Cytarabine 5'-O-amino-acid ester, salts thereof and preparation method thereof

Abstract

The invention belongs to the technical field of medicines and discloses cytarabine 5'-O-amino-acid ester, pharmaceutically acceptable salts thereof and a preparation method thereof. The preparation method comprises the following steps of: slowly dropping carbobenzoxy chloride into a solution formed by cytarabine, sodium bicarbonate and N,N-dimethylacetylamide, and obtaining a compound A after reacting at room temperature; using the compound A and N-butyloxy formoxyl-amino acid as raw materials; adding a reagent to the solution to carry out an esterification reaction to obtain the cytarabine 5'-O-amino-acid ester; and then adding acid to obtain a finished product. The pharmaceutically acceptable salts comprise hydrochlorides, sulfates, formates, acetates, mesylates, propionates, butyrates, p-toluene sulphonates, phosphates, bisulfates, maleates, lactates, carbonates, bicarbonates, malonates, and salts formed with acidic amino acids, and the like. The invention can obviously improve the membrane permeability of the cytarabine so as to improve the bioavailability of the cytarabine.

Description

Technical field: The invention belongs to the technical field of medicine, and relates to cytarabine 5'-O-amino acid esters and salts thereof and preparation methods thereof, in particular to a drug 1-β-D-arabinofuranosyl-4-amino- 5'-O-amino acid ester of 2(1H)-cytosine, its pharmaceutically acceptable salt and its preparation method. Background technique: The chemical name of the compound commonly known as cytarabine is 1-β-D-arabinofuranosyl-4-amino-2(1H)-cytosine. Cytarabine is converted into active cytarabine triphosphate in the body. Cytarabine triphosphate inhibits DNA polymerase and penetrates into DNA in a small amount, prevents DNA synthesis and inhibits cell growth. Clinically, cytarabine mainly For the treatment of acute myeloid leukemia. However, the molecular polarity of cytarabine is very large, which leads to poor membrane permeability of the small intestine, so the poor membrane permeability makes the oral bioavailability of cytarabine very low (about 20%)....

AI Technical Summary

Problems solved by technology

However, the polarity of the cytarabine molecule is very large, resulting in poor membrane permeability of the small intestine, so the poor membrane permeability makes the oral bioavailability of cytarabine very low (about 20%)

Therefore, it is necessary to find a way to improve the poor membrane permeability of cytarabine, and then improve its oral bioavailability

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