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Updated: Jul 12, 2026

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
Discovery of novel and orally active NR2B-selective N-methyl-D-aspartate (NMDA) antagonists, pyridinol derivatives
Makoto Kawai1, Hiroshi Nakamura, Isao Sakurada
1Discovery Chemistry, Pfizer Global Research & Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2393, Japan. makoto.kawai@pfizer.com
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).
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