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Literature summary for 3.4.21.98 extracted from

  • Belfrage, A.K.; Abdurakhmanov, E.; Kerblom, E.; Brandt, P.; Oshalim, A.; Gising, J.; Skogh, A.; Neyts, J.; Danielson, U.H.; Sandstroem, A.
    Discovery of pyrazinone based compounds that potently inhibit the drug-resistant enzyme variant R155K of the hepatitis C virus NS3 protease (2016), Bioorg. Med. Chem., 24, 2603-2620 .
    View publication on PubMed

Application

Application Comment Organism
drug development NS3 protease represents a drug target for treatment of HCV infections, development of inhibitors less sensitive to drug resistance, overview Hepacivirus C

Protein Variants

Protein Variants Comment Organism
R155K drug-resistant mutant enzyme variant Hepacivirus C

Inhibitors

Inhibitors Comment Organism Structure
1-(2-(6-Benzyl-3-(3-(tert-butyl)ureido)-2-oxopyrazin-1(2H)-yl)acetamido)-3-hydroxy-N-((4-(trifluoromethyl)phenyl)sulfonyl)cyclobutane-1-carboxamide
-
Hepacivirus C
1-(2-(6-benzyl-3-(3-(tert-butyl)ureido)-5-chloro-2-oxopyrazin-1(2H)-yl)acetamido)-3-(benzyloxy)-N-((4-(trifluoromethyl)phenyl)sulfonyl)cyclobutane-1-carboxamide
-
Hepacivirus C
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-4-(pyrimidin-5-yl)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
-
Hepacivirus C
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-4-fluoro-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
-
Hepacivirus C
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((2-(trifluoromethyl)phenyl)sulfonyl)benzamide
-
Hepacivirus C
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((3-(trifluoromethyl)phenyl)sulfonyl)benzamide
-
Hepacivirus C
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)-4-vinylbenzamide
-
Hepacivirus C
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-Nmethyl-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
-
Hepacivirus C
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-Ntosylbenzamide
-
Hepacivirus C
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)benzoic acid
-
Hepacivirus C
2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-2-oxo-6-(2-phenylethyl)pyrazin-1(2H)-yl]acetamido)-4-chloro-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide
-
Hepacivirus C
2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl]acetamido)-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide lead compound Hepacivirus C
2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-6-[(naphthalen-1-yl)methyl]-2-oxopyrazin-1(2H)-yl]acetamido)-4-chloro-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide
-
Hepacivirus C
2-(2-[6-benzyl-3-[(tert-butylcarbamoyl)amino]-5-chloro-2-oxopyrazin-1(2H)-yl]acetamido)-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide
-
Hepacivirus C
2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)-N-(4-(2-oxo-2-(4-(trifluoromethyl)phenylsulfonamido)ethyl)phenyl)acetamide
-
Hepacivirus C
2-(6-benzyl-3-(3-(tert-butyl)ureido)-5-chloro-2-oxopyrazin-1(2H)-yl)acetate
-
Hepacivirus C
3-(2-(3-(3-(tert-b-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-5-(trifluoromethyl)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
-
Hepacivirus C
3-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
-
Hepacivirus C
3-(benzyloxy)-1-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)cyclobutane-1-carboxamide
-
Hepacivirus C
4-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
-
Hepacivirus C
4-bromo-2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide
-
Hepacivirus C
danoprevir approved drug for HCV treatment Hepacivirus C
methyl 2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)benzoate
-
Hepacivirus C
additional information discovery and synthesis of pyrazinone-based compounds that potently inhibit the drug-resistant enzyme variant R155K of the hepatitis C virus NS3 protease, molecular docking and modeling, overview. The compounds, that are very different to the approved drugs and clinical candidates, have potential in the development of inhibitors less sensitive to drug resistance Hepacivirus C
N-((2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(naphthalen-1-ylmethyl)-2-oxopyrazin-1(2H)-yl)acetamido)phenyl)sulfonyl)-4-(trifluoromethyl)benzamide
-
Hepacivirus C
N-((3-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(naphthalen-1-ylmethyl)-2-oxopyrazin-1(2H)-yl)acetamido)phenyl)sulfonyl)-4-(trifluoromethyl)benzamide
-
Hepacivirus C
N-((4-(2-(3-(3-(tert-butyl)ureido)-5-chloro- 6-(naphthalen-1-ylmethyl)-2-oxopyrazin-1(2H)-yl)acetamido)phenyl)sulfonyl)-4-(trifluoromethyl)benzamide
-
Hepacivirus C
N-[2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-2-oxo-6-(2-phenylethyl)pyrazin-1(2H)-yl]acetamido)-4-chlorobenzene-1-sulfonyl]-4-(trifluoromethyl)benzamide
-
Hepacivirus C
paritaprevir approved drug for HCV treatment Hepacivirus C
simeprevir approved drug for HCV treatment Hepacivirus C
sofosbuvir approved drug for HCV treatment Hepacivirus C
telaprevir
-
Hepacivirus C

