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Literature summary for 3.4.23.46 extracted from

  • Malamas, M.S.; Erdei, J.; Gunawan, I.; Turner, J.; Hu, Y.; Wagner, E.; Fan, K.; Chopra, R.; Olland, A.; Bard, J.; Jacobsen, S.; Magolda, R.L.; Pangalos, M.; Robichaud, A.J.
    Design and synthesis of 5,5-disubstituted aminohydantoins as potent and selective human beta-secretase (BACE1) inhibitors (2010), J. Med. Chem., 53, 1146-1158.
    View publication on PubMed
Search for more literature for 3.4.23.46

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli Homo sapiens
expression in CHO cell line Mus musculus
expression in CHO cell line Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
hanging drop vapor diffusion method, using 6% (w/v) PEG3350, 0.1 M sodium acetate, pH 5.4 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(5S)-2-amino-5-[3-fluoro-5-(2-fluoropyridin-3-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one aminohydantoin inhibitor, EC50 value in ELISA-assay 20 nM, and demonstrates more than 100fold selectivity for the other structurally related aspartyl proteases BACE2, cathepsinD, renin, and pepsin Homo sapiens
(5S)-2-amino-5-[3-fluoro-5-(2-fluoropyridin-3-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one aminohydantoin inhibitor, EC50 value in ELISA-assay 20 nM, and demonstrates more than 100fold selectivity for the other structurally related aspartyl proteases BACE2, cathepsinD, renin, and pepsin. Acute oral administration at 100 mg/kg results in a 69% reduction of plasma amyloid beta40 at 8 h in a Tg2576 mouse Mus musculus
2-amino-3-ethyl-5,5-diphenyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-5-[3-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-3-methyl-5-phenyl-5-(tricyclo[3.3.1.13,7]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5,5-diphenyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(1,3-benzodioxol-5-yl)-3-methyl-5-[3-(pyridin-3-yl)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-methyl-5-[3-(pyridin-3-yl)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(2,3-dihydro-1-benzofuran-5-yl)-3-methyl-5-[3-(pyridin-3-yl)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(3,4-dimethoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(3-butoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(3-chlorophenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(3-ethoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(3-methoxy-4-methylphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(3-methoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(3-methoxyphenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(4-chlorophenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(4-ethyl-3-methoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(4-methoxy-3-methylphenyl)-3-methyl-5-(6-methylbiphenyl-3-yl)-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(4-methoxy-3-methylphenyl)-3-methyl-5-[3-(pyrimidin-5-yl)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(4-methoxyphenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-(3,4-dimethoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-(3-butoxy-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-(3-chloro-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-(3-cyclopentyl-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-(3-ethoxy-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-(3-ethoxy-4-propoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-(3-fluoro-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-[3-(cyclopentyloxy)-4-methoxyphenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-[4-methoxy-3-(propan-2-yloxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-(biphenyl-3-yl)-5-[4-methoxy-3-(trifluoromethyl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-[2-fluoro-3-(pyrimidin-5-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-[3-(2-methoxypyridin-3-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-[3-(6-fluoropyridin-3-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-[3-(6-methoxypyridin-3-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-[3-fluoro-5-(pyrimidin-5-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-[4-fluoro-3-(pyrimidin-5-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
-
 Homo sapiens
2-amino-5-[4-fluoro-3-(pyrimidin-5-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one aminohydantoin inhibitor, shows comparable activity in a cell-based assay, and demonstrates more than 100fold selectivity for the other structurally related aspartyl proteases BACE2, cathepsinD, renin, and pepsin Homo sapiens
5-[2-amino-4-(4-methoxy-3-methylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]biphenyl-2-carbonitrile
-
 Homo sapiens
5-[2-amino-4-(biphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-2-methoxybenzonitrile
-
 Homo sapiens
OM99-2
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
amyloid precursor protein + H2O Homo sapiens
-
 fragments of amyloid precursor protein
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Homo sapiens P56817
-
-
Mus musculus
-
-
-

Purification (Commentary)

Purification (Comment) Organism
protein-A sepharose column chromatography and gel filtration Homo sapiens

Renatured (Commentary)

Renatured (Comment) Organism
-
 Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Abz-SEVNLDAEFR-Dpa + H2O
-
 Mus musculus ?
-
 ?
Abz-SEVNLDAEFR-Dpa + H2O
-
 Homo sapiens ?
-
 ?
amyloid precursor protein + H2O
-
 Homo sapiens fragments of amyloid precursor protein
-
 ?

