Novel P1 chain-extended HIV protease inhibitors possessing potent anti-HIV activity and remarkable inverse antiviral resistance profiles.
A novel series of tyrosine-derived HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and two protease inhibitor-resistant viruses. All of the compounds had wild-type antiviral activities that were similar to or greater than several currently marketed HIV protease inhibitors. In addition, a number of compounds in this series were more potent against the drug-resistant mutant viruses than they were against wild-type virus.
GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. john.6.miller@gsk.com
John F
JF
Miller
Michael
M
Brieger
Eric S
ES
Furfine
Richard J
RJ
Hazen
Istvan
I
Kaldor
David
D
Reynolds
Ronald G
RG
Sherrill
Andrew
A
Spaltenstein
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D004285:Dogs; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects* / Q000235:genetics; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009154:Mutation; D051381:Rats; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors