First dual M3 antagonists-PDE4 inhibitors: Synthesis and SAR of 4,6-diaminopyrimidine derivatives

SAR around 4,6-diaminopyrimidine derivatives allowed the discovery of the first potent dual M3 antagonists and PDE4 inhibitors. Various chemical modulations around that scaffold led to the discovery of ucb-101333-3 which is characterized by the most interesting profile on both targets.

Graphical abstractThe synthesis and SAR around 4,6-diaminopyrimidine derivatives as dual M3 antagonists and PDE4 inhibitors are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide