1-[(1-Methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines as mGluR2 Positive Allosteric Modulators for the Treatment of Psychosis
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- 作者：Lei Zhang ; 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 ; III ; Andy Q. Zhang
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：March 24, 2011
- 年：2011
- 卷：54
- 期：6
- 页码：1724-1739
- 全文大小：1209K
- 年卷期：v.54,no.6(March 24, 2011)
- ISSN：1520-4804
文摘
A novel series of mGluR2 positive allosteric modulators (PAMs), 1-[(1-methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines, is herein disclosed. Structure鈭抋ctivity 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.