Synthesis and In vitro P-Glycoprotein Inhibitory Activity of Novel 1,4-Dihydropyridine Derivatives

Abstract


 Two series of new symmetrical 4-aryl-2,6-dimethyl-3,5-bis-N-(aryl/heteroaryl)-carbamoyl-1,4-dihydropyridines (4a-f) and asymmetrical 4-aryl-2,6-dimethyl-3-N-(aryl/hetero-aryl)-carbamoyl-5-ethyl carboxylate-1,4-dihydro-pyridines (5a-f) have been synthesized by simple, economical and eco-friendly, modified Hantzsch reaction using N-aryl/heteroarylacetoacetamides (3a-c), ethylaceto-acetate (for asymmetric), arylaldehydes and urea in presence of catalytic amounts of LiBr/Iodine and by microwave irradiation methods. The newly synthesized compounds were characterized by physical and spectral data, and evaluated for their possible in vitro MDR reversal activity by everted sac method using verapamil as standard P-gp inhibitor and domperidone as the standard P-gp substrate. Amongst the compounds tested, compound 4f exhibited the highest in vitro P-gp inhibitory activity. It was found to be more potent than the standard verapamil.