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Literature summary for 1.13.11.27 extracted from

  • Xu, Y.L.; Lin, H.Y.; Cao, R.J.; Ming, Z.Z.; Yang, W.C.; Yang, G.F.
    Pyrazolone-quinazolone hybrids a novel class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors (2014), Bioorg. Med. Chem., 22, 5194-5211 .
    View publication on PubMed
Search for more literature for 1.13.11.27

Application

Application Comment Organism
drug development the enzyme is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism Homo sapiens
medicine compounds N-(4-methoxyphenyl)-7-nitro-2,1,3-benzoxadiazol-4-amine and 3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one can be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene HPD, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3) Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
3-(2,4-dimethylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2,4-dimethylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-chloro-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-chloro-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-fluoro-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-fluoro-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(2-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(3,4-dichlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(3-bbromophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(3-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(3-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(3-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(3-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(3-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-bromophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-chloro-2-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-chloro-2-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-fluoro-2-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-fluoro-2-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
3-(4-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-m-tolylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-o-tolylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-p-tolylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-(2-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-(3-(trifluoromethoxy)phenyl) quinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-(4-(trifluoromethoxy)phenyl) quinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-m-tolylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-o-tolylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-p-tolylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-phenylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(2-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(3-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
 Homo sapiens
additional information structure-based design of a series of pyrazolone-quinazolone hybrids, as a class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors, synthesis, overview. Molecular modeling indicates that the interaction between the pyrazolone ring and ferrous ion, and the hydrophobic interaction of quinazolone with its surrounding residues, such as Phe347 and Phe364, contribute greatly to the high potency of these inhibitors. Compounds N-(4-methoxyphenyl)-7-nitro-2,1,3-benzoxadiazol-4-amine and 3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one can be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation Homo sapiens
nitisinone NBTC, in clinical use Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ a Fe(II)-dependent non-heme oxygenase Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4-hydroxyphenylpyruvate + O2 Homo sapiens
-
 homogentisate + CO2
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P32754
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and ultrafiltration Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4-hydroxyphenylpyruvate + O2
-
 Homo sapiens homogentisate + CO2
-
 ?

Synonyms

Synonyms Comment Organism
HPD
-
 Homo sapiens
HPPD
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
 assay at Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
 additional information inhibition kinetics Homo sapiens
0.00001
-
 3-(3-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000011
-
 3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000013
-
 6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-m-tolylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000014
-
 3-(3-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000015
-
 3-(2-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000018
-
 3-(4-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000019
-
 6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-phenylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.00002
-
 3-(3-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000022
-
 3-(2-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000022
-
 3-(4-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000024
-
 3-(2-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000025
-
 6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-p-tolylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000025
-
 3-(3,4-dichlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000031
-
 6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-(3-(trifluoromethoxy)phenyl) quinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000032
-
 3-(4-chloro-2-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000034
-
 6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(3-methoxyphenyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000034
-
 3-(4-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000037
-
 nitisinone pH 7.0, 30°C, recombinant His-tagged enzyme Homo sapiens
0.000038
-
 6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(2-methoxyphenyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.00004
-
 3-(4-fluoro-2-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000058
-
 6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-o-tolylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000059
-
 3-(2,4-dimethylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.00006
-
 6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000074
-
 6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-m-tolylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000079
-
 3-(2-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000081
-
 3-(2-fluoro-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000086
-
 3-(2-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000087
-
 3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.00009
-
 3-(3-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.00009
-
 3-(2-chloro-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000093
-
 3-(3-bbromophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000109
-
 3-(2-chloro-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.00013
-
 3-(4-bromophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000156
-
 6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-p-tolylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.00016
-
 6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-(4-(trifluoromethoxy)phenyl) quinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000161
-
 3-(2,4-dimethylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.00017
-
 3-(2-fluoro-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000173
-
 3-(3-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000177
-
 3-(4-chloro-2-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000207
-
 6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-(2-methoxyphenyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000219
-
 3-(4-fluoro-2-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000237
-
 3-(4-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000238
-
 6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000247
-
 3-(4-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens
0.000248
-
 6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-o-tolylquinazolin-4(3H)-one recombinant His-tagged enzyme, pH 7.0, 30°C Homo sapiens