Mycobacterium tuberculosis PptT Inhibitors Based on Heterocyclic Replacements of Amidinoureas.

ABSTRACT: 4'-Phosphopantetheinyl transferase (PptT) is an essential enzyme for Mycobacterium tuberculosis (Mtb) survival and virulence and therefore an attractive target for a tuberculosis therapeutic. In this work, two modeling-informed approaches toward the isosteric replacement of the amidinourea moiety present in the previously reported PptT inhibitor AU 8918 are reported. Although a designed 3,5-diamino imidazole unexpectedly adopted an undesired tautomeric form and was inactive, replacement of the amidinourea moiety afforded a series of active PptT inhibitors containing 2,6-diaminopyridine scaffolds.

SUBMITTER: Ottavi S 

PROVIDER: S-EPMC10351052 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature