US 10,888,550 B2
Pyrazole derivatives as MALT1 inhibitors
Tianbao Lu, Churchville, PA (US); Peter J. Connolly, New Providence, NJ (US); Maxwell David Cummings, Ambler, PA (US); Gaston Stanislas Marcella Diels, Turnhout (BE); Jan Willem Thuring, Antwerp (BE); Ulrike Philippar, Antwerp (BE); James Patrick Edwards, Ambler, PA (US); Didier Jean-Claude Berthelot, La Neuville Chang d'Oisel (FR); and Tongfei Wu, Hever (BE)
Assigned to Janssen Pharmaceutica NV, Beerse (BE)
Filed by Janssen Pharmaceutica NV, Beerse (BE)
Filed on Jun. 13, 2019, as Appl. No. 16/440,356.
Claims priority of provisional application 62/686,451, filed on Jun. 18, 2018.
Prior Publication US 2019/0381012 A1, Dec. 19, 2019
Int. Cl. A61K 31/437 (2006.01); A61P 35/00 (2006.01); A61K 31/519 (2006.01); C07D 471/04 (2006.01); C07K 16/28 (2006.01)
CPC A61K 31/437 (2013.01) [A61K 31/519 (2013.01); A61P 35/00 (2018.01); C07D 471/04 (2013.01); C07K 16/2887 (2013.01); C07K 16/2896 (2013.01)] 10 Claims
 
1. A compound independently selected from the group consisting of:
5-(4-((5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)imidazo[1,2-a]pyridine-8-carboxamide;
N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1-(8-cyanoimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-(5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-N-(6-(methylsulfonyl)-5-(trifluoromethyl)pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-(5-chloro-6-(oxazol-2-yl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1-(8-methylimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(methylsulfonyl)-1H-pyrazole-4-carboxamide;
N-(5-chloro-6-(5-methyloxazol-2-yl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-(5-chloro-6-(4-methyloxazol-2-yl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
1-(7-cyanopyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide;
4-(5-(trifluoromethyl)-4-((2-(trifluoromethyl)pyridin-4-yl)carbamoyl)-1H-pyrazol-1-yl)pyrazolo[1,5-a]pyridine-7-carboxamide;
N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1-(7-cyanopyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
1-(7-chloropyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide;
N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1-(7-chloropyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide
4-(4-((5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)pyrazolo[1,5-a]pyridine-7-carboxamide;
(*S)—N-(5-chloro-6-(1-methoxyethyl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*R)—N-(5-chloro-6-(tetrahydrofuran-2-yl)pyridin-3-yl)-1-(8-chloroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*R)—N-(5-chloro-6-(1-methoxyethyl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*S)—N-(5-chloro-6-(tetrahydrofuran-2-yl)pyridin-3-yl)-1-(8-chloroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*S)—N-(5-chloro-6-(tetrahydrofuran-2-yl)pyridin-3-yl)-1-(7-chloropyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*R)—N-(5-chloro-6-(tetrahydrofuran-2-yl)pyridin-3-yl)-1-(7-chloropyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*S)—N-(5-chloro-6-(tetrahydrofuran-2-yl)pyridin-3-yl)-1-(7-cyanopyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*R)—N-(5-chloro-6-(tetrahydrofuran-2-yl)pyridin-3-yl)-1-(7-cyanopyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*S)—N-(5-chloro-6-(1-methoxyethyl)pyridin-3-yl)-1-(7-cyanopyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*R)—N-(5-chloro-6-(1-methoxyethyl)pyridin-3-yl)-1-(7-cyanopyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*S)—N-(5-chloro-6-(1-methoxyethyl)pyridin-3-yl)-1-(7-chloropyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
(*R)—N-(5-chloro-6-(1-methoxyethyl)pyridin-3-yl)-1-(7-chloropyrazolo[1,5-a]pyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-(6-((dimethyl(oxo)-λ6-sulfanylidene)amino)-5-methylpyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-(6-((dimethyl(oxo)-λ6-sulfanylidene)amino)-5-(trifluoromethyl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-N-(6-(S-methylsulfonimidoyl)-5-(trifluoromethyl)pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
N-(6-((dimethyl(oxo)-λ6-sulfanylidene)amino)-5-fluoropyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;
and
N-(5-chloro-6-((dimethyl(oxo)-λ6-sulfanylidene)amino)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide
or an enantiomer, diastereomer, or a pharmaceutically acceptable salt form thereof.