Pyridinylpyrrolyl analogs of isoniazid: Synthesis and antimycobacterial activities

Pyridinylpyrrolyl analogs of isoniazid (INH) were prepared by reaction of e thyl 3-(4-pyridinyl)-2-propenoate with toluenesulfonylmethylisocyanide (Tos MIC). The pyrrole esters which formed were reacted with hydrazine hydrate t o afford INH analogs 7-10. These compounds and various related derivatives were tested against a number of mycobacteria in comparison with INH and str eptomycin (SM). Although 4-(4-pyridinyl)pyrrole-3-carboxyhydrazide 34 was n ot active, some related derivatives showed interesting antitubercular activ ities. hmong them, derivative 19 was the most potent both against M. tuberc ulosis (MIC = 1.47 mu M) and M. avium (MIC = 4.40 mu M), a non-tuberculous agent responsible of fatal infection in AIDS patients. Compounds 15 and 33 also were endowed with appreciable activities against M tuberculosis and il l. avium.