Novel azacyclic ureas that are potent inhibitors of HIV-1 protease.
A series of novel, azacyclic ureas which are highly potent inhibitors of the HIV-1 protease (IC50 = 4.1 to < 0.5 nM) were synthesized. Aqueous solubilities of this series of compounds were improved by incorporating polar functional groups at the P1' P2 and P2' positions. These compounds also possess good anti-viral activity by inhibition of the cytopathic effect of HIV-13B in MT-4 cells in vitro.
Sham
H L
HL
Abbott Laboratories, Abbott Park, Illinois 60064-3500, USA.
Zhao
C
C
Marsh
K C
KC
Betebenner
D A
DA
Lin
S
S
Rosenbrook
W
W
Herrin
T
T
Li
L
L
Madigan
D
D
Vasavanonda
S
S
Molla
A
A
Saldivar
A
A
McDonald
E
E
Wideburg
N E
NE
Kempf
D
D
Norbeck
D W
DW
Plattner
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
D017320:HIV Protease Inhibitors; D011994:Recombinant Proteins; D014508:Urea; D016333:HIV Protease