Carboxylate bioisosteres of gabapentin

A series of carboxylate bioisosteres of structures related to gabapentin 1 have been prepared. When the carboxylate was replaced by a tetrazole, this group was recognized by the α2-δ protein. Further characterization of α2-δ binding compounds 14a and 14b revealed a similar pattern of functional in vitro and in vivo activity to gabapentin 1.

Ring expansion and acid replacement with tetrazole furnished a compound with a similar pattern of activity to gabapentin.Figure optionsDownload as PowerPoint slide