Synthesis and calcium modulatory activity of 3-alkyloxycarbonyl-4-(disubstituted)aryl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives

In this study, twelve hexahydroquinoline derivatives which are condensed analogs of the 1,4-DHP molecule were synthesized and evaluated for their calcium-antagonistic activity. The results indicated that all compounds and nifedipine produced concentration-dependent relaxation in rabbit gastric fundus smooth muscle strips. The relaxant effects of the compounds on the tissues were expressed as percentage of the precontraction using Ca2+. The maximum response (E-max) and pD(2) values (the negative logarithm of the concentration for the half-maximal response (EC50)) were calculated. It is generally believed that introduction of a second electron-withdrawing substituent into the phenyl ring increases the mentioned activity. Methyl-2,7,7-trimethyl-4-(2-nitro-5-chlorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate 2a has been found to be the most active compound in this serie.