Dharuman, Suresh; Wallace, Miranda J.; Reeve, Stephanie M.; Bulitta, Jurgen B.; Lee, Richard E. published the artcile< Synthesis and Structure-Activity Relationship of Thioacetamide-Triazoles against Escherichia coli>, Electric Literature of 387350-39-2, the main research area is thioacetamide triazole preparation SAR antibacterial; 1,2,3-triazoles; antibiotics; antimetabolite; gram-negative active compounds.
Infections due to Gram-neg. bacteria are increasingly dangerous due to the spread of multi-drug resistant strains, emphasizing the urgent need for new antibiotics with alternative modes of action. Authors have previously identified a novel class of antibacterial agents, thioacetamide-triazoles, using an antifolate targeted screen and determined their mode of action which is dependent on activation by cysteine synthase A. Herein, authors report a detailed examination of the anti-E. coli structure-activity relationship of the thioacetamide-triazoles. Analogs of the initial hit compounds were synthesized to study the contribution of the aryl, thioacetamide, and triazole sections. A clear structure-activity relationship was observed generating compounds with excellent inhibition values. Substitutions to the aryl ring were generally best tolerated, including the introduction of thiazole and pyridine heteroaryl systems. Substitutions to the central thioacetamide linker section were more nuanced; the introduction of a Me branch to the thioacetamide linker substantially decreased antibacterial activity, but the isomeric propionamide and N-benzamide systems retained activity. Changes to the triazole portion of the mol. dramatically decreased the antibacterial activity, further indicating that 1,2,3-triazole is critical for potency. From these studies, authors have identified new lead compounds with desirable in-vitro ADME properties and in-vivo pharmacokinetic properties.
Molecules published new progress about Acetamides Role: PAC (Pharmacological Activity), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses) (Thio). 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Electric Literature of 387350-39-2.