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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / classification
  • Biomimetic Materials / metabolism
  • Biomimetic Materials / pharmacology*
  • Cannabinoids / chemistry*
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / classification
  • Indoles / pharmacology*
  • Molecular Structure
  • Pentanes / chemistry*
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / agonists
  • Receptor, Cannabinoid, CB2 / metabolism
  • Structure-Activity Relationship


  • Cannabinoids
  • Indoles
  • Pentanes
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • pentane