13339-11-2Relevant academic research and scientific papers
Design, synthesis, and pharmacological evaluation of glutamate carboxypeptidase II (GCPII) inhibitors based on thioalkylbenzoic acid scaffolds
Stoermer, Doris,Vitharana, Dilrukshi,Hin, Niyada,Delahanty, Greg,Duvall, Bridget,Ferraris, Dana V.,Grella, Brian S.,Hoover, Randall,Rojas, Camilo,Shanholtz, Megan K.,Smith, Kyle P.,Stathis, Marigo,Wu, Ying,Wozniak, Krystyna M.,Slusher, Barbara S.,Tsukamoto, Takashi
, p. 5922 - 5932 (2012/07/30)
A series of thiol-based glutamate carboxypeptidase II (GCPII) inhibitors have been synthesized with either a 3-(mercaptomethyl)benzoic acid or 2-(2-mercaptoethyl)benzoic acid scaffold. Potent inhibitors were identified from each of the two scaffolds with IC50 values in the single-digit nanomolar range, including 2-(3-carboxybenzyloxy)-5-(mercaptomethyl)benzoic acid 27c and 3-(2-mercaptoethyl)biphenyl-2,3'-dicarboxylicacid 35c. Compound 35c was found to be metabolically stable and selective over a number of targets related to glutamate-mediated neurotransmission. Furthermore, compound 35c was found to be orally available in rats and exhibited efficacy in an animal model of neuropathic pain following oral administration.
