1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles: new high affinity ligands for the cannabinoid CB1 and CB2 receptors

Bioorg Med Chem Lett. 2006 Oct 15;16(20):5432-5. doi: 10.1016/j.bmcl.2006.07.051. Epub 2006 Aug 4.


Two series of 1-alkyl-2-aryl-4-(1-naphthoyl)pyrroles were synthesized and their affinities for the cannabinoid CB(1) and CB(2) receptors were determined. In the 2-phenyl series (5) the N-alkyl group was varied from n-propyl to n-heptyl. A second series of 23 1-pentyl-2-aryl-4-(1-naphthoyl)-pyrroles (6) was also prepared. Several compounds in both series have CB(1) receptor affinities in the 6-30nM range. The high affinities of these pyrrole derivatives relative to JWH-030 (1, R=C(5)H(11)) support the hypothesis that these pyrroles interact with the CB(1) receptor primarily by aromatic stacking.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding, Competitive / drug effects
  • Ligands
  • Molecular Structure
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship


  • Ligands
  • Pyrroles
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2