Synthetic sequences were developed (Schemes 1 to 6) for the syntheses of various Delta(8)-THC analogs with either a rigid acetylenic linkage or a cis-double bond in different positions in the side chain. Various alkyne and cis-ene-Delta(8)-THC analogs were also synthesized carrying a functional group such as a cyano, isothiocyano, azido, amino, nitro, bromo, hydroxy, fluoro and a methoxy group at the chain terminal. The in vitro and in vivo pharmacology of these unique analogs have provided several ligands which are partial agonists or antagonists of the cannabinoid receptor CB1. The 2'-position in the side chain was found to be optimum for activity. (C) 1999 Elsevier Science Ltd. All rights reserved
Development of agonists, partial agonists and antagonists in the Delta(8)-tetrahydrocannabinol series
Crocker, PJ., Saha, B., Ryan, WJ., Wiley, J., Martin, BR., Ross, RA., ... Razdan, RK. (1999). Development of agonists, partial agonists and antagonists in the Delta(8)-tetrahydrocannabinol series. Tetrahedron, 55(49), 13907-13926.