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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | (+)-17e |
| Topics | Mescaline |
| Keywords | Allosteric regulation Methamphetamine Pharmacology Allosteric modulator Stereochemistry Combinatorial chemistry |
| Citations | 32 |
| Key points | 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.
Comparable studies
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| Lysergic Acid Diethylamide- and Mescaline-Induced Attenuation of the Effect of Punishment in the Rat Rats | 1976 | Experimental study | |
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