3,4-Disubstituted benzofuran P1′ MMP-13 inhibitors: Optimization of selectivity and reduction of protein binding

Potent 3,4-disubstituted benzofuran P1′ MMP-13 inhibitors have been prepared. Selectivity over MMP-2 was achieved through a substituent at the C4 position of the benzofuran P1′ moiety of the molecule. By replacing a backbone benzene with a pyridine and valine with threonine, compounds (e.g., 44) with greatly reduced plasma protein binding were also obtained.

Graphical abstractPotent and selective 3,4-disubstituted benzofuran P1′ MMP-13 inhibitors have been prepared with a substituent at the C4 position of the benzofuran P1′ moiety of the molecule.Figure optionsDownload full-size imageDownload as PowerPoint slide