Carboxylate bioisosteres of pregabalin

Several β-amino tetrazole analogs of gabapentin 1 and pregabalin 2 were prepared by one of two convergent, highly efficient routes, and their affinity for the α2–δ protein examined. Two select compounds with potent affinity for α2–δ, 8a and 16a, were subsequently tested in vivo in an audiogenic seizure model and found to elicit protective effects.

Truncation and acid replacement with tetrazole furnished a compound with a similar pattern of activity to pregabalin.Figure optionsDownload as PowerPoint slide