Discovery and Optimization of Imidazothiazole Carboxamides as Novel Anti-Tuberculosis Agents
Year: 2026
Type: preprint
Abstract: Screening of the open-access CRESTdb small-molecule library identified the imidazothiazole carboxamide sCQG20 0 ( 1 ) as an initial hit, with activity against H37Rv and Erdman Mycobacterium tuberculosis strains in cholesterol-containing medium (MIC 90 = 6.88 µM and 4.48 µM, respectively) and against intracellular Mtb (EC 50 = 3.80 µM). sCQG200 retained activity against drug-resistant Mtb strains, including clinical MDR/XDR isolates. SAR optimization led to analogs 21 and 24 with substantially improved antimycobacterial potency. Mouse pharmacokinetic studies following oral and intravenous administration showed 62.1% and 29.5% oral bioavailability for 21 and 24 , respectively. This structurally differentiated chemotype provides a promising starting point for further optimization as antitubercular agent.
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G5721702266
OpenAlex ID: W7214197786