| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1373527 | Bioorganic & Medicinal Chemistry Letters | 2010 | 5 Pages |
Abstract
Several structure-guided optimisation strategies were explored in order to improve the hERG selectivity profile of cathepsin K inhibitor 1, whilst maintaining its otherwise excellent in vitro and in vivo profile. Ultimately, attenuation of c log P and pKa properties proved a successful approach and led to the discovery of a potent analogue 23, which, in addition to the desired selectivity over hERG (>1000-fold), displayed a highly attractive overall profile.
Graphical abstractStructure-guided optimisation strategies which led to a successful attenuation of hERG block in 2-cyano-pyrimidine series of catK inhibitors are described.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Zoran Rankovic, Jiaqiang Cai, Jennifer Kerr, Xavier Fradera, John Robinson, Ashvin Mistry, William Finlay, George McGarry, Fiona Andrews, Wilson Caulfield, Iain Cumming, Maureen Dempster, John Waller, Wullie Arbuckle, Mark Anderson, Iain Martin,