Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of unsymmetrical 1-hydroxy-4,4-dialkyl-3-oxo-3,4-dihydronaphthalene benzothiadiazine derivatives

A Chris Krueger; Darold L Madigan; Brian E Green; Douglas K Hutchinson; Wen W Jiang; Warren M Kati; Yaya Liu; Clarence J Maring; Sherie V Masse; Keith F McDaniel; Tim R Middleton; Hongmei Mo; Akhteruzzaman Molla; Debra A Montgomery; Teresa I Ng; Dale J Kempf

doi:10.1016/j.bmcl.2007.01.072

Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of unsymmetrical 1-hydroxy-4,4-dialkyl-3-oxo-3,4-dihydronaphthalene benzothiadiazine derivatives

Bioorg Med Chem Lett. 2007 Apr 15;17(8):2289-92. doi: 10.1016/j.bmcl.2007.01.072. Epub 2007 Jan 27.

Authors

A Chris Krueger¹, Darold L Madigan, Brian E Green, Douglas K Hutchinson, Wen W Jiang, Warren M Kati, Yaya Liu, Clarence J Maring, Sherie V Masse, Keith F McDaniel, Tim R Middleton, Hongmei Mo, Akhteruzzaman Molla, Debra A Montgomery, Teresa I Ng, Dale J Kempf

Affiliation

¹ Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. [email protected]

PMID: 17300933
DOI: 10.1016/j.bmcl.2007.01.072

Abstract

Substituted 1-hydroxy-4,4-dialkyl-3-oxo-3,4-dihydronaphthalene benzothiadiazine derivatives were investigated as inhibitors of genotype 1 HCV polymerase. Structure-activity relationship patterns for this class of compounds are discussed. It was found that the saturated alkane dialkyl units provided the most active analogs.

MeSH terms

Alkanes
Antiviral Agents / chemical synthesis*
Antiviral Agents / pharmacology
Benzothiadiazines / chemical synthesis*
Benzothiadiazines / pharmacology*
Hepacivirus / drug effects*
Hepacivirus / enzymology
Inhibitory Concentration 50
Replicon / drug effects
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Alkanes
Antiviral Agents
Benzothiadiazines
Viral Nonstructural Proteins
NS-5 protein, hepatitis C virus