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 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.
Receveur
J M
JM
Parke-Davis Neuroscience Research Centre, Cambridge University Forvie Site, UK.
Bryans
J S
JS
Field
M J
MJ
Singh
L
L
Horwell
D C
DC
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
D000085:Acetates; D000588:Amines; D018712:Analgesics, Non-Narcotic; D003292:Convulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin