Synthesis of 4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamides with broad-spectrum human herpesvirus polymerase inhibition

Mark E Schnute; Roger J Brideau; Sarah A Collier; Michele M Cudahy; Todd A Hopkins; Mary L Knechtel; Nancee L Oien; Robert S Sackett; Allen Scott; Mari L Stephan; Michael W Wathen; Janet L Wieber

doi:10.1016/j.bmcl.2008.06.060

Synthesis of 4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamides with broad-spectrum human herpesvirus polymerase inhibition

Bioorg Med Chem Lett. 2008 Jul 15;18(14):3856-9. doi: 10.1016/j.bmcl.2008.06.060. Epub 2008 Jun 20.

Authors

Mark E Schnute¹, Roger J Brideau, Sarah A Collier, Michele M Cudahy, Todd A Hopkins, Mary L Knechtel, Nancee L Oien, Robert S Sackett, Allen Scott, Mari L Stephan, Michael W Wathen, Janet L Wieber

Affiliation

¹ Global Research and Development, Pfizer Inc., 700 Chesterfield Parkway West, St. Louis, MO 63017, USA. mark.e.schnute@pfizer.com

PMID: 18595689
DOI: 10.1016/j.bmcl.2008.06.060

Abstract

A versatile synthesis of 4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxylate esters has been developed which has lead to the identification of a new series of non-nucleoside inhibitors of human herpesvirus polymerases HCMV, HSV-1, EBV, and VZV with high specificity compared to human DNA polymerases.

MeSH terms

Antiviral Agents / chemical synthesis*
Antiviral Agents / pharmacology
Chemistry, Pharmaceutical / methods
Cytomegalovirus / enzymology
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Esters
Furans / chemical synthesis*
Furans / pharmacology
Herpesviridae / drug effects*
Herpesvirus 3, Human / enzymology
Herpesvirus 4, Human / enzymology
Inhibitory Concentration 50
Models, Chemical
Molecular Conformation
Nucleic Acid Synthesis Inhibitors*
Pyridones / chemical synthesis*
Pyridones / pharmacology
Simplexvirus / enzymology

Substances

4-oxo-4,7-dihydrofuro(2,3-b)pyridine-5-carboxamide
Antiviral Agents
Enzyme Inhibitors
Esters
Furans
Nucleic Acid Synthesis Inhibitors
Pyridones