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Literature summary for 1.1.1.21 extracted from

  • Mylari, B.L.; Armento, S.J.; Beebe, D.A.; Conn, E.L.; Coutcher, J.B.; Dina, M.S.; OGorman, M.T.; Linhares, M.C.; Martin, W.H.; Oates, P.J.; Tess, D.A.; Withbroe, G.J.; Zembrowski, W.J.
    A novel series of non-carboxylic acid, non-hydantoin inhibitors of aldose reductase with potent oral activity in diabetic rat models: 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and congeners (2005), J. Med. Chem., 48, 6326-6339.
    View publication on PubMed
Search for more literature for 1.1.1.21

Inhibitors

Inhibitors Comment Organism Structure
6-(2,3-dichlorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 55 nM Rattus norvegicus
6-(2,3-dichlorophenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 35 nM Rattus norvegicus
6-(2,3-difluorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 390 nM Rattus norvegicus
6-(2,3-difluorophenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 257 nM Rattus norvegicus
6-(2,4-dichlorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 190 nM Rattus norvegicus
6-(2,4-dichlorophenylsulfonyl)-2H-pyridazin-3-one
-
 Rattus norvegicus
6-(2,4-difluorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 870 nM Rattus norvegicus
6-(2,5-dichlorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 73 nM Rattus norvegicus
6-(2,6-dichlorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 50 nM Rattus norvegicus
6-(2,6-dichlorophenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 52 nM Rattus norvegicus
6-(2-bromobenzenesulfonyl)-2H-pyridazin-3-one IC50: 210 nM Rattus norvegicus
6-(2-chloro-4-fluorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 280 nM Rattus norvegicus
6-(2-chloro-6-fluorophenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 26 nM Rattus norvegicus
6-(2-chlorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 170 nM Rattus norvegicus
6-(2-chlorophenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 118 nM Rattus norvegicus
6-(2-fluoro-3-chlorophenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 54 nM Rattus norvegicus
6-(2-fluoro-3-trifluoromethylphenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 44 nM Rattus norvegicus
6-(2-fluoro-4-bromophenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 667 nM Rattus norvegicus
6-(2-fluorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 540 nM Rattus norvegicus
6-(2-fluorophenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 422 nM Rattus norvegicus
6-(2-trifluoromethylphenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 500 nM Rattus norvegicus
6-(3,4-dichlorobenzenesulfonyl)-2H-pyridazin-3-one
-
 Rattus norvegicus
6-(3,5-dichlorobenzenesulfonyl)-2H-pyridazin-3-one
-
 Rattus norvegicus
6-(3,5-dimethylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 13 nM Rattus norvegicus
6-(3-chlorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 240 nM Rattus norvegicus
6-(3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 140 nM Rattus norvegicus
6-(3-phenylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 23 nM Rattus norvegicus
6-(3-trifluoromethylbenzenesulfonyl)-2H-pyridazin-3-one IC50: 175 nM Rattus norvegicus
6-(3-trifluoromethylphenylmethanesulfonyl)-2H-pyridazin-3-one IC50: 72 nM Rattus norvegicus
