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

被引:107
作者
Poppe, SM
Slade, DE
Chong, KT
Hinshaw, RR
Pagano, PJ
Markowitz, M
Ho, DD
Mo, H
Gorman, RR
Dueweke, TJ
Thaisrivongs, S
Tarpley, WG
机构
[1] PHARMACIA & UPJOHN INC,KALAMAZOO,MI 49001
[2] NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY
[3] WAYNE STATE UNIV,SCH MED,DETROIT,MI 48202
关键词
D O I
10.1128/AAC.41.5.1058
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 far clinical evaluation.
引用
收藏
页码:1058 / 1063
页数:6
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