Identification of N-Benzyl 3,5-Dinitrobenzamides Derived from PBTZ169 as Antitubercular Agents.

A series of benzamide scaffolds were designed and synthesized by the thiazinone ring opening of PBTZ169, and N-benzyl 3,5-dinitrobenzamides were finally identified as anti-TB agents in this work. 3,5-Dinitrobenzamides D5, 6, 7, and 12 exhibit excellent in vitro activity against the drug susceptive Mycobacterium tuberculosis H37Rv strain (MIC: 0.0625 μg/mL) and two clinically isolated multidrug-resistant strains (MIC < 0.016-0.125 μg/mL). Compound D6 displays acceptable safety and better pharmacokinetic profiles than PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.