Tricyclic dihydroquinazolinones as novel 5-HT2C selective and orally efficacious anti-obesity agents

被引：18

作者：

Ahmad, Saleem ^{[1
]}

Ngu, Khehyong ^{[1
]}

Miller, Keith J. ^{[1
]}

Wu, Ginger ^{[1
]}

Hung, Chen-pin ^{[1
]}

Malmstrom, Sarah ^{[1
]}

Zhang, Ge ^{[1
]}

O'Tanyi, Eva ^{[1
]}

Keim, William J. ^{[1
]}

Cullen, Mary Jane ^{[1
]}

Rohrbach, Kenneth W. ^{[1
]}

Thomas, Michael ^{[1
]}

Ung, Thao ^{[1
]}

Qu, Qinling ^{[1
]}

Gan, Jinping ^{[1
]}

Narayanan, Rangaraj ^{[1
]}

Pelleymounter, Mary Ann ^{[1
]}

Robl, Jeffrey A. ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Res & Dev, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 03期

关键词：

Serotonin; 5-HT2C; Obesity; RECEPTOR AGONISTS; D-FENFLURAMINE; BODY-WEIGHT; FOOD-INTAKE; 5-HYDROXYTRYPTAMINE(2C); LORCASERIN; DISCOVERY;

D O I：

10.1016/j.bmcl.2009.12.014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Agonists of the 5-HT2C receptor have been shown to suppress appetite and reduce body weight in animal models as well as in humans. However, agonism of the related 5-HT2B receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and highly selective dihydroquinazolinone-derived 5-HT2C agonists with no detectable agonism of the 5-HT2B receptor is described. Among these, compounds (+)-2a and (+)-3c were identified as potent and highly selective agonists which exhibited weight loss in a rat model upon oral dosing. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1128 / 1133

页数：6

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