Synthesis, biological evaluation and X-ray crystallographic studies of imidazo[1,2-a]-pyridine based Mycobacterium tuberculosis glutamine synthetase inhibitors
2012 (English)In: MedChemComm, ISSN 2040-2503, E-ISSN 2040-2511, Vol. 3, no 5, 620-626 p.Article in journal (Refereed) Published
Based on an imidazo[1,2-a]pyridine hit from a high-throughput screen directed at the M. tuberculosis enzyme glutamine synthetase, a hit expansion was performed by synthesizing a series of analogs. A set of 16 molecules was first synthesized according to a statistical molecular design approach. One potent inhibitor was identified (IC50 = 3.0 µM), which led to the synthesis of 17 additional imidazo[1,2-a]pyridines in a follow-up study. Among these, several inhibitors were identified showing single digit micromolar potency. An X-ray structure of one of these revealed the binding mode of this class of inhibitors in the ATP-binding site, and allowed us to rationalize some of the structure-activity relationships observed.
Place, publisher, year, edition, pages
2012. Vol. 3, no 5, 620-626 p.
Medicinal Chemistry Medical and Health Sciences
Research subject Chemistry with specialization in Organic Chemistry; Medicinal Chemistry
IdentifiersURN: urn:nbn:se:uu:diva-100359DOI: 10.1039/c2md00310dISI: 000304387300013OAI: oai:DiVA.org:uu-100359DiVA: diva2:210170