P1' oxadiazole protease inhibitors with excellent activity against native and protease inhibitor-resistant HIV-1.
HIV-1 protease inhibitors (PI's) bearing 1,3,4-oxadiazoles at the P1' position were prepared by a novel method involving the diastereoselective installation of a carboxylic acid and conversion to the P1' heterocycle. The compounds are picomolar inhibitors of native HIV-1 protease, with most of the compounds maintaining excellent antiviral activity against a panel of PI-resistant strains.
Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. ron_kim@merck.com
Ronald M
RM
Kim
Elizabeth A
EA
Rouse
Kevin T
KT
Chapman
William A
WA
Schleif
David B
DB
Olsen
Mark
M
Stahlhut
Carrie A
CA
Rutkowski
Emilio A
EA
Emini
James R
JR
Tata
D045744:Cell Line, Tumor; D024921:Drug Resistance, Multiple, Viral; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D006801:Humans; D019469:Indinavir / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry; D013237:Stereoisomerism
D017320:HIV Protease Inhibitors; D010069:Oxadiazoles; D011725:Pyridines; D019469:Indinavir