Sadakatali S Gori, Ajit G Thomas, Arindom Pal, Robyn Wiseman, Dana V Ferraris, Run-Duo Gao, Ying Wu, Jesse Alt, Takashi Tsukamoto, Barbara S Slusher, Rana Rais
Glutamate carboxypeptidase-II (GCPII) is a zinc-dependent metalloenzyme implicated in numerous neurological disorders. The pharmacophoric requirements of active-site GCPII inhibitors makes them highly charged, manifesting poor pharmacokinetic (PK) properties. Herein, we describe the discovery and characterization of catechol-based inhibitors including L-DOPA, D-DOPA, and caffeic acid, with sub-micromolar potencies. Of these, D-DOPA emerged as the most promising compound, with good metabolic stability, and excellent PK properties...
September 23, 2022: Pharmaceutics