Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-resistant viral strains.
Indinavir analogues with blocked metabolism sites show highly improved pharmacokinetic profiles in animals. The cis-aminochromanol substituted analogues exhibited excellent potency against both the wild-type (NL4-3) virus and protease inhibitor-resistant HIV strains.
Cheng
Yuan
Y
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. yuan_cheng@merck.com
Zhang
Fengqi
F
Rano
Thomas A
TA
Lu
Zhijian
Z
Schleif
William A
WA
Gabryelski
Lori
L
Olsen
David B
DB
Stahlhut
Mark
M
Rutkowski
Carrie A
CA
Lin
Jiunn H
JH
Jin
Lixia
L
Emini
Emilio A
EA
Chapman
Kevin T
KT
Tata
James R
JR
D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D004351:Drug Resistance; D006678:HIV / Q000187:drug effects*; D016333:HIV Protease / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D019469:Indinavir / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D020128:Inhibitory Concentration 50; D008657:Metabolic Clearance Rate; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D017320:HIV Protease Inhibitors; D019469:Indinavir; D016333:HIV Protease