Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595159 | Bioorganic & Medicinal Chemistry Letters | 2013 | 5 Pages |
Abstract
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 Pâ² 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.
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Authors
Peter W. Glunz, Xiaojun Zhang, Yan Zou, Indawati Delucca, Alexandra 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,