Dérivés 6,7-dihydro-5h-pyrido[2,3-c]pyridazine et composés similaires en tant qu'inhibiteurs de la protéine bcl-xl et agents pro-apoptotiques pour le traitement du cancer

The present invention discloses 6,7-dihydro-5h-pyrido[2,3- c]pyridazine, 1,2,3,4-tetrahydroquinoline, 1h-indole, 3,4- dihydro-2h-1,4-benzoxazine, 1h-pyrrolo[2,3-b]pyridin-1-yl, 7h- pyrrolo[2,3-c]pyridazine, 5h,6h,7h,8h,9h-pyridazino[3,4-b]azepine derivatives and related compounds of formula (i) as bcl-xl protein inhibitors for use as pro-apoptotic agents for treating cancer, autoimmune diseases or immune system diseases. Formula (i). The description discloses the preparation of exemplary compounds (e.G. Pages 113 to 354 examples 1 to 221) as well as pharmacological studies with relevant data (e.G. Pages 355 to 367; examples a to e; tables 1 to 5). Exemplary compounds are e.G. 2-{6-[(1,3-benzothiazol-2-yl) amino]-1,2,3,4-tetrahydroquinolin-1-yl}-1,3-thiazole-4-carboxylic acid (example 1) or e.G. 3-{1-[(adamantan-1-yl)methyl]-5- methyl-1h-pyrazol-4-yl}-6-{3-[(1,3-benzothiazol-2-yl)amino]-4- methyl-5h,6h,7h,8h-pyrido[2,3-c]pyridazin-8-yl]pyridine-2-carboxylic acid (example 24). Compounds of formula (I):wherein Het, Het1, Het2, A4, A5, Z1, R1, R2 and R3 are as defined in the description. Medicaments.