| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1377403 | Bioorganic & Medicinal Chemistry Letters | 2007 | 5 Pages |
Abstract
The structure–activity relationship (SAR) of the vinyl pyridine region of himbacine derived thrombin receptor (PAR-1) antagonists is described. A 2-vinylpyridyl ring substituted with an aryl or a heteroaryl group at the 5-position showed the best overall PAR-1 affinity and pharmacokinetic properties. One of the newly discovered analogs bearing a 5-(3-pyridyl) substituent showed excellent PAR-1 affinity (Ki = 22 nM) and oral activity with reduced C log P and improved off-target selectivity compared to an earlier development candidate.
Graphical abstractThe SAR of the pyridine ring of himbacine derived thrombin receptor (PAR-1) antagonists is described.Figure optionsDownload full-size imageDownload as PowerPoint slide
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Yan Xia, Samuel Chackalamannil, Martin Clasby, Darío Doller, Keith Eagen, William J. Greenlee, Hsingan Tsai, Jacqueline Agans-Fantuzzi, Ho-Sam Ahn, George C. Boykow, Yunsheng Hsieh, Charles A. Lunn, Madhu Chintala,