Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.7.7.48 extracted from

  • Ellis, D.A.; Blazel, J.K.; Tran, C.V.; Ruebsam, F.; Murphy, D.E.; Li, L.S.; Zhao, J.; Zhou, Y.; McGuire, H.M.; Xiang, A.X.; Webber, S.E.; Zhao, Q.; Han, Q.; Kissinger, C.R.; Lardy, M.; Gobbi, A.; Showalter, R.E.; Shah, A.M.; Tsan, M.; Patel, R.A.; LeBrun, L.A.; Kamran, R.; Bartkowski, D.M.; Nolan, T.G.; Norris, D.A.; S, S.e.
    5,5- and 6,6-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase (2009), Bioorg. Med. Chem. Lett., 19, 6047-6052.
    View publication on PubMed

Crystallization (Commentary)

Crystallization (Comment) Organism
HCV NS5B polymerase by hanging drop method at room temperature using a well buffer of 20% PEG 4000, 50 mM ammonium sulfate, 100 mM sodium acetate, pH 4.7, with 5 mM DTT, complexes are prepared by soaking the crystals for 3-24 h in solutions containing 15-20% DMSO, 20% glycerol, 20% PEG 4000, 0.1 M Hepes and 10 mM MgCl2 at pH 7.6 and an inhibitor concentration of 2-10 mM, X-ray diffraction structure determination and analysis at 2.6 A resolution for compound 29 and 2.15 A for compound 49 Hepacivirus C

Inhibitors

Inhibitors Comment Organism Structure
additional information 5,5- and 6,6-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase, overview Hepacivirus C
N-[3-[(4aR,7aS)-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-cyclopenta[b]pyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(4R)-5-(4-fluorobenzyl)-8-hydroxy-4-methyl-6-oxo-5-azaspiro[2.5]oct-7-en-7-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclobutyl-4-hydroxy-5-methyl-2-oxo-5-propyl-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclobutyl-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclobutyl-5-(2-cyclopropylethyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclobutyl-5-(3,3-dimethylbutyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclohexyl-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclohexyl-5-(3,3-dimethylbutyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclohexyl-5-(4-fluorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopentyl-4-hydroxy-5-(3-methylbut-2-en-1-yl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopentyl-4-hydroxy-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopentyl-4-hydroxy-5-methyl-2-oxo-5-prop-2-yn-1-yl-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopentyl-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopentyl-5-(2-cyclopropylethyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopentyl-5-(3,3-dimethylbutyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopentyl-5-(4-fluorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopentyl-5-ethyl-4-hydroxy-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopropyl-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopropyl-5-(3,3-dimethylbutyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-1-cyclopropyl-5-(4-fluorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1-phenyl-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-5-butyl-1-cyclobutyl-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5R)-6-(4-fluorobenzyl)-9-hydroxy-5-methyl-7-oxo-6-azaspiro[3.5]non-8-en-8-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5S)-1,5-bis(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5S)-1-(4-fluorobenzyl)-4-hydroxy-5-(3-methylbut-2-en-1-yl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5S)-1-(4-fluorobenzyl)-4-hydroxy-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5S)-1-(4-fluorobenzyl)-4-hydroxy-5-methyl-2-oxo-5-phenyl-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5S)-1-(4-fluorobenzyl)-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(5S)-5-ethyl-1-(4-fluorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(6R)-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-6-phenyl-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(6R)-1-(4-fluorobenzyl)-4-hydroxy-6-(1-methylethyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(6R)-1-(4-fluorobenzyl)-4-hydroxy-6-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(6R)-6-ethyl-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(6R)-6-tert-butyl-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(6S)-1-(4-fluorobenzyl)-4-hydroxy-6-(1-methylethyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(6S)-1-(4-fluorobenzyl)-6-(4-fluorophenyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(6S)-6-(1-ethylpropyl)-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[(6S)-6-ethyl-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[1-(4-fluorobenzyl)-4-hydroxy-5,5-dimethyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[6-(4-fluorobenzyl)-9-hydroxy-7-oxo-6-azaspiro[4.5]dec-8-en-8-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C
N-[3-[7-(4-fluorobenzyl)-10-hydroxy-8-oxo-7-azaspiro[4.5]dec-9-en-9-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
-
Hepacivirus C