6-(3-[4-fluorophenyl]benzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 49 nM Rattus norvegicus
6-(4-bromo-2-fluorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 140 nM Rattus norvegicus
6-(4-bromobenzenesulfonyl)-2H-pyridazin-3-one IC50: 350 nM Rattus norvegicus
6-(4-chlorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 380 nM Rattus norvegicus
6-(4-fluorobenzenesulfonyl)-2H-pyridazin-3-one IC50: 474 nM Rattus norvegicus
6-(4-methoxybenzenesulfonyl)-2H-pyridazin-3-one IC50: 0.002 mM Rattus norvegicus
6-(4-trifluoromethylbenzenesulfonyl)-2H-pyridazin-3-one IC50: 360 nM Rattus norvegicus
6-(5,6-methylenedioxyindole-2-sulfonyl)-2H-pyridazin-3-one IC50: 0.0038 mM Rattus norvegicus
6-(5,7-dichlorobenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 87 nM Rattus norvegicus
6-(5,7-dichloroindole-2-sulfonyl)-2H-pyridazin-3-one IC50: 200 nM Rattus norvegicus
6-(5-chloro-3-ethylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 6 nM Rattus norvegicus
6-(5-chloro-3-isopropylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 92 nM Rattus norvegicus
6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 0.001 mM Rattus norvegicus
6-(5-chloro-3-methylbenzothiophene-2-sulfonyl)-2H-pyridazin-3-one IC50: 55 nM Rattus norvegicus
6-(5-chloro-3-phenylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 34 nM Rattus norvegicus
6-(5-chlorobenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 25 nM Rattus norvegicus
6-(5-chloroindole-2-sulfonyl)-2H-pyridazin-3-one IC50: 0.0011 mM Rattus norvegicus
6-(5-fluoro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 3 nM Rattus norvegicus
6-(5-methoxybenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 230 nM Rattus norvegicus
6-(5-methylbenzothiophene-2-sulfonyl)-2H-pyridazin-3-one IC50: 160 nM Rattus norvegicus
6-(5-trifluoromethyl-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 5 nM Rattus norvegicus
6-(6-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 190 nM Rattus norvegicus
6-(6-chloroindole-2-sulfonyl)-2H-pyridazin-3-one IC50: 645 nM Rattus norvegicus
6-(6-fluoroindole-2-sulfonyl)-2H-pyridazin-3-one IC50: 0.0014 mM Rattus norvegicus
6-(7-chloroindole-2-sulfonyl)-2H-pyridazin-3-one IC50: 450 nM Rattus norvegicus
6-(alpha-naphthylmethylbenzenesulfonyl)-2H-pyridazin-3-one IC50: 150 nM Rattus norvegicus
6-(benzofuran-2-sulfonyl)-2H-pyridazin-3-one IC50: 150 nM Rattus norvegicus
6-(benzothiazole-2-sulfonyl)-2H-pyridazin-3-one IC50: 450 nM Rattus norvegicus
6-(benzothiophene-2-sulfonyl)-2H-pyridazin-3-one IC50: 180 nM Rattus norvegicus
6-(beta-naphthylmethylbenzenesulfonyl)-2H-pyridazin-3-one IC50: 360 nM Rattus norvegicus
6-(biphenyl-2-sulfonyl)-2H-pyridazin-3-one IC50: 0.0022 mM Rattus norvegicus
6-(indole-2-sulfonyl)-2H-pyridazin-3-one IC50: 590 nM Rattus norvegicus
8-phenylsulfonylphthalazin-2H-3-one IC50: 55 nM Rattus norvegicus
minalrestat
-
 Rattus norvegicus
additional information synthesis and structure-activity relationship study of inhibitors, overview Rattus norvegicus
ponalrestat
-
 Rattus norvegicus
ranirestat
-
 Rattus norvegicus
sorbinil IC50: 140 nM Rattus norvegicus
Tolrestat
-
 Rattus norvegicus
zopolrestat IC50: 4 nM Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
aldose + NADPH + H+ Rattus norvegicus first and rate-limiting step in the polyol pathway, pathway network overview alditol + NADP+
-
 ?

