Discovery and optimization of orally active cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors
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- 作者：John S. Debenham ; Thomas H. Graham ; Andreas Verras ; Yong Zhang ; Matthew J. Clements ; Jeffrey T. Kuethe ; Christina Madsen-Duggan ; Wensheng Liu ; Urmi R. Bhatt ; Dunlu Chen ; Qing Chen ; Margarita Garcia-Calvo ; Wayne M. Geissler ; Huaibing He ; Xiaohua Li ; JeanMarie Lisnock ; Zhu Shen ; Xinchun Tong ; Elaine C. Tung ; Judyann Wiltsie ; et al.
- 关键词：PrCP ; Prolylcarboxypeptidase ; Serine protease ; Inhibitor ; Obesity
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：1 December, 2013
- 年：2013
- 卷：23
- 期：23
- 页码：6228-6233
- 全文大小：2455 K
文摘
The synthesis, SAR, binding affinities and pharmacokinetic profiles are described for a series of cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors discovered by high throughput screening. Compounds show high levels of ex vivo target engagement in mouse plasma 20 h post oral dose.