Differential activities of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives against different human immunodeficiency virus type 1 mutant strains.

Antimicrobial Agents and Chemotherapy
J BalzariniE De Clercq

Abstract

A series of 23 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives that were highly potent inhibitors of wild-type human immunodeficiency virus type 1 strain IIIB (HIV-1/IIIB) replication in CEM cells were evaluated against a panel of HIV-1 mutant strains containing the replacement of leucine by isoleucine at position 100 (100-Leu-->Ile), 103-Lys-->Asn, 106-Val-->Ala, 138-Glu-->Lys, 181-Tyr-->Cys, 181-Tyr-->Ile, or 188-Tyr-->His in their reverse transcriptase (RT). A different structure-antiviral activity relationship was found, depending on the nature of the mutated amino acid in the HIV-1 RT. The results show that 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylbenzyl)uracil, 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylphenylthio)uracil, and 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylphenylthio)-2-thiouracil remain active against the majority of viruses containing single mutations which confer resistance to nonnucleoside RT inhibitors.

References

Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D RichmanJ Griffin
Dec 1, 1989·Journal of Medicinal Chemistry·T MiyasakaE De Clercq
Dec 29, 1989·Biochemical and Biophysical Research Communications·M BabaT Miyasaka
Jan 20, 1994·Biochemical Pharmacology·E De Clercq

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Citations

Jan 1, 1996·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·E De Clercq
May 8, 2009·European Journal of Medicinal Chemistry·Osama I el-SabbaghAdel A Rashad
Apr 3, 2014·Nucleosides, Nucleotides & Nucleic Acids·Najim A Al-MasoudiNabeel A Abdul-Reda
Sep 27, 2012·Antiviral Chemistry & Chemotherapy·Nadhir N A JafarChristophe Pannecouque
Mar 11, 2018·Biochemistry. Biokhimii︠a︡·V T Valuev-Elliston, S N Kochetkov
Oct 23, 1997·Clinical Microbiology Reviews·E De Clercq

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