SYNTHESIS AND BIOCHEMICAL-STUDIES OF SPIROCYCLIC AMINO-ACIDS .2. ACTIVITY OF 2-AZASPIRO[5.5]UNDECANE-7-CARBOXYLATES AS GABA-UPTAKE INHIBITORS

Novel GABA analogous spirocyclic amino acids were prepared and investi gated for interaction with GABA-A and GABA-B receptors as well as the GABA uptake system. Starting from known bromopropyl lactones and aryla lkylamines, spirocyclic hydroxyalkyl lactams were obtained, which were reduced by LiAlH4 to yield spirocyclic hydroxymethyl piperidines. Oxi dation by Jones' reagent followed by subsequent esterification gave th e title compounds which represent conformationally restricted analogue s of GABA. Whereas the new spirocyclic amino acids showed no activity at GABA receptors they proved to be active as GABA uptake inhibitors. An examination of the relationship between structure and GABA uptake i nhibition;revealed a strong dependence of activity on the length of th e aikyl chain in N-arylalkyl substituents.