title: 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.
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.
authors.affiliation: Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064-6217, USA. rockway@abbott.com
authors.forename: Todd W
authors.initials: TW
authors.lastname: Rockway
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Dachun
authors.initials: D
authors.lastname: Liu
authors.forename: David A
authors.initials: DA
authors.lastname: Betebenner
authors.forename: Keith F
authors.initials: KF
authors.lastname: McDaniel
authors.forename: John K
authors.initials: JK
authors.lastname: Pratt
authors.forename: David
authors.initials: D
authors.lastname: Beno
authors.forename: Debra
authors.initials: D
authors.lastname: Montgomery
authors.forename: Wen W
authors.initials: WW
authors.lastname: Jiang
authors.forename: Sherie
authors.initials: S
authors.lastname: Masse
authors.forename: Warren M
authors.initials: WM
authors.lastname: Kati
authors.forename: Tim
authors.initials: T
authors.lastname: Middleton
authors.forename: Akhteruzzaman
authors.initials: A
authors.lastname: Molla
authors.forename: Clarence J
authors.initials: CJ
authors.lastname: Maring
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Kempf
mesh_terms: D001581:Benzothiadiazines / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D005838:Genotype; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D020128:Inhibitory Concentration 50; D009287:Naphthyridines / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D001581:Benzothiadiazines; D004791:Enzyme Inhibitors; D006841:Hydrocarbons, Aromatic; D009287:Naphthyridines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase