Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route

This paper reports the synthesis and biological activity of a novel series of aryl-morpholine dopamine receptor agonists. Several compounds show high levels of functional selectivity for the D3 over the D2 dopamine receptor. Compound 26 has >1000-fold functional selectivity and has been successfully progressed in vivo using an intranasal delivery route.

Synthesis and dopamine receptor agonist activity of a novel series of aryl-morpholines is disclosed. Compound 26 shows high functional in vitro selectivity for activation the dopamine D3 receptor. In vivo properties of this compound are also reported.Figure optionsDownload as PowerPoint slide