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Updated: Jun 6, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
4-aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators
Hui Xiong1, Todd A Brugel, Michael Balestra
1CNS Discovery, AstraZeneca Pharmaceuticals, Wilmington, DE, USA. hui.xiong@astrazeneca.com
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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