Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake ihnibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring