532392-52-2Relevant academic research and scientific papers
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: Discovery of an orally active GCP II inhibitor
Majer, Pavel,Jackson, Paul F.,Delahanty, Greg,Grella, Brian S.,Ko, Yao-Sen,Li, Weixing,Liu, Qun,Maclin, Keith M.,Poláková, 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
, p. 1989 - 1996 (2007/10/03)
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 of each of the two zinc-binding groups in GCP II inhibition. The most potent thiol-based inhibitor, 2-(3-mercaptopropyl)pentanedioic acid (IC50 = 90 nM), was found to be orally bioavailable in rats and exhibited efficacy in an animal model of neuropathic pain following oral administration.
