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. 1997 May;41(5):1058–1063. doi: 10.1128/aac.41.5.1058

Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor.

S M Poppe 1, D E Slade 1, K T Chong 1, R R Hinshaw 1, P J Pagano 1, M Markowitz 1, D D Ho 1, H Mo 1, R R Gorman 3rd 1, T J Dueweke 1, S Thaisrivongs 1, W G Tarpley 1
PMCID: PMC163850  PMID: 9145869

Abstract

PNU-140690 is a member of a new class of nonpeptidic human immunodeficiency virus (HIV) protease inhibitors (sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrones) discovered by structure-based design. PNU-140690 has excellent potency against a variety of HIV type 1 (HIV-1) laboratory strains and clinical isolates, including those resistant to the reverse transcriptase inhibitors zidovudine or delavirdine. When combined with either zidovudine or delavirdine, PNU-140690 contributes to synergistic antiviral activity. PNU-140690 is also highly active against HIV-1 variants resistant to peptidomimetic protease inhibitors, underscoring the structural distinctions between PNU-140690 and substrate analog protease inhibitors. PNU-140690 retains good antiviral activity in vitro in the presence of human plasma proteins, and preclinical pharmacokinetic studies revealed good oral bioavailability. Accordingly, PNU-140690 is a candidate for clinical evaluation.

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Selected References

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