Author/Authors :
YOSHIHIRO MATSUDA AND MAKOTO KAWAI، نويسنده , , HIROSHI NAKAMURA، نويسنده , , Isao Sakurada، نويسنده , , Hirohisa Shimokawa، نويسنده , , Hirotaka Tanaka، نويسنده , , Miyako Matsumizu، نويسنده , , Kazuo Ando، نويسنده , , Kazunari Hattori، نويسنده , , Atsuko Ohta، نويسنده , , Seiji Nukui، نويسنده , , Atsushi Omura، نويسنده , , and Mitsuhiro Kawamura، نويسنده ,
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 > 30 μM). 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).
Keywords :
HERG , NMDA , pain , Solubility , NR2B
