Discovery of Orally Efficacious Tetracyclic Metabotropic Glutamate Receptor 1 (mGluR1) Antagonists for the Treatment of Chronic Pain

详细信息    查看全文

• 作者：Wen-Lian Wu ; Duane A. Burnett ; Martin Domalski ; William J. Greenlee ; Cheng Li ; Rosalia Bertorelli ; Silva Fredduzzi ; Gianluca Lozza ; Alessio Veltri ; Angelo Reggiani
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 15, 2007
• 年：2007
• 卷：50
• 期：23
• 页码：5550 - 5553
• 全文大小：82K
• 年卷期：v.50,no.23(November 15, 2007)
• ISSN：1520-4804

文摘

Metabotropic glutamate receptor 1 (mGluR1) plays importantroles in the neurotransmission and pathogenesis of several neurologicaldisorders, including chronic pain. Antagonists of mGlur1 are suggestedto be useful for the treatment of pain. Herein, we report the discoveryof a novel series of tetracyclic mGluR1 antagonists, such as 23c and23e, with oral efficacy of ED₅₀ of 8 and 5.1 mg/kg, respectively, in ratspinal nerve ligation neuropathic pain model.