[1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone as a bioisostere of a carboxylic acid aldose reductase inhibitor

Ioannis Nicolaou; Chariklia Zika; Vassilis J Demopoulos

doi:10.1021/jm031060t

[1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone as a bioisostere of a carboxylic acid aldose reductase inhibitor

J Med Chem. 2004 May 6;47(10):2706-9. doi: 10.1021/jm031060t.

Authors

Ioannis Nicolaou¹, Chariklia Zika, Vassilis J Demopoulos

Affiliation

¹ Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.

PMID: 15115413
DOI: 10.1021/jm031060t

Abstract

[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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetates / chemistry*
Aldehyde Reductase / antagonists & inhibitors*
Aldehyde Reductase / chemistry
Animals
Fructose / chemistry
Phenols / chemical synthesis*
Phenols / chemistry
Pyrroles / chemical synthesis*
Pyrroles / chemistry*
Rats
Serum Albumin, Bovine / chemistry

Substances

(1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl)phenylmethanone
(3-benzoylpyrrol-1-yl)acetic acid
Acetates
Phenols
Pyrroles
Serum Albumin, Bovine
Fructose
Aldehyde Reductase