Synthesis and biological activity of novel 4-phenyl-1,8-naphthyridin-2(1H)-on-3-yl ureas: Potent acyl-CoA:cholesterol acyltransferase inhibitor with improved aqueous solubility

4-Aryl-1,8-naphthyridin-2(1H)-on-3-yl urea derivatives with hydrophilic groups were synthesized in order to improve aqueous solubility and pharmacokinetic property. SMP-797 possessing (4-aminophenyl)ureido and 3-(hydroxypropoxyphenyl) moieties showed potent ACAT inhibitory activity and excellent oral efficacy.

Graphical abstractThe synthesis and structure–activity relationships of 4-aryl-1,8-naphthyridin-2(1H)-on-3-yl urea derivatives with hydrophilic groups are described as a novel potent ACAT inhibitor.Figure optionsDownload full-size imageDownload as PowerPoint slide