Ivy Carroll F, Yokota Yasuno, Ma Wei, Lee Jeffrey R, Brieaddy Lawrence E, Burgess Jason P, Navarro Hernán A, Damaj M I, Martin Billy R
Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709, USA.
Bioorg Med Chem. 2008 Jan 15;16(2):746-54. doi: 10.1016/j.bmc.2007.10.027. Epub 2007 Oct 13.
A series of 3'-(substituted phenyl)deschloroepibatidine analogs (5a-j) were synthesized. The alpha4beta2( *) and alpha7 nicotinic acetylcholine receptor (nAChR) binding properties and functional activity in the tail-flick, hot-plate, locomotor, and body temperature tests in mice of 5a-j were compared to those of the nAChR agonist, nicotine (1), epibatidine (4), and deschloroepibatidine (13), the partial agonist, varenicline (3), and the antagonist 2'-fluoro-3'-(substituted phenyl)deschloroepibatidine analogs (7a-j). Unlike epibatidine and deschloroepibatidine, which are potent agonists in the tail-flick test, 5a-k show no or very low antinociceptive activity in the tail-flick or hot-plate test. However, they are potent antagonists in nicotine-induced antinociception in the tail-flick test, but weaker than the corresponding 2'-fluoro-3'-(substituted phenyl)deschloroepibatidines.
合成了一系列3'-(取代苯基)去氯埃博霉素类似物(5a-j)。将5a-j在小鼠甩尾、热板、运动和体温测试中的α4β2(*)和α7烟碱型乙酰胆碱受体(nAChR)结合特性及功能活性，与nAChR激动剂尼古丁(1)、埃博霉素(4)和去氯埃博霉素(13)、部分激动剂伐尼克兰(3)以及拮抗剂2'-氟-3'-(取代苯基)去氯埃博霉素类似物(7a-j)的进行了比较。与在甩尾试验中为强效激动剂的埃博霉素和去氯埃博霉素不同，5a-k在甩尾或热板试验中无抗伤害感受活性或抗伤害感受活性非常低。然而，它们在甩尾试验中对尼古丁诱导的抗伤害感受是强效拮抗剂，但比相应的2'-氟-3'-(取代苯基)去氯埃博霉素弱。
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