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Kojic amine--a novel gamma-aminobutyric acid analogue.

Abstract
A series of compounds containing the 3-hydroxy-4H-pyran-4-one nucleus has been synthesized and tested as potential skeletal muscle relaxants. Reduction of 2-(azidomethyl)-5-hydroxy-4H-pyran-4-one (4) with HBr in HOAc--phenol yielded 2-(aminomethyl)-5-hydroxy-4H-pyran-4-one (kojic amine, 3) in 81% yield. Reaction of 2-[(tosyloxy)-methyl]-5-(benzyloxy)-4H-pyran-4-one (5) with NH3 gave a 40% yield of the O-benzyl ether of kojic amine, which was N-acylated with a series of carbobenzyloxy-protected amino acids. Complete deprotection with HBr--HOAc gave the following amino acid amides of kojic amine: glycyl (23), alpha-alanyl (24), beta-alanyl (25), gamma-aminobutyryl (26), and glycylglycyl (27). Among the analogues of kojic amine prepared was a series of one-carbon homologues: 2-[(methylamino)methyl]-5-hydroxy-4H-pyran-4-one (7a), 2-(1-aminoethyl)-5-hydroxy-4H-pyran-4-one (8), 6-(aminomethyl)-3-hydroxy-2-methyl-4H-pyran-4-one (12), and 2-(2-aminoethyl)-5-hydroxy-4H-pyran-4-one (16). Kojic amine (3) has been found to possess certain of the properties to be expected in a gamma-aminobutyric acid mimetic agent, notably skeletal muscle relaxant activity. In the chronic spinal cat preparation, ED70 values for reduction of flexor spasms of 2.2 and 4.0 mg/kg by iv and po routes of administration, respectively, were observed for kojic amine, which was the most potent of the various hydroxypyrone derivatives investigated.
AuthorsJ G Atkinson, Y Girard, J Rokach, C S Rooney, C S McFarlane, A Rackham, N N Share
JournalJournal of medicinal chemistry (J Med Chem) Vol. 22 Issue 1 Pg. 99-106 (Jan 1979) ISSN: 0022-2623 [Print] United States
PMID423190 (Publication Type: Journal Article)
Chemical References
  • Anticonvulsants
  • Muscle Relaxants, Central
  • Pyrones
  • gamma-Aminobutyric Acid
  • kojic amine
Topics
  • Animals
  • Anticonvulsants (chemical synthesis)
  • Cats
  • Female
  • Male
  • Mice
  • Muscle Relaxants, Central (chemical synthesis)
  • Pyrones
  • Rats
  • Spinal Cord (physiology)
  • Structure-Activity Relationship
  • gamma-Aminobutyric Acid

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