Patent Number: 8,497,245

Title: Trypsin-like serine protease inhibitors, their preparation and use as selective inhibitors of the clotting factors IIa and Xa

Abstract: The invention provides methods of making and using compounds of the formula: ##STR00001## or a pharmaceutically acceptable salt thereof; wherein n is an integer between 1 and 2 inclusively; m is an integer between 0 and 2 inclusively; X is selected from the group consisting of CH or N; R.sub.1 is selected from the group consisting of --CH.sub.2NH.sub.2, and ##STR00002## R.sub.2 is selected from the group consisting of --H, --OH, --NH.sub.2 and acetyl; R.sub.3 is selected from the group consisting of --H, benzyloxycarbonyl and benzylsulfonyl; and R.sub.4 is selected from the group consisting of --OH, ##STR00003## wherein p is an integer between 0 and 2 inclusively, Y is selected from the group consisting of --O--, --S--, --S(.dbd.O)--, --SO.sub.2--, methylene, --CH(OH)--, --CH(NH.sub.2)--, --CH(CH.sub.2--OH)--, --CH(CH.sub.2--NH.sub.2)-- or --N(R.sub.6)--, R.sub.5 is selected from the group consisting of --H or a simple (C.sub.1-C.sub.3) alkyl and R.sub.6 is selected from the group consisting of --H, a simple (C.sub.1-C.sub.3) alkyl or a simple (C.sub.1-C.sub.3) acyl. These compounds are useful as anticoagulant agents as a result of their selective dual inhibition of thrombin and prothrombinase.

Inventors: Herold; Peter (Muenchenstein, CH), Jelakovic; Stjepan (Freiburg, DE), Daghish; Mohammed (Leipzig, DE), Reichelt; Claudia (Leipzig, DE), Schulze; Alexander (Bad Liebenwerda, DE), Schweinitz; Andrea (Jena, DE), Ludwig; Friedrich-Alexander (Leipzig, DE), Far; Adel Rafai (Kirkland, CA), Kang; Ting (Mount-Royal, CA)

Assignee: The Medicines Company (Leipzig) GmbH

International Classification: A61K 38/05 (20060101)

Expiration Date: 2021-07-30 0:00:00