PBTZ169 is a piperazinobenzothiazinone derivative optimized by medicinal chemistry from the lead BTZ043. PBTZ169 has several advantages compared to BTZ043, amongst which are easier chemical synthesis, due to the absence of chiral centers, low cost of goods and better pharmacodynamics. PBTZ169 covalently inhibits DprE1, an enzyme essential for the biosynthesis of key cell wall components. The drug has additive effects with many TB therapeutic agents, both marketed and in development, and has synergic effects with bedaquiline and clofazimine in preclinical models.

The São Paulo State University (UNESP), School of Pharmaceutical Sciences synthesized 22 new N-oxide-containing compounds and evaluated in vitro and in vivo antitubercular potential against M. tuberculosis. Compound 8 was found to be the most promising compound, with MIC₉₀ values of 1.10 and 6.62 μM against active and nonreplicating Mtb, respectively. Studies of cytotoxicity, safety, absorption, distribution, and metabolism of compound 8 support its candidacy.