-heptaene-13,17-dione; (17S,20S)-18-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-oxa-9,12,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 [Octadecano-1(26),2,4,6(28),7,22,24-heptaene-13,16-dione;] (18S,21S)-20-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-17-oxa-1,4,20,23,26,33-hexaazahexacyclic[24.2.2.1] 4,7 .1 12,16 .1 18,21 .0 6,11 [Trin-5,7(33),8,10,12(32),13,15-heptaen-22-one;] (16S,19S)-17-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-20-oxa-9,14,17,22,27-pentazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] (17S,25S,28S)-26-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-15,29-dioxa-9,12,19,23,26,36-hexaazahexacyclic[28.3.1.1] 6,9 .1 25,28 .0 2,7 .0 12,17 ] 36-carbon-1(33),2,4,6(36),7,30(34),31-heptaene-18,24-dione; (17R,25S,28S)-26-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-15,29-dioxa-9,12,19,23,26,36-hexaazahexacyclic[28.3.1.1] 6,9 .1 25,28 .0 2,7 .0 12,17 ] 36-carbon-1(33),2,4,6(36),7,30(34),31-heptaene-18,24-dione; (6S,9S)-7-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-10,29-dioxa-1,4,7,23,26,33,36,41-octaazaheptacyclo[34.2.2.1] 6,9 .1 11,15 .1 20,23 .0 16,21 .0 26,31 [Forty-three carbon-11(42),12,14,16,18,20(41),21-heptaene-5,32-dione;] (23S,26S)-24-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15,27-dioxa-9,12,18,21,24,35-hexaazahexane[26.3.1.1] 6,9 .1 12,16 .1 23,26 .0 2,7 [35-C-1(31),2,4,6(35),7,28(32),29-Heptadene-17,22-Dietone;] (24S,27S)-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15,28-dioxa-9,12,18,22,25,36-hexaazahexane[27.3.1.1] 6,9 .1 12,16 .1 24,27 .0 2,7 ] 36-carbon-1(32),2,4,6(36),7,29(33),30-heptaene-17,23-dione; (24S,27S)-25-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-15,28-dioxa-9,12,19,22,25,35-hexaazahexane[27.3.1.1] 6,9 .1 24,27 .0 2,7 .0 12,17 [35-carbocarbon-1(32),2,4,6(35),7,29(33),30-heptaene-18,23-dione;] (21S,24S,27S)-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18,23-dioxo-15,28-dioxa-9,12,19,22,25,35-hexaazahexacyclic[27.3.1.1] 6,9 .1 24,27 .0 2,7 .0 12,17 Methyl heptadecyl-1(32),2,4,6(35),7,29(33),30-heptadecyl-21-carboxylate; (20S,24S,27S)-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18,23-dioxo-15,28-dioxa-9,12,19,22,25,35-hexaazahexacyclic[27.3.1.1] 6,9 .1 24,27 .0 2,7 .0 12,17 Methyl 35-carbon-1(32),2,4,6(35),7,29(33),30-heptaene-20-carboxylic acid; (16R,23S,26S)-24-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-14,14-difluoro-27-oxa-9,12,18,21,24,34-hexaazahexacyclic[26.3.1.1] 6,9 .1 23,26 .0 2,7 .0 12,16 [34-carbocarbon-1(31),2,4,6(34),7,28(32),29-heptaene-17,22-dione;] (16R,24S,27S)-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-14,14-difluoro-28-oxa-9,12,18,22,25,35-hexaazahexane[27.3.1.1] 6,9 .1 24,27 .0 2,7 .0 12,16 [35-carbocarbon-1(32),2,4,6(35),7,29(33),30-heptaene-17,23-dione;] (25S,28S)-26-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methyl-29-oxa-9,12,15,19,23,26,36-heptaazahexacyclo[28.3.1.1] 6,9 .1 25,28 .0 2,7 .0 12,17 ] 36-carbon-1(33),2,4,6(36),7,30(34),31-heptaene-18,24-dione; (17S,21S,24S,27S)-N-benzyl-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18,23-dioxo-15,28-dioxa-9,12,19,22,25,35-hexaazahexacyclic[27.3.1.1] 6,9 .1 24,27 .0 2,7 .0 12,17 ]35-carbon-1(32),2,4,6(35),7,29(33),30-heptaene-21-carboxamide; (17R,21S,24S,27S)-N-benzyl-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18,23-dioxo-15,28-dioxa-9,12,19,22,25,35-hexaazahexacyclic[27.3.1.1] 6,9 .1 24,27 .0 2,7 .0 12,17 ]35-carbon-1(32),2,4,6(35),7,29(33),30-heptaene-21-carboxamide; (17S,20R,24S,27S)-N-benzyl-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18,23-dioxo-15,28-dioxa-9,12,19,22,25,35-hexaazahexacyclic[27.3.1.1] 6,9 .1 24,27 .0 2,7 .0 12,17 ]35-carbon-1(32),2,4,6(35),7,29(33),30-heptaene-20-carboxamide; (17R,20R,24S,27S)-N-benzyl-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18,23-dioxo-15,28-dioxa-9,12,19,22,25,35-hexaazahexacyclic[27.3.1.1] 6,9 .1 24,27 .0 2,7 .0 12,17 ]35-carbon-1(32),2,4,6(35),7,29(33),30-heptaene-21-carboxamide; (17S,21S,24S,27S)-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-(4-methylpiperazin-1-carbonyl)-15,28-dioxa-9,12,19,22,25,35-hexaazahexane[27.3.1.1] 6,9 .1 24,27 .0 2,7 .0 12 ,17 [35-carbocarbon-1(32),2,4,6(35),7,29(33),30-heptaene-18,23-dione;] (17S,25S,28S)-26-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-8-methyl-15-oxa-8,12,19,23,26,29,33,34,36-nonazahexacyclo[28.3.1.1] 6,9 .1 25,28 .0 2,7 .0 12,17 ]36-carbon-1(33),2,4,6,9(36),30(34),31-heptaene-18,24-dione; (16R,17S,21S,24S,27S)-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-[(3-methylimidazol-4-yl)methyl]-15,28-dioxa-9,12,19,22,25,36-hexaazaheptacyclo[27.3.1.1] 6,9 .1 16, 19 .1 24,27 .0 2,7 .0 12,17 ] 36-carbon-1(32),2,4,6(36),7,29(33),30-heptaene-20,23-dione; (17S,21S,24S,27S)-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-[4-(2-pyridyl)piperazine-1-carbonyl]-15-oxa-9,12,19,22,25,28,32,33,35-nonazahexacyclo[27.3.1.1] 6,9 .1 24 ,27 .0 2,7 .0 12,17 [35-carbocarbon-1(32),2,4,6(35),7,29(33),30-heptaene-18,23-dione;] (17S,21S,24S,27S)-25-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-[4-(2-pyridyl)piperazine-1-carbonyl]-15-oxa-9,12,19,22,25,28,32,33,35-nonazahexacyclo[27.3.1.1] 6,9 .1 24 ,27 .0 2,7 .0 12,17 [35-carbocarbon-1(32),2,4,6(35),7,29(33),30-heptaene-18,23-dione;] (17S,25S,28S)-26-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-8-methyl-15,29-dioxa-8,12,19,23,26,36-hexaazahexane[28.3.1.1] 6,9 .1 25,28 .0 2,7 .0 12,17 ]36-carbon-1(33),2,4,6,9(36),30(34),31-heptaene-18,24-dione; (17S,25S,28S)-26-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-oxa-9,12,19,23,26,29,33,34,36-nonazahexacyclo[28.3.1.1] 6,9 .1 25,28 .0 2,7 .0 12,17 ] 36-carbon-1(33),2,4,6(36),7,30(34),31-heptaene-18,24-dione; (18S,21S)-19-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-11-methyl-22-oxa-11,16,19,29-tetraazapentacyclo[21.3.1.1] 6,9 .1 18,21 .0 2,7 ] 29-carbon-1(26),2(7),3,5,8,23(27),24-heptaene-10,17-dione; (17S,20S)-18-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-21-oxa-6,10,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 ] 28-octadec-1(25),2,4,7,9(28),22(26),23-heptaen-16-one; (15S,18S)-16-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-9,13,16,19,24,26-hexaazapentacyclo[18.3.1.1] 6,9 .1 15,18 .0 2,7 ] Twenty-hexacarbon-1(24),2,4,6(26),7,20,22-heptaen-14-one; (15S,18S)-16-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-19-oxa-9,13,16,26-tetraazapentacyclo[18.3.1.1] 6,9 .1 15,18 .0 2,7 ] Twenty-hexacarbon-1(24),2,4,6(26),7,20,22-heptaen-14-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7,10,13,19,21,26-hexaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 [Hexaco-1(24),2(26),3,5,17,20,22-heptaen-12-one;] (16S,19S)-17-[2-(2,4-difluorophenyl)-3-methyl-imidazol-4-carbonyl]-14-(2-morpholinoethyl)-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] (8S,11S)-10-[2-(2,4-difluorophenyl)-3-methyl-imidazol-4-carbonyl]-7-oxa-10,13,18,24-tetraazatetracyclo[18.3.1.1] 2,6 .1 8,11 ] Hexaco-1(23),2(26),3,5,20(24),21-hexaen-12,19-dione; (16S,19S)-17-[2-(2,4-difluorophenyl)-3-methyl-imidazol-4-carbonyl]-20-oxa-9,14,17-triazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6,21,23-hexaden-15,27-dione;] (3S,6S)-5-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-15-ethyl-8-methyl-2,5,8,14,15,17,22-heptaazatetracyclo[16.3.1.1] 3,6 .0 12,16 ] Tridecano-1(21), 12(16), 13, 18(22), 19-pentaen-7-one; (3S,6S)-5-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-2,5,8,13,14,17,22-heptaazatetracyclo[16.3.1.1] 3,6 .0 12,16 ] Tridecano-1(21), 12(16), 14, 18(22), 19-pentaen-7-one; (3S,6S)-5-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-8,13,17-trimethyl-2,5,8,13,14,17,22-heptaazatetracyclo[16.3.1.1] 3,6 .0 12,16 ] Tridecano-1(21), 12(16), 14, 18(22), 19-pentaen-7-one; (3S,6S)-5-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-8,13-dimethyl-17-oxa-2,5,8,13,14,22-hexaazatetracyclo[16.3.1.1] 3,6 .0 12,16 ] Tridecano-1(21), 12(16), 14, 18(22), 19-pentaen-7-one; (3S,6S)-5-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-8,13-dimethyl-2,5,8,13,14,17,22-heptaazatetracyclo[16.3.1.1] 3,6 .0 12,16 ] Tridecano-1(21), 12(16), 14, 18(22), 19-pentaen-7-one; (13S,16S)-14-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-4-methyl-17-oxa-3,4,6,11,14-pentazatetracyclo[16.3.1.1] 13,16 .0 2,6 ] Tridecano-1(22),2,18,20-tetraene-5,12-dione; (3S,6S)-5-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-8-methyl-2,5,8,13,17,22-hexaazatetracyclo[16.3.1.1] 3,6 .1 12,16 ] Twenty-four carbon-1(21),12(23),13,15,18(22),19-hexane-7-one; (3S,6S)-5-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-8-methyl-2,5,8,14,18,23-hexaazatetracyclo[17.3.1.1] 3,6 .0 12,17 ] Twenty-four carbon-1(22), 12, 14, 16, 19(23), 20-hexaeno-7-one; (14S,17S)-15-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-4-methyl-18-oxa-3,4,6,12,15-pentazatetracyclo[17.3.1.1] 14,17 .0 2,6 ] Twenty-four carbon-1(23),2,19,21-tetraene-5,13-dione; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-methyl-1,7,10,13,18,19,25-heptaazapentacyclo[15.5.1.1] 2,6 .1 8,11 .0 20,23 ]25-pentacarbon-2,4,6(25),17(23),19-pentaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-1,10,13,20-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 21,24 [26),3,5,17,19,21(24)-hexadecen-12-one; (16S,19S)-17-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-14,20-dioxa-9,17,27-triazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 ] Heptadec-1(24),2,4,6(27),7,21(25),22-heptaen-15-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-methyl-13-(3-phenylpropyl)-7-oxa-5,10,13,18,19-pentazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexacarbon-1(23),2,4,6(26),17(24),19,21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-methyl-7-oxa-4,10,13,18,19-pentazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexacarbon-1(23),2,4,6(26),17(24),19,21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-morpholinoethyl)-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 [Hexaco-1(24),2(26),3,5,20,22-hexaen-12,18-dione;] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(2-morpholinoethyl)-7-oxa-10,13,19,24-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 [Hexaco-1(23),2(26),3,5,17,19,21-heptaen-12-one;] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-methoxypropyl)-7-oxa-10,13,19,24-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 [Hexaco-1(23),2(26),3,5,17,19,21-heptaen-12-one;] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(thiazolyl-4-ylmethyl)-7-oxa-10,13,19,24-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 [Hexaco-1(23),2(26),3,5,17,19,21-heptaen-12-one;] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-19-thia-10,13,17-triazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(24),2,4,6(26),20,22-hexaen-12,18-dione; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-10,13,19,20-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexacarbon-1(23),2,4,6(26),17(24),18,21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,18,19,21,26-heptaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexacarbon-1(23),2,4,6(26),17,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,18,19,26-hexaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexacarbon-1(23),2,4,6(26),17,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-7,10,13,16,18,19,26-heptaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexacarbon-1(23),2,4,6(26),17(24),19,21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-13-methyl-7,10,13,18,19,26-hexaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexacarbon-1(23),2,4,6(26),17,20(24),21-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-13-methyl-7,10,13,17,19,26-hexaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 [Hexaco-1(24),2(26),3,5,20,22-hexaen-12,18-dione;] (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-methyl-6-nitro-8-oxa-12,15,18,23-tetraazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2(7),3,5,19,21-hexane-13-one; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-8,12-dimethyl-6-nitro-8,12,15,18,23-pentaazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2(7),3,5,19,21-hexane-13-one; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-methyl-13-oxo-8,12,15,18,23-pentazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2(7),3,5,19,21-hexane-6-carboxynitrile; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-methyl-6-(trifluoromethyl)-8,12,15,18,23-pentaazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2(7),3,5,19,21-hexane-13-one; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-N,12-dimethyl-13-oxo-8,12,15,18,23-pentazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2(7),3,5,19,21-hexane-6-carboxamide; (8S,11S)-10-[1-(4-fluoro-2-methoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,17,18,26-hexaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexacarbon-1(23),2,4,6(26),18,20(24),21-heptaen-12-one; (13S,16S)-14-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-3,11-dimethyl-8-oxa-3,5,11,14,17,22-hexaazatetracyclo[16.3.1.1] 13,16 .0 2,6 ] Tridecano-1(22),2(6),4,18,20-pentaen-12-one; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-methyl-5-thia-3,8,12,15,18,23-hexaazatetracyclo[17.3.1.1] 14,17 .0 2,6 ] Twenty-four carbon-1(23),2(6),3,19,21-pentane-7,13-dione; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-7-oxa-10,13,17,19-tetraazapentacyclo[15.5.2.1] 2,6 .1 8,11 .0 20,24 ] 26-hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (16S,19S)-17-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-N-methyl-15-oxo-20-oxa-10,14,17-triazatetracyclo[19.3.1.1] 16,19 .0 2,7 ] 2,4,6,21(25),22-hexaeno-10-carboxamide; (17S,20S)-18-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-N-methyl-16-oxo-21-oxa-10,15,18-triazatetracyclo[20.3.1.1] 17,20 .0 2,7 ] Heptadecano-1(25),2,4,6,22(26),23-hexadecano-10-carboxamide; (16S,19S)-10-acetyl-17-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-20-oxa-10,14,17-triazatetracyclo[19.3.1.1] 16,19 .0 2,7 ] 26-hexadecane-1(24),2,4,6,21(25),22-hexaen-15-one; (16S,19S)-17-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-10-pyrimidin-2-yl-20-oxa-10,14,17-triazatetracyclo[19.3.1.1] 16,19 .0 2,7 ] 