Straightforward synthesis of new tetrahydroquinoline derivatives

Abstract

To identify novel classes of glycine antagonists, compounds potentially useful as neuroprotective after stroke, novel substituted tetrahydroquinoline derivatives, satisfying the key pharmacophoric requirements for glycine antagonists, were designed. To explore the SAR of these compounds an efficient synthetic route was set up exploiting the outstanding reactivity of suitable N-aryl imine derivatives. In particular an allylmetalation reaction or the addition of bis(trimethyldisilyl)ketene acetals allowed the preparation of versatile intermediates which were smoothly transformed into the desired bicycle tetrahydroquinoline derivatives by a Heck-type cyclization reaction.Key words: glycine antagonists, neuroprotection, tetrahydroquinolines, synthesis, allylmetalation.