Design, synthesis, and bioevaluation of a novel class of (E)-4-oxo-crotonamide derivatives as potent antituberculosis agents.

A series of novel (E)-4-oxo-2-crotonamide derivatives were designed and synthesized to find potent antituberculosis agents. All the target compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv(MTB). Results reveal that 4-phenyl moiety at part A and short methyl group at part C were found to be favorable. Most of the derivatives displayed promising activity against MTB with MIC ranging from 0.125 to 4 µg/mL. Especially, compound IIIa16 was found to have the best activity with MIC of 0.125 µg/mL against MTB and with MIC in the range of 0.05-0.48 µg/mL against drug-resistant clinical MTB isolates.