Prolinamide derivatives as thrombin inhibitors, preparation method and application thereof

摘要

Provided are a compound of formula (I), pharmaceutically acceptable salts thereof, preparation methods and applications thereof for inhibiting thrombin, and applications in the treatment and prevention of thrombin-mediated and thrombin-related diseases.

主权项

1. A compound of formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable prodrug thereof: wherein:
A represents —SO2R1, —COR1, —R2COR1, or —R2CO2R1; wherein:
R1 represents cycloalkyl, aryl, —R3-cycloalkyl, —R3-aryl, or —NR4R5;wherein cycloalkyl and aryl are substituted with 1 or 2 substituents selected from the group consisting of hydroxyl, carboxyl, halogen, C1-4 alkyl, C1-4 alkoxy, acyl, sulfonyl, sulfhydryl, alkylthio, cycloalkyl, heterocycloalkyl, amino, alkylamino, dialkylamino, cyano, ester group, trifluoromethyl, and CONH2;R2 and R3 represent unsubstituted C1˜6 alkyl;R4 and R5 represent independently H or unsubstituted C1˜6 alkyl;D represents F represents —NH—(CH2)m—R6;wherein:m represents 1;R6 represents unsubstituted G represents wherein:n represents 0; andR7 represents H.