Discovery of (-)-6-[2-[4-(3-fluorophenyl)-4-hydroxy-l-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone -: A potent NR2B-selective N-methyl D-aspartate (NMDA) antagonist for the treatment of pain

被引：17

作者：

Kawai, Makoto

Ando, Kazuo

Matsumoto, Yukari

Sakurada, Isao

Hirota, Masako

Nakamura, Hiroshi

Ohta, Atsuko

Sudo, Masaki

Hattori, Kazunari

Takashima, Tadashi

Hizue, Masanori

Watanabe, Shuzo

Fujita, Isami

Mizutani, Mayumi

Kawamura, Mitsuhiro

机构：

[1] Pfizer Global Res & Dev, Nagoya Labs, Discovery Chem, Aichi 4702393, Japan

[2] Pfizer Global Res & Dev, Nagoya Labs, Discovery Biol, Aichi 4702393, Japan

[3] Pfizer Global Res & Dev, Nagoya Labs, Pharmacokinet Dynam & Metab, Aichi 4702393, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 20期

关键词：

NMDA; NR2B antagonist; PK variability; CYP2D6; HERG;

D O I：

10.1016/j.bmcl.2007.08.014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(-)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-l-piperidinyl]-l-hyd roxyethyl]-3,4-di hydro-2(1H)-quinolin one 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. (c) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5558 / 5562

页数：5

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