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

US8497245B2 · kind B2 · utility

Assignee

• THE MEDICINES COMPANY (LEIPZIG) GMBH · DE

Inventors

• Peter Herold · Allschwil, CH
• Stjepan Jelakovic · Allschwil, CH
• Mohammed Daghish · Leipzig, DE
• Claudia Reichelt · Leipzig, DE
• Alexander Schulze · Bad Liebenwerda, DE
• Andrea Schweinitz · Jena, DE
• Friedrich-Alexander Ludwig · Leipzig, DE
• Adel Rafai Far · Saint-Laurent, CA
• Ting-Cih KANG · New Taipei, TW

Key dates

• Filing date: Dec 21, 2011
• Grant date: Jul 30, 2013
• Expiry date: Dec 21, 2031

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention provides methods of making and using compounds of the formula: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; R1 is selected from the group consisting of —CH2NH2, andR2 is selected from the group consisting of —H, —OH, —NH2 and acetyl; R3 is selected from the group consisting of —H, benzyloxycarbonyl and benzylsulfonyl; and R4 is selected from the group consisting of —OH,wherein p is an integer between 0 and 2 inclusively, Y is selected from the group consisting of —O—, —S—, —S(═O)—, —SO2—, methylene, —CH(OH)—, —CH(NH2)—, —CH(CH2—OH)—, —CH(CH2—NH2)— or —N(R6)—, R5 is selected from the group consisting of —H or a simple (C1-C3) alkyl and R6 is selected from the group consisting of —H, a simple (C1-C3) alkyl or a simple (C1-C3) acyl. These compounds are useful as anticoagulant agents as a result of their selective dual inhibition of thrombin and prothrombinase.