Synthesis and biological evaluation of some new 1,4-dihydropyridines containing different ester substitute and diethyl carbamoyl group as anti-tubercular agents

Bioorganic & Medicinal Chemistry
2009.0

Abstract

Tuberculosis is a leading infectious cause of death worldwide. Because of the concern of the resistance to most of the commonly used drugs displayed by the considered mycobacteria, most efforts have been done to introduce new anti-tubercular agents. Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant anti-tubercular activity. In this study, we synthesized new derivatives of 1,4-dihydropyridines in which different alkyl and aryl esters and diethyl carbamoyl are substituted in C-3 and C-5 of the DHP ring. In addition nitroimidazole ring is substitutes at C-4 position. These asymmetric analogues were synthesized by a modified Hantzsh reaction using procedure reported by Meyer. The in vitro anti-tubercular activity of compounds against Mycobacterium tuberculosis was evaluated. The results indicate that the compounds containing aromatic esters are more potent than alkyl ones. The most potent aromatic compound (R=3-phenylpropyl) exhibits comparable anti-tubercular activity (MIC=1 micromol/ml) with reference compound isoniazide (INH) (MIC=1 micromol/ml). Conformational analysis, SAR studies of these compounds showed that increasing in lipophilicity and rotable bonds of these compounds resulted in increasing anti-tubercular activity.

Knowledge Graph

Similar Paper

Synthesis and biological evaluation of some new 1,4-dihydropyridines containing different ester substitute and diethyl carbamoyl group as anti-tubercular agents
Bioorganic & Medicinal Chemistry 2009.0
Synthesis and biological evaluation of some novel N-aryl-1,4-dihydropyridines as potential antitubercular agents
Bioorganic & Medicinal Chemistry Letters 2011.0
Synthesis and antitubercular activity of novel 4-substituted imidazolyl-2,6-dimethyl-N3,N5-bisaryl-1,4-dihydropyridine-3,5-dicarboxamides
European Journal of Medicinal Chemistry 2009.0
Synthesis, antibacterial and antimycobacterial activities of some new 4-aryl/heteroaryl-2,6-dimethyl-3,5-bis-N-(aryl)-carbamoyl-1,4-dihydropyridines
European Journal of Medicinal Chemistry 2011.0
Novel dihydropyrimidines as a potential new class of antitubercular agents
Bioorganic & Medicinal Chemistry Letters 2010.0
Design, synthesis and evaluation of diarylpiperazine derivatives as potent anti-tubercular agents
European Journal of Medicinal Chemistry 2015.0
Synthesis and antimycobacterial activities of some new N-acylhydrazone and thiosemicarbazide derivatives of 6-methyl-4,5-dihydropyridazin-3(2H)-one
Medicinal Chemistry Research 2012.0
1,4–Diarylpiperazines and analogs as anti-tubercular agents: Synthesis and biological evaluation
European Journal of Medicinal Chemistry 2012.0
4,5-Dihydro-1H-pyrazolo[3,4-d]pyrimidine containing phenothiazines as antitubercular agents
Bioorganic & Medicinal Chemistry Letters 2014.0
Design, Synthesis, and Biological Evaluation of New Cinnamic Derivatives as Antituberculosis Agents
Journal of Medicinal Chemistry 2011.0