Synthesis and Biological Evaluation of Some Novel 1,4-Dihydropyridines as Potential AntiTubercular Agents

Authors: Trivedi, Amit; Dodiya, Dipti; Dholariya, Bipin; Kataria, Vipul; Bhuva, Vimal; Shah, Viresh

Source: Chemical Biology & Drug Design, Volume 78, Number 5, 1 November 2011 , pp. 881-886(6)

Buy & download fulltext article:

Price: $48.00 plus tax (Refund Policy)

Abstract:

Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant antitubercular activity. In this study, we have synthesized new derivatives of 1,4-dihydropyridines bearing carbmethoxy and carbethoxy group at C-3 and C-5 of the 1,4-dihydropyridine ring. In addition, 1H-pyrazole ring is substituted at C-4 position. These analogues were synthesized by multi-component Hantzsch reaction. The in vitro antitubercular activity of compounds against Mycobacterium tuberculosis H₃₇Rv was evaluated. The lowest minimum inhibitory concentration value, 0.02 μg/mL and SI > 500, was found for dimethyl 1,4-dihydro-4-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethylpyridine-3,5-dicarboxylate 3f, diethyl 1,4-dihydro-4-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethylpyridine-3,5-dicarbo-xylate 4c and diethyl 1,4-dihydro-4-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethyl pyridine-3,5-dicarboxylate 4e, making them more potent than first-line antitubercular drug isoniazid. In addition, these compounds exhibited relatively low cytotoxicity.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1747-0285.2011.01233.x

Affiliations: 1: Department of Chemistry, Saurashtra University, Rajkot-360005, Gujarat, India

Publication date: 2011-11-01