【文章名】A Novel Class of Cycloalkano[b]pyridines as Potent and Orally Active Opioid Receptor-like 1 Antagonists with Minimal Binding Affinity to the hERG K+ Channel.
A Novel Class of Cycloalkano[b]pyridines as Potent and Orally Active Opioid Receptor-like 1 Antagonists with Minimal Binding Affinity to the hERG K+ Channel.
[摘要]：A series of compds. based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5H-cyclo hepta[b]pyridine-9-ol ((-)-I), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepd. and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K+ channel. From these studies, II was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K+channel. Furthermore, II showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.
