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

Citations Over TimeTop 21% of 2008 papers

Abstract

A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5 H-cyclohepta[ b]pyridine-9-ol ( (-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared 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, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K (+)channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.

Related Papers

• → Recent advances in selective opioid receptor agonists and antagonists(2003)163 cited
• → Are μ-opioid receptor polymorphisms important for clinical opioid therapy?(2005)144 cited
• → Receptor‐selective changes in µ‐, δ‐ and κ‐opioid receptors after chronic naltrexone treatment in mice(2003)74 cited
• → Evidence for Multiple Opioid Receptors in the Human Posterior Pituitary(1996)29 cited
• → Opioid-induced modification of granulocyte function(1988)25 cited