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ID: ALA1137458
Journal: Bioorg Med Chem Lett
Title: Discovery of novel and orally active NR2B-selective N-methyl-D-aspartate (NMDA) antagonists, pyridinol derivatives with reduced HERG binding affinity.
Authors: Kawai M, Nakamura H, Sakurada I, Shimokawa H, Tanaka H, Matsumizu M, Ando K, Hattori K, Ohta A, Nukui S, Omura A, Kawamura M.
Abstract: Novel NR2B antagonists with an amide tether were found by an approach to avoid pharmacophoric similarity to dofetilide. Structure-activity relationship investigation led to N-[cis-4-hydroxy-4-(5-hydroxypyridin-2-yl)cyclohexyl]-3-henylpropanamide as an orally active NR2B-subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist with very weak HERG (human ether-a-go-go related gene) binding (IC(50)> 30 microM). This compound exhibited potent in vivo anti-allodynic activity in the mouse partial sciatic nerve ligation (PSL) model (minimum effective dose=10 mg/kg, po).
CiteXplore: 17768047