Prolinamide derivatives as thrombin inhibitors, preparation method and application thereof
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.
1. A compound of formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable prodrug thereof:
wherein:
A represents —SO 2 R 1 , —COR 1 , —R 2 COR 1 , or —R 2 CO 2 R 1 ;
wherein:
R 1 represents cycloalkyl, aryl, —R 3 -cycloalkyl, —R 3 -aryl, or —NR 4 R 5 ;
wherein cycloalkyl and aryl are substituted with 1 or 2 substituents selected from the group consisting of hydroxyl, carboxyl, halogen, C 1-4 alkyl, C 1-4 alkoxy, acyl, sulfonyl, sulfhydryl, alkylthio, cycloalkyl, heterocycloalkyl, amino, alkylamino, dialkylamino, cyano, ester group, trifluoromethyl, and CONH 2 ;
R 2 and R 3 represent unsubstituted C 1˜6 alkyl;
R 4 and R 5 represent independently H or unsubstituted C 1˜6 alkyl;
D represents
F represents —NH—(CH 2 ) m —R 6 ;
wherein:
m represents 1;
R 6 represents unsubstituted
G represents
wherein:
n represents 0; and
R 7 represents H.
2. The compound of formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable prodrug thereof according to claim 1 , characterized in that the compound is:
N,N-dimethylaminosulfonyl-D-leucyl-L-prolyl-[(4-amidinophenyl)methyl]amide hydrochloride.