Synthesis and biological evaluation of conformationally restricted Gabapentin analogues

Bioorg Med Chem Lett. 1999 Aug 16;9(16):2329-34. doi: 10.1016/s0960-894x(99)00383-2.

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.

MeSH terms

  • Acetates / chemical synthesis
  • Acetates / chemistry*
  • Acetates / pharmacology
  • Amines*
  • Analgesics, Non-Narcotic / chemical synthesis
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Convulsants / chemical synthesis
  • Convulsants / pharmacology
  • Cyclohexanecarboxylic Acids*
  • Gabapentin
  • Molecular Structure
  • Rats
  • gamma-Aminobutyric Acid*

Substances

  • Acetates
  • Amines
  • Analgesics, Non-Narcotic
  • Convulsants
  • Cyclohexanecarboxylic Acids
  • gamma-Aminobutyric Acid
  • Gabapentin