Béguin Cécile, Richards Michele R, Wang Yulin, Chen Yong, Liu-Chen Lee-Yuan, Ma Zhongze, Lee David Y W, Carlezon William A, Cohen Bruce M
Molecular Pharmacology Laboratory, McLean Hospital, Belmont, MA 02478, USA.
Bioorg Med Chem Lett. 2005 Jun 2;15(11):2761-5. doi: 10.1016/j.bmcl.2005.03.113.
Salvinorin A is the only known non-nitrogenous and specific kappa-opioid agonist. A series of salvinorin A derivatives were prepared and tested for in vitro activity at the kappa-opioid receptor. Unsubstituted carbamate 9 was a potent kappa-agonist (EC(50) = 6.2 nM) and should be more stable than salvinorin A toward metabolic transformations. Compound 10, containing an N-methyl carbamate at C(2), showed partial agonist activity with 81% efficacy when compared with the full agonist U50,488H. No antagonist ligands were observed.
萨尔维诺灵A是唯一已知的非含氮特异性κ-阿片受体激动剂。制备了一系列萨尔维诺灵A衍生物，并对其在κ-阿片受体上的体外活性进行了测试。未取代的氨基甲酸酯9是一种强效κ-激动剂（半数有效浓度EC(50)=6.2 nM），并且在代谢转化方面应该比萨尔维诺灵A更稳定。化合物10在C(2)位含有N-甲基氨基甲酸酯，与完全激动剂U50,488H相比，显示出81%效能的部分激动剂活性。未观察到拮抗剂配体。
