1-[(1-Methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines as mGluR2 Positive Allosteric Modulators for the Treatment of Psychosis
Lei Zhang, Michael A. Brodney, John Candler, Angela C. Doran, Allen J. Duplantier, Ivan Efremov, E Evrard, Kenneth G. Kraus, Alan H. Ganong, Jessica 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, Andy Q. Zhang
Journal of Medicinal Chemistry March 2, 2011 DOI: 10.1021/jm101414h via OpenAlex
Summary
AI-generated from the abstractA new class of compounds, 1-[(1-methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines, acts as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2). Structure-activity relationship studies produced potent and selective mGluR2 PAMs with favorable pharmacokinetic properties. The lead compound (+)-17e dose-dependently reduced methamphetamine-induced hyperactivity and mescaline-induced scratching in mice, suggesting potential for treating psychosis.
Study at a glance
| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice |
| Topics | Mescaline |
| Keywords | Allosteric regulation Methamphetamine Pharmacology Allosteric modulator |
| Citations | 32 |
| Key finding | The lead compound (+)-17e dose-dependently inhibited methamphetamine-induced hyperactivity and mescaline-induced scratching in mice. |
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.