3-（1',1'-二甲基丁基）-1-脱氧-δ8-四氢大麻酚及相关化合物：CB2受体选择性配体的合成
3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC and related compounds: synthesis of selective ligands for the CB2 receptor.
作者信息
Huffman J W, Liddle J, Yu S, Aung M M, Abood M E, Wiley J L, Martin B R
机构信息
Howard L. Hunter Laboratory, Clemson University, SC 29634-1905, USA.
出版信息
Bioorg Med Chem. 1999 Dec;7(12):2905-14. doi: 10.1016/s0968-0896(99)00219-9.
The synthesis and pharmacology of 15 1-deoxy-delta8-THC analogues, several of which have high affinity for the CB2 receptor, are described. The deoxy cannabinoids include 1-deoxy-11-hydroxy-delta8-THC (5), 1-deoxy-delta8-THC (6), 1-deoxy-3-butyl-delta8-THC (7), 1-deoxy-3-hexyl-delta8-THC (8) and a series of 3-(1',1'-dimethylalkyl)-1-deoxy-delta8-THC analogues (2, n = 0-4, 6, 7, where n = the number of carbon atoms in the side chain-2). Three derivatives (17-19) of deoxynabilone (16) were also prepared. The affinities of each compound for the CB1 and CB2 receptors were determined employing previously described procedures. Five of the 3-(1',1'-dimethylalkyl)-1-deoxy-delta8-THC analogues (2, n = 1-5) have high affinity (Ki = < 20 nM) for the CB2 receptor. Four of them (2, n = 1-4) also have little affinity for the CB1 receptor (Ki = > 295 nM). 3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC (2, n = 2) has very high affinity for the CB2 receptor (Ki = 3.4 +/- 1.0 nM) and little affinity for the CB1 receptor (Ki = 677 +/- 132 nM).
本文描述了15种1-脱氧-δ8-四氢大麻酚类似物的合成及药理作用，其中几种对CB2受体具有高亲和力。脱氧大麻素包括1-脱氧-11-羟基-δ8-四氢大麻酚（5）、1-脱氧-δ8-四氢大麻酚（6）、1-脱氧-3-丁基-δ8-四氢大麻酚（7）、1-脱氧-3-己基-δ8-四氢大麻酚（8）以及一系列3-(1',1'-二甲基烷基)-1-脱氧-δ8-四氢大麻酚类似物（2，n = 0 - 4、6、7，其中n为侧链-2中的碳原子数）。还制备了脱氧那比隆（16）的三种衍生物（17 - 19）。采用先前描述的方法测定了每种化合物对CB1和CB2受体的亲和力。3-(1',1'-二甲基烷基)-1-脱氧-δ8-四氢大麻酚类似物中的五种（2，n = 1 - 5）对CB2受体具有高亲和力（Ki = < 20 nM）。其中四种（2，n = 1 - 4）对CB1受体的亲和力也很低（Ki = > 295 nM）。3-(1',1'-二甲基丁基)-1-脱氧-δ8-四氢大麻酚（2，n = 2）对CB2受体具有非常高的亲和力（Ki = 3.4 +/- 1.0 nM），对CB1受体的亲和力很低（Ki = 677 +/- 132 nM）。
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