1. The discovery and structure–activity relationships of indole-based inhibitors of glutamate carboxypeptidase II
- Author
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Barbara S. Slusher, Marigo Stathis, Dana Ferraris, Brian S. Grella, Chiyou Ni, Jessica Adams, Greg Delahanty, James F. Berry, Scott A. Shuler, Krupa Shukla, Pavel Majer, and Takashi Tsukamoto
- Subjects
Glutamate Carboxypeptidase II ,Indoles ,Metallopeptidase ,Stereochemistry ,Clinical Biochemistry ,Carboxylic Acids ,Drug Evaluation, Preclinical ,Pharmaceutical Science ,Biochemistry ,Chemical synthesis ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Glutamate carboxypeptidase II ,Protease Inhibitors ,Molecular Biology ,Indole test ,chemistry.chemical_classification ,Carboxybenzyl ,biology ,Organic Chemistry ,Active site ,Enzyme ,chemistry ,biology.protein ,Thiol ,Molecular Medicine - Abstract
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.
- Published
- 2010