HIV protease inhibitory bis-benzamide cyclic ureas: a quantitative structure-activity relationship analysis.
A series of N,N'-disubstituted cyclic urea 3-benzamides has been synthesized and evaluated for HIV protease inhibition and antiviral activity. Some of these benzamides have been shown to be potent inhibitors of HIV protease with Ki < 0.050 nM and IC90 < 20 nM for viral replication and, as such, may be useful in the treatment of AIDS. The synthesis and quantitative structure-activity relationship for this benzamide series will be discussed.
Wilkerson
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WW
DuPont Merck Pharmaceutical Company, E500/3203 Experimental Station, Wilmington, Delaware 19880-0500, USA.
Akamike
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E
Cheatham
W W
WW
Hollis
A Y
AY
Collins
R D
RD
DeLucca
I
I
Lam
P Y
PY
Ru
Y
Y
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D017320:HIV Protease Inhibitors / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D007700:Kinetics; D012367:RNA, Viral / Q000378:metabolism; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D001549:Benzamides; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D014508:Urea