کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1377742 | 981986 | 2006 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and in vitro evaluation of salvinorin A analogues: Effect of configuration at C(2) and substitution at C(18) Synthesis and in vitro evaluation of salvinorin A analogues: Effect of configuration at C(2) and substitution at C(18)](/preview/png/1377742.png)
κ-opioid receptor ligands have raised interest for their apparent effects on mood. The potent and selective κ-agonist salvinorin A has short-lasting (15 min) depressive-like effects in rats in behavioral models used to study mood disorders. Two series of salvinorin derivatives modified at C(2) and C(18), respectively, were synthesized and their κ-opioid receptor affinities, potencies, and efficacies were evaluated using in vitro receptor binding and biochemical functional assays. Modification at C(2) yielded potent κ-agonists that are predicted to have improved metabolic stability (14a, 15a) or increased water solubility (10b). Our preliminary SAR study at C(18) suggested that this part of the molecule interacts with a tight lipophilic pocket of the κ-receptor.
Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 17, 1 September 2006, Pages 4679–4685