2. Academic Validation
  3. 1-[(1-methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines as mGluR2 positive allosteric modulators for the treatment of psychosis

1-[(1-methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines as mGluR2 positive allosteric modulators for the treatment of psychosis

  • J Med Chem. 2011 Mar 24;54(6):1724-39. doi: 10.1021/jm101414h.
Lei Zhang 1,  Michael A Brodney,  John Candler,  Angela C Doran,  Allen J Duplantier,  Ivan V Efremov,  Edel Evrard,  Kenneth Kraus,  Alan H Ganong,  Jessica A Haas,  Ashley N Hanks,  Keith Jenza,  John T Lazzaro,  Noha Maklad,  Sheryl A McCarthy,  Weimin Qian,  Bruce N Rogers,  Melinda D Rottas,  Christopher J Schmidt,  Judith A Siuciak,  F David Tingley 3rd,  Andy Q Zhang
Affiliations

Affiliation

  • 1 Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States. Lei.Zhang3@pfizer.com
PMID: 21366332 DOI: 10.1021/jm101414h
Abstract

A novel series of mGluR2 positive allosteric modulators (PAMs), 1-[(1-methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines, is herein disclosed. Structure-activity relationship studies led to potent, selective mGluR2 PAMs with excellent pharmacokinetic profiles. A representative lead compound (+)-17e demonstrated dose-dependent inhibition of methamphetamine-induced hyperactivity and mescaline-induced scratching in mice, providing support for potential efficacy in treating psychosis.

Figures