The role of fluorine substitution in the structure-activity relationships (SAR) of classical cannabinoids.
A facile synthesis of 1-fluoro-1-deoxy-Delta(8)-THC analogs with side chains seven carbons in length, in the alkane/ene/yne- series (6, 5, and 4), was achieved from 1-fluoro-3,5-dimethoxybenzene (1). In vitro studies show that substitution by a fluorine has a significant detrimental effect on CB1 binding which is supported by in vivo testing. The implications of these results on the SAR of classical cannabinoids are discussed.
Crocker
Peter J
PJ
Organix Inc., 240 Salem Street, Woburn, MA 01801, USA.
Mahadevan
Anu
A
Wiley
Jenny L
JL
Martin
Billy R
BR
Razdan
Raj K
RK
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002186:Cannabinoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005461:Fluorine / Q000737:chemistry*; D007202:Indicators and Reagents; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects; D013329:Structure-Activity Relationship
D002186:Cannabinoids; D007202:Indicators and Reagents; D043884:Receptor, Cannabinoid, CB1; D005461:Fluorine