2'-fluoroncucleosides

Abstract

2'-fluoronucleoside compounds are disclosed for use in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cell proliferation including tumors and cancers. These compounds have the general formula (I), (II), (III), (IV) or pharmaceutically acceptable salts thereof, wherein the base is a purine or pyrimidine base; R 1 is OH, H, OR 3 , N 3 , CN, halogen including F, or CF 3 , lower alkyl, amino, lower alkylamino, two lower alkylamino, or alkoxy; R 2 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stable phosphate prodrug; acyl, or other pharmaceutically acceptable leaving group that provides R when used in vivo 2 Compounds that are H or phosphate; sulfonates include alkyl or aralkylsulfonyl, including methylsulfonyl, benzyl, wherein phenyl is optionally substituted by one or more of the substituents described above in the definition of aryl substitution, lipid, amino acid, peptide or cholesterol; and R 3 is an acyl, alkyl, phosphate or other pharmaceutically acceptable leaving group, ie, a group that cleaves to the parent compound when used in vivo.

Description

[0001] This application is a divisional application of the invention patent application PCT / US99 / 04051 filed on February 25, 1999, entitled "2'-Fluoronucleoside", and the Chinese patent application number of the original application is 99805472.0. [0002] The invention described herein was made with government support under Grant No. AI32351 awarded by the National Department of Health. The United States Government has asserted rights in this invention. technical field [0003] The invention belongs to the field of medicinal chemistry, and specifically includes 2'-fluoronucleosides, a preparation method and application thereof. Background technique [0004] Synthetic nucleosides such as 5-iodo-2'-deoxyuridine and 5-fluoro-2'-deoxyuridine have been used for some years in the treatment of cancer and herpes viruses. Since the 1980s, synthetic nucleosides have also been beneficial in the treatment of HIV, hepatitis and Epstein-Barr virus. [0005] In 1981, Acquired Immunodefi...

AI Technical Summary

Problems solved by technology

At least with respect to 2′-ribofuranosyl nucleosides, this may be due to the previous perception that placing the fluorine group in the 2′-ribofuranosyl configuration was difficult

For L-2'-fluoro-2',3'-unsaturated purine nucleosides, it may be due to the instability of purine nucleosides in acidic media, resulting in the cleavage of the glucosyl bond

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