Synthesis, calcium-channel blocking activity, and conformational analysis of some novel 1,4-dihydropyridines: Application of PM3 and DFT computational methods

Abstract

Novel 1,4-dihydropyridines were synthesized and subjected to calcium-channel blocking evaluation and conformational analysis using semi-empirical (PM3) and density functional theory (DFT) as computational methods. All molecules had a boat-like 1,4-dihydropyridine ring in both the methods. In PM3 method almost 54% of the molecules were deviated from planarity, but in DFT method all the molecules had perfect flattened-boat conformation. Using both the methods, the C-4 substituent was pseudoaxial with its phenylamino substitution in sp orientation in 82.14% of the molecules. Trans-trans and cis-cis conformation had the greatest and lowest proportion in the molecules, respectively. Trans-trans conformers which possessed sp conformation for the substituted group on the imidazole ring were active calcium-channel blocking agents. © Springer Science+Business Media, LLC 2011.