[Calcium modulators of the anellated dihydropyridine type. Synthesis and pharmacologic action]

The anellated dihydropyridines 4a-l can be gained by Hantzsch-like synthesis from 5,5-dimethylcyclohexanedione (1), the aromatic aldehydes 2a-l and methyl-beta-aminocrotonate (3). Cyclisation of the side chains with bromosuccinimide or pyridiniumbromideperbromide leads to the octahydrofuro[3,4-b]chinoline-diones 4m-p. Structures of type 4 are characterized by the spectroscopic data. Positive inotropic effects, caused by calcium agonism, are exerted by the tested substances at the isolated, electrically stimulated left guinea pig atrium, 4j being the most potent with an intrinsic activity of 0.79, compared with ethyl 4-[2-(difluoromethoxy)phenyl]-1, 4,5,7-tetrahydro-2-methyl-5-oxo-furo[3,4-b]pyridine-3-carboxylate. BaCl2-induced contractions at the guinea pig ileum are suppressed dose-dependently.