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 11, 1992·Journal of Medicinal Chemistry·H TanakaT Miyasaka
Feb 1, 1990·Nature·R PauwelsJ Heykants
Mar 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M BabaS Mori
Sep 1, 1991·Journal of Virology·J H NunbergM E Goldman
Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D RichmanJ Griffin
Oct 11, 1991·Antiviral Research·E L WhiteM A Chirigos
Jan 24, 1992·Journal of Medicinal Chemistry·H TanakaT Miyasaka
Jan 1, 1991·Journal of Medicinal Chemistry·H TanakaS Shigeta
Apr 1, 1991·Journal of Medicinal Chemistry·H TanakaT Miyasaka
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
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·J BalzariniE De Clercq
Jan 12, 1995·Nature·X WeiB H Hahn
May 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·T J DuewekeW G Tarpley
Jan 1, 1993·Virology·J BalzariniE De Clercq
Aug 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J BalzariniA San-Félix
Aug 1, 1993·Antimicrobial Agents and Chemotherapy·J P KleimA Paessens
Citations
Jun 1, 1996·Reviews in Medical Virology· De Clercq E
Jun 1, 1996·Antiviral Research·M OkamotoM Baba
Jan 1, 1996·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·E De Clercq
May 13, 1999·Il Farmaco·E De Clercq
Oct 1, 1998·Antiviral Research·E De Clercq
Jun 1, 1997·International Journal of Antimicrobial Agents·E De Clercq
Oct 13, 2001·Bioorganic & Medicinal Chemistry Letters·D P WangW L Jorgensen
Apr 24, 2001·AIDS·K Van LaethemA M Vandamme
May 8, 2009·European Journal of Medicinal Chemistry·Osama I el-SabbaghAdel A Rashad
Sep 17, 2013·Archiv der Pharmazie·Osama I El-Sabbagh
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
Jul 1, 2020·ACS Omega·Mamdouh Attia Abu-ZaiedGalal Hamza Elgemeie
Oct 23, 1997·Clinical Microbiology Reviews·E De Clercq
Feb 19, 2002·Chemical Reviews·Rajni GargCorwin Hansch