Synthesis of pyrrolo[2,3-d]pyrimidine nucleoside derivatives as potential anti-HCV agents

Chamakura V N S Varaprasad; Kanda S Ramasamy; Jean-Luc Girardet; Esmir Gunic; Vicky Lai; Weidong Zhong; Haoyun An; Zhi Hong

doi:10.1016/j.bioorg.2006.07.003

Synthesis of pyrrolo[2,3-d]pyrimidine nucleoside derivatives as potential anti-HCV agents

Bioorg Chem. 2007 Feb;35(1):25-34. doi: 10.1016/j.bioorg.2006.07.003. Epub 2006 Sep 1.

Authors

Chamakura V N S Varaprasad¹, Kanda S Ramasamy, Jean-Luc Girardet, Esmir Gunic, Vicky Lai, Weidong Zhong, Haoyun An, Zhi Hong

Affiliation

¹ Drug Discovery, Valeant Pharmaceuticals Research and Development, 3300 Hyland Avenue, Costa Mesa, CA 92626, USA. [email protected]

PMID: 16945403
DOI: 10.1016/j.bioorg.2006.07.003

Abstract

Several Toyocamycin (4) analogues were examined for their ability to inhibit HCV RNA in a replicon assay. Among the compounds examined 4-methylthio (18) and 5-carboxamide oxime derivatives (23 and 27) of Toyocamycin were found to have good activity and selectivity.

MeSH terms

Antiviral Agents / chemical synthesis*
Antiviral Agents / pharmacology
Hepatitis C / drug therapy
Hepatitis C / metabolism
Hepatitis C / virology
Humans
Magnetic Resonance Spectroscopy
Molecular Structure
Pyrimidine Nucleosides / chemistry
Pyrimidines / chemistry
Pyrroles / chemistry
RNA-Dependent RNA Polymerase / antagonists & inhibitors
RNA-Dependent RNA Polymerase / metabolism
Toyocamycin / analogs & derivatives
Toyocamycin / chemical synthesis*
Toyocamycin / pharmacology
Viral Nonstructural Proteins / antagonists & inhibitors
Viral Nonstructural Proteins / metabolism

Substances

Antiviral Agents
Pyrimidine Nucleosides
Pyrimidines
Pyrroles
Pyrrolo(2,3-d)pyrimidine
Viral Nonstructural Proteins
NS-5 protein, hepatitis C virus
RNA-Dependent RNA Polymerase
Toyocamycin