2. Academic Validation
  3. 4-aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators

4-aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators

  • Bioorg Med Chem Lett. 2010 Dec 15;20(24):7381-4. doi: 10.1016/j.bmcl.2010.10.036.
Hui Xiong 1,  Todd A Brugel,  Michael Balestra,  Dean G Brown,  Kelly A Brush,  Caprice Hightower,  Lindsay Hinkley,  Valerie Hoesch,  James Kang,  Gerard M Koether,  John P McCauley Jr,  Francis M McLaren,  Laura M Panko,  Thomas R Simpson,  Reed W Smith,  James M Woods,  Becky Brockel,  Vijay Chhajlani,  Reto A Gadient,  Nathan Spear,  Linda A Sygowski,  Minli Zhang,  Jalaj Arora,  Nathalie Breysse,  Julie M Wilson,  Methvin Isaac,  Abdelmalik Slassi,  Megan M King
Affiliations

Affiliation

  • 1 CNS Discovery, AstraZeneca Pharmaceuticals, Wilmington, DE, USA. hui.xiong@astrazeneca.com
PMID: 21067920 DOI: 10.1016/j.bmcl.2010.10.036
Abstract

Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent activity and desired drug-like properties. Compound 2b was further characterized as a PAM using several in vitro experiments, and produced robust activity in several preclinical animal models.

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