1-(5-Carboxyindazol-1-yl)propan-2-ones as dual inhibitors of cytosolic phospholipase A₂α and fatty acid amide hydrolase: bioisosteric replacement of the carboxylic acid moiety

Abstract

Indazole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position 1 were previously reported to be potent dual inhibitors of cytosolic phospholipase A₂α (cPLA₂α) and fatty acid amide hydrolase (FAAH). In continuation of our structure-activity studies on cPLA₂α and FAAH inhibitors, a number of derivatives of these substances characterized by bioisosteric replacement of the carboxylic acid functionality by inverse amides, sulfonylamides, carbamates and ureas were prepared. The biological evaluation of the obtained compounds showed that the carboxylic acid functionality of the lead compounds is of special importance for a pronounced inhibition of cPLA₂α and FAAH.

Keywords:

• Bioisosteric replacement
• cytosolic phospholipase A₂α
• fatty acid amide hydrolase
• indazol-1-ylpropan-2-ones
• inhibitor

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Supplementary material available online