Synthesis, Biological Evaluation, in silico ADMET and Molecular Docking of new 1,4‐Dihydropyridine Derivatives Bearing Ether Substitution as Calcium Channel Blockers

Abstract

AbstractA set of 1,4‐dihydropyridine derivatives were synthesized, possessing methyl or ethyl esters at positions 3 and 5, an aliphatic or aromatic ether group at position 2, and a thienyl ring at position 4. The calcium channel blocking activity of these derivatives was investigated using K+‐induced contraction on the longitudinal smooth muscles of guinea pig ileum (GPILSM). Our findings showed that the derivatives had IC50 ranging from 0.5 to 5.2 μM. Among the synthesized compounds, compound including methoxy group in position 2 and ethyl acetate in positions 3 and 5, with IC50=0.55±0.58 μM was almost comparable to that of nifedipine (IC50=0.27±1.23 μM). The results of docking studies and biological evaluation of synthetic compounds were consistent. According to the physicochemical and drug‐likeness parameters, it is predicted that the synthesized compounds can be a suitable candidate for calcium channel blocking.