Novel arylsulfonamides possessing sub-picomolar HIV protease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains.
A novel series of P1' chain-extended arylsufonamides was synthesized and evaluated for wild-type HIV protease inhibitory activity and in vitro antiviral activity against wild type virus and two protease inhibitor-resistant mutant viruses. All of the compounds showed dramatic increases in enzyme activity as compared to the currently marketed HIV protease inhibitors amprenavir, indinavir, and nelfinavir. In addition, significant improvements in antiviral potencies against wild type and the two mutant viruses were also realized.
Miller
John F
JF
GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. john.6.miller@gsk.com
Furfine
Eric S
ES
Hanlon
Mary H
MH
Hazen
Richard J
RJ
Ray
John A
JA
Robinson
Laurence
L
Samano
Vicente
V
Spaltenstein
Andrew
A
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects / Q000235:genetics*; D006678:HIV / Q000187:drug effects / Q000235:genetics*; D016333:HIV Protease / Q000187:drug effects* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009154:Mutation; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D016333:HIV Protease