IP Library › Granted Patent US 12,331,039
Granted Patent B2
US 12,331,039 · App. 17/702,444 · Granted Jun 17, 2025

Inhibitors of fibroblast growth factor receptor kinases

Inventors: Stephen W. Kaldor (San Diego, CA); John Tyhonas (San Diego, CA); Eric A. Murphy (San Marcos, CA); Toufike Kanouni (Rancho Santa Fe, CA); Lee D. Arnold (Rancho Santa Fe, CA); Robert Kania (Del Mar, CA); Jason M. Cox (Rancho Santa Fe, CA)
Assignee: Khora SPV 1, LLC
C07D403/14A61K45/06C07D401/14C07D405/14C07D413/04C07D417/14C07D471/04C07D487/04
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Quick Facts
Patent No.
US 12,331,039
App. No.
17/702,444
Granted
Jun 17, 2025
Kind
B2
Abstract

Provided herein are heteroaryl inhibitors of fibroblast growth factor receptor kinases, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.

Claims (299)

1. A compound, or pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of:

1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-3-[2-(2-methyl-3H-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)pyrazole-4-carboxamide;

(S)-1-(1-acryloylpyrrolidin-3-yl)-3-((2-methyl-1H-benzo[d]imidazol-6-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(1-ethyl-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-3-[2-(1-methyl-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1,2-dimethyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

(S)-1-(1-acryloylpyrrolidin-3-yl)-3-((1,2-dimethyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-methyl-1H-indazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((2-methyl-2H-indazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-methyl-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((4,6-difluoro-1-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-1H-indazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((2-ethyl-2H-indazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-4,6-difluoro-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((4,6-difluoro-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((4,6-difluoro-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((4,6-difluoro-1-methyl-1H-indazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((4-fluoro-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-4-fluoro-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((3-ethyl-2-methyl-3H-imidazo[4,5-b]pyridin-6-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((3-methyl-3H-imidazo[4,5-b]pyridin-6-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-cyano-1-ethyl-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((2-cyclopropyl-1-ethyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-(benzo[d]isoxazol-6-ylethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-fluoro-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-4,6-difluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-(difluoromethyl)-4,6-difluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-(difluoromethyl)-4,6-difluoro-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-chloro-1-ethyl-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((4,6-difluoro-2-methyl-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(3-ethyl-4-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-ethyl-6-fluoro-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(4-chloro-1-ethyl-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-[1-ethyl-2-methylimidazo[4,5-b]pyridin-5-yl]ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-fluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(4-fluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(2-cyclopropyl-1H-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(2-cyclopropyl-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-3-[2-(3-methyl-1,2-benzoxazol-6-yl)ethynyl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(2-cyclopropyl-1-ethyl-4,6-difluoro-1,3-benzodiazol-5-yl) ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl) pyrrolidin-3-yl]-5-(methylamino) pyrazole-4-carboxamide;

3-[2-[4,6-difluoro-2-(trifluoromethyl)-1H-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-[1-(difluoromethyl)-4,6-difluoro-2-methyl-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-[3-Ethyl-2-methylimidazo[4,5-c]pyridin-6-yl]ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(2-Amino-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(2-Cyclopropyl-4,6-difluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((2-cyclopropyl-4-fluoro-1-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl) pyrrolidin-3-yl]-5-(methylamino)-3-[2-(quinolin-7-yl) ethynyl]pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-(2-[pyrazolo[1,5-a]pyrimidin-5-yl]ethynyl)pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-(imidazo[1,2-a]pyridin-7-ylethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-(imidazo[1,2-a]pyridin-6-ylethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-(2-[pyrazolo[1,5-a]pyridin-5-yl]ethynyl)pyrazole-4-carboxamide;

