Antimycobacterial activity of substituted isosteres of pyridine- and pyrazinecarboxylic acids. 2.

Pyridines and pyrazines substituted with 1,2,4-oxadiazole-5-ones, 1,2,4-oxa diazole-5-thiones, and 1,3,4-oxathiazoline-2-ones were synthesized and test ed against Mycobacterium tuberculosis. The two former ring systems were doc umented in the literature to act as carboxylic acid isosteres. The latter s eries was synthesized as possible synthetic intermediates to 1,2,4-thiadiaz ole-3-ones and was included in this study due to their interesting activity . Pivaloyl-oxymethyl derivatives of the isosteres were also prepared in ord er to increase their lipophilicity and therefore improve their cellular per meability. The derivatized isosteres were expected to be biotransformed by esterases to the active species after penetration of the mycobacterial cell wall. Biological properties of the compounds were compared with the unmodi fied polar isosteres of pyrazinoic and nicotinic acids. The majority of the compounds exhibited activities ranging from 0.5 to 16 times the potency of pyrazinamide.