Organism

Organism UniProt Comment Textmining
Hepacivirus C
-
-
-

Synonyms

Synonyms Comment Organism
NS3 protease
-
Hepacivirus C

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000015
-
telaprevir pH and temperature not specified in the publication Hepacivirus C
0.000015
-
methyl 2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)benzoate inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.000017
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)benzoic acid inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00002
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-4-fluoro-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00002
-
3-(benzyloxy)-1-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)cyclobutane-1-carboxamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.000024
-
2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)-N-(4-(2-oxo-2-(4-(trifluoromethyl)phenylsulfonamido)ethyl)phenyl)acetamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00003
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-4-(pyrimidin-5-yl)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00003
-
2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl]acetamido)-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00003
-
N-((2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(naphthalen-1-ylmethyl)-2-oxopyrazin-1(2H)-yl)acetamido)phenyl)sulfonyl)-4-(trifluoromethyl)benzamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00004
-
N-[2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-2-oxo-6-(2-phenylethyl)pyrazin-1(2H)-yl]acetamido)-4-chlorobenzene-1-sulfonyl]-4-(trifluoromethyl)benzamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00006
-
4-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00006
-
N-((3-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(naphthalen-1-ylmethyl)-2-oxopyrazin-1(2H)-yl)acetamido)phenyl)sulfonyl)-4-(trifluoromethyl)benzamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00007
-
2-(2-[6-benzyl-3-[(tert-butylcarbamoyl)amino]-5-chloro-2-oxopyrazin-1(2H)-yl]acetamido)-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.00007
-
3-(benzyloxy)-1-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)cyclobutane-1-carboxamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00009
-
2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-6-[(naphthalen-1-yl)methyl]-2-oxopyrazin-1(2H)-yl]acetamido)-4-chloro-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide inhibition of enzyme mutant R155K, pH and temperature not specified in the publication Hepacivirus C
0.0001
-
3-(2-(3-(3-(tert-b-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-5-(trifluoromethyl)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00011
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-4-fluoro-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00012
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-4-(pyrimidin-5-yl)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00012
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)-4-vinylbenzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00012
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-Ntosylbenzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00012
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)benzoic acid inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00012
-
methyl 2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)benzoate inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00013
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((2-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00014
-
2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl]acetamido)-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00014
-
2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)-N-(4-(2-oxo-2-(4-(trifluoromethyl)phenylsulfonamido)ethyl)phenyl)acetamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00015
-
1-(2-(6-benzyl-3-(3-(tert-butyl)ureido)-5-chloro-2-oxopyrazin-1(2H)-yl)acetamido)-3-(benzyloxy)-N-((4-(trifluoromethyl)phenyl)sulfonyl)cyclobutane-1-carboxamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00015
-
4-bromo-2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00017
-
3-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00017
-
N-((4-(2-(3-(3-(tert-butyl)ureido)-5-chloro- 6-(naphthalen-1-ylmethyl)-2-oxopyrazin-1(2H)-yl)acetamido)phenyl)sulfonyl)-4-(trifluoromethyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00017
-
N-[2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-2-oxo-6-(2-phenylethyl)pyrazin-1(2H)-yl]acetamido)-4-chlorobenzene-1-sulfonyl]-4-(trifluoromethyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00018
-
N-((2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(naphthalen-1-ylmethyl)-2-oxopyrazin-1(2H)-yl)acetamido)phenyl)sulfonyl)-4-(trifluoromethyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00019
-
N-((3-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(naphthalen-1-ylmethyl)-2-oxopyrazin-1(2H)-yl)acetamido)phenyl)sulfonyl)-4-(trifluoromethyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00022
-
2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-2-oxo-6-(2-phenylethyl)pyrazin-1(2H)-yl]acetamido)-4-chloro-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00023
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((3-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00026
-
2-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-Nmethyl-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00026
-
4-(2-(3-(3-(tert-butyl)ureido)-5-chloro-6-(2-cyclohexylethyl)-2-oxopyrazin-1(2H)-yl)acetamido)-N-((4-(trifluoromethyl)phenyl)sulfonyl)benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00027
-
2-(2-[6-benzyl-3-[(tert-butylcarbamoyl)amino]-5-chloro-2-oxopyrazin-1(2H)-yl]acetamido)-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00031
-
2-(2-[3-[(tert-butylcarbamoyl)amino]-5-chloro-6-[(naphthalen-1-yl)methyl]-2-oxopyrazin-1(2H)-yl]acetamido)-4-chloro-N-[4-(trifluoromethyl)benzene-1-sulfonyl]benzamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.00045
-
1-(2-(6-Benzyl-3-(3-(tert-butyl)ureido)-2-oxopyrazin-1(2H)-yl)acetamido)-3-hydroxy-N-((4-(trifluoromethyl)phenyl)sulfonyl)cyclobutane-1-carboxamide inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C
0.01
-
2-(6-benzyl-3-(3-(tert-butyl)ureido)-5-chloro-2-oxopyrazin-1(2H)-yl)acetate inhibition of full-length wild-type enzyme, pH and temperature not specified in the publication Hepacivirus C