1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles

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• 作者：John W. Huffman ; Paul V. Szklennik ; Amanda Almond ; Kristen Bushell ; Dana E. Selley ; Hengjun He ; Michael P. Cassidy ; Jenny L. Wiley and Billy R. Martin
• 关键词：Cannabinoids ; Structure– ; activity relationships ; Cannabinoid receptors ; Aminoalkylindole
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2005
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：2005
• 卷：15
• 期：18
• 页码：4110-4113
• 文件大小：517 K

摘要

A new class of cannabimimetic indoles, with 3-phenylacetyl or substituted 3-phenylacetyl substituents, has been prepared and their affinities for the cannabinoid CB₁ and CB₂ receptors have been determined. In general those compounds with a 2-substituted phenylacetyl group have good affinity for both receptors. The 4-substituted analogs have little affinity for either receptor, while the 3-substituted compounds are intermediate in their affinities. Two of these compounds, 1-pentyl-3-(2-methylphenylacetyl)indole (JWH-251) and 1-pentyl-3-(3-methoxyphenylacetyl)indole (JWH-302), have 5-fold selectivity for the CB₁ receptor with modest affinity for the CB₂ receptor. GTPγS determinations indicate that both compounds are highly efficacious agonists at the CB₁ receptor and partial agonists at the CB₂ receptor.