Novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n] naphthyridines as potent and selective agonists of the 5-HT2C receptor

A series of novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines were identified as potent and selective agonists of the 5-HT2C receptor. Optimizations performed on a previously reported series of racemic tetrahydroquinoline-based tricyclic amines, delivered an advanced drug lead, (R)-4-(3,3,3-trifluoropropyl)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,8]naphthyridine, which displayed excellent in vitro and in vivo pharmacological profiles.

Automated summary

A series of novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines have been identified as potent and selective agonists of the 5-HT2C receptor. Optimizations on a previously reported series of compounds have led to the discovery of an advanced drug lead with excellent in vitro and in vivo pharmacological profiles.