Synthesis and in vitro pharmacological evaluation of salvinorin A analogues modified at C(2)

被引：61

作者：

Béguin, C

Richards, MR

Wang, YL

Chen, Y

Liu-Chen, LY

Ma, ZZ

Lee, DYW

Carlezon, WA

Cohen, BM

机构：

[1] McLean Hosp, Mol Pharmacol Lab, Belmont, MA 02478 USA

[2] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA

[3] McLean Hosp, Bioorgan & Nat Prod Res Lab, Belmont, MA 02478 USA

[4] McLean Hosp, Behav Genet Lab, Belmont, MA 02478 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 11期

关键词：

salvinorin; kappa-opioid receptor; structure-activity relationship; agonist; partial agonist;

D O I：

10.1016/j.bmcl.2005.03.113

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Salvinorin A is the only known non-nitrogenous and specific K-opioid agonist. A series of salvinorin A derivatives were prepared and tested for in vitro activity at the K-opioid receptor. Unsubstituted carbamate 9 was a potent K-agonist (EC50 = 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. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2761 / 2765

页数：5

共 18 条

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