Development of novel tail-modified anandamide analogs

Bioorg Med Chem Lett. 2008 Nov 15;18(22):5912-5. doi: 10.1016/j.bmcl.2008.07.110. Epub 2008 Jul 31.


To explore the hydrophobic groove subsite within the CB1 cannabinoid receptor we have designed and synthesized a group of tail-substituted anandamide analogs. Our design involves the introduction of aryl or heterocyclic ring as terminal substituents that are connected to the last cis-arachidonyl double bond through aliphatic chains of variable lengths. Our results indicate that there are strict stereochemical requirements for the interaction of such analogs with the CB1 receptor. The optimal pharmacophore includes the phenyl, p-substituted phenyl, or 3-furyl substituents attached to the cis-double bond through a four methylene chain.

Publication types

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

MeSH terms

  • Arachidonic Acids / chemical synthesis*
  • Arachidonic Acids / chemistry
  • Arachidonic Acids / pharmacology
  • Cannabinoids / chemistry*
  • Endocannabinoids
  • Molecular Structure
  • Polyunsaturated Alkamides / chemical synthesis*
  • Polyunsaturated Alkamides / chemistry
  • Polyunsaturated Alkamides / pharmacology
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB1 / chemistry
  • Receptor, Cannabinoid, CB2 / agonists
  • Receptor, Cannabinoid, CB2 / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship


  • Arachidonic Acids
  • Cannabinoids
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • anandamide