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

…, H Nakamura, I Sakurada, H Shimokawa…

Index: Kawai, Makoto; Nakamura, Hiroshi; Sakurada, Isao; Shimokawa, Hirohisa; Tanaka, Hirotaka; Matsumizu, Miyako; Ando, Kazuo; Hattori, Kazunari; Ohta, Atsuko; Nukui, Seiji; Omura, Atsushi; Kawamura, Mitsuhiro Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 20 p. 5533 - 5536

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Citation Number: 9

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 14e 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 (IC50> 30μM). This compound ...