Synthesis, biological evaluation, and structure-activity relationships for 5-[(E)-2-arylethenyl]-3-isoxazolecarboxylic acid alkyl ester derivatives as valuable antitubercular chemotypes.
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| Abstract |
Tuberculosis (TB), mostly caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death from infectious disease worldwide. Its coinfection with HIV and the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains have further worsened the TB pandemic. Despite its global impact, TB is considered a neglected disease and no new anti-TB therapeutics have been introduced over the last four decades. The nonreplicating persistent form of TB (NRP-TB) is responsible for the length of the treatment and is the putative cause of treatment failure. Therefore, new anti-TB agents, which are active against both the replicating form of Mtb (R-TB) and NRP-TB, are urgently needed. Herein, we report the synthesis and structure-activity relationships (SAR) of a series of 5-[(E)-2-arylethenyl]-3-isoxazolecarboxylic acid alkyl esters as potent anti-TB agents. Several compounds had submicromolar minimum inhibitory concentrations (MIC) against R-TB and were active against NRP-TB in the low micromolar range, thus representing attractive lead compounds for the possible development of new anti-TB agents.
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| Authors | Marco Pieroni, Annamaria Lilienkampf, Baojie Wan, Yuehong Wang, Scott G Franzblau, Alan P Kozikowski |
| Journal | Journal of medicinal chemistry (J Med Chem) Vol. 52 Issue 20 Pg. 6287-96 (Oct 22 2009) ISSN: 1520-4804 [Electronic] United States |
| PMID | 19757815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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