3-(2-[Imidazo[1,2-a]pyrimidin-6-yl]ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-[Imidazo[1,2-a]pyrimidin-7-yl]ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-Tert-butyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-[2-(Dimethylamino)-1-methyl-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(2-Cyclopropyl-4,6-difluoro-1H-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(2-Cyclopropyl-6-fluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-[2-Cyclopropyl-3-methylimidazo[4,5-c]pyridin-6-yl]ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl) pyrrolidin-3-yl]-5-(methylamino)-3-[2-(quinoxalin-6-yl) ethynyl]pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-5-(methylamino)-3-((3-methylquinolin-7-yl)ethynyl)-1H-pyrazole-4-carboxamide;

3-(2-[Imidazo[1,2-b]pyridazin-7-yl]ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-(2-[pyrazolo[1,5-a]pyridin-6-yl]ethynyl)pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-4-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-5-(methylamino)-3-((2-methylquinoxalin-6-yl)ethynyl)-1H-pyrazole-4-carboxamide;

3-[2-[1-(Difluoromethyl)-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((4-fluoro-1-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-5-(methylamino)-3-((3-methylquinoxalin-6-yl)ethynyl)-1H-pyrazole-4-carboxamide;

3-[2-[3-(Difluoromethyl)-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-[2-(4-methylquinolin-7-yl)ethynyl]pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-(2-[3-methylimidazo[1,2-a]pyridin-7-yl]ethynyl)pyrazole-4-carboxamide;

3-[2-[3-(Difluoromethyl)-6-fluoro-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-[1-(Difluoromethyl)-6-fluoro-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-Cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Fluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S,5R)-1-(prop-2-enoyl)-5-[(trifluoromethoxy)methyl]pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-Ethyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S,5R)-1-(prop-2-enoyl)-5-[(trifluoromethoxy)methyl]pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-[1-(Difluoromethyl)-6-fluoro-1,3-benzodiazol-5-yl]ethynyl]-5-(methylamino)-1-[(3S,5R)-1-(prop-2-enoyl)-5-[(trifluoromethoxy)methyl]pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-Chloro-1,2-dimethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-[2-(2-methylquinolin-7-yl)ethynyl]pyrazole-4-carboxamide;

3-[2-(4,6-Difluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S,5R)-1-(prop-2-enoyl)-5-[(trifluoromethoxy)methyl]pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-Ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S,5R)-1-(prop-2-enoyl)-5-[(trifluoromethoxy)methyl]pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-Fluoro-1H-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S,5R)-1-(prop-2-enoyl)-5-[(trifluoromethoxy)methyl]pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-Chloro-2-methyl-1H-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S,5R)-1-(prop-2-enoyl)-5-[(trifluoromethoxy)methyl]pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-Chloro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Chloro-1-ethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Fluoro-1H-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Fluoro-2-methyl-1H-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Chloro-1H-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-[6-Chloro-3-(difluoromethyl)-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-[6-Chloro-1-(difluoromethyl)-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-[6-Chloro-3-(difluoromethyl)-2-methyl-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-[6-Chloro-1-(difluoromethyl)-2-methyl-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(4,6-Difluoro-1-methyl-1,2,3-benzotriazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Chloro-2-methyl-1H-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Chloro-1-ethyl-4-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Chloro-4-fluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6,7-Difluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1,3-Benzothiazol-2-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1,3-Benzothiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-[Imidazo[1,2-a]pyridin-2-yl]ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((3-cyanoimidazo[1,2-a]pyridin-2-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-(2-[[1,2,4]triazolo[1,5-a]pyridin-6-yl]ethynyl)pyrazole-4-carboxamide;

1-[(3S,5R)-5-(Methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-(2-[[1,2,4]triazolo[1,5-a]pyridin-7-yl]ethynyl)pyrazole-4-carboxamide;

3-[2-(1,3-Benzoxazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

5-[(Cyclopropylmethyl)amino]-3-[2-(1-ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-[1-(Difluoromethyl)-4,6-difluoro-2-methyl-1,3-benzodiazol-5-yl]ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-Ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-[[3-(morpholin-4-yl)propyl]amino]pyrazole-4-carboxamide;

