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Literature summary for 1.1.1.2 extracted from

  • Qin, X.; Hao, X.; Han, H.; Zhu, S.; Yang, Y.; Wu, B.; Hussain, S.; Parveen, S.; Jing, C.; Ma, B.; Zhu, C.
    Design and synthesis of potent and multifunctional aldose reductase inhibitors based on quinoxalinones (2015), J. Med. Chem., 58, 1254-1267.
    View publication on PubMed

Inhibitors

Inhibitors Comment Organism Structure
(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetic acid 32.8% inhibition at 0.010 mM Rattus norvegicus
2-(3,7-bis(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid 41.0% inhibition at 0.010 mM Rattus norvegicus
2-(3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid 36.6% inhibition at 0.010 mM Rattus norvegicus
2-(3-(3-indolyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid 32.3% inhibition at 0.010 mM Rattus norvegicus
2-(3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid 12.8% inhibition at 0.010 mM Rattus norvegicus
2-(3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid 42.4% inhibition at 0.010 mM Rattus norvegicus
2-(3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid 31.8% inhibition at 0.010 mM Rattus norvegicus
2-(3-(4-hydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid 34.6% inhibition at 0.010 mM Rattus norvegicus
2-(3-phenoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid 6.6% inhibition at 0.010 mM Rattus norvegicus
2-(3-phenyl-2-oxoquinoxalin-1(2H)-yl)acetic acid 25.4% inhibition at 0.010 mM Rattus norvegicus
2-(3-thiophenoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid 32.2% inhibition at 0.010 mM Rattus norvegicus
2-(6-bromo-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 38.1% inhibition at 0.010 mM Rattus norvegicus
2-(6-bromo-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 8.7% inhibition at 0.010 mM Rattus norvegicus
2-(6-chloro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 46.5% inhibition at 0.010 mM Rattus norvegicus
2-(6-fluoro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 42.5% inhibition at 0.010 mM Rattus norvegicus
2-(7-(4-fluorobenzyl)-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid 11.6% inhibition at 0.010 mM Rattus norvegicus
2-(7-bromo-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 35.9% inhibition at 0.010 mM Rattus norvegicus
2-(7-bromo-3-(3-indolyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid 17.5% inhibition at 0.010 mM Rattus norvegicus
2-(7-bromo-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 24.0% inhibition at 0.010 mM Rattus norvegicus
2-(7-bromo-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 10.2% inhibition at 0.010 mM Rattus norvegicus
2-(7-chloro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 44.5% inhibition at 0.010 mM Rattus norvegicus
2-(7-chloro-3-(2-benzothiophene)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 53.3% inhibition at 0.010 mM Rattus norvegicus
2-(7-chloro-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 14.1% inhibition at 0.010 mM Rattus norvegicus
2-(7-chloro-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 17.3% inhibition at 0.010 mM Rattus norvegicus
2-(7-chloro-3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid 23.6% inhibition at 0.010 mM Rattus norvegicus
2-(7-fluoro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 46.2% inhibition at 0.010 mM Rattus norvegicus
2-(7-fluoro-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 45.5% inhibition at 0.010 mM Rattus norvegicus
2-(7-fluoro-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid 29.5% inhibition at 0.010 mM Rattus norvegicus
2-(7-fluoro-3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid 35.8% inhibition at 0.010 mM Rattus norvegicus
epalrestat 73.6% inhibition at 0.010 mM Rattus norvegicus
additional information design and synthesis of inhibitors based on quinoxalinones, overview. Phenolic structure is installed in the compounds for the combination of antioxidant activity and strengthening the ability to fight against diabetic complications, radical scavenging activity using the model reaction with the stable free radicals of 2,2-diphenyl-1-picrylhydrazyl Rattus norvegicus
[2-oxo-3-(2-phenylethyl)quinoxalin-1(2H)-yl]acetic acid 22.0% inhibition at 0.010 mM Rattus norvegicus
[2-oxo-3-[(Z)-2-phenylethenyl]quinoxalin-1(2H)-yl]acetic acid 32.0% inhibition at 0.010 mM Rattus norvegicus
[3-[(E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid 32.6% inhibition at 0.010 mM Rattus norvegicus
[3-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid 42.4% inhibition at 0.010 mM Rattus norvegicus
[3-[(E)-2-(4-methoxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid 21.8% inhibition at 0.010 mM Rattus norvegicus
[3-[2-(4-hydroxyphenyl)ethyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid 12.2% inhibition at 0.010 mM Rattus norvegicus
[7-fluoro-3-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid 36.2% inhibition at 0.010 mM Rattus norvegicus
[7-fluoro-3-[2-(4-hydroxyphenyl)ethyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid 23.0% inhibition at 0.010 mM Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
D-glucose + NADPH + H+ Rattus norvegicus
-
sorbitol + NADP+
-
?
D-glucose + NADPH + H+ Rattus norvegicus Wistar
-
sorbitol + NADP+
-
?

Organism

Organism UniProt Comment Textmining
Rattus norvegicus P51635
-
-
Rattus norvegicus Wistar P51635
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
D-glucose + NADPH + H+
-
Rattus norvegicus sorbitol + NADP+
-
?
D-glucose + NADPH + H+
-
Rattus norvegicus Wistar sorbitol + NADP+
-
?
DL-glyceraldehyde + NADPH + H+
-
Rattus norvegicus ? + NADP+
-
?
DL-glyceraldehyde + NADPH + H+
-
Rattus norvegicus Wistar ? + NADP+
-
?

Synonyms

Synonyms Comment Organism
AKR1A1
-
Rattus norvegicus
aldose reductase
-
Rattus norvegicus
ALR1
-
Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.2
-
assay at Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Rattus norvegicus

General Information

General Information Comment Organism
metabolism ALR2 is the first rate-determining enzyme in the polyol pathway and catalyzes the reduction of glucose to sorbitol in the presence of NADPH as a cofactor. Sorbitol is in turn converted into fructose with accompanied reduction of NAD+ by sorbitol dehydrogenase. Under normal circumstances, glucose is predominantly converted to glucose-6-phosphate by hexokinase and then enters the glycolytic pathway, whereas only a small amount of glucose is metabolized through the polyol pathway due to a relatively low affinity of ALR2 for this substrate. During hyperglycemia, the polyol metabolic pathway is activated and the increased flux of glucose through the polyol pathway triggers the accumulation of sorbitol, which mainly happens in tissues demonstrating insulin-independent uptake of glucose, such as lens, kidney, retina, and peripheral nerves Rattus norvegicus