Synthesis and pharmacology of a hybrid cannabinoid.
A pentacyclic hybrid cannabinoid (4) has been synthesized, which combines structural elements of traditional cannabinoids and cannabmimetic indoles. Cannabinoid 4 contains a 1-pentylindole structure fused to the 2,3-positions of the partially reduced hydroxydibenzopyran system of THC. The successful approach to 4 employed 9-benzoyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole (17) as the starting material. Dehydrogenation to carbazole 18, followed by demethylation and condensation with trans-p-menthadienol gave N-benzoyl hybrid cannabinoid 22, N-alkylation of which afforded target cannabinoid 4. The hybrid cannabinoid had affinity for the CB1 receptor approximately equal to that of delta8-THC (Ki = 19.3+/-3 nM), and shows comparable potency in vivo.
Huffman
J W
JW
Howard L. Hunter Laboratory, Clemson University, SC 29634-1905, USA. huffman@clemson.edu
Lu
J
J
Dai
D
D
Kitaygorodskiy
A
A
Wiley
J L
JL
Martin
B R
BR
D000818:Animals; D002186:Cannabinoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects
D002186:Cannabinoids