4-(3-Chloro-5-(trifluoromethyl) pyridin-2-yl)-N-(4-methoxypyridin-2-yl) piperazine-1-carbothioamide (ML267), a potent inhibitor of bacterial phosphopantetheinyl …

…, T Daniel, HL Baker, M Attene-Ramos…

Index: Foley, Timothy L.; Rai, Ganesha; Yasgar, Adam; Daniel, Thomas; Baker, Heather L.; Attene-Ramos, Matias; Kosa, Nicolas M.; Leister, William; Burkart, Michael D.; Jadhav, Ajit; Simeonov, Anton; Maloney, David J. Journal of Medicinal Chemistry, 2014 , vol. 57, # 3 p. 1063 - 1078

Full Text: HTML

Citation Number: 11

Abstract

4′-Phosphopantetheinyl transferases (PPTases) catalyze a post-translational modification essential to bacterial cell viability and virulence. We present the discovery and medicinal chemistry optimization of 2-pyridinyl-N-(4-aryl) piperazine-1-carbothioamides, which exhibit submicromolar inhibition of bacterial Sfp-PPTase with no activity toward the human orthologue. Moreover, compounds within this class possess antibacterial activity in the ...