Design and synthesis of N-(3,5-difluoro-4-hydroxyphenyl)benzenesulfonamides as aldose reductase inhibitors.
N-(3,5-Difluoro-4-hydroxyphenyl)benzenesulfonamide (4) and its derivatives 5-7 were prepared as putative bioisosteres of the previously reported aldose reductase inhibitors, which are the N-benzenesulfonylglycine derivatives I-IV. The in vitro aldose reductase inhibitory activity of the prepared compounds is higher than that of the respective glycine derivatives. Furthermore, the parent compound 4 reveals high antioxidant potential. Additionally, the intestine permeability of 4 is determined, and there is initial evidence that there is an operating influx mechanism. Overall, the data indicate that the presented chemotype could serve as a core structure for the design of putative pharmacotherapeutic agents, aiming to the long-term complications of diabetes mellitus.
Alexiou
Polyxeni
P
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Nicolaou
Ioannis
I
Stefek
Milan
M
Kristl
Albin
A
Demopoulos
Vassilis J
VJ
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005123:Eye / Q000187:drug effects / Q000201:enzymology; D005260:Female; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006834:Hydrazines / Q000378:metabolism; D006900:Hydroxylation; D007583:Jejunum / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D010851:Picrates; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000449:Aldehyde Reductase; D000975:Antioxidants; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D017611:Fluorine Compounds; D006834:Hydrazines; D010851:Picrates; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C004931:1,1-diphenyl-2-picrylhydrazyl