ANTIBACTERIAL LEAD OPTIMIZATION OF 4-AMINOTHIAZOLYL ANALOGUES OF GE2270 A: THE CYCLOALKYLCARBOXYLIC ACIDS
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Lamarche, Matthew, Leeds, Jennifer, Brewer, Jason, Bushell, Simon, Dewhurst, Janetta, Jain, Akash, Mullin, Steve, Neckermann, Georg, Palestrant, Deborah, Patane, Michael, Rann, Elin, Sachdeva, Meena, Shao, Jian, Whitehead, Lewis, Tiamfook, Stacey and Yu, Donghui (2011) ANTIBACTERIAL LEAD OPTIMIZATION OF 4-AMINOTHIAZOLYL ANALOGUES OF GE2270 A: THE CYCLOALKYLCARBOXYLIC ACIDS. Journal of Medicinal Chemistry, 54 (7). pp. 2517-2521. ISSN 0022-2623
Abstract
4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of Gram positive bacterial infections. Lead optimization efforts of the 4-aminothiazolyl natural product template focused on improving aqueous solubility while maintaining in vitro and in vivo antibacterial activity. Structure-activity relationships were defined, and the solubility and efficacy profiles were improved. These studies culminated in the identification of the cycloalkyl-carboxylic acid class of EF-Tu inhibitors, and development candidates amide 48 and urethane 58.
| Item Type: | Article |
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| Additional Information: | archiving not formally supported by this publisher |
| Keywords: | GE2270 A, Curtius, elongation factor Tu, antibiotic, drug discovery, lead optimization. |
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| Date Deposited: | 13 Oct 2015 13:15 |
| Last Modified: | 13 Oct 2015 13:15 |
| URI: | https://oak.novartis.com/id/eprint/4553 |