Ring-substituted imidazoles as a new class of anti-tuberculosis agents.
We describe in vitro anti-Mycobacterium tuberculosis activities of ring-substituted-1H-imidazole-4-carboxylic acid derivatives (1-6), and 3-(2-alkyl-1H-imidazol-4-yl)-propionic acid derivatives (7-13) against drug-sensitive and drug-resistant M. tuberculosis H37Rv strains. The most effective analogues, 2f (R=R(1)=c-C(5)H(9)), and 2h (R=R(1)=c-C(6)H(11)) have produced >90% inhibition at a concentration of <6.25 microg/ml in the drug-sensitive screen. Upon further evaluation against drug-resistant strains, both analogues 2f and 2h produced an MIC value of 25.0 microg/ml. The observation of significant anti-tuberculosis activity in some of these analogues describes the discovery of novel ring-substituted-1H-imidazole-4-carboxylic acid ethyl esters as a new class of anti-tuberculosis agents.
Gupta
Preeti
P
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.
Hameed
Shahul
S
Jain
Rahul
R
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
D000995:Antitubercular Agents; D007093:Imidazoles