Title of article :
Discovery of (−)-6-[2-[4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone—A potent NR2B-selective N-methyl d-aspartate (NMDA) antagonist for the treatment of pain
Author/Authors :
YOSHIHIRO MATSUDA AND MAKOTO KAWAI، نويسنده , , Kazuo Ando، نويسنده , , Yukari Matsumoto، نويسنده , , Isao Sakurada، نويسنده , , Masako Hirota، نويسنده , , HIROSHI NAKAMURA، نويسنده , , Atsuko Ohta، نويسنده , , Masaki Sudo، نويسنده , , Kazunari Hattori، نويسنده , , Tadashi Takashima، نويسنده , , Masanori Hizue، نويسنده , , Shuzo Watanabe، نويسنده , , Isami Fujita، نويسنده , , Mayumi Mizutani، نويسنده , , and Mitsuhiro Kawamura، نويسنده ,
Abstract :
(−)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone was identified as an orally active NR2B-subunit selective N-methyl-d-aspartate (NMDA) receptor antagonist. It has very high selectivity for NR2B subunits containing NMDA receptors versus the HERG-channel inhibition (therapeutic index = 4200 vs NR2B binding IC50). This compound has improved pharmacokinetic properties compared to the prototype CP-101,606.
Keywords :
NMDA , NR2B antagonist , PK variability , CYP2D6 , HERG
