Pyrazinoic acid esters with broad spectrum in vitro antimycobacterial activity

A series of substituted pyrazinoic acid esters has been prepared and examined for their in vitro activity against Mycobacterium avium and Mycobacterium kansasii as well as Mycobacterium tuberculosis. Modification of both the pyrazine nucleus and the ester functionality have been very successful in expanding the activity of pyrazinamide to include M. avium and M. kansasii, organisms normally not susceptible to pyrazinamide. Several of these compounds have activities 100-1000-fold greater than that of pyrazinamide against M. tuberculosis.