Identification of <i>N</i>-Benzyl 3,5-Dinitrobenzamides Derived from PBTZ169 as Antitubercular Agents

Abstract

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