Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385.
A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385.
Miller
John F
JF
GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. john.6.miller@gsk.com
Andrews
C Webster
CW
Brieger
Michael
M
Furfine
Eric S
ES
Hale
Michael R
MR
Hanlon
Mary H
MH
Hazen
Richard J
RJ
Kaldor
Istvan
I
McLean
Ed W
EW
Reynolds
David
D
Sammond
Douglas M
DM
Spaltenstein
Andrew
A
Tung
Roger
R
Turner
Elizabeth M
EM
Xu
Robert X
RX
Sherrill
Ronald G
RG
D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
C494906:GW0385; D017320:HIV Protease Inhibitors; D013449:Sulfonamides