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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 treatment with other drugs in combination or in alternation
This unpredictability is exacerbated by the lack of kinetic parameters of resistance in long-term cell cultures treated with contemporary antiretroviral drugs

Method used

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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 present invention discloses a method for treating HIV that includes administering beta -D-D4FC or its pharmaceutically acceptable salt or prodrug to a human in need of therapy in combination or alternation with a drug that induces a mutation in HIV-1 at a location other than the 70(K to N), 90 or the 172 codons of the reverse transcriptase region. Also disclosed is a method for using beta -D-D4FC as "salvage therapy" to patients which exhibit drug resistance to other anti-HIV agents. beta -D-D4FC can be used generally as salvage therapy for any patient which exhibits resistance to a drug that induces a mutation at other than the 70(K to N), 90 or the 172 codons.

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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