3-[2-(1-Ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-[[2-(morpholin-4-yl)ethyl]amino]-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-Chloro-7-fluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1,3-Benzoxazol-2-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Fluoro-1,3-benzoxazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-Ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-[(2-hydroxyethyl)amino]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-Ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-[(2-methoxyethyl)amino]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-[(Cyclopropylmethyl)amino]-3-[2-(1-ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-Ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-[(2-methoxyethyl)amino]-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-Ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-[[3-(morpholin-4-yl)propyl]amino]-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((7-fluoro-1-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-(2-[7-Fluoro-[1,2,4]triazolo[1,5-a]pyridin-6-yl]ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide

3-[2-(1-Ethyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-[(2-hydroxy;ethyl)amino]-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-Chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-Ethyl-6,7-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Chloro-1-ethyl-7-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6,7-Difluoro-1,2-dimethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl) pyrrolidin-3-yl]-5-(methylamino) pyrazole-4-carboxamide;

3-[2-(6-Chloro-7-fluoro-1,2-dimethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Chloro-1-ethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-1-(2-fluoroprop-2-enoyl)-5-(methoxymethyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-[6-Fluoro-[1,2,4]triazolo[1,5-a]pyridin-7-yl]ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Fluoro-1,3-benzothiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-fluoroimidazo[1,2-a]pyridin-7-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(6-Chloro-4-fluoro-1,2-dimethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Chloro-1,3-benzothiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-Cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-Cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

1-((3S,5R)-1-(but-2-ynoyl)-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-4,6-difluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-((methoxy-d3)methyl)pyrrolidin-3-yl)-3-((6-chloro-1-ethyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(6-fluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-ethyl-6,7-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-chloro-1-ethyl-7-fluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-chloro-7-fluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-ethyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-chloro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6,7-difluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-chloro-1-cyclopropyl-7-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-fluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(fluoromethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-[2-(4,6,7-trifluoro-1,2-dimethyl-1,3-benzodiazol-5-yl)ethynyl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-2-methyl-1,3-benzodiazol-5-yl) ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6,7-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)-3-[2-(4,6,7-trifluoro-1-methyl-1,3-benzodiazol-5-yl)ethynyl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6,7-trifluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-5-[(difluoromethoxy)methyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]-3-[2-(1-ethyl-6,7-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(difluoromethoxy)methyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-((difluoromethoxy)methyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-4,6-difluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(1-ethyl-4,6,7-trifluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6,7-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5S)-5-methyl-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5S)-5-methyl-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-((difluoromethoxy)methyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(6-Chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(difluoromethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(difluoromethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-methylpyrrolidin-3-yl)-3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-methyl-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-methylpyrrolidin-3-yl)-3-((6-chloro-1-cyclopropyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

1-((3S,5S)-1-acryloyl-5-methylpyrrolidin-3-yl)-3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(difluoromethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6,7-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-1-(1-(2-fluoroacryloyl)azetidin-3-yl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-((1-cyclopropyl-4,6-difluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-1-(1-(2-fluoroacryloyl)azetidin-3-yl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(hydroxymethyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

tert-butyl 3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[1-(prop-2-enoyl)azetidin-3-yl]pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(fluoromethyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((4,6-difluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(fluoromethyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(fluoromethyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-4,6-difluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5S)-5-(fluoromethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5S)-5-(fluoromethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-1-((3S,5R)-5-(methoxymethyl)-1-propioloylpyrrolidin-3-yl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-(but-2-ynoyl)-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-ynoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-[(3S,5R)-1-(but-2-ynoyl)-5-(methoxymethyl)pyrrolidin-3-yl]-3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(hydroxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[1-(prop-2-ynoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-chloro-1-ethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(hydroxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-chloro-1-ethyl-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[1-(prop-2-enoyl)azetidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[1-(prop-2-enoyl)azetidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(6-chloro-1-ethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(hydroxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(hydroxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

5-amino-3-[2-(6-chloro-1-ethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-[1-(prop-2-enoyl)azetidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(hydroxymethyl)-1-(prop-2-ynoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

5-amino-3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(hydroxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(hydroxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[1-(prop-2-enoyl)azetidin-3-yl]pyrazole-4-carboxamide;

