Development of agonists, partial agonists and antagonists in the Δ8-tetrahydrocannabinol series

被引:18
作者
Crocker, PJ
Saha, B
Ryan, WJ
Wiley, JL
Martin, BR
Ross, RA
Pertwee, RG
Razdan, RK [1 ]
机构
[1] Organix Inc, Woburn, MA 01801 USA
[2] Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA
[3] Univ Aberdeen, Dept Biomed Sci, Aberdeen AB25 2ZD, Scotland
基金
英国惠康基金;
关键词
cannabinoids; alkynes; alkenes; pharmacologically active compounds;
D O I
10.1016/S0040-4020(99)00849-2
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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.
引用
收藏
页码:13907 / 13926
页数:20
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