3-(1′,1′-dimethylbutyl)-1-deoxy-Δ8-THC and related compounds:: Synthesis of selective ligands for the CB2 receptor
3-(1′,1′-dimethylbutyl)-1-deoxy-Δ8-THC and related compounds:: Synthesis of selective ligands for the CB2 receptor
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DOI：
10.1016/s0968-0896(99)00219-9
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发表时间：
1999-12-01
影响因子：
3.5
通讯作者：
Martin, BR
中科院分区：
文献类型：
--
作者：
Huffman, JW;Liddle, J;Martin, BR
描述了15种1-脱氧-Delta（8）-THC类似物的合成和药理学，其中几种对CB 2受体具有高亲和力。脱氧大麻素包括1-脱氧-11-羟基-Δ（8）-THC（5）、1-脱氧-Δ（8）-THC（6）、1-脱氧-3-丁基-Δ（8）-THC（7）、1-脱氧-3-己基-Δ（8）-THC（8）和一系列3-羟基-Δ（8）-THC（7）。（1 ′，1 ′-二甲基烷基）-1-脱氧-Δ（8）-THC类似物（2，n= 0-4，6，7，其中n=侧链中的碳原子数-2）。还制备了脱氧那比隆（16）的三种衍生物（17-19）。采用先前描述的程序测定每种化合物对CB 1和CB 2受体的亲和力。5种3-（1 ′，1 ′-二甲基烷基）-1-脱氧-Δ（8）-THC类似物（2，n = 1-5）对CB 2受体具有高亲和力（Ki = < 20 nM）。其中4个（2，n= 1-4）对CB 1受体也具有很小的亲和力（Ki = > 295 nM）。3-（1 '，1'-二甲基丁基）-1-脱氧-δ（8）-THC（2，n = 2）对CB 2受体具有非常高的亲和力（Ki = 3.4 +/- 1.0 nM），对CB 1受体具有很小的亲和力（Ki = 677 +/- 132 nM）。(C)1999 Elsevier Science Ltd.保留所有权利。
The synthesis and pharmacology of 15 1-deoxy-Delta(8)-THC analogues, several of which have high affinity for the CB2 receptor, are described. The deoxy cannabinoids include 1-deoxy-11-hydroxy-Delta(8)-THC (5), 1-deoxy-Delta(8)-THC (6), 1-deoxy-3-butyl-Delta(8)-THC (7), 1-deoxy-3-hexyl-Delta(8)-THC (8) and a series of 3-(1',1'-dimethylalkyl)-1-deoxy-Delta(8)-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-Delta(8)-THC analogues (2, n = 1-5) have high affinity (K-i = < 20 nM) for the CB2 receptor. Four of them (2, n= 1-4) also have little affinity for the CB1 receptor (K-i = > 295 nM). 3-(1',1'-Dimethylbutyl)-1-deoxy-Delta(8)-THC (2, n = 2) has very high affinity for the CB2 receptor (K-i = 3.4 +/- 1.0 nM) and little affinity for the CB1 receptor (K-i = 677 +/- 132 nM). (C) 1999 Elsevier Science Ltd. All rights reserved.