Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design
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- 作者：Gui-Bai Liang ; Xiaoxia Qian ; Tesfaye Biftu ; Suresh Singh ; Ying-Duo Gao ; Giovanna Scapin ; Sangita Patel ; Barbara Leiting ; Reshma Patel ; Joseph Wu ; Xiaoping Zhang ; Nancy A. Thornberry ; Ann E. Weber
- 关键词：Diabetes ; DPP-4 inhibitors ; Fluorine H-bond
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 出版时间：1 July 2008
- 年：2008
- 卷：18
- 期：13
- 页码：3706-3710
- 全文大小：427 K
文摘
Probing with tool molecules, and by modeling and X-ray crystallography the binding modes of two structurally distinct series of DPP-4 inhibitors led to the discovery of a rare aromatic fluorine H-bond and the spatial requirement for better biaryl binding in the DPP-4 enzyme active site. These newly found binding elements were successfully incorporated into novel DPP-4 inhibitors.