Abstract
Five structurally related thiophene and furane analogues of the oxathiin carboxanilide derivative NSC 615985 (UC84) (designated UC10, UC68, UC81, UC42, and UC16) were identified as potent inhibitors of HIV-1 replication in cell culture and HIV-1 reverse transcriptase activity. These compounds were markedly active against a series of mutant HIV-1 strains, containing the Leu-100-->Ile, Val-106-->Ala, Glu-138-->Lys, or Tyr-181-->Cys mutations in their reverse transcriptase. However, the thiocarboxanilide derivatives selected for mutations at amino acid positions 100 (Leu-->Ile), 101 (Lys-->Ile/Glu), 103 (Lys-->Thr/Asp) and 141 (Gly-->Glu) in the HIV-1 reverse transcriptase. The compounds completely suppressed HIV-1 replication and prevented the emergence of resistant virus strains when used at 1.3-6.6 microM--that is, 10- to 25-fold lower than the concentration required for nevirapine and bis(heteroaryl)piperazine (BHAP) U90152 to do so. If UC42 was combined with the [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide)]-beta-D-pentofuranosyl (TSAO) derivative of N3-methylthymine (TSAO-m3T), virus breakthrough could be prevented for a much longer time, and at much lower concentrations, than i...Continue Reading
References
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J BalzariniE De Clercq
Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J P BaderM R Boyd
Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D RichmanJ Griffin
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·Antimicrobial Agents and Chemotherapy·J P KleimA Paessens
Citations
Jun 1, 1996·Reviews in Medical Virology· De Clercq E
Jan 1, 1996·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·E De Clercq
Apr 21, 2004·Journal of Molecular Biology·J RenD K Stammers
May 13, 1999·Il Farmaco·E De Clercq
Jun 27, 2000·Antiviral Research·M WitvrouwK Andries
Oct 1, 1998·Antiviral Research·E De Clercq
Jun 3, 1998·Journal of Pharmaceutical and Biomedical Analysis·A A NomeirM Chadwick
Jun 1, 1997·International Journal of Antimicrobial Agents·E De Clercq
Sep 3, 2003·Bioorganic & Medicinal Chemistry Letters·Marina Udier-BlagovićWilliam L Jorgensen
Jul 24, 1998·AIDS·J BalzariniE De Clercq
Jul 23, 1999·AIDS·E MagiorkinisA Hatzakis
May 1, 1997·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·J BalzariniK Uberla
Apr 2, 2005·AIDS·P Richard HarriganLee T Bacheler
Dec 1, 1995·Antimicrobial Agents and Chemotherapy·R W BuckheitR J Schultz
Oct 3, 2013·PloS One·Hartmut M Hanauske-AbelMichael B Mathews
Jul 2, 2005·Expert Opinion on Emerging Drugs·M L AndreolaM Legraverend
Mar 27, 1998·Biochemical Pharmacology·J BalzariniJ P Kleim
May 19, 2016·PloS One·Deepti SaxenaHartmut M Hanauske-Abel
Mar 15, 1997·AIDS·G PirasM Baba
Mar 21, 2003·AIDS·Ariela ZussmanGadi Borkow
Jan 30, 1999·Antimicrobial Agents and Chemotherapy·G BorkowM A Parniak
Sep 20, 2008·Journal of Medicinal Chemistry·Alon Herschhorn, Amnon Hizi
Oct 23, 1997·Clinical Microbiology Reviews·E De Clercq
Jun 1, 1996·Antimicrobial Agents and Chemotherapy·J BalzariniE De Clercq
May 1, 1997·Antimicrobial Agents and Chemotherapy·S M PoppeW G Tarpley