Cyclodextrin inclusion compound of prasugrel and acid addition salt thereof and preparation method thereof

Abstract

The invention provides a cyclodextrin inclusion compound of prasugrel and acid addition salt thereof, which has stable inclusion structure, can be easily synthesized and saved and are stable in the air, and the water solubility of the prasugrel and the acid addition salt thereof is increased. The prasugrel and the acid addition salt thereof react with various cyclodextrins in water and organic solvents to prepare the stable inclusion compound which can be used as a therapeutic drug or has potential application.

Description

technical field The invention relates to a chemical synthesis preparation process, in particular to a platelet inhibitor prasugrel and a cyclodextrin inclusion complex of an acid addition salt thereof and a preparation method thereof. Background technique Thienopyridines such as ticlopidine and clopidogrel have been used to treat thrombosis and related diseases. Prasugrel ({2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine}) as A new generation of thienopyridine oral antiplatelet drugs is also on the market with the trade name Effient. Prasugrel structural formula such as I, is a kind of adenosine diphosphate (ADP) receptor antagonist, it belongs to prodrug, itself does not have activity and effectively converts into its active metabolite R-138727 in vivo; R- 138727 reduces the dependence on cytochrome P-450 enzymes, and rapidly, specifically, and irreversibly binds to the purine base receptors of platelet P2Y12, inhibiting ADP-regu...

AI Technical Summary

Problems solved by technology

However, there are some shortcomings in using prasugrel directly as a pharmaceutical preparation. For example, patent WO2008073759 points out that prasugrel is easy to be hydrolyzed and oxidized during storage. salt, but its stability and bioavailability have not changed much, and cyclodextrin drug inclusion complexes have been widely used in pharmacy, such as increasing the solubility of drugs, improving the stability of drugs, and improving the efficacy of drugs. Bioavailability, etc. Therefore, the cyclodextrin inclusion complex of prasugrel and its acid addition salts may be able to overcome the shortcomings of prasugrel and its acid addition salts, and improve their stability and bioavailability

Images