A thienopyridazinone-based melanin-concentrating hormone receptor 1 antagonist with potent in vivo anorectic properties

被引：35

作者：

Dyck, Brian ^{[1
]}

Markison, Stacy ^{[1
]}

Zhao, Liren ^{[1
]}

Tamiya, Junko ^{[1
]}

Grey, Jonathan ^{[1
]}

Rowbottom, Martin W. ^{[1
]}

Zhang, Mingzhu ^{[1
]}

Vickers, Troy ^{[1
]}

Sorensen, Katie ^{[1
]}

Norton, Christi ^{[1
]}

Wen, Jenny ^{[1
]}

Heise, Christopher E. ^{[1
]}

Saunders, John ^{[1
]}

Conlon, Paul ^{[1
]}

Madan, Ajay ^{[1
]}

Schwarz, David ^{[1
]}

Goodfellow, Val S. ^{[1
]}

机构：

[1] Neurocrine Biosci Inc, San Diego, CA 92130 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 13期

关键词：

D O I：

10.1021/jm051263c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Melanin-concentrating hormone receptor antagonists containing thieno- and a benzopyridazinone cores were designed and tested as potential anorectic agents. These ligands showed high affinity for the receptor, potent functional activity in vitro, and good oral bioavailabilty in rats. The thiophene analogue exhibited low iv clearance, long half-life, and high brain penetration. In obese rats, the thienopyridazinone demonstrated a dose-dependent reduction in feeding and body weight with doses between 1 and 10 mg kg(-1).

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收藏

页码：3753 / 3756

页数：4

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