Development of novel tail-modified anandamide analogs.
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.
Yao
Fenmei
F
Center for Drug Discovery, Northeastern University, 116 Mugar Life Sciences Building, 360 Huntington Avenue, Boston, MA 02115, USA.
Li
Chen
C
Vadivel
Subramanian K
SK
Bowman
Anna L
AL
Makriyannis
Alexandros
A
D001095:Arachidonic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002186:Cannabinoids / Q000737:chemistry*; D063388:Endocannabinoids; D015394:Molecular Structure; D053284:Polyunsaturated Alkamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000737:chemistry; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C078814:anandamide