Synthesis and SAR of novel 1,1-dialkyl-2(1H)-naphthalenones as potent HCV polymerase inhibitors.
A series of gem-dialkyl naphthalenone derivatives with varied alkyl substitutions were synthesized and evaluated according to their structure-activity relationship. This investigation led to the discovery of potent inhibitors of the hepatitis C virus at low nanomolar concentrations in both enzymatic and cell-based HCV genotype 1a assays.
Bosse
Todd D
TD
Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. todd.bosse@abbott.com
Larson
Daniel P
DP
Wagner
Rolf
R
Hutchinson
Doug K
DK
Rockway
Todd W
TW
Kati
Warren M
WM
Liu
Yaya
Y
Masse
Sherie
S
Middleton
Tim
T
Mo
Hongmei
H
Montgomery
Debra
D
Jiang
Wen
W
Koev
Gennadiy
G
Kempf
Dale J
DJ
Molla
Akhter
A
D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005838:Genotype; D016174:Hepacivirus / Q000201:enzymology* / Q000235:genetics; D009281:Naphthalenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D012321:DNA-Directed RNA Polymerases