Burroughs Wellcome Co.

University of Michigan

Glaxo Wellcome Inc.

George A Freeman

Janet L Rideout

Sammy Ray Shaver

Leroy B Townsend

John Charles Drach

Merrick R Almond

Lowrie M Beacham, Iii

Jon L Collins

Harry S LeBlanc

Steven A Short

This invention pertains to nucleoside analogs which have antiviral activity and improved metabolic stability. More specifically, this invention pertains to modified sugar benzimidazole nucleosides, as exemplified by compounds such as benzimidazole nucleosides possessing a fluorinated sugar-like moiety (for example, a 2'-fluoro-furanosyl moiety or a 3'-fluoro-furanosyl moiety), and may be represented by the following formula, ##STR1## wherein R.sup.1 is a fluorinated sugar-like moiety; and R.sup.2, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are benzimidazole substituents, such as --H, halogens (e.g., --F, --Cl, --Br, --I), --NO.sub.2, --NR.sub.2 (where R is independently --H or an alkyl group having 1-6 carbon atoms), --OR (where R is --H or an alkyl group having 1-6 carbon atoms), --SR (where R is --H or a hydrocarbyl of 1-10 carbon atoms), and --CF.sub.3. In one embodiment, R.sup.1 is 2'-fluoro-furanosyl or 3'-fluoro-furanosyl; R.sup.2 is --H, --F, --Cl, --Br, --I, or --NR.sub.2, wherein R is independently --H or an alkyl group having 1-6 carbon atoms; R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are independently --H, --F, --Cl, --Br, or --I.

Modified benzimidazole nucleosides as antiviral agents

The present invention relates to 3'-azido purine nucleosides and their use in medical therapy, particularly for the treatment of human immunodeficiency virus and hepatitis B virus infections, to methods for their preparation and to compositions containing them.

3'-Azido nucleoside compound

Several novel 3-azido-2,3-dideoxy-.beta.-D-erythro-pentofuranosyl derivatives of substituted pyrimidinones having antiretroviral, especially anti-AIDS, activity are described.

Therapeutic nucleosides

A compound 1-(3-azido-2,3-dideoxy-.beta.-D-erythro-pentofuranoxyl)-5-methyl-2(1H)-pyr imidinone and its use in a method of generating (forming, providing) 3'-azido-3'-deoxythymidine (zidovudine sometimes referred to as AZT) in the body of an animal (a mammal such as human) by systemically administering 1-(3-azido-2,3-dideoxy-.beta.-D-erythro-pentofuranosyl)-5-methyl-2(1H)-pyr iminone to said animal (mammal such as a human) is disclosed. AZT is approved and used for treating HIV infections, e.g., AIDS and ARC in humans and also has activity against gram-negative bacteria in animals.

Nucleoside and use thereof

Treatment of susceptible gram-negative infections in animals is disclosed using the compound 3'-azido-3'-deoxythymidine or a pharmaceutically acceptable basic salt thereof. Also disclosed is the use of the 5'-mono-, di- and triphosphate of 3'-azido-3'-deoxythymidine or a pharmaceutically acceptable basic salt thereof for the same purpose.

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Raleigh, NC, United States of America

George A Freeman