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.