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Synthesis and Biological Evaluation of Some Novel 1,4‐Dihydropyridines as Potential AntiTubercular Agents
Author(s) -
Trivedi Amit,
Dodiya Dipti,
Dholariya Bipin,
Kataria Vipul,
Bhuva Vimal,
Shah Viresh
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01233.x
Subject(s) - chemistry , isoniazid , pyrazole , mycobacterium tuberculosis , ring (chemistry) , cytotoxicity , pyridine , dihydropyridine , stereochemistry , in vitro , moiety , medicinal chemistry , organic chemistry , tuberculosis , biochemistry , calcium , medicine , pathology
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, 1 H ‐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 H 37 Rv 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‐1 H ‐pyrazol‐4‐yl)‐2,6‐dimethylpyridine‐3,5‐dicarboxylate 3f , diethyl 1,4‐dihydro‐4‐(3‐(4‐fluorophenyl)‐1‐phenyl‐1 H ‐pyrazol‐4‐yl)‐2,6‐dimethylpyridine‐3,5‐dicarbo‐xylate 4c and diethyl 1,4‐dihydro‐4‐(3‐(4‐bromophenyl)‐1‐phenyl‐1 H ‐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.