Benzoheterocyclic Oxime Carbamates Active against <i>Mycobacterium tuberculosis</i>: Synthesis, Structure–Activity Relationship, Metabolism, and Biology Triaging

Screening of a library small polar molecules against Mycobacterium tuberculosis (Mtb) led to the identification potent benzoheterocyclic oxime carbamate hit series. This series was subjected medicinal chemistry progression underpinned by structure–activity relationship studies toward identifying compound for proof-of-concept and defining lead optimization strategy. Carbamate free frontrunner compounds with good stability in liver microsomes no hERG channel inhibition liability were identified evaluated vivo pharmacokinetic properties. Mtb-mediated permeation metabolism revealed that carbamates acting as prodrugs. Toward mechanism action elucidation, selected tested biology triage assays assess their activity known promiscuous targets. Taken together, these data suggest novel yet unknown mode antitubercular hits.