Huffman John W, Szklennik Paul V, Almond Amanda, Bushell Kristen, Selley Dana E, He Hengjun, Cassidy Michael P, Wiley Jenny L, Martin Billy R
Howard L. Hunter Laboratory, Clemson University, Clemson, SC 29634-0973, USA.
Bioorg Med Chem Lett. 2005 Sep 15;15(18):4110-3. doi: 10.1016/j.bmcl.2005.06.008.
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. GTPgammaS determinations indicate that both compounds are highly efficacious agonists at the CB1 receptor and partial agonists at the CB2 receptor.
已制备出一类新的具有3-苯乙酰基或取代3-苯乙酰基取代基的大麻素类吲哚，并测定了它们对大麻素CB1和CB2受体的亲和力。一般来说，那些具有2-取代苯乙酰基的化合物对两种受体都有良好的亲和力。4-取代类似物对任何一种受体的亲和力都很小，而3-取代化合物的亲和力则处于中间水平。其中两种化合物，1-戊基-3-(2-甲基苯乙酰基)吲哚(JWH-251)和1-戊基-3-(3-甲氧基苯乙酰基)吲哚(JWH-302)，对CB1受体具有5倍的选择性，对CB2受体具有适度的亲和力。GTPγS测定表明，这两种化合物在CB1受体上都是高效激动剂，在CB2受体上是部分激动剂。
