Adefovir dipivoxil compound and novel preparation method thereof

Abstract

The invention aims to provide an adefovir dipivoxil compound and a novel preparation method thereof; the method specifically comprises the following steps that: (2-p-toluenesulfonyloxy ethoxy) diethyl methylphosphonate is hydrolyzed at low temperature, to prepare (2-p-toluenesulfonyloxy ethoxy) methyl phosphonic acid; chloro methyl pivalate is added in to react and prepare an intermediate body (II) under the action of triethylamine; and adenine and the intermediate body (II) react to prepare adefovir dipivoxil under the catalysis of anhydrous potassium carbonate. The invention reduces the introduction of impurities, improves the purity, and lays foundation for industrial production.

Description

technical field The invention relates to an adefovir dipivoxil compound, belonging to the technical field of medicine. Background technique Adefovir dipivoxil, chemical name: 9-[2-[bis(pivaloyloxymethoxy)phosphorylmethoxy]ethyl]adenine, molecular formula C 20 h 32 N 5 o 8 P, molecular weight 501.47, its structural formula is: Adefovir is an acyclic nucleoside analog of adenosine monophosphate, which is phosphorylated into an active metabolite, adefovir diphosphate, under the action of cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) in the following two ways; one is to compete with the natural substrate deoxyadenosine triphosphate, and the other is to cause DNA chain elongation and termination after being integrated into viral DNA. The inhibition constant (Ki) of adefovir diphosphate to HBV DNA polymerase is 0.1 μM, but the inhibitory effect on human DNA polymerase α and γ is weak, with Ki values ​​of 1.18 μM and 0.97 μM, respe...

AI Technical Summary

Problems solved by technology

The adefovir dipivoxil obtained by the above-mentioned patented method has low purity, is not easy to purify, has high production cost, and is not easy to produce on a large scale

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