Gabapentin analogues

Bryans J. S., Morrell, A. 1., Novel stereoselective processes for preparation of gabapentin analogues W09914184 (Warner-Lambert Company (USA)), 1999. 

Receveur, J.M., Bryans, J.S., Field, M., Singh, L. and Horwell, D.C. (1999) Synthesis and biological evaluation of conformationally restricted gabapentin analogues. Bioorg. Med Chem. Lett. 9 2329-2339. 

Gabapentin is an analogue of GABA that is sufficiently lipid soluble to cross the blood-brain barrier but its mode of action is uncertain. It is excreted unchanged and, unlike other antiepUepsy agents, does not induce or inhibit hepatic metabolism of other drugs. 

Gabapentin was designed as a GABA analogue and is an effective anticonvulsant but it does not work on GABA receptors. 

Fig. 15.8 Analogues of gabapentin with binding data against pH] gabapentin. In compounds 2a, 3, 4a and 4a" the methyl substituent(s) and the aminomethyl side chain are in 1,3 equatorial orientation (for drawing simplification purposes this appears as a c/s relationship). The assumed bioactive conformation is representative for those conformations.

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