Synonyms

Synonyms Comment Organism
BACE2
-
 Homo sapiens
beta-secretase
-
 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00001
-
 pH not specified in the publication, temperature not specified in the publication Homo sapiens (5S)-2-amino-5-[3-fluoro-5-(2-fluoropyridin-3-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00002
-
 pH not specified in the publication, temperature not specified in the publication Homo sapiens 2-amino-5-[4-fluoro-3-(pyrimidin-5-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00017
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-(3-butoxy-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.0002
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-(3-ethoxy-4-propoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.0003
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-[3-(cyclopentyloxy)-4-methoxyphenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00042
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(3-chlorophenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
0.0005
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-methyl-5-[3-(pyridin-3-yl)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00052
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-(3-fluoro-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00054
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(1,3-benzodioxol-5-yl)-3-methyl-5-[3-(pyridin-3-yl)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00055
-
 pH and temperature not specified in the publication Homo sapiens 5-[2-amino-4-(biphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-2-methoxybenzonitrile
0.00056
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-(3-chloro-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.0006
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-(3-ethoxy-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00068
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(3-methoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
0.00078
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00078
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00083
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-3-methyl-5-phenyl-5-(tricyclo[3.3.1.13,7]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
0.00096
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-(3-cyclopentyl-4-methoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00096
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(4-methoxy-3-methylphenyl)-3-methyl-5-(6-methylbiphenyl-3-yl)-3,5-dihydro-4H-imidazol-4-one
0.001
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-[4-methoxy-3-(trifluoromethyl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00113
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(2,3-dihydro-1-benzofuran-5-yl)-3-methyl-5-[3-(pyridin-3-yl)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00119
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(3-methoxyphenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
0.00126
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-[3-fluoro-5-(pyrimidin-5-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00159
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(4-methoxy-3-methylphenyl)-3-methyl-5-[3-(pyrimidin-5-yl)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00172
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(4-methoxyphenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
0.00184
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(4-chlorophenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
0.00184
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-[4-methoxy-3-(propan-2-yloxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00184
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00232
-
 pH and temperature not specified in the publication Homo sapiens 5-[2-amino-4-(4-methoxy-3-methylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]biphenyl-2-carbonitrile
0.00248
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-[3-(6-fluoropyridin-3-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00251
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-[3-(2-methoxypyridin-3-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00253
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(3-ethoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
0.0028
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-[4-fluoro-3-(pyrimidin-5-yl)phenyl]-5-(4-methoxy-3-methylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00387
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-5-[3-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00417
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(biphenyl-3-yl)-5-(3,4-dimethoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
0.00433
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(4-ethyl-3-methoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
0.00504
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-[2-fluoro-3-(pyrimidin-5-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00516
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-3-ethyl-5,5-diphenyl-3,5-dihydro-4H-imidazol-4-one
0.00555
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(3-butoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
0.00599
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-[3-(6-methoxypyridin-3-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.00629
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(3-methoxy-4-methylphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
0.00959
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-(3,4-dimethoxyphenyl)-3-methyl-5-(tricyclo[3.3.1.1(3,7)]dec-1-yl)-3,5-dihydro-4H-imidazol-4-one
0.00969
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5-[4-fluoro-3-(pyrimidin-5-yl)phenyl]-3-methyl-5-[4-(trifluoromethoxy)phenyl]-3,5-dihydro-4H-imidazol-4-one
0.08719
-
 pH and temperature not specified in the publication Homo sapiens 2-amino-5,5-diphenyl-3,5-dihydro-4H-imidazol-4-one