The discovery and structure–activity relationships of indole-based inhibitors of glutamate carboxypeptidase II
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- 作者：Brian Grella ; Jessica Adams ; James F. Berry ; Greg Delahanty ; Dana V. Ferraris ; Pavel Majer ; Chiyou Ni ; Krupa Shukla ; Scott A. Shuler ; Barbara S. Slusher ; Marigo Stathis ; Takashi Tsukamoto
- 关键词：Glutamate carboxypeptidase II ; Inhibitor ; Indole ; Metallopeptidase ; Thiol
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2010
- 出版时间：15 December 2010
- 年：2010
- 卷：20
- 期：24
- 页码：7222-7225
- 全文大小：687 K
文摘
A series of N-substituted 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acids were synthesized as inhibitors of glutamate carboxypeptidase II (GCPII). Those containing carboxybenzyl or carboxyphenyl groups at the N-position exhibited potent inhibitory activity against GCPII. These indole-based compounds represent the first example of achiral GCPII inhibitors and demonstrate greater tolerance of the GCPII active site for ligands with significant structural difference from the endogenous substrate, N-acetyl-aspartylglutamate.