Discovery of pyrano[3,4-b]indoles as potent and selective HCV NS5B polymerase inhibitors

Ariamala Gopalsamy; Kitae Lim; Gregory Ciszewski; Kaapjoo Park; John W Ellingboe; Jonathan Bloom; Shabana Insaf; Janis Upeslacis; Tarek S Mansour; Girija Krishnamurthy; Murthy Damarla; Yelena Pyatski; Douglas Ho; Anita Y M Howe; Mark Orlowski; Boris Feld; John O'Connell

doi:10.1021/jm0401255

Discovery of pyrano[3,4-b]indoles as potent and selective HCV NS5B polymerase inhibitors

J Med Chem. 2004 Dec 16;47(26):6603-8. doi: 10.1021/jm0401255.

Authors

Ariamala Gopalsamy¹, Kitae Lim, Gregory Ciszewski, Kaapjoo Park, John W Ellingboe, Jonathan Bloom, Shabana Insaf, Janis Upeslacis, Tarek S Mansour, Girija Krishnamurthy, Murthy Damarla, Yelena Pyatski, Douglas Ho, Anita Y M Howe, Mark Orlowski, Boris Feld, John O'Connell

Affiliation

¹ Chemical and Screening Sciences and Infectious Diseases, Wyeth Research, Pearl River, New York 10965, USA. [email protected]

PMID: 15588095
DOI: 10.1021/jm0401255

Abstract

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.

MeSH terms

Antiviral Agents / chemical synthesis*
Antiviral Agents / chemistry
Crystallography, X-Ray
DNA-Directed RNA Polymerases / antagonists & inhibitors*
DNA-Directed RNA Polymerases / chemistry
Hepacivirus / enzymology*
Indoles / chemical synthesis*
Indoles / chemistry
Pyrans / chemical synthesis*
Pyrans / chemistry
Stereoisomerism
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*
Viral Nonstructural Proteins / chemistry

Substances

(5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyrano(3,4-b)indol-1-yl)acetic acid
Antiviral Agents
Indoles
Pyrans
Viral Nonstructural Proteins
NS-5 protein, hepatitis C virus
DNA-Directed RNA Polymerases