1-Hydroxypyrazole as a bioisostere of the acetic acid moiety in a series of aldose reductase inhibitors.

Abstract

Therapeutic intervention with aldose reductase inhibitors appears to be promising for major pathological conditions (i.e., long-term diabetic complications and inflammatory pathologies). So far, however, clinical candidates have failed due to adverse side-effects (spiroimides) or poor bioavailability (carboxylic acids). In this work, we succeeded in the bioisosteric replacement of an acetic acid moiety with that of 1-hydroxypyrazole. This new scaffold appears to have a superior physicochemical profile, while attaining inhibitory activity in the submicromolar range.

• Authors: Nikolaos Papastavrou, Maria Chatzopoulou, Kyriaki Pegklidou, Ioannis Nicolaou
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 21 Issue 17 Pg. 4951-7 (Sep 01 2013) ISSN: 1464-3391 [Electronic] England
• PMID: 23891165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Pyrazoles
• pyrazole
• Aldehyde Reductase
• Acetic Acid

Topics

• Acetic Acid (chemistry)
• Aldehyde Reductase (antagonists & inhibitors, metabolism)
• Animals
• Enzyme Inhibitors (chemical synthesis, chemistry, metabolism)
• Kidney (enzymology)
• Kinetics
• Lens Cortex, Crystalline (enzymology)
• Protein Binding
• Pyrazoles (chemical synthesis, chemistry, metabolism)
• Rats
• Structure-Activity Relationship