PMID: 9171223Jun 10, 1997Paper

Efficacy, pharmacokinetics, and in vivo antiviral activity of UC781, a highly potent, orally bioavailable nonnucleoside reverse transcriptase inhibitor of HIV type 1

AIDS Research and Human Retroviruses
R W BuckheitJ P Bader

Abstract

A series of compounds related to oxathiin carboxanilide has been identified as nonnucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1, and structure-activity relationships have been described (Buckheit RW, et al.: Antimicrob Agents Chemother 1995;39:2718-2727). Three new analogs (UC040, UC82, and UC781) inhibited laboratory and clinical isolates of HIV-1, including isolates representative of the various clades of HIV-1 found worldwide, in both established and fresh human cells. Virus isolates with the amino acid changes L100I, K103N, V106I, and Y181C in the reverse transcriptase were partially resistant to these compounds. However, UC781 inhibited these virus isolates at low nontoxic concentrations, presenting a broad in vitro therapeutic index. As with other NNRTIs, each of the compounds synergistically interacted with AZT to inhibit HIV-1 replication. UC781 possesses a favorable pharmacokinetic profile in mice with a high level of oral bioavailability. Plasma concentrations reached maximum levels within 2 to 4 hr of oral administration and remained in excess of those required for in vitro anti-HIV activity for at least 24 hr after a single oral dose. When evaluated in a murine hollow fiber implant model of HIV infec...Continue Reading

References

Feb 1, 1992·AIDS Research and Human Retroviruses·P M GrobV J Merluzzi
Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J P BaderM R Boyd
Oct 1, 1990·Antiviral Research·M N Prichard, C Shipman

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Citations

Feb 18, 1999·Bioorganic & Medicinal Chemistry Letters·Z Q XuM T Flavin
Oct 19, 2002·Proceedings of the National Academy of Sciences of the United States of America·J RenD K Stammers
Sep 25, 2004·Antimicrobial Agents and Chemotherapy·Charlene S DezzuttiClyde E Hart
Dec 1, 2012·Drug Delivery and Translational Research·Christopher McConvilleR Karl Malcolm
Aug 2, 2002·Expert Opinion on Investigational Drugs·Jim A Turpin
Aug 16, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Lee T. Bacheler
Mar 20, 2015·Drug Delivery and Translational Research·Christopher McConvilleR Karl Malcolm
Jan 25, 2006·The Journal of Antimicrobial Chemotherapy·Osmond J D'Cruz, Fatih M Uckun

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