Synthesis and activity of N-acyl azacyclic urea HIV-1 protease inhibitors with high potency against multiple drug resistant viral strains.
As part of our efforts to identify potent HIV-1 protease inhibitors that are active against resistant viral strains, structural modification of the azacyclic urea (I) was undertaken by incorporating acyl groups as P(1)' ligands. The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains.
Zhao
Chen
C
GPRD, Abbott Laboratories, Abbott Park, IL 60064-6123, USA. chen.zhao@abbott.com
Sham
Hing L
HL
Sun
Minghua
M
Stoll
Vincent S
VS
Stewart
Kent D
KD
Lin
Shuqun
S
Mo
Hongmei
H
Vasavanonda
Sudthida
S
Saldivar
Ayda
A
Park
Chang
C
McDonald
Edith J
EJ
Marsh
Kennan C
KC
Klein
Larry L
LL
Kempf
Dale J
DJ
Norbeck
Daniel W
DW
D001372:Aza Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D018432:Drug Resistance, Multiple; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D008024:Ligands; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D019438:Ritonavir / Q000138:chemical synthesis / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology
D001372:Aza Compounds; D017320:HIV Protease Inhibitors; D008024:Ligands; D014508:Urea; D019438:Ritonavir