Oximinoarylsulfonamides as potent HIV protease inhibitors.
The need for a potent HIV protease inhibitor (PI) to combat emerging PI-resistant viruses is anticipated. Analogs formulated from the combination of structural fragments of Ritonavir, Lopinavir, and Amprenavir were synthesized. Analogs containing the oxime pharmacophore were found to have improved activities against both wild type and resistant (A17) viruses. The synthesis and structure-activity relationships (SAR) based upon the in vitro IC50 of this series of compounds are reported.
Yeung
Clinton M
CM
Abbott Laboratories, GPRD, D-47D, Building AP52N, 200 Abbott Park Road, Abbott Park, IL 60064-3501, USA. clinton.yeung@abbott.com
Klein
Larry L
LL
Flentge
Charles A
CA
Randolph
John T
JT
Zhao
Chen
C
Sun
MingHua
M
Dekhtyar
Tatyana
T
Stoll
Vincent S
VS
Kempf
Dale J
DJ
D001665:Binding Sites; D002219:Carbamates; D015195:Drug Design; D005663:Furans; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D061466:Lopinavir; D008958:Models, Molecular; D008968:Molecular Conformation; D011744:Pyrimidinones / Q000737:chemistry; D019438:Ritonavir / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; C095108:amprenavir; D016333:HIV Protease; D019438:Ritonavir