title: Advent of Imidazo[1,2-a]pyridine-3-carboxamides with Potent Multi- and Extended Drug Resistant Antituberculosis Activity.
abstract: A set of nine 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamides and one 2,6-dimethylimidazo[1,2-a]pyrimidine-3-carboxamide were synthesized. The compounds were evaluated for their in vitro anti-tuberculosis activity versus replicating, non-replicating, multi- and extensive drug resistant Mtb strains. The MIC(90) values of seven of these agents were ≤ 1 μM against the various tuberculosis strains tested. A representative compound of this class (1) was screened against seven non-tubercular strains as well as other non-mycobacteria organisms and demonstrated remarkable microbe selectivity. A transcriptional profiling experiment of Mtb treated with compound 1 was performed to give a preliminary indication of the mode of action. Lastly, the in vivo ADME properties of compounds 1, 3, 4, and 6 were assessed. The 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamides are a drug-like and synthetically accessible class of anti-TB agents that have excellent selective potency against multi- and extensive drug resistant TB and encouraging pharmacokinetics.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556.
authors.forename: Garrett C
authors.initials: GC
authors.lastname: Moraski
authors.forename: Lowell D
authors.initials: LD
authors.lastname: Markley
authors.forename: Philip A
authors.initials: PA
authors.lastname: Hipskind
authors.forename: Helena
authors.initials: H
authors.lastname: Boshoff
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Cho
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Miller