Organism

Organism UniProt Comment Textmining
Rattus norvegicus
-
 diabetic rats
-

Source Tissue

Source Tissue Comment Organism Textmining
lens of diabetic rats Rattus norvegicus
-
nerve of diabetic rats Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
aldose + NADPH + H+
-
 Rattus norvegicus alditol + NADP+
-
 ?
aldose + NADPH + H+ first and rate-limiting step in the polyol pathway, pathway network overview Rattus norvegicus alditol + NADP+
-
 ?

Synonyms

Synonyms Comment Organism
aldose reductase
-
 Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
24
-
 assay at Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
 assay at Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
NADPH
-
 Rattus norvegicus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000003
-
 IC50: 3 nM Rattus norvegicus 6-(5-fluoro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.000004
-
 IC50: 4 nM Rattus norvegicus zopolrestat
0.000005
-
 IC50: 5 nM Rattus norvegicus 6-(5-trifluoromethyl-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.000006
-
 IC50: 6 nM Rattus norvegicus 6-(5-chloro-3-ethylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.000013
-
 IC50: 13 nM Rattus norvegicus 6-(3,5-dimethylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.000023
-
 IC50: 23 nM Rattus norvegicus 6-(3-phenylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.000025
-
 IC50: 25 nM Rattus norvegicus 6-(5-chlorobenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.000026
-
 IC50: 26 nM Rattus norvegicus 6-(2-chloro-6-fluorophenylmethanesulfonyl)-2H-pyridazin-3-one
0.000034
-
 IC50: 34 nM Rattus norvegicus 6-(5-chloro-3-phenylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.000035
-
 IC50: 35 nM Rattus norvegicus 6-(2,3-dichlorophenylmethanesulfonyl)-2H-pyridazin-3-one
0.000044
-
 IC50: 44 nM Rattus norvegicus 6-(2-fluoro-3-trifluoromethylphenylmethanesulfonyl)-2H-pyridazin-3-one
0.000049
-
 IC50: 49 nM Rattus norvegicus 6-(3-[4-fluorophenyl]benzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.00005
-
 IC50: 50 nM Rattus norvegicus 6-(2,6-dichlorobenzenesulfonyl)-2H-pyridazin-3-one
0.000052
-
 IC50: 52 nM Rattus norvegicus 6-(2,6-dichlorophenylmethanesulfonyl)-2H-pyridazin-3-one
0.000054
-
 IC50: 54 nM Rattus norvegicus 6-(2-fluoro-3-chlorophenylmethanesulfonyl)-2H-pyridazin-3-one
0.000055
-
 IC50: 55 nM Rattus norvegicus 6-(2,3-dichlorobenzenesulfonyl)-2H-pyridazin-3-one
0.000055
-
 IC50: 55 nM Rattus norvegicus 8-phenylsulfonylphthalazin-2H-3-one
0.000055
-
 IC50: 55 nM Rattus norvegicus 6-(5-chloro-3-methylbenzothiophene-2-sulfonyl)-2H-pyridazin-3-one
0.000072
-
 IC50: 72 nM Rattus norvegicus 6-(3-trifluoromethylphenylmethanesulfonyl)-2H-pyridazin-3-one
0.000073
-
 IC50: 73 nM Rattus norvegicus 6-(2,5-dichlorobenzenesulfonyl)-2H-pyridazin-3-one
0.000087
-
 IC50: 87 nM Rattus norvegicus 6-(5,7-dichlorobenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.000092
-
 IC50: 92 nM Rattus norvegicus 6-(5-chloro-3-isopropylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.000118
-
 IC50: 118 nM Rattus norvegicus 6-(2-chlorophenylmethanesulfonyl)-2H-pyridazin-3-one
0.00014
-
 IC50: 140 nM Rattus norvegicus sorbinil
0.00014
-
 IC50: 140 nM Rattus norvegicus 6-(4-bromo-2-fluorobenzenesulfonyl)-2H-pyridazin-3-one
0.00014
-
 IC50: 140 nM Rattus norvegicus 6-(3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.00015
