Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1' side chain.

@article{Majer2006StructuralOO,
  title={Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1' side chain.},
  author={Pavel Majer and Bunda Hin and Doris Stoermer and Jessica Adams and Weizhen Xu and Bridget R Duvall and Greg Delahanty and Qun Liu and Marigo J Stathis and Krystyna M. Wozniak and Barbara S. Slusher and Takashi Tsukamoto},
  journal={Journal of medicinal chemistry},
  year={2006},
  volume={49 10},
  pages={
          2876-85
        }
}
A series of thiol-based inhibitors containing a benzyl moiety at the P1' position have been synthesized and tested for their abilities to inhibit glutamate carboxypeptidase II (GCP II). 3-(2-Carboxy-5-mercaptopentyl)benzoic acid 6c was found to be the most potent inhibitor with an IC(50) value of 15 nM, 6-fold more potent than 2-(3-mercaptopropyl)pentanedioic acid (2-MPPA), a previously discovered, orally active GCP II inhibitor. Subsequent SAR studies have revealed that the phenoxy and… Expand
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