PYRAZINE COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE

摘要

593316 The present disclosure relates to pyrazine compounds of formula (Ia) wherein L, n, R1, and R2 are as described in the specification. These compounds are useful as inhibitors of ATR protein kinase. The disclosure also relates to pharmaceutically acceptable compositions comprising the compounds of the disclosure; methods of treating of various diseases, disorders, and conditions using the compounds of the disclosure; processes for preparing the compounds of the disclosure; intermediates for the preparation of the compounds of the disclosure; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. Compounds of the present disclosure include: 2-[5-Amino-6-[5-[4-(methylaminomethyl)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N-ethyl-cyclopropanecarboxamide, 1-(4-(5-Amino-6-(5-( 4-((methylamino)methyl)phenyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)piperidin-1-yl)propan-1-one, 1-(7-(5-Amino-6-(5-( 4-CCmethylamino)methy])phenyl)-I,3A-oxadiazol-2-y])pyrazin-2-y])-2,7-diazaspiro[4,4]nonan-2-y])propan-1-one, 1-{ 7-(5-Amino-6-(5-(4-((methylamino)methyllphenyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-2,7-diazaspiro[4,4]nonan-2-yl} propan-1-one, 1-[S-amino-6-(S-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yI]-3 ,6-dihydro-2H-pyridine-4-carboxylic acid, 3-{ [1,2,4(triazolo[1,S-alpyridin-2-y])-S-(1-(ethylsulfony])-1,2,3,6-tetrahydropyridin-4-y])pyrazin-2-amine, 3-amino-N-(pyridin-2-yl)-6-(4-(thiophen-3-ylsulfonyl)piperazin-1-yl)pyrazine-2-carboxamide, 3-amino-6-(4-(phenylcarbonyl)piperazin-1-yl)-N-(pyridin-2-yl)pyrazine-2-carboxamide, 3-(1H-benzo[d]imidazol-2-yl)-5-(1-(thiophen-2-ylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)pyrazin-2-amine and 4-(5-amino-6-(3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-yl)-N,N-dimethyl-5,6-dihydropyridine-1(2H)-sulfonamide