Dabigatran ester derivatives as prodrug

Abstract

The invention relates to dabigatran ester derivatives as shown in a constitutional formula I, pharmaceutically acceptable nontoxic salts thereof, medical composite containing the compounds as active components, and application of thrombin inhibitor of the compounds and medical composites, wherein R1 represents H or C1 to C5 alkyl; R2 represents H, or C1 to C3 alkyl; and R3 represents C1 to C8 alkyl or substituted alkyl.

Description

technical field

[0001] The present invention relates to new ester derivatives of dabigatran and their non-toxic pharmaceutically acceptable salts, as well as pharmaceutical compositions containing these compounds as active ingredients, and the compounds and pharmaceutical compositions as thrombin inhibitors use. Background technique

[0002] Dabigatran is a selective and highly effective thrombin inhibitor. However, due to the presence of a strong basic amidine group, it cannot be absorbed orally. In order to improve its bioavailability, the free carboxyl group in the dabigatran molecule is converted into ethyl ester, and the amidine group is converted into hexyl carbamate to obtain its double prodrug dabigatran diester (Dabigatran Etexilate). After oral administration, dabigatran diester is absorbed from the gastrointestinal tract, and then converted into the active form of dabigatran in the body to exert anticoagulant effect. Dabigatran diester was launched in 2008 and ...

Images