Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor

…, Q Liu, KM Maclin, J Poláková, KA Shaffer…

Index: Majer, Pavel; Jackson, Paul F.; Delahanty, Greg; Grella, Brian S.; Ko, Yao-Sen; Li, Weixing; Liu, Qun; Maclin, Keith M.; Polakova, Jana; Shaffer, Kathryn A.; Stoermer, Doris; Vitharana, Dilrukshi; Yanjun Wang, Eric; Zakrzewski, Anthony; Rojas, Camilo; Slusher, Barbara S.; Wozniak, Krystyna M.; Burak, Eric; Limsakun, Tharin; Tsukamoto, Takashi Journal of Medicinal Chemistry, 2003 , vol. 46, # 10 p. 1989 - 1996

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Citation Number: 62

Abstract

A series of 2-(thioalkyl) pentanedioic acids were synthesized and evaluated as inhibitors of glutamate carboxypeptidase II (GCP II, EC 3.4. 17.21). The inhibitory potency of these thiol- based compounds against GCP II was found to be dependent on the number of methylene units between the thiol group and pentanedioic acid. A comparison of the SAR of the thiol- based inhibitors to that of the phosphonate-based inhibitors provides insight into the role ...