| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 10587099 | Bioorganic & Medicinal Chemistry Letters | 2014 | 5 Pages |
Abstract
Thrombin is a serine protease that plays a key role in blood clotting. Pyrrolidine 1 is a potent thrombin inhibitor discovered at Merck several years ago. Seven analogs (2-8) of 1 in which the pyrrolidine core was replaced with various heterocycles were prepared and evaluated for activity against thrombin, clotting factors VIIa, IXa, Xa, and XIIa, and trypsin. The thiomorpholine analog 6 was the most active, essentially matching the thrombin inhibitory activity of 1 with slightly improved selectivity over trypsin.
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Authors
Timothy A. Blizzard, Sanjay Singh, Basanagoud Patil, Naresh Chidurala, Venukrishnan Komanduri, Samarpita Debnath, Sergei Belyakov, Alejandro Crespo, Alice Struck, Marc Kurtz, Judyann Wiltsie, Xun Shen, Lisa Sonatore, Marta Arocho, Dale Lewis,