Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda6-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones: Part 4. Optimization of DMPK properties.
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as potent inhibitors of genotype 1 HCV NS5B polymerase focusing on the optimization of their drug metabolism and pharmacokinetics (DMPK) profiles. This investigation led to the discovery of potent inhibitors with improved DMPK properties.
Sergeeva
Maria V
MV
Anadys Pharmaceuticals, Inc., Medicinal Chemistry, 3115 Merryfield Row, San Diego, CA 92121, USA.
Zhou
Yuefen
Y
Bartkowski
Darian M
DM
Nolan
Thomas G
TG
Norris
Daniel A
DA
Okamoto
Ellen
E
Kirkovsky
Leo
L
Kamran
Ruhi
R
Lebrun
Laurie A
LA
Tsan
Mei
M
Patel
Rupal
R
Shah
Amit M
AM
Lardy
Matthew
M
Gobbi
Alberto
A
Li
Lian-Sheng
LS
Zhao
Jingjing
J
Bertolini
Thomas
T
Stankovic
Nebojsa
N
Sun
Zhongxiang
Z
Murphy
Douglas E
DE
Webber
Stephen E
SE
Dragovich
Peter S
PS
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D000882:Haplorhini; D016174:Hepacivirus / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D011724:Pyridazines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase