CYANOINDAZOLE COMPOUNDS AND USES THEREOF
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Abstract
Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.
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Citations
40 Claims
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1. A compound of Formula I:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 36, 37, 38, 39, 40)
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2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl;
- wherein said phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10;
orR1 is selected from pyridin-4-yl and pyrimidin-4-yl;
wherein said pyridin-4-yl and pyrimidin-4-yl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R5.
- wherein said phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10;
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3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl;
- wherein said phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl are each optionally substituted with 1 or 2 substituents independently selected from R10;
orR1 is selected from pyridin-4-yl and pyrimidin-4-yl;
wherein said pyridin-4-yl and pyrimidin-4-yl are each optionally substituted with 1 or 2 substituents independently selected from R15.
- wherein said phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl are each optionally substituted with 1 or 2 substituents independently selected from R10;
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4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-5-yl, pyrazolyl, oxazolyl, isoxazolyl, and isothiazolyl;
- wherein said phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-5-yl, pyrazolyl, oxazolyl, isoxazolyl, and isothiazolyl are each optionally substituted with 1 or 2 substituents independently selected from R10;
orR1 is pyridin-4-yl;
wherein said pyridin-4-yl is optionally substituted with 1 or 2 substituents independently selected from R5.
- wherein said phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-5-yl, pyrazolyl, oxazolyl, isoxazolyl, and isothiazolyl are each optionally substituted with 1 or 2 substituents independently selected from R10;
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5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from phenyl and pyrazolyl;
- wherein said phenyl and pyrazolyl are each optionally substituted with 1 or 2 substituents independently selected from R10.
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6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from pyridin-2-yl and pyridin-3-yl, wherein said pyridin-2-yl and pyridin-3-yl are optionally substituted with 1 or 2 substituents independently selected from R10;
- or
R1 is selected from pyridin-4-yl;
wherein said pyridin-4-yl is optionally substituted with R15.
- or
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7. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R10 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1 wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11.
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8. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R10 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, halo, ORa1, C(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, and S(O)2Rb1;
- wherein said C1-6 alkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, and C6-10 aryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11.
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9. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R10 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, halo, ORa1, C(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, and S(O)2Rb1;
- wherein said C1-6 alkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, and C6-10 aryl-C1-3 alkylene are each optionally substituted with 1 or 2 substituents independently selected from R11.
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10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R10 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, halo, ORa1, C(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, and S(O)2Rb1;
- wherein said C1-6 alkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and C6-10 aryl, are each optionally substituted with 1 or 2 substituents independently selected from R11.
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11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R15 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, and OC(O)NRc1Rd1;
- wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R11.
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12. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R15 is C1-6 alkyl optionally substituted with 1 or 2 substituents independently selected from R11.
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13. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R11 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3S(O)Rb3, NRc3S(O)2Rb3, and NRc3S(O)2NRc3Rd3;
- wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl, are each optionally substituted with 1, 2, or 3 substituents independently selected from R12.
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14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R11 is independently selected from C1-6 alkyl, halo, CN, ORa3, C(O)Rb3, and NRc3Rd3;
- wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R12.
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15. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is optionally substituted with 1 or 2 substituents independently selected from:
- —
CH3, —
CH2CH3, —
OCH3, cyclopropyl, —
CH2CF3, 2-chlorophenyl, —
CH(CH3)2, —
CH2OH, —
C(O)NHCH3, —
C(O)N(CH3)2, —
NHC(O)CH3, —
CF3, —
CH2CN, —
F, —
SO2CH3, —
C(CH3)2CN, 1-cyanocyclopropyl, —
C(O)NHCH(CH3)2, —
Cl, —
SO2CH(CH3)2, 4-methylpiperazin-1-yl, morpholinyl, 4-acetylpiperazin-1-yl, tetrahydro-2H-pyran-4-yl, —
C(CH3)2OH, 3-fluoropyrrolidin-1-yl, 4-hydroxypiperidin-1-yl, —
NHCH(CH3)CH2CH3, 3-(hydroxymethyl)azetidin-1-yl, and 3-(dimethylamino)pyrrolidin-1-yl.
- —
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16. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyA is phenyl;
- wherein phenyl is optionally substituted by 1, 2, 3, or 4 substituents independently selected from R20.
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17. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyA is phenyl;
- wherein phenyl is substituted by 1, 2, 3, or 4 substituents independently selected from R20.
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18. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyA is phenyl;
- wherein phenyl is substituted by 1, 2, or 3 substituents independently selected from R20.
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19. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R20 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2 NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, and NRc2S(O)2NRc2Rd2;
- wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21.
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20. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R20 is independently selected from C1-6 alkyl, halo, and ORa2;
- wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R21.
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21. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R21 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, and BRh4Ri4.
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22. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R21 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4S(O)Rb4, NRc4S(O)2Rb4, and NRc4S(O)2NRc4Rd3.
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23. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R20 is independently selected from C1-6 alkyl, halo, and ORa2;
- wherein said C1-6 alkyl is optionally substituted with NRc4Rf4.
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24. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyA is phenyl optionally substituted with 1, 2, or 3 substituents independently selected from —
- F, —
CH3, —
CH2NHCH3, and —
OCH3.
- F, —
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25. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyA is phenyl optionally substituted with 1, 2, or 3 substituents independently selected from —
- F, —
CH3, and —
CH2NHCH3.
- F, —
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26. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, D, OH, halo, and C1-3 alkyl.
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27. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, D, OH, and halo.
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28. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is H.
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29. The compound of claim 1 having Formula (IIa1), Formula (IIa2), Formula (IIa3), Formula (IIa4), Formula (IIa5), Formula (IIa6), Formula (IIa7), Formula (IIa8), or Formula (IIa9):
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30. The compound of claim 1 having Formula (IIb1):
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31. The compound of claim 1 having Formula (IIb2):
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32. The compound of claim 1 selected from:
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3-(1-Ethyl-1H-pyrazol-4-yl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 3-(1-Cyclopropyl-1H-pyrazol-4-yl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(1H-pyrazol-4-yl)-1H-indazole-6-carbonitrile; 3-(1-(2-Chlorophenyl)-1H-pyrazol-4-yl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(1-isopropyl-1H-pyrazol-4-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(4-(hydroxymethyl)phenyl)-1H-indazole-6-carbonitrile; 4-(6-Cyano-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazol-3-yl)-N-methylbenzamide; 4-(6-Cyano-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazol-3-yl)-N,N-dimethylbenzamide; N-(4-(6-Cyano-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazol-3-yl)phenyl)acetamide; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-p-tolyl-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(3-methoxyphenyl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(4-methoxyphenyl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carbonitrile; 3-(4-Cyclopropylphenyl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 3-(4-(Cyanomethyl)phenyl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 4-(6-Cyano-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazol-3-yl)-2-fluoro-N-methylbenzamide; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-1H-indazole-6-carbonitrile; 3-(4-(2-Cyanopropan-2-yl)phenyl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 3-(4-(1-Cyanocyclopropyl)phenyl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 4-(6-Cyano-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazol-3-yl)-2-fluoro-N,N-dimethylbenzamide; 3-Chloro-4-(6-cyano-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazol-3-yl)-N-isopropylbenzamide; 3-(3-Fluoro-4-(methylsulfonyl)phenyl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 3-(2-Chloro-4-(methylsulfonyl)phenyl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(4-(isopropylsulfonyl)phenyl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(2-(4-methylpiperazin-1-yl)pyrimidin-5-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-morpholinopyridin-3-yl)-1H-indazole-6-carbonitrile; N-(5-(6-Cyano-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazol-3-yl)pyridin-2-yl)acetamide; 3-(6-(4-Acetylpiperazin-1-yl)pyridin-3-yl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(2-methylpyridin-4-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-(tetrahydro-2H-pyran-4-yl)pyridin-3-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-methylpyridin-3-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(2-methoxypyrimidin-5-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(oxazol-5-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(isothiazol-4-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(isoxazol-4-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(2-methyloxazol-5-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-((S)-3-fluoropyrrolidin-1-yl)pyridin-3-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-(4-hydroxypiperidin-1-yl)pyridin-3-yl)-1H-indazole-6-carbonitrile; 3-(6-(((R)-sec-Butyl)amino)pyridin-3-yl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-(3-(hydroxymethyl)azetidin-1-yl)pyridin-3-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-(4-hydroxypiperidin-1-yl)pyridin-2-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-(4-methylpiperazin-1-yl)pyridin-2-yl)-1H-indazole-6-carbonitrile; 3-(6-((S)-3-(Dimethylamino)pyrrolidin-1-yl)pyridin-2-yl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-indazole-6-carbonitrile; 3-(1-Methyl-1H-pyrazol-4-yl)-5-o-tolyl-1H-indazole-6-carbonitrile; 5-(2-Fluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-6-carbonitrile; 5-(2-Fluoro-6-methoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-6-carbonitrile; and 5-(2-Fluoro-6-methylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-6-carbonitrile; or a pharmaceutically acceptable salt thereof.
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36. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.
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37. A method of inhibiting HPK1 activity, said method comprising administering to a patient a compound of claim 1, or a pharmaceutically acceptable salt thereof.
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38. A method of treating a disease or disorder associated with inhibition of HPK1 interaction, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.
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39. A method for treating a cancer in a patient, said method comprising:
- administering to the patient a therapeutically effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof.
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40. The method of claim 39, wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.
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2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from phenyl, pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl;
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33. A compound of Formula I:
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34. A compound of Formula I:
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35. A compound of Formula I:
Specification
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Current AssigneeIncyte Corporation
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Original AssigneeIncyte Corporation
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InventorsVechorkin, Oleg, Atasoylu, Onur, Ye, Hai Fen, Liu, Kai, Zhang, Ke, Yao, Wenqing
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Granted Patent
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Time in Patent OfficeDays
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Field of Search
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US Class Current
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CPC Class CodesA61K 31/416 condensed with carbocyclic ...A61K 31/454 containing a five-membered ...A61P 35/00 Antineoplastic agentsC07D 231/56 Benzopyrazoles; Hydrogenate...C07D 401/04 directly linked by a ring-m...C07D 401/14 containing three or more he...C07D 403/04 directly linked by a ring-m...C07D 405/10 linked by a carbon chain co...C07D 405/14 containing three or more he...C07D 413/04 directly linked by a ring-m...C07D 417/04 directly linked by a ring-m...