Benzofuranones as potential antinociceptive agents: Structure–activity relationships

This work evaluates the antinociceptive properties of benzofuranones using chemically induced models of pain and the hot plate test. All the compounds exhibited significant antinociceptive activity, with 3-[2-(4-chlorophenyl)-2-oxoetil]-2-benzofuran-1(3H)-one (3d) being the most active. According to the application of the Topliss method, the 2π–π2 parameter was the preponderant one, indicating that the hydrophobicity (π) seems to be more involved in the antinociceptive activity. Based on the table of other possible substituents proposed by Topliss, three derived from compound 3d were tested. 3-[2-(3-methoxyphenyl)-2-oxoetil]-2-benzofuran-1(3H)-one (3g) showed greater antinociceptive activity with better pharmacokinetic properties predicted. These results show the efficiency of the Topliss Method as a research tool for the discovery of potential candidate molecules for a new antinociceptive drug.

Figure optionsDownload as PowerPoint slideHighlights
► 3-[2-(3-Methoxyphenyl)-2-oxoetil]-2-benzofuran-1(3H)-one (3g) was the most active.
► The 2π–π2 parameter was the preponderant in the Topliss method evaluated.
► The benzofuranone 3g presented the better pharmacokinetic properties predicted.