Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of N-1-benzyl and N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine analogs containing substituents on the aromatic ring

Todd W Rockway; Rong Zhang; Dachun Liu; David A Betebenner; Keith F McDaniel; John K Pratt; David Beno; Debra Montgomery; Wen W Jiang; Sherie Masse; Warren M Kati; Tim Middleton; Akhteruzzaman Molla; Clarence J Maring; Dale J Kempf

doi:10.1016/j.bmcl.2006.04.022

Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of N-1-benzyl and N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine analogs containing substituents on the aromatic ring

Bioorg Med Chem Lett. 2006 Jul 15;16(14):3833-8. doi: 10.1016/j.bmcl.2006.04.022. Epub 2006 May 2.

Authors

Todd W Rockway¹, Rong Zhang, Dachun Liu, David A Betebenner, Keith F McDaniel, John K Pratt, David Beno, Debra Montgomery, Wen W Jiang, Sherie Masse, Warren M Kati, Tim Middleton, Akhteruzzaman Molla, Clarence J Maring, Dale J Kempf

Affiliation

¹ Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064-6217, USA. rockway@abbott.com

PMID: 16650984
DOI: 10.1016/j.bmcl.2006.04.022

Abstract

A series of non-nucleoside HCV NS5B polymerase inhibitors based on the N-1-benzyl or N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine core substituted in the D-ring aromatic moiety have been prepared and evaluated. Aromatic substituents extending from position 7 of the D-ring exhibited excellent potency against both genotypes 1a and 1b.

MeSH terms

Benzothiadiazines / chemical synthesis
Benzothiadiazines / pharmacology*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology*
Genotype
Hydrocarbons, Aromatic / chemistry
Inhibitory Concentration 50
Naphthyridines / chemistry
RNA-Dependent RNA Polymerase / antagonists & inhibitors*
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*
Virus Replication / drug effects*

Substances

Benzothiadiazines
Enzyme Inhibitors
Hydrocarbons, Aromatic
Naphthyridines
Viral Nonstructural Proteins
NS-5 protein, hepatitis C virus
RNA-Dependent RNA Polymerase