-
 IC50: 150 nM Rattus norvegicus 6-(alpha-naphthylmethylbenzenesulfonyl)-2H-pyridazin-3-one
0.00015
-
 IC50: 150 nM Rattus norvegicus 6-(benzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.00016
-
 IC50: 160 nM Rattus norvegicus 6-(5-methylbenzothiophene-2-sulfonyl)-2H-pyridazin-3-one
0.00017
-
 IC50: 170 nM Rattus norvegicus 6-(2-chlorobenzenesulfonyl)-2H-pyridazin-3-one
0.000175
-
 IC50: 175 nM Rattus norvegicus 6-(3-trifluoromethylbenzenesulfonyl)-2H-pyridazin-3-one
0.00018
-
 IC50: 180 nM Rattus norvegicus 6-(benzothiophene-2-sulfonyl)-2H-pyridazin-3-one
0.00019
-
 IC50: 190 nM Rattus norvegicus 6-(2,4-dichlorobenzenesulfonyl)-2H-pyridazin-3-one
0.00019
-
 IC50: 190 nM Rattus norvegicus 6-(6-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.0002
-
 IC50: 200 nM Rattus norvegicus 6-(5,7-dichloroindole-2-sulfonyl)-2H-pyridazin-3-one
0.00021
-
 IC50: 210 nM Rattus norvegicus 6-(2-bromobenzenesulfonyl)-2H-pyridazin-3-one
0.00023
-
 IC50: 230 nM Rattus norvegicus 6-(5-methoxybenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.00024
-
 IC50: 240 nM Rattus norvegicus 6-(3-chlorobenzenesulfonyl)-2H-pyridazin-3-one
0.000257
-
 IC50: 257 nM Rattus norvegicus 6-(2,3-difluorophenylmethanesulfonyl)-2H-pyridazin-3-one
0.00028
-
 IC50: 280 nM Rattus norvegicus 6-(2-chloro-4-fluorobenzenesulfonyl)-2H-pyridazin-3-one
0.00035
-
 IC50: 350 nM Rattus norvegicus 6-(4-bromobenzenesulfonyl)-2H-pyridazin-3-one
0.00036
-
 IC50: 360 nM Rattus norvegicus 6-(4-trifluoromethylbenzenesulfonyl)-2H-pyridazin-3-one
0.00036
-
 IC50: 360 nM Rattus norvegicus 6-(beta-naphthylmethylbenzenesulfonyl)-2H-pyridazin-3-one
0.00038
-
 IC50: 380 nM Rattus norvegicus 6-(4-chlorobenzenesulfonyl)-2H-pyridazin-3-one
0.00039
-
 IC50: 390 nM Rattus norvegicus 6-(2,3-difluorobenzenesulfonyl)-2H-pyridazin-3-one
0.000422
-
 IC50: 422 nM Rattus norvegicus 6-(2-fluorophenylmethanesulfonyl)-2H-pyridazin-3-one
0.00045
-
 IC50: 450 nM Rattus norvegicus 6-(7-chloroindole-2-sulfonyl)-2H-pyridazin-3-one
0.00045
-
 IC50: 450 nM Rattus norvegicus 6-(benzothiazole-2-sulfonyl)-2H-pyridazin-3-one
0.000474
-
 IC50: 474 nM Rattus norvegicus 6-(4-fluorobenzenesulfonyl)-2H-pyridazin-3-one
0.0005
-
 IC50: 500 nM Rattus norvegicus 6-(2-trifluoromethylphenylmethanesulfonyl)-2H-pyridazin-3-one
0.00054
-
 IC50: 540 nM Rattus norvegicus 6-(2-fluorobenzenesulfonyl)-2H-pyridazin-3-one
0.00059
-
 IC50: 590 nM Rattus norvegicus 6-(indole-2-sulfonyl)-2H-pyridazin-3-one
0.000645
-
 IC50: 645 nM Rattus norvegicus 6-(6-chloroindole-2-sulfonyl)-2H-pyridazin-3-one
0.000667
-
 IC50: 667 nM Rattus norvegicus 6-(2-fluoro-4-bromophenylmethanesulfonyl)-2H-pyridazin-3-one
0.00087
-
 IC50: 870 nM Rattus norvegicus 6-(2,4-difluorobenzenesulfonyl)-2H-pyridazin-3-one
0.001
-
 IC50: 0.001 mM Rattus norvegicus 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one
0.0011
-
 IC50: 0.0011 mM Rattus norvegicus 6-(5-chloroindole-2-sulfonyl)-2H-pyridazin-3-one
0.0014
-
 IC50: 0.0014 mM Rattus norvegicus 6-(6-fluoroindole-2-sulfonyl)-2H-pyridazin-3-one
0.002
-
 IC50: 0.002 mM Rattus norvegicus 6-(4-methoxybenzenesulfonyl)-2H-pyridazin-3-one
0.0022
-
 IC50: 0.0022 mM Rattus norvegicus 6-(biphenyl-2-sulfonyl)-2H-pyridazin-3-one
0.0038
-
 IC50: 0.0038 mM Rattus norvegicus 6-(5,6-methylenedioxyindole-2-sulfonyl)-2H-pyridazin-3-one