Synthesis and in vitro Calcium Channel Blocking Activity of Symmetrical and Unsymmetrical Substituted 1,4-Dihydropyridine Derivatives

Abstract

Symmetrical substituted 1,4-dihydropyridines (3a-e) was synthesized by Hantzsch synthesis method. In the first step benzaldehydes (1a-e) was treated with methyl acetoacetate (2) in the presence of ammonia and methanol to afford diester compound 3a-e. Further these diester 3a-e was reacted with ammonia solution (25 %) to give the compound 4a-b and with hydrazine hydrate to form hydrazides 5a-b. The unsymmetrical substituted 1,4-dihydropyridine was prepared by modified Hantzsch method. Here the α,β-unsaturated ketone reacted with β- amino crotonate in the methyl alcohol at room temperature to afford unsymmetrical 1,4-dihydropyridine (8a-b). The required α,β-unsaturated ketone was prepared by the reaction of substituted benzaldehyde with ethylaceto acetate in the presence of acetic acid and piperidine at room temperature. Whereas β-amino crotonate was prepared by the reaction of methylaceto acetate in the presence of ammonia and methanol at ice bath temperature for 2 h. Six compounds were screened for calcium channel blocking activity using guinea pig ileum. The 3a, 3b, 8b were shown promising activity compared with standard felodipine.