3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-1-((3S,5R)-1-(4-hydroxy-4-methylpent-2-ynoyl)-5-(methoxymethyl)pyrrolidin-3-yl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-{1-[(2E)-4-(dimethylamino)but-2-enoyl]azetidin-3-yl}-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(ethylamino)-1H-pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(hydroxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[1-(prop-2-enoyl)azetidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(6-chloro-1-ethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[1-(prop-2-enoyl)azetidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[1-(prop-2-enoyl)azetidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(difluoromethoxy)methyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(difluoromethoxy)methyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(methylamino)-1-{[1-(prop-2-enoyl)azetidin-3-yl]methyl}pyrazole-4-carboxamide;

5-amino-3-[2-(6-chloro-1-cyclopropyl-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(difluoromethoxy)methyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-5-(cyclopropylamino)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(2-hydroxypropan-2-yl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1R)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1S)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-((R)-1-hydroxyethyl)pyrrolidin-3-yl)-3-((6-chloro-1-cyclopropyl-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-((S)-1-hydroxyethyl)pyrrolidin-3-yl)-3-((6-chloro-1-cyclopropyl-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1R)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-Chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1S)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1R)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1S)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-1-(4-hydroxy-4-methylpent-2-ynoyl)-5-(methoxymethyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-1-(4-hydroxy-4-methylpent-2-ynoyl)-5-(methoxymethyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-chloro-1-cyclopropyl-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-1-(4-hydroxy-4-methylpent-2-ynoyl)-5-(methoxymethyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-cyclobutyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-cyclobutyl-6-fluoro-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(6-chloro-1-cyclobutyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-chloro-1-cyclobutyl-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-{2-[6-fluoro-1-(oxetan-3-yl)-1,3-benzodiazol-5-yl]ethynyl}-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-{2-[6-fluoro-2-methyl-1-(oxetan-3-yl)-1,3-benzodiazol-5-yl]ethynyl}-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-fluoro-3-methylquinolin-7-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-fluoro-1-isopropyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-{2-[6-fluoro-1-(1-methylcyclopropyl)-1,3-benzodiazol-5-yl]ethynyl}-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-(1-cyanocyclopropyl)-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1R)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1S)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1R)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1S)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-((R)-1-hydroxyethyl)pyrrolidin-3-yl)-5-amino-3-((6-chloro-1-cyclopropyl-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-Acryloyl-5-((S)-1-hydroxyethyl)pyrrolidin-3-yl)-5-amino-3-((6-chloro-1-cyclopropyl-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-1H-pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1R)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

5-amino-3-[2-(1-cyclopropyl-6-fluoro-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-[(1S)-1-hydroxyethyl]-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-{2-[6-chloro-1-(oxetan-3-yl)-1,3-benzodiazol-5-yl]ethynyl}-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-{2-[6-chloro-2-methyl-1-(oxetan-3-yl)-1,3-benzodiazol-5-yl]ethynyl}-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-5-[(2-hydroxyethyl)amino]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-5-[(2-hydroxyethyl)amino]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-fluoro-2-methyl-1,3-benzodiazol-5-yl)ethynyl]-5-[(2-hydroxyethyl)amino]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-chloro-1-cyclopropyl-2-methyl-1H-benzo[d]imidazol-5-yl)ethynyl)-5-((2-hydroxyethyl)amino)-1H-pyrazole-4-carboxamide;

