3u6b

Publication Abstract from PubMed

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.

Antibacterial optimization of 4-aminothiazolyl analogues of the natural product GE2270 A: identification of the cycloalkylcarboxylic acids.,LaMarche MJ, Leeds JA, Amaral K, Brewer JT, Bushell SM, Dewhurst JM, Dzink-Fox J, Gangl E, Goldovitz J, Jain A, Mullin S, Neckermann G, Osborne C, Palestrant D, Patane MA, Rann EM, Sachdeva M, Shao J, Tiamfook S, Whitehead L, Yu D J Med Chem. 2011 Dec 8;54(23):8099-109. Epub 2011 Nov 1. PMID:21999529^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.