Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity

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• 作者：Harry R. Chobanian ; Yan Guo ; Ping Liu ; Marc Chioda ; Thomas J. Lanza ; Jr. ; Linda Chang ; Theresa M. Kelly ; Yanqing Kan ; Oksana Palyha ; Xiao-Ming Guan ; Donald J. Marsh ; Joseph M. Metzger ; Judith N. Gorski ; Kate Raustad ; Sheng-Ping Wang ; Alison M. Strack ; Randy Miller ; Jianmei Pang ; Maria Madeira ; Kathy Lyons ; Jasminka Dragovic ; Marc L. Reitman ; Ravi P. Nargund ; Linus S. Lin
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：March 8, 2012
• 年：2012
• 卷：3
• 期：3
• 页码：252-256
• 全文大小：345K
• 年卷期：v.3,no.3(March 8, 2012)
• ISSN：1948-5875

文摘

Extensive structure鈥揳ctivity relationship studies of a series derived from atropisomer 1, a previously described chiral benzodiazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.

Keywords:

Bombesin receptor subtype-3; BRS-3; agonist; obesity; benzodiazepine sulfonamide; atropisomer; MK-7725