26-hexadecane-1(24),2,4,6,21(25),22-hexaen-15-one; (16S,19S)-17-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-10-(1H-imidazo-2-carbonyl)-20-oxa-10,14,17-triazatetracyclo[19.3.1.1] 16,19 .0 2,7 ] 26-hexadecane-1(24),2,4,6,21(25),22-hexaen-15-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-20-methyl-7,10,13,14,15,19,21,27,29-nonazahexacyclo[17.6.1.1] 2,6 .1 8,11 .1 12,15 .0 22,26 ] 29-carbon-1(26),2,4,6(29),12(27),13,20,22,24-nonene; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-19-methyl-7,10,13,14,15,18,20,26,28-nonazahexacyclo[16.6.1.1] 2,6 .1 8,11 .1 12,15 .0 21,25 [Octadec-1(25),2,4,6(28),12(26),13,19,21,23-nonaene;] 1-[1-(2,4-difluorophenyl)-4-[(8S,11S)-13,18-dimethyl-12-oxo-7-oxa-10,13,18,19-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 [Hexaco-1(23),2(26),3,5,17(24),19,21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azacyclobutane-3-carboxylonitrile; (8S,11S)-10-[1-(2,4-difluorophenyl)-6-[3-methyl-3,6-diazabicyclo[3.1.1]heptane-6-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-13,18-dimethyl-5,7,10,13,18,19,26-heptaazapentacyclo[15.6.1.1] 2, 6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(23),2(26),3,5,17(24),19,21-heptaen-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]-13,18-dimethyl-5,7,10,13,18,19,26-heptaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(23),2(26),3,5,17(24),19,21-heptaen-12-one; (8S,11S)-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]-13,18-dimethyl-5,7,10,13,18,19,26-heptaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(23),2(26),3,5,17(24),19,21-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-7-oxa-5,10,13,17,19-pentazapentacyclo[15.6.1.1] 2,6 .1 8, 11 .0 20,24 [Hexaco-1(24),2(26),3,5,18,20,22-heptaen-12-one;] (8S,11S,15R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methoxy-11,13,18-trimethyl-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-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-11,13,18-trimethyl-7-oxa-10,13,17,19-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (16S,19S)-17-[1-(2-chloro-4-fluoro-phenyl)pyrazole-4-carbonyl]-20-oxa-11,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6,8,21,23-heptaene-10,15-dione;] (12E,17S,20S)-18-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-21-oxa-6,10,15,18,28-pentazapentacyclo[20.3.1.1] 6,9 .1 17,20 .0 2,7 ] Octadec-1(25),2,4,7,9(28),12,22(26),23-octaen-16-one; (13S,16S)-14-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-17-oxa-7,11,14-triazatetracyclo[16.3.1.1] 13,16 .0 2,7 [Typico-1(22),2,4,18,20-pentane-6,12-dione;] (20S,23S)-21-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-24-oxa-9,12,16,17,18,21,31,32-octaazahexacyclo[23.3.1.1] 6,9 .1 16,19 .1 20,23 .0 2,7 [32-carbon-1(28),2,4,6(32),7,17,19(31),25(29),26-nonen-11-one;] (20S,23S)-21-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-24-oxa-9,12,16,17,18,21,31,32-octaazahexacyclo[23.3.1.1] 6,9 .1 16,19 .1 20,23 .0 2,7 [32-carbon-1(28),2,4,6(32),7,17,19(31),25(29),26-nonen-11-one;] (8S,11S)-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-13-methyl-7,10,13,17,18,19,26-heptaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexadecane-1(23),2(26),3,5,18,20(24),21-heptaen-12-one; (43S,45S)-41-(1-(2,4-difluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-6-methyl-11H-3,6-diaza-1(7,1)-benzo[d][1,2,3]triazolo-2(2,6)-pyridazolo-4(3,5)-pyrrolidine heterocyclic nonafenone; (20S,23S)-21-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-12-methyl-24-oxa-9,12,16,17,18,21,31,32-octaazahexacyclo[23.3.1.1] 6,9 .1 16,19 .1 20,23 .0 2,7 [32-carbon-1(28),2,4,6(32),7,17,19(31),25(29),26-nonen-11-one;] (14S,17S)-15-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-7,12,15,18,23-pentaazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2,4,19,21-pentane-6,13-dione; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-methyl-7-oxa-1,10,13,18,19-pentazapentacyclo[15.5.1.1] 2,6 .1 8,11 .0 20,23 ]25-pentadecano-2(25),3,5,17(23),19-pentadecano-12-one; (8S,11S)-10-[7-(2,4-difluorophenyl)imidazo[5,1-f][1,2,4]triazine-4-yl]-13,18-dimethyl-7,10,13,18,19,26-hexaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(23),2(26),3,5,17(24),19,21-heptaen-12-one; (8S,11S,17R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-oxa-7,10,13,20,27-pentazapentacyclo[15.7.1.1] 2,6 .1 8,11 .0 21,25 ] Heptadecan-1(24),2,4,6(27),21(25),22-hexadecan-12,19-dione; (8S,11S,17S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-18-oxa-7,10,13,20,27-pentazapentacyclo[15.7.1.1] 2,6 .1 8,11 .0 21,25 ] Heptadecan-1(24),2,4,6(27),21(25),22-hexadecan-12,19-dione; (1S,3S)-31-(2,4-difluorophenyl)-4,15,17,21,26,30,32,36,39,41-decaazaoctane[19.15.1.1] 3,36 .1 5,9 .1 10,14 .1 28,35 .0 30,34 .0 17,40 ]Forty-one carbon-5,7,9(41),10,12,14(40),15,28,31,33,35(39)-undecene-27,37-dione; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-1,7,10,13,19,26-hexaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 21,24 ] 26-hexadecane-2(26),3,5,17,19,21(24),22-heptaen-12-one; (8S,11S)-22-chloro-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-1,7,10,13,19,26-hexaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 21,24 ] 26-hexadecane-2(26),3,5,17,19,21(24),22-heptaen-12-one; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-16-hydroxy-13,18-dimethyl-7,10,13,18,19,26-hexaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(23),2(26),3,5,17(24),19,21-heptaen-12-one; (8S,11S,15R)-10-[1-(2,4-difluorophenyl)-6-(oxecyclobutane-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-ethoxy-22-fluoro-13,18-dimethyl-7-oxa-5,10,13,17,19-pentazapentacyclo[15.6.1.1] 2, 6 .1 8,11 .0 20,24 [Hexaco-1(24),2(26),3,5,18,20,22-heptaen-12-one;] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-10,13,19-triazapentacyclo[14.6.1.1] 2,6 .1 8,11 .0 19,23 ]Twenty-five carbon-1(23),2(25),3,5,21-pentane-12,20-dione; (14S,17S)-4-chloro-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-6,12-dimethyl-6,8,12,15,18,23-hexaazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2(7),3,19,21-pentane-5,13-dione; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-5,12-dimethyl-5,8,12,15,18,23-hexaazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2(7),3,19,21-pentane-6,13-dione; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-13,17-dimethyl-7,10,13,16,18,25-hexaazapentacyclo[14.6.1.1] 2,6 .1 8,11 .0 19,23 [Twenty-five carbon-1(23),2(25),3,5,17,19,21-heptaen-14-one;] (8S,11S)-10-[1-(2,4-difluorophenyl)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 [Hexaco-1(24),2(26),3,5,18,20,22-heptaen-14-one;] (17S,20S)-18-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-15-methyl-8,15,18,21,26-pentazapentacyclo[20.3.1.1] 17,20 .0 2,7 .0 8,12 [Heptadec-1(26),2,4,6,22,24-hexaden-9,16-dione;] (6S,9S)-8-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-16-methyl-5-oxa-8,11,16,17-tetraazatetracyclo[13.6.1.1] 6,9 .0 18,22 ] Tridecano-1(21),2,15(22),17,19-pentene-10-one; (8S,11S,17R)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-10,13,19-triazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(23),2(26),3,5,20(24),21-hexaen-12,18-dione; (8S,11S,17S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7-oxa-10,13,19-triazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(23),2(26),3,5,20(24),21-hexaen-12,18-dione; (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-methyl-7,10,13,18,19,24,26-heptaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 [Hexaco-1(23),2(26),3,5,17,19,21-heptaen-12-one;] (16S,19S)-17-[5-(2-chloro-4-fluoro-phenyl)pyrazin-2-yl]-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] (8S,11S)-13-benzyl-10-[3-(2,4-difluorophenyl)imidazo[1,5-a]pyrazin-8-yl]-18-methyl-7-oxa-10,13,18,19-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(23),2(26),3,5,17(24),19,21-heptaen-12-one; (8S,11S)-10-[1-[(2,4-difluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-yl]-18-methyl-7-oxa-10,13,18,19-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] Twenty-hexacarbon-1(23),2(26),3,5,17(24),19,21-heptaen-12-one; 4-[3-[(8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-18-methyl-12-oxo-7-oxa-10,13,18,19-tetraazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 [Hexaco-1(23),2(26),3,5,17(24),19,21-heptaen-13-yl]propyl]morpholine-3-carboxylic acid; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-methyl-6-nitro-8,12,15,18,23-pentaazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2,4,6,19,21-hexane-13-one; (14S,17S)-8-acetyl-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-methyl-8,12,15,18,23-pentazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2,4,6,19,21-hexane-13-one; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-methyl-8,12,15,18,23-pentazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2,4,6,19,21-hexane-13-one; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-N,12-dimethyl-13-oxo-8,12,15,18,23-pentazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-tetracarbon-1(23),2,4,6,19,21-hexane-8-carboxamide; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-methyl-8-(2-pyrazol-1-ylacetyl)-8,12,15,18,23-pentazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2,4,6,19,21-hexane-13-one; (14S,17S)-15-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-12-methyl-8-[2-(4-pyridyl)acetyl]-8,12,15,18,23-pentaazatetracyclo[17.3.1.1] 14,17 .0 2,7 ] Twenty-four carbon-1(23),2,4,6,19,21-hexane-13-one; (16S,19S)-17-[1-(4-fluorophenyl)pyrazolo[4,3-c]pyridin-4-yl]-20-oxa-9,14,17,27-tetraazapentacyclo[19.3.1.1] 6,9 .1 16,19 .0 2,7 [Heptadec-1(25),2,4,6(27),7,21,23-heptaen-15-one;] (8S,11S)-10-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-13-(3-methoxypropyl)-7-oxa-10,13,18,19,24-pentaazapentacyclo[15.6.1.1] 2,6 .1 8,11 .0 20,24 ] 26-hexacarbon-2(26),3,5,17,19-pentene-12-one; (7S,10S)-9-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-14-methoxy-12,17-dimethyl-25-thia-4,6,9,12,16,18-hexaazapentacyclo[14.6.1.1] 2,5 .1 7,10 .0 19,23 ] 25-carbon-1(22), 2, 4, 17, 19(23), 20-hexene-11-one; (7S,10S,14R)-9-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-14-methoxy-12,17-dimethyl-6-oxa-4-thia-9,12,16,18,25-pentazapentacyclo[14.6.1.1] 2,5 .1 7,10 .0 19,23 ]Twenty-five carbon-1(22),2,5(25),17,19(23),20-hexene-11-one; (7S,10S,14R)-9-[1-(2,4-difluorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-21-fluoro-14-methoxy-12,17-dimethyl-4-thia-6,9,12,16,18,25-hexaazapentacyclo[14.6.1.1] 2,5 .1 7,10 .0 19,23 ] 25-carbon-1(22), 2,5(25), 17, 19(23), 20-hexane-11-one; and 2-[(2S)-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 [23),2(26),3,5,18,20(24),21-heptaen-10-yl]pyrazolo[3,4-d]pyrimidin-6-yl]azacyclobutane-2-yl]acetonitrile; Or its pharmaceutically acceptable salt.

