Discovery, synthesis, selectivity modulation and DMPK characterization of 5-azaspiro[2.4]heptanes as potent orexin receptor antagonists.

Starting from a orexin 1 receptor selective antagonist 4,4-disubstituted piperidine series a novel potent 5-azaspiro[2.4]heptane dual orexin 1 and orexin 2 receptor antagonist class has been discovered. SAR and Pharmacokinetic optimization of this series is herein disclosed.

Phenylethynyl-pyrrolo[1,2-a]pyrazine: a new potent and selective tool in the mGluR5 antagonists arena.

The synthesis and the structure activity of a new series of pyrrolo[1,2-a]pyrazine is reported. These molecules are potent and selective non-competitive mGluR5 antagonists and may shed new light on the pattern of substitution tolerated by this receptor.