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

Huffman, J. W., Szklennik, P. V., Almond, A., Bushell, K., Selley, D. E., He, H. J., ... Martin, B. R. (2005). 1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles. Bioorganic and Medicinal Chemistry Letters, 15(18), 4110-4113.

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. GTP gamma S determinations indicate that both compounds are highly efficacious agonists at the CB1 receptor and partial agonists at the CB2 receptor. (c) 2005 Elsevier Ltd. All rights reserved