[1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone as a bioisostere of a carboxylic acid aldose reductase inhibitor.
[1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone (6) was synthesized as a putative bioisostere of the known aldose reductase (AR) inhibitor (3-benzoylpyrrol-1-yl)acetic acid (I). It was found that 6 is approximately 5 times more potent as an in vitro inhibitor of AR than I, with an IC(50) value in the submicromolar range. Furthermore, 6 showed considerable activity in an in vitro experimental glycation model of diabetes mellitus. Our results support the notion that 6 might become a useful lead structure.
Nicolaou
Ioannis
I
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Zika
Chariklia
C
Demopoulos
Vassilis J
VJ
D000085:Acetates / Q000737:chemistry*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D005632:Fructose / Q000737:chemistry; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000737:chemistry
C486795:(1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl)phenylmethanone; C486796:(3-benzoylpyrrol-1-yl)acetic acid; D000085:Acetates; D010636:Phenols; D011758:Pyrroles; D012710:Serum Albumin, Bovine; D005632:Fructose; D000449:Aldehyde Reductase