Referenced in: none

Automatically associated channels: Kv11.1

Title: Discovery of novel and orally active NR2B-selective N-methyl-D-aspartate (NMDA) antagonists, pyridinol derivatives with reduced HERG binding affinity.

Authors: Makoto Kawai, Hiroshi Nakamura, Isao Sakurada, Hirohisa Shimokawa, Hirotaka Tanaka, Miyako Matsumizu, Kazuo Ando, Kazunari Hattori, Atsuko Ohta, Seiji Nukui, Atsushi Omura, Mitsuhiro Kawamura

Journal, date & volume: Bioorg. Med. Chem. Lett., 2007 Oct 15 , 17, 5533-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17768047

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).