Development of a novel class of monocyclic and bicyclic alkyl amides that exhibit CB1 and CB2 cannabinoid receptor affinity and receptor activation

Barbara A. Berglund, Paul R. Fleming, Kenner C. Rice, Joung Yoon Shim, William J. Welsh, Allyn C. Howlett

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

CB1 and CB2 cannabinoid receptors can be activated by several different classes of agonists, including cannabinoids such as Δ9-tetrahydrocannabinol and 9-nor-9β-hydroxyhexahydrocannabinol, and eicosanoids such as arachidonylethanolamide. Structure-activity relationship studies have identified potential pharmacophoric elements for binding to cannabinoid receptors by both cannabinoids and eicosanoids. Molecular models have hypothesized conformational, spatial, and pharmacophoric distance requirements based upon radioligand binding data whereby overlap of pharmacophoric elements of the two classes disclose a low energy conformation of arachidonylethanolamide that can occupy the same receptor space as cannabinoid ligands. To test this model, we have developed a novel class of monocyclic and bicyclic alkyl amide cannabinoid receptor ligands. Further, we predicted a spatial conformation for these compounds in a molecular model based on the pharmacophoric and structural requirements for binding to the CB1 cannabinoid receptor.

Original languageEnglish (US)
Pages (from-to)281-294
Number of pages14
JournalDrug Design and Discovery
Volume16
Issue number4
StatePublished - 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Keywords

  • Adenylyl cyclase
  • DISCO
  • G proteins
  • GTPγS binding
  • Gi
  • Signal transduction

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