960062-83-3Relevant articles and documents
Antibacterial optimization of 4-aminothiazolyl analogues of the natural product GE2270 A: Identification of the cycloalkylcarboxylic acids
Lamarche, Matthew J.,Leeds, Jennifer A.,Amaral, Kerri,Brewer, Jason T.,Bushell, Simon M.,Dewhurst, Janetta M.,Dzink-Fox, Joanne,Gangl, Eric,Goldovitz, Julie,Jain, Akash,Mullin, Steve,Neckermann, Georg,Osborne, Colin,Palestrant, Deborah,Patane, Michael A.,Rann, Elin M.,Sachdeva, Meena,Shao, Jian,Tiamfook, Stacey,Whitehead, Lewis,Yu, Donghui
, p. 8099 - 8109 (2012/01/30)
4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for their activity against Gram positive bacterial infections. Optimization efforts focused on improving the physicochemical properties (e.g., aqueous solubility and chemical stability) of the 4-aminothiazolyl natural product template while improving the in vitro and in vivo antibacterial activity. Structure-activity relationships were defined, and the solubility and efficacy profiles were improved over those of previous analogues and 1. These studies identified novel, potent, soluble, and efficacious elongation factor-Tu inhibitors, which bear cycloalkylcarboxylic acid side chains, and culminated in the selection of development candidates amide 48 and urethane 58.
