Structural modifications of the cannabinoid side chain towards C3-aryl and 1',1'-cycloalkyl-1'-cyano cannabinoids.
The compounds reported in this study are Delta(8)-THC analogues in which the C3 five-carbon linear side chain of Delta(8)-THC was replaced with aryl and 1',1'-cycloalkyl substituents. Of the compounds described here analogues 2d (CB(1), K(i)=11.7 nM. CB(2), K(i)=9.39 nM) and 2f (CB(1), K(i)=8.26 nM. CB(2), K(i)=3.86 nM) exhibited enhanced binding affinities for CB(1) and CB(2), exceeding that of Delta(8)-THC. Efficient procedures for the synthesis of these novel cannabinoid analogues are described.
Papahatjis
Demetris P
DP
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vass. Constantinou, Athens 116-35, Greece. dpapah@eie.gr
Nahmias
Victoria R
VR
Andreou
Thanos
T
Fan
Pusheng
P
Makriyannis
Alexandros
A
D000818:Animals; D001665:Binding Sites; D013759:Dronabinol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D016548:Prosencephalon / Q000187:drug effects; D011619:Psychotropic Drugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects
D008024:Ligands; D011619:Psychotropic Drugs; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013759:Dronabinol