%0 Journal Article %A Lilienkampf, Annamaria %A Pieroni, Marco %A Wan, Baojie %A Wang, Yuehong %A Franzblau, Scott G. %A Kozikowski, Alan P. %D 2010 %T Rational Design of 5-Phenyl-3-isoxazolecarboxylic Acid Ethyl Esters as Growth Inhibitors of Mycobacterium tuberculosis. A Potent and Selective Series for Further Drug Development %U https://acs.figshare.com/articles/journal_contribution/Rational_Design_of_5_Phenyl_3_isoxazolecarboxylic_Acid_Ethyl_Esters_as_Growth_Inhibitors_of_i_Mycobacterium_tuberculosis_i_A_Potent_and_Selective_Series_for_Further_Drug_Development/2796481 %R 10.1021/jm901273n.s001 %2 https://ndownloader.figshare.com/files/4490848 %K Drug DevelopmentNew antituberculosis %K Selective Series %K SAR %K 128 μ M %K Growth Inhibitors %K series %K exhibit nanomolar activity %K Ethyl Esters %K INH %K Mycobacterium tuberculosis %K phenoxy derivatives %K RMP %K Mtb strains %K Vero cells %K SM %K Several compounds %K TB drug development %K IC 50 %K drug design approach %K Rational Design %K micromolar activity %K nonreplicating bacteria %X New antituberculosis (anti-TB) drugs are urgently needed to shorten the 6−12 month treatment regimen and especially to battle drug-resistant Mycobacterium tuberculosis (Mtb) strains. In this study, we have continued our efforts to develop isoxazole-based anti-TB compounds by applying rational drug design approach. The biological activity and the structure−activity relationships (SAR) for a designed series of 5-phenyl-3-isoxazolecarboxylic acid ethyl ester derived anti-TB compounds were investigated. Several compounds were found to exhibit nanomolar activity against the replicating bacteria (R-TB) and low micromolar activity against the nonreplicating bacteria (NRP-TB). The series showed excellent selectivity toward Mtb, and in general, no cytotoxicity was observed in Vero cells (IC50 > 128 μM). Notably, selected compounds also retained their activity against isoniazid (INH), rifampin (RMP), and streptomycin (SM) resistant Mtb strains. Hence, benzyloxy, benzylamino, and phenoxy derivatives of 5-phenyl-3-isoxazolecarboxylic acid ethyl esters represent a highly potent, selective, and versatile series of anti-TB compounds and as such present attractive lead compounds for further TB drug development. %I ACS Publications