US 12,227,507 B2
Pharmaceutical compounds
George Stuart Cockerill, Stevenage (GB); James Good, Stevenage (GB); Craig Alex Avery, Nottingham (GB); Andrew Joseph Warner, Nottingham (GB); and Edward James Cochrane, Nottingham (GB)
Assigned to Pfizer Inc., New York, NY (US)
Appl. No. 17/636,510
Filed by Pfizer Inc., New York, NY (US)
PCT Filed Aug. 20, 2020, PCT No. PCT/GB2020/052008
§ 371(c)(1), (2) Date Feb. 18, 2022,
PCT Pub. No. WO2021/032992, PCT Pub. Date Feb. 25, 2021.
Claims priority of application No. 1911944 (GB), filed on Aug. 20, 2019.
Prior Publication US 2022/0306639 A1, Sep. 29, 2022
Int. Cl. A61K 31/5513 (2006.01); A61K 45/06 (2006.01); A61P 31/14 (2006.01); C07D 487/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [A61K 31/5513 (2013.01); A61K 45/06 (2013.01); A61P 31/14 (2018.01); C07D 519/00 (2013.01)] 7 Claims
 
1. A compound which is a benzodiazepine derivative selected from
2-[4-(Methylamino)phenyl]-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-2-Oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-[4-(propan-2-ylamino)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(1-Methyl-2,3-dihydroindol-6-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluoro-4-methoxyphenyl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluoro-4-propan-2-yloxyphenyl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[2-Fluoro-4-(methylamino)phenyl]-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide;
6-Chloro-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-methylimidazo[1,2-b]pyridazine-3-carboxamide;
6-Chloro-2-methyl-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-(furan-3-yl)-2-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluoro-5-methylphenyl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluoro-5-methylphenyl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(5-Chloropyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(5-Chloropyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Cyclopropylpyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Cyclopropylpyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(5-Cyclopropylpyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluoro-5-methylpyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluorophenyl)-6-methyl-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)-6-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2,4-Difluorophenyl)-5-methyl-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2,4-Difluorophenyl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluorophenyl)-7-methyl-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)-7-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluorophenyl)-5-(morpholin-4-yl)-N-[(3S)-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)-5-pyrrolidin-1-ylpyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluorophenyl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-5-pyrrolidin-1-ylpyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2,3-Difluorophenyl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2,3-Difluorophenyl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2,6-Difluorophenyl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluoro-4-pyrrolidin-1-ylphenyl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
6-Methyl-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-[5-(trifluoromethyl) pyridin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methyl-2-[5-(trifluoromethyl) pyridin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
2-[6-(Cyclopropylamino)-2-fluoropyridin-3-yl]-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Methylpyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(6-methylpyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[6-(2-methoxyethyl) pyridin-3-yl]-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-methylpyridin-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Ethoxypyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Ethylpyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Ethylpyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Ethyl-2-methylpyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Ethyl-2-methylpyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Propan-2-ylpyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(6-Propan-2-ylpyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[2-Methyl-6-(propan-2-ylamino)pyridin-3-yl]-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[2-Methyl-6-(propan-2-ylamino)pyridin-3-yl]-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[4-Methyl-6-(propan-2-ylamino)pyridin-3-yl]-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(1-methylindazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(5-methylpyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[6-(Ethylamino)-2-fluoropyridin-3-yl]-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[6-(Ethylamino)-2-fluoropyridin-3-yl]-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[6-(3-Methylmorpholin-4-yl) pyridin-3-yl]-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[6-(3-Methylmorpholin-4-yl) pyridin-3-yl]-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[2-Fluoro-6-(propan-2-ylamino)pyridin-3-yl]-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-[2-fluoro-6-(propan-2-ylamino)pyridin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(1-methylpyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(6-morpholin-4-ylpyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-[6-(propan-2-ylamino)pyridin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-[6-(propan-2-ylamino)pyridin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(6-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-[6-(2-Hydroxy-2-methylpropyl)pyridin-3-yl]-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(5-fluoropyridin-2-yl)-6-methylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1] heptan-2-yl]-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-[(1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1] heptan-2-yl]-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1] heptan-5-yl]-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-morpholin-4-yl-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)-5-[(1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1] heptan-2-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Fluoro-6-methylpyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
2-(2-Methoxy-6-methylpyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
2-(2,4-Difluorophenyl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
2-(2,4-Difluorophenyl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
2-(2,4-Difluorophenyl)-6-methyl-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
2-(2,4-Difluorophenyl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methylimidazo[1,2-b]pyridazine-3-carboxamide;
6-Methyl-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methyl-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
6-(Azetidin-1-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)-6-(4-methylpiperazin-1-yl) imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methyl-2-pyridin-3-ylimidazo[1,2-b]pyridazine-3-carboxamide;
6-Methyl-2-(2-methylpyridin-4-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methyl-2-(2-methylpyridin-4-yl) imidazo[1,2-b]pyridazine-3-carboxamide;
2-(3-Fluoropyridin-4-yl)-6-methyl-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(3-fluoropyridin-4-yl)-6-methylimidazo[1,2-b]pyridazine-3-carboxamide;
2-(5-Fluoropyridin-3-yl)-6-methyl-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(5-fluoropyridin-3-yl)-6-methylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methyl-2-(5-methylpyridin-3-yl) imidazo[1,2-b]pyridazine-3-carboxamide;
6-Methyl-2-(6-morpholin-4-ylpyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methyl-2-(6-morpholin-4-ylpyridin-3-yl) imidazo[1,2-b]pyridazine-3-carboxamide;
6-(Ethylamino)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)-6-(1-methylazetidin-3-yl)oxyimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-(1-methylazetidin-3-yl)oxy-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-Fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)-6-(2-methoxyethoxy) imidazo[1,2-b]pyridazine-3-carboxamide;
6-Methoxy-N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-phenyl-6-(trideuteriomethoxy) imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methoxy-2-phenylimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-phenyl-6-(trideuteriomethoxy) imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)-6-methoxyimidazo[1,2-b]pyridazine-3-carboxamide;
6-Chloro-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(2-fluorophenyl)imidazo[1,2-b]pyridazine-3-carboxamide;
6-Chloro-2-(6-ethylpyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methoxy-2-(5-methylpyridin-3-yl) imidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(3-fluoropyridin-4-yl)-6-methoxyimidazo[1,2-b]pyridazine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-6-methoxy-2-(6-methylpyridin-3-yl) imidazo[1,2-b]pyridazine-3-carboxamide;
2-(6-Ethylpyridin-3-yl)-6-methoxy-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
6-Ethoxy-2-(6-ethylpyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]imidazo[1,2-b]pyridazine-3-carboxamide;
2-(6-Ethylpyridin-3-yl)-N-[(3S)-9-fluoro-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]-6-(2H3) methoxyimidazo[1,2-b]pyridazine-3-carboxamide;
2-(6-[(3S*)-3-methylmorpholin-4-yl]pyridin-3-yl)-N-[(3S)-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]-2-{6-[(3S*)-3-methylmorpholin-4-yl]pyridin-3-yl}pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]-2-{6-[(3S*)-3-methylmorpholin-4-yl]pyridin-3-yl}pyrazolo[1,5-a]pyrimidine-3-carboxamide;
N-[(3S)-9-fluoro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]-2-(1H-indazol-5-yl) imidazo[1,2-b]pyridazine-3-carboxamide;
and the pharmaceutically acceptable salts thereof.