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: 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; Ris selected from the group consisting of —CHNH, and Ris selected from the group consisting of —H, —OH, —NHand acetyl; Ris selected from the group consisting of —H, benzyloxycarbonyl and benzylsulfonyl; and Ris 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)—, —SO—, methylene, —CH(OH)—, —CH(NH)—, —CH(CH—OH)—, —CH(CH—NH)— or —N(R)—, Ris selected from the group consisting of —H or a simple (C-C) alkyl and Ris selected from the group consisting of —H, a simple (C-C) alkyl or a simple (C-C) acyl. These compounds are useful as anticoagulant agents as a result of their selective dual inhibition of thrombin and prothrombinase.