title: Synthesis and biological evaluation of conformationally restricted Gabapentin analogues.
abstract: 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 120 nM, similar to that of Gabapentin (IC50 = 140 nM), at the Gabapentin binding site on the alpha2delta subunit of a calcium channel. Compound (3a) also reversed carrageenan induced hyperalgesia in rats.
authors.affiliation: Parke-Davis Neuroscience Research Centre, Cambridge University Forvie Site, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Receveur
authors.forename: J S
authors.initials: JS
authors.lastname: Bryans
authors.forename: M J
authors.initials: MJ
authors.lastname: Field
authors.forename: L
authors.initials: L
authors.lastname: Singh
authors.forename: D C
authors.initials: DC
authors.lastname: Horwell
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000588:Amines; D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D003292:Convulsants / Q000138:chemical synthesis / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D015394:Molecular Structure; D051381:Rats; D005680:gamma-Aminobutyric Acid
chemical_list: D000085:Acetates; D000588:Amines; D018712:Analgesics, Non-Narcotic; D003292:Convulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin