Eisai Research Institute, Baltimore, MD 21224, USA.
Bioorg Med Chem Lett. 2010 Dec 15;20(24):7222-5. doi: 10.1016/j.bmcl.2010.10.109. Epub 2010 Oct 26.
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.
合成了一系列 N-取代的 3-(2-巯基乙基)-1H-吲哚-2-羧酸作为谷氨酸羧肽酶 II (GCPII) 的抑制剂。那些在 N-位含有羧基苄基或羧基苯基的化合物对 GCPII 表现出很强的抑制活性。这些基于吲哚的化合物代表了第一个手性 GCPII 抑制剂的例子，并证明了 GCPII 活性位点对配体的更大容忍度，这些配体与内源性底物 N-乙酰天冬氨酸-谷氨酸具有显著的结构差异。