3-[2-(6-fluoro-2H-1,3-benzodioxol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(3-chloro-6-fluoroquinolin-7-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-fluoro-3-methylimidazo[1,2-a]pyridin-7-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-chloro-3-methylquinolin-7-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(1-cyclopropyl-6-methyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((7-fluoro-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-6-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-(2-{6-chloro-3-cyclopropylimidazo[1,2-a]pyridin-7-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-{3-cyano-6-fluoroimidazo[1,2-a]pyridin-7-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-{3-cyanopyrazolo[1,5-a]pyridin-6-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(3, 6-difluoroquinolin-7-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(3,6-dimethylquinolin-7-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-fluoro-4-methylcinnolin-7-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(6-chloro-3-fluoroquinolin-7-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-chloro-4-methylcinnolin-7-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-(2-{3-cyanoimidazo[1,2-a]pyridin-7-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((3-cyano-4-methoxypyrazolo[1,5-a]pyridin-6-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-(2-{1-[(1S)-2,2-Difluorocyclopropyl]-6-fluoro-1,3-benzodiazol-5-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-{2-[1-((R)-(2,2-difluorocyclopropyl)-6-fluoro-1,3-benzodiazol-5-yl]ethynyl}-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-{2-[3-(difluoromethyl)-6-fluoroquinolin-7-yl]ethynyl}-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-fluoro-4-methylquinolin-7-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-methyl-1H-indazol-4-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-[2-(1-cyclopropylindazol-4-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-{imidazo[1,5-a]pyridin-8-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-{imidazo[1,5-a]pyridin-5-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-{6-chloro-1-[(1R)-2,2-difluorocyclopropyl]-1,3-benzodiazol-5-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-{6-Chloro-1-[(1S)-2,2-difluorocyclopropyl]-1,3-benzodiazol-5-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-[2-(6-chloro-4-methylquinolin-7-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((6-fluoro-3,4-dimethylquinolin-7-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-(2-{3-cyclopropyl-6-fluoroimidazo[1,2-a]pyridin-7-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-{3-cyclopropyl-4-methoxypyrazolo[1,5-a]pyridin-6-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((7-chloro-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-6-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-cyclopropyl-5-fluoro-1H-indazol-4-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide;

3-(2-{6-chloro-3-[(1R)-2,2-difluorocyclopropyl]-1,3-benzodiazol-5-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide;

3-(2-{6-chloro-3-[(1S)-2,2-difluorocyclopropyl]-1,3-benzodiazol-5-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide; and

3-(2-{3-chloro-6-fluoroimidazo[1,2-a]pyridin-7-yl}ethynyl)-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide.

2. A pharmaceutical composition comprising a compound described in claim 1 , or pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

3. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: 1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-4,6-difluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide.

4. The pharmaceutical composition of claim 2 , comprising the compound having the structure of: 1-((3S,5R)-1-acryloyl-5-(methoxymethyl)pyrrolidin-3-yl)-3-((1-ethyl-4,6-difluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-5-(methylamino)-1H-pyrazole-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

5. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: 3-[2-(1-Cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide.

6. The pharmaceutical composition of claim 2 , comprising the compound having the structure of: 3-[2-(1-Cyclopropyl-4,6-difluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

7. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: 3-[2-(6-Chloro-1-ethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide.

8. The pharmaceutical composition of claim 2 , comprising the compound having the structure of: 3-[2-(6-Chloro-1-ethyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

9. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: 3-[2-(6-Chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide.

10. The pharmaceutical composition of claim 2 , comprising the compound having the structure of: 3-[2-(6-Chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

11. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: 3-[2-(1-Cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide.

12. The pharmaceutical composition of claim 2 , comprising the compound having the structure of: 3-[2-(1-Cyclopropyl-6-fluoro-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

13. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: 5-amino-3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide.

14. The pharmaceutical composition of claim 2 , comprising the compound having the structure of: 5-amino-3-[2-(6-chloro-1-cyclopropyl-1,3-benzodiazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-(prop-2-enoyl)pyrrolidin-3-yl]pyrazole-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2025
From: KINNATE BIOPHARMA INC.
To: KHORA SPV 1, LLC
Reel/Frame 070901/0510 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 23, 2022
From: KALDOR, STEPHEN W.; TYHONAS, JOHN; MURPHY, ERIC A.; KANOUNI, TOUFIKE; ARNOLD, LEE D.; KANIA, ROBERT; COX, JASON M.
To: KINNATE BIOPHARMA INC.
Reel/Frame 059485/0108 →
Continuity (4)
Continuation 17339123 · Jun 4, 2021
Provisional Application 63106812 · Oct 28, 2020
Provisional Application 63035155 · Jun 5, 2020
Related Publication 20230078839A1 · Mar 16, 2023
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