Series of halogenated tetracyclic triterpene derivatives and their preparation and application

Abstract

The invention provides a series of halogenated tetracyclic triterpene derivatives and their preparation and application. It is represented by the following general structural formula: R1 is halogen, R2 is H, and the halogen is selected from fluorine, chlorine, bromine or iodine; or R1 and R2 are each fluorine, and R3 is an amine, alcohol, amino acid, peptide or phosphate linked to oxygen through an acyl group. The derivatives are relatively stable in rat whole blood through pharmacokinetic studies. The absolute bioavailability after a single intragastric administration for male and female rats was 15.6% and 28.4% respectively. The mean bioavailability was 22%. The derivatives showed better in vivo activities compared with the existing standard drugs enalapril and sacubitril valsartan sodium. Meanwhile, hydrophilic prodrugs of the tetracyclic triterpenoid derivatives in the present invention were prepared. The derivatives of the present invention can be used for preparing cardiovascular medicines.

Dependencies are inferred from the claim text.