Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds.
A novel series of HIV protease inhibitors containing cyclic P1/P2 scaffolds has been synthesized and evaluated for biological activity. The trans 3,5-dibenzyl-2-oxo pyrrolidinone ring system resulted in a 50 pM enzyme inhibitor against HIV protease in vitro when combined with an indanolamine derived P'-backbone. This compound also shows comparable activity to currently marketed drugs in the MT-4 cell-based antiviral assay.
Spaltenstein
A
A
Glaxo Wellcome Inc, NC 27709, USA. as11513@glaxowellcome.com
Almond
M R
MR
Bock
W J
WJ
Cleary
D G
DG
Furfine
E S
ES
Hazen
R J
RJ
Kazmierski
W M
WM
Salituro
F G
FG
Tung
R D
RD
Wright
L L
LL
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D013844:Thiazoles