Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1373534 | Bioorganic & Medicinal Chemistry Letters | 2010 | 5 Pages |
Abstract
Selective inhibition of the aspartyl protease renin has gained attraction as an interesting approach to control hypertension and associated cardiovascular risk factors given its unique position in the renin–angiotensin system. Using a combination of high-throughput screening, parallel synthesis, X-ray crystallography and structure-based design, we identified and optimized a novel series of potent and non-chiral indole-3-carboxamides with remarkable potency for renin. The most potent compound 5k displays an IC50 value of 2 nM.
Graphical abstractRenin-Inhibitor (IC50 = 0.002 μM).Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Bodo Scheiper, Hans Matter, Henning Steinhagen, Ulrich Stilz, Zsolt Böcskei, Valérie Fleury, Gary McCort,