Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors
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- 作者：Peter W. Glunz ; Xiaojun Zhang ; Yan Zou ; Indawati Delucca ; Alex ; ra H. Nirschl ; Xuhong Cheng ; Carolyn A. Weigelt ; Daniel L. Cheney ; Anzhi Wei ; Rushith Anumula ; Joseph M. Luettgen ; Alan R. Rendina ; Mark Harpel ; Gang Luo ; Robert Knabb ; Pancras C. Wong ; Ruth R. Wexler ; E. Scott Priestley
- 关键词：Factor VIIa ; Tissue factor ; TF-FVIIa inhibitor ; Serine protease inhibitors ; Structure-based design
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：15 September, 2013
- 年：2013
- 卷：23
- 期：18
- 页码：5244-5248
- 全文大小：1623 K
文摘
Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P¡ä binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype.