Microwave-assisted synthesis of condensed 1,4-dihydropyridines as potential calcium channel modulators

Abstract

This study reports the design, synthesis, and calcium channel modulatory activity evaluation of a series of 14 novel fused 1,4-dihydropyridine derivatives. The molecular design of the compounds was based on modifications of nifedipine, which is a calcium channel blocker. The compounds were achieved by one-pot microwave-assisted reaction of 4,4-dimethyl-1,3-cyclohexanedione, 5-chlorosalicylaldehyde/3,5-dichlorosalicylaldehyde, an appropriate alkyl acetoacetate, and ammonium acetate in ethanol according to a modified Hantzsch reaction. The structures of the compounds were confirmed by spectral methods and elemental analysis. To evaluate their relaxant activities, the maximum relaxant response (E$_{\max})$ and pD$_{2}$ values of the compounds and nifedipine were determined on isolated rat aorta rings. The obtained results indicated that all compounds produced concentration-dependent relaxation on the rings possibly due to the blockade of calcium channels. The E$_{\max}$ values (a measure of efficacy) of five compounds were higher than those of nifedipine.