Organism

Organism UniProt Comment Textmining
Hepacivirus C P26663 i.e. HCV, genotype 1b, strain BKDELTA21
-

Synonyms

Synonyms Comment Organism
NS5B
-
Hepacivirus C
NS5B polymerase
-
Hepacivirus C
RNA-dependent RNA polymerase
-
Hepacivirus C

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000025
-
above Hepacivirus C N-[3-[(4aR,7aS)-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-cyclopenta[b]pyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000025
-
above Hepacivirus C N-[3-[(5R)-1-cyclobutyl-5-(2-cyclopropylethyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000025
-
above Hepacivirus C N-[3-[(6S)-6-ethyl-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000026
-
-
Hepacivirus C N-[3-[(6R)-1-(4-fluorobenzyl)-4-hydroxy-6-(1-methylethyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000037
-
-
Hepacivirus C N-[3-[(4R)-5-(4-fluorobenzyl)-8-hydroxy-4-methyl-6-oxo-5-azaspiro[2.5]oct-7-en-7-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000042
-
-
Hepacivirus C N-[3-[(6R)-6-ethyl-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000042
-
-
Hepacivirus C N-[3-[(6R)-6-tert-butyl-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000044
-
-
Hepacivirus C N-[3-[(5R)-1-cyclobutyl-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000045
-
-
Hepacivirus C N-[3-[(5S)-5-ethyl-1-(4-fluorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000048
-
-
Hepacivirus C N-[3-[(5R)-1-cyclopentyl-5-ethyl-4-hydroxy-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000049
-
-
Hepacivirus C N-[3-[(5R)-5-butyl-1-cyclobutyl-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000057
-
-
Hepacivirus C N-[3-[(5R)-1-cyclopentyl-5-(2-cyclopropylethyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000061
-
-
Hepacivirus C N-[3-[(5R)-1-cyclopentyl-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000061
-
-
Hepacivirus C N-[3-[(6S)-6-(1-ethylpropyl)-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000068
-
-
Hepacivirus C N-[3-[(5R)-1-cyclopropyl-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000075
-
-
Hepacivirus C N-[3-[(5R)-1-cyclopropyl-5-(3,3-dimethylbutyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.000085
-
-
Hepacivirus C N-[3-[1-(4-fluorobenzyl)-4-hydroxy-5,5-dimethyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.0001
-
-
Hepacivirus C N-[3-[(6S)-1-(4-fluorobenzyl)-6-(4-fluorophenyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00011
-
-
Hepacivirus C N-[3-[(5R)-1-cyclobutyl-4-hydroxy-5-methyl-2-oxo-5-propyl-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00012
-
-
Hepacivirus C N-[3-[(5R)-1-cyclopentyl-4-hydroxy-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00012
-
-
Hepacivirus C N-[3-[(5R)-6-(4-fluorobenzyl)-9-hydroxy-5-methyl-7-oxo-6-azaspiro[3.5]non-8-en-8-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00015
-
-
Hepacivirus C N-[3-[6-(4-fluorobenzyl)-9-hydroxy-7-oxo-6-azaspiro[4.5]dec-8-en-8-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00017
-
-
Hepacivirus C N-[3-[(5R)-1-cyclobutyl-5-(3,3-dimethylbutyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00017
-
-
Hepacivirus C N-[3-[(5R)-1-cyclohexyl-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00017
-
-
Hepacivirus C N-[3-[(6R)-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-6-phenyl-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00018
-
-
Hepacivirus C N-[3-[1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00022
-
-
Hepacivirus C N-[3-[7-(4-fluorobenzyl)-10-hydroxy-8-oxo-7-azaspiro[4.5]dec-9-en-9-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.00065
-
-
Hepacivirus C N-[3-[(5R)-1-cyclopentyl-4-hydroxy-5-(3-methylbut-2-en-1-yl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
0.0014
-
-
Hepacivirus C N-[3-[(5S)-1-(4-fluorobenzyl)-4-hydroxy-5-(3-methylbut-2-en-1-yl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide