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.
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.
Rockway
Todd W
TW
Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064-6217, USA. rockway@abbott.com
Zhang
Rong
R
Liu
Dachun
D
Betebenner
David A
DA
McDaniel
Keith F
KF
Pratt
John K
JK
Beno
David
D
Montgomery
Debra
D
Jiang
Wen W
WW
Masse
Sherie
S
Kati
Warren M
WM
Middleton
Tim
T
Molla
Akhteruzzaman
A
Maring
Clarence J
CJ
Kempf
Dale J
DJ
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*
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