Synthesis and pharmacological activities of calcium modulatory hexahydroquinolinones

Hexahydroquinolinones of type 6 are accessible from Hantzsch-like cyclization of 1,3-cyclohexanedione with aromatic aldehydes and different beta-aminocrotonates and acetoacetates/ammonia, respectively. Reaction with pyridiniumbromideperbromide leads to the octahydrofuro[3,4-b] guinoline-diones 6h and 6i. 6j was obtained by N-alkylation. Positive inotropic effects were observed on electrically stimulated left atria of guinea pigs whereas BaCl2-induced contractions of the ileum were inhibited in a dose dependent manner. On electrically stimulated guinea pig papillary muscle 6h exhibits contractility promoting effects which can be attributed to calcium agonism.