Discovery and characterization of aminopiperidinecoumarin melanin concentrating hormone receptor 1 antagonists

被引：53

作者：

Kym, PR

Iyengar, R

Souers, AJ

Lynch, JK

Judd, AS

Gao, J

Freeman, J

Mulhern, M

Zhao, G

Vasudevan, A

Wodka, D

Blackburn, C

Brown, J

Che, JL

Cullis, C

Lai, SJ

LaMarche, MJ

Marsilje, T

Roses, J

Sells, T

Geddes, B

Govek, E

Patane, M

Fry, D

Dayton, BD

Brodjian, S

Falls, D

Brune, M

Bush, E

Shapiro, R

Knourek-Segel, V

Fey, T

McDowell, C

Reinhart, GA

Preusser, LC

Marsh, K

Hernandez, L

Sham, HL

Collins, CA

机构：

[1] Abbott Labs, Metab Dis Res, Abbott Pk, IL 60064 USA

[2] Millennium Pharmaceut, Cambridge, MA 02139 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 19期

关键词：

D O I：

10.1021/jm050598r

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

4-(1-Benzo[1,3]dioxol-5-ylmethylpiperidine-4-ylmethyl)-6-chlorochromen-2-one (7) is a potent, orally bioavailable melanin concentrating hormone receptor 1 (MCHr1) antagonist that causes dose-dependent weight loss in diet-induced obese mice. Further evaluation of 7 in an anesthetized dog model of cardiovascular safety revealed adverse hemodynamic effects at a plasma concentration comparable to the minimally effective therapeutic concentration. These results highlight the need for scrutiny of the cardiovascular safety profile of MCHr1 antagonists.

引用

页码：5888 / 5891

页数：4

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