Synthesis and biological evaluation of conformationally restricted gabapentin analogues

A series of conformationally restricted Gabapentin analogues has been synthesised. The pyrrolidine analogue (R)-2-Aza-spiro[4.5]decane-4-carboxylic acid hydrochloride (3a) had an IC50 of 120nM, similar to that of Gabapentin (IC50 = 140nM), at the Gabapentin binding site on the α2δ subunit of a calcium channel. Compound (3a) also reversed carrageenan induced hyperalgesia in rats.