22. A method for preparing a compound according to any one of claims 1 to 21, the method comprising the following steps: a) via the compound of formula (VII) in the presence of a base, (VII), with R 2 Nucleophilic substitution between X; or via compound of formula (VII) with R in the presence of a catalyst. 2 The Buchwald-Hartwig reaction between X; or via the reaction of compound (VII) with R in the presence of a coupling agent. 2 The condensation reaction between OH groups forms a compound of formula (Ia). (Ia); in The base mentioned in step a) is DIEA; The coupling reagent in step a) is HATU; The catalyst mentioned in step a) is Pd2(dba)3; X is a halogen; R e For H or C 1-6 Alkyl; R f For R or R 7 ; Q 1 To Q 3 M 1 and M 2 As defined in any one of claims 1 to 19.

23. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 21, which is used as a therapeutically active substance.

24. A pharmaceutical composition comprising: a compound according to any one of claims 1 to 21; and a pharmaceutically acceptable excipient.

25. Use of the compound according to any one of claims 1 to 21 for the treatment or prevention of autoimmune diseases, inflammatory diseases, neurological disorders, metabolic diseases, cardiovascular diseases, eye diseases, or selective cancer types involving overexpression or activation of STING.

26. The compound or pharmaceutically acceptable salt of any one of claims 1 to 21, used to prepare a medicament for the treatment or prevention of autoimmune diseases, inflammatory diseases, neurological disorders, metabolic diseases, cardiovascular diseases, eye diseases, or selective cancer types involving overexpression or activation of STING.

27. Use of the compound according to any one of claims 1 to 21 for treating a subject suffering from interferon disease or autoinflammatory disease in which STING activation is the root cause of the disease pathology.

28. The use of the compound according to any one of claims 1 to 21 for the treatment or prevention of systemic lupus erythematosus (SLE), dermatomyositis, diabetic nephropathy (DKD), diabetic retinopathy (DR), age-related macular degeneration (AMD), antineutrophil cytoplasmic autoantibody (ANCA) vasculitis, STING-associated vascular disease (SAVI) with infancy, familial frostbite-like lupus (FCL), Niemann-Pick disease type C (NPC), Aicardi-Goutières syndrome (AGS), COPA syndrome, or Wescott-Aldrich syndrome.

29. Use of the compound according to any one of claims 1 to 21 for the preparation of a medicament for the treatment or prevention of systemic lupus erythematosus (SLE), dermatomyositis, diabetic nephropathy (DKD), diabetic retinopathy (DR), age-related macular degeneration (AMD), antineutrophil cytoplasmic autoantibody (ANCA) vasculitis, STING-associated vascular disease (SAVI) with infancy, familial frostbite-like lupus (FCL), Niemann-Pick disease type C (NPC), Aicardi-Goutières syndrome (AGS), COPA syndrome, or Wescott-Aldrich syndrome.

30. Use of the compound according to any one of claims 1 to 21 for inhibiting STING.

31. Use of the compound according to any one of claims 1 to 21 for the preparation of a medicament for inhibiting STING.

32. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 21, manufactured according to the method of claim 22.

33. A method for treating or preventing an autoimmune disease, the method comprising administering a therapeutically effective amount of a compound as defined in any one of claims 1 to 21.

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