Synthesis and evaluation of novel potent HCV NS5A inhibitors.
Judicious modifications to the structure of the previously reported HCV NS5A inhibitor 1, resulted in more potent anti-HCV compounds with similar and in some cases improved toxicity profiles. The synthesis of 19 new NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. For the most potent compounds chemical stability, stability in liver microsomes and inhibition of relevant CYP450 enzymes is also presented.
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Decatur, GA 30033, USA.
Hongwang
H
Zhang
Longhu
L
Zhou
Franck
F
Amblard
Junxing
J
Shi
Drew R
DR
Bobeck
Sijia
S
Tao
Tamara R
TR
McBrayer
Phillip M
PM
Tharnish
Tony
T
Whitaker
Steven J
SJ
Coats
Raymond F
RF
Schinazi
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000998:Antiviral Agents