Phenylsulfonylnitromethanes as potent irreversible inhibitors of aldose reductase

• Published in: European journal of medicinal chemistry Vol. 34; no. 9; pp. 745 - 751
• Main Authors: Saab, Nada H, Donkor, Isaac O, Rodriguez, Libaniel, Kador, Peter F, Miller, Duane D
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.09.1999; Elsevier
• Subjects: aldose reductase; aldose reductase inhibitors; Biological and medical sciences; Chemistry, Medicinal; diabetic complication; Eye; irreversible inhibitors; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; phenylsulphonyl-nitromethane; Science & Technology; aldose reductase; aldose reductase inhibitors; diabetic complication; irreversible inhibitors; phenylsulphonyl-nitromethane; SITE; RAT; EXPRESSION; Nitro compound; Rat; Sulfone; Enzyme; Diabetes mellitus; Rodentia; Enzyme inhibitor; In vitro; Prevention; Vertebrata; Eye disease; Mammalia; Structure activity relation; Animal; Organic isothiocyanate; Aldehyde reductase; Complication; Benzenic compound; Aromatic compound; Lens; Oxidoreductases; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(99)00219-6

Aldose reductase (AR) inhibition provides a viable pharmacologically direct mode for the treatment of diabetic complications. We have synthesized a series of N-4 substituted analogues ( 15–21) of the known aldose reductase inhibitor phenyl-sulfonylnitromethane. The compounds are potent inhibitors of AR with IC 50s between 0.01 and 0.19 μM. Some of the compounds are also potent affinity labels for AR. Compound 19 exhibits the highest and almost complete irreversible inhibition of AR known to date.