Lamarche, Matthew, Leeds, Jennifer, Neckermann, Georg, Osborne, Colin, Palestrant, Deborah, Patane, Michael, Raimondi, Alejandra, Rann, Elin, Sachdeva, Meena, Shao, Jian, Tiamfook, Stacey, Whitehead, Lewis, Brewer, Jason, Yu, Donghui, Amaral, Kerri, Goldovitz, Julie, Bushell, Simon, Deng, Gejing, Dewhurst, Janetta, Dzink-Fox, Joann, Gangl, Eric, Jain, Akash and Mullin, Steve (2011) Antibacterial Optimization of 4-Aminothiazolyl Analogues of the Natural Product GE2270 A: Identification of the Cycloalkylcarboxylic Acids. Journal of Medicinal Chemistry, 54 (23). pp. 8099-8109. ISSN 0022-2623

Abstract

4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A were designed, synthesized, and optimized for the treatment of Gram positive bacterial infections which culminated in the identification of development candidates 1 and 2. In support of development candidate selection, amide 1 and urethane 2 were profiled for antibacterial activity, mechanism of action, antibacterial, selectivity, solubility, formulability, in pharmacokinetic studies, and in the mouse sepsis and thigh animal models of infection. In addition, 1 and 2 were compared to marketed antibiotics used to treat Gram positive bacterial infections.

Item Type:	Article
Additional Information:	Accoridn to the publication plan, this manuscript will be submitted back to back with "ANTIBACTERIAL LEAD OPTIMIZATION OF 4-AMINOTHIAZOLYL ANALOGUES OF GE2270 A: THE CYCLOALKYLCARBOXYLIC ACIDS"
Keywords:	GE2270 A, Curtius, elongation factor Tu, antibiotic, drug discovery, lead optimization.
Date Deposited:	13 Oct 2015 13:15
Last Modified:	13 Oct 2015 13:15
URI:	https://oak.novartis.com/id/eprint/4555