HIV-1 mutation selecting from beta-2',3'-didehydro-2',3-dideoxy-5-fluorocytidine

A HIV-1, dideoxythymidine technology, applied in the preparation of mutants, medical preparations containing active ingredients, antibacterial drugs, etc., can solve the problem of unpredictable induction of which mutations are permanent or temporary, and exacerbate unpredictability. , the lack of kinetic parameters of drug resistance, etc.

Inactive Publication Date: 2002-02-27
EMORY UNIVERSITY
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Problems solved by technology

However, one cannot predict what mutations a given drug will induce in the HIV-1 genome, whether the mutations are permanent or temporary, or how cells infected with mutated HIV-1 sequences will respond to tr...

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  • HIV-1 mutation selecting from beta-2',3'-didehydro-2',3-dideoxy-5-fluorocytidine
  • HIV-1 mutation selecting from beta-2',3'-didehydro-2',3-dideoxy-5-fluorocytidine

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[0015](i) a method of treating HIV infections in the human body, including β-D-D4FC or pharmaceutically acceptable precursor or salt thereof or salt thereof to the person to give an effective amount to the human body, with one in HIV- 1 In the case where the mutation is induced or alternately induced by a drug in which the mutation is induced by the 70 (k mutant to n), 90 or 172-bit codon in the reverse transcription enzyme region, the drug is not a cis-2-hydroxymethyl group. -5- (5-fluoroamidine-1-yl) -1,3-oxide ring, 顺 -2-hydroxymethyl-5- (cytosine-1-yl) -1,3-oxygen Ring, 9- [4- (hydroxymethyl) -2-cyclopentene-1-yl]-guanine (carbovir), 9- [2- (hydroxyethoxy) methyl] - guanine Lown, Interferon, 3'-deoxidation-3'-azide-thymidine (AZT), 2 ', 3'-diboxide (DDI), 2', 3'-diodeobide ( DDC), (-) - 2'-fluoro-5-methyl-β-L-Arabicanurine (L-FMAU) or 2 ', 3'-dihydrophyde-2', 3'-di deoxyridine (D4T).

[0016] (ii) a method of treating HIV infections in the human body, including β-D-D4FC or pha...

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Abstract

The invention discloses a method for treating HIV, which comprises administering β-D-D4FC or its pharmaceutically acceptable precursor or salt to a person in need of treatment, which is combined or alternately combined with a HIV-1 antiretroviral agent Drugs that induce mutations at sites other than codon 70 (K to N), 90 or 172 in the transcriptase region are used in combination. Also disclosed is a method for using β-D-D4FC as "salvage therapy" in patients who have demonstrated resistance to other anti-HIV drugs. β-D-D4FC can usually be used as salvage therapy in any patient who exhibits resistance to drugs that induce mutations at positions other than codons 70 (K to N), 90, or 172.

Description

[0001] This invention was partially funded by the National Institutes of Health Fund, the license number is 1R01-A1-41980-01. The U.S. government has certain rights in this invention. [0002] This application claims the priority of U.S. Provisional Patent Application 60 / 116,773 filed on January 22, 1999. Background of the invention [0003] In 1983, the etiological cause of AIDS was determined to be human immunodeficiency virus (HIV). In 1985, it was reported that the synthetic nucleoside 3'-azido-3'-deoxythymidine (AZT) inhibited the replication of human immunodeficiency virus. Since then, some other synthetic nucleosides have been proven to be effective against HIV, including 2',3'-dideoxyinosine (DDI), 2',3'-dideoxycytidine (DDC), 2', 3 '-Didehydro-2',3'-Dideoxythymidine (D4T), cis-2-hydroxymethyl-5-(5-fluorocytosine-1-yl)-1,3-oxothiolane (FTC), (-)-cis-2-hydroxymethyl-5-(cytosine-1-yl)-1,3-oxothiolane (3TC). After cellular kinases cause the cell to phosphorylate to 5'-triphosp...

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Application Information

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IPC IPC(8): C12N15/01A61K31/513A61K31/70A61K31/7068A61K45/00A61K45/06A61P31/18
CPCA61K31/513A61K31/7068A61K31/52A61K45/06A61K31/70A61P31/08A61P31/18A61K31/535A61K2300/00A61K38/21
Inventor 雷蒙德·F·斯基纳茨珍妮弗·哈蒙德约翰·W·梅勒斯丹尼斯·C·利奥塔
Owner EMORY UNIVERSITY
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