Novel C-Ring-Hydroxy-Substituted Controlled Deactivation Cannabinergic Analogues.
J Med Chem
; 59(14): 6903-19, 2016 07 28.
Article
in En
| MEDLINE
| ID: mdl-27367336
ABSTRACT
In pursuit of safer controlled-deactivation cannabinoids with high potency and short duration of action, we report the design, synthesis, and pharmacological evaluation of novel C9- and C11-hydroxy-substituted hexahydrocannabinol (HHC) and tetrahydrocannabinol (THC) analogues in which a seven atom long side chain, with or without 1'-substituents, carries a metabolically labile 2',3'-ester group. Importantly, in vivo studies validated our controlled deactivation approach in rodents and non-human primates. The lead molecule identified here, namely, butyl-2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-3-yl]-2-methylpropanoate (AM7499), was found to exhibit remarkably high in vitro and in vivo potency with shorter duration of action than the currently existing classical cannabinoid agonists.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cannabinol
/
Receptors, Cannabinoid
/
Cannabinoid Receptor Agonists
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2016
Document type:
Article
Affiliation country: