Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor
| Autor: | D D Ho, P J Pagano, K T Chong, W. G. Tarpley, T J Dueweke, D E Slade, rd R R Gorman, S M Poppe, M Markowitz, S Thaisrivongs, R. R. Hinshaw, H Mo |
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| Rok vydání: | 1997 |
| Předmět: |
Indoles
Genotype Anti-HIV Agents Pyridines medicine.medical_treatment Drug Evaluation Preclinical Virus Replication Antiviral Agents Piperazines Virus Zidovudine medicine Humans HIV Protease Inhibitor Delavirdine Pharmacology (medical) Protease inhibitor (pharmacology) Cells Cultured Pharmacology Sulfonamides Protease biology Drug Synergism HIV Protease Inhibitors Virology Drug Combinations Infectious Diseases Pyrones Enzyme inhibitor HIV-1 biology.protein Reverse Transcriptase Inhibitors Tipranavir Research Article medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 41:1058-1063 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.41.5.1058 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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