Discovery of CP-866,087, a mu opioid receptor antagonist for the treatment of alcohol abuse and dependence

被引：21

作者：

McHardy, Stanton F. ^{[1
]}

Heck, Steven D. ^{[1
]}

Guediche, Sara ^{[1
]}

Kalman, Monica ^{[1
]}

Allen, Martin P. ^{[1
]}

Tu, Meihua ^{[1
]}

Bryce, Dianne K. ^{[2
]}

Schmidt, Anne W. ^{[2
]}

Vanase-Frawley, Michelle ^{[2
]}

Callegari, Ernesto ^{[3
]}

Doran, Shawn ^{[3
]}

Grahame, Nicholas J. ^{[4
]}

McLean, Stafford ^{[2
]}

Liras, Spiros ^{[1
]}

机构：

[1] Pfizer Inc, Worldwide Res & Dev, Worldwide Med Chem, Groton, CT 06340 USA

[2] Pfizer Inc, Worldwide Res & Dev, Neurosci Biol, Groton, CT 06340 USA

[3] Pfizer Inc, Worldwide Res & Dev, Pharmacokinet Dynam & Metab, Groton, CT 06340 USA

[4] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA

来源：

MEDCHEMCOMM | 2011年 / 2卷 / 10期

关键词：

CYTOCHROME-P450; 2D6; DRUG; METABOLISM; PATHWAYS;

D O I：

10.1039/c1md00164g

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

CP-866,087 (compound 15) is a novel, potent and selective mu opioid receptor antagonist. The design rationale, synthesis, in vitro and in vivo biological evaluation are reported herein. Preclinical efficacy data in disease relevant models measuring reduction of alcohol intake are presented, along with preclinical pharmacokinetic properties which supported the selection of the title compound for clinical evaluation.

引用

页码：1001 / 1005

页数：5

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