Synthesis of derivatives of the keto-pyrrolyl-difluorophenol scaffold: some structural aspects for aldose reductase inhibitory activity and selectivity

Eleni Kotsampasakou; Vassilis J Demopoulos

doi:10.1016/j.bmc.2012.12.015

Synthesis of derivatives of the keto-pyrrolyl-difluorophenol scaffold: some structural aspects for aldose reductase inhibitory activity and selectivity

Bioorg Med Chem. 2013 Feb 15;21(4):869-73. doi: 10.1016/j.bmc.2012.12.015. Epub 2012 Dec 20.

Authors

Eleni Kotsampasakou¹, Vassilis J Demopoulos

Affiliation

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

PMID: 23312612
DOI: 10.1016/j.bmc.2012.12.015

Abstract

Seven novel ARIs (3a-c, 4a-c and 5) were synthesized with the implementation of an optimized and, partially, selective synthetic procedure, via a Friedel-Crafts acylation reaction. The synthesized ARIs have values of IC(50)(ALR2) ranging from 0.19μM (in case of compound 3b) to 2.3μM (in case of compound 4a), while the values of selectivity index towards ALR1 range from 1 (in case of compound 3b) to 238 (in case of compound 3a). Finally, we found out that the presence of an additional (secondary) aromatic area is not a prerequisite feature for ARI activity.

MeSH terms

Aldehyde Reductase / antagonists & inhibitors*
Aldehyde Reductase / metabolism
Animals
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / metabolism
Female
Male
Phenol / chemical synthesis
Phenol / chemistry*
Phenol / metabolism
Protein Binding
Pyrroles / chemistry*
Rats

Substances

Enzyme Inhibitors
Pyrroles
Phenol
Aldehyde Reductase