Design, Synthesis and Evaluation of Antitubercular Activity of Novel Dihydropyridine Containing Imidazolyl Substituent



Iman M¹ ; Davood A² ; Dehqani G² ; Lotfinia M² ; Sardari S³ ; Azerang P³ ; Amini M⁴ Show Affiliations
Source: Iranian Journal of Pharmaceutical Research Published:2015

Abstract

Recent studies have indicated that 1, 4-dihydropyridine-3, 5-dicarboxamide derivatives show significant anti-tubercular activity. In this research, new derivatives of 1, 4-dihydropyridine were designed and synthesized using Hantzsch condensation in which dicyclohexyl and different dicyclohexylcarbamoyl were substituted at C-3 and C-5 positions of the DHP ring. In addition, 4 (5)-chloro-2-methyl-5 (4)-imidazolyl moiety was substituted at C-4 position of DHP. The structure of synthetized compounds were characterized by TLC, IR, elemental analysis and proton NMR. Based on the in vitro screening data, all of the designed and synthetized compounds (3a-3g) showed a good ability to inhibit the mycobacterium tuberculosis growth in terms of MIC. Aromatic carboxamide containing compounds were more potent than cyclohexyl derivative and the most potent compound was 3a (4-nitrophenyl derivative). The experimental data are in agreement with our computational predictions in terms of partial atomic charge of carbonyl moieties at the C-3 and C-5 positions of DHP ring and partition coefficient of the molecules. © 2015 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services.