Dual M3 antagonists-PDE4 inhibitors. Part 2: Synthesis and SAR of 3-substituted azetidinyl derivatives.

Introduction of 3-substituted azetidinyl substituents onto the 4,6-diaminopyrimidine scaffold allowed the improvement of PDE4 inhibiting activities. Preliminary in vivo activity in pulmonary inflammation models is reported.

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 M(3) 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.