Discovery of pyrano[3,4-b]indoles as potent and selective HCV NS5B polymerase inhibitors.
A novel series of HCV NS5B RNA-dependent RNA polymerase inhibitors containing a pyrano[3,4-b]indole scaffold is described leading to the discovery of compound 16, a highly potent and selective inhibitor that is active in the replicon system.
Gopalsamy
Ariamala
A
Chemical and Screening Sciences and Infectious Diseases, Wyeth Research, Pearl River, New York 10965, USA. gopalsa@wyeth.com
Lim
Kitae
K
Ciszewski
Gregory
G
Park
Kaapjoo
K
Ellingboe
John W
JW
Bloom
Jonathan
J
Insaf
Shabana
S
Upeslacis
Janis
J
Mansour
Tarek S
TS
Krishnamurthy
Girija
G
Damarla
Murthy
M
Pyatski
Yelena
Y
Ho
Douglas
D
Howe
Anita Y M
AY
Orlowski
Mark
M
Feld
Boris
B
O'Connell
John
J
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D016174:Hepacivirus / Q000201:enzymology*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D012321:DNA-Directed RNA Polymerases; D007211:Indoles; D011714:Pyrans; D017361:Viral Nonstructural Proteins; C495221:(5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyrano(3,4-b)indol-1-yl)acetic acid; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase