3-Thienyl- And 3-furylaminobutyric Acids. Synthesis and Binding GABAB Receptor Studies

J Med Chem. 1991 Aug;34(8):2557-60. doi: 10.1021/jm00112a033.

Abstract

Baclofen (beta-(p-chlorophenyl)-GABA) is a selective agonist for the bicuculline-insensitive GABAB receptor. The search for new compounds that bind to the GABAB receptor is very important to clarify structural requirements. We report herein the synthesis and the binding studies of variously substituted 3-thienyl- and 3-furylaminobutyric acids. 4-Amino-3-(5-methyl-2-thienyl)butyric acid (5d) and 4-amino-3-(5-chloro-2-thienyl)butyric acid (5h) are potent and specific ligands for GABAB receptor. The IC50 values for the displacement of (R)-(-)-[3H]baclofen are 1.34 and 0.61 microM for 5d and 5h, respectively, as compared to 0.33 microM for baclofen.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Baclofen / metabolism
  • Binding, Competitive
  • Brain / metabolism
  • Chemical Phenomena
  • Chemistry
  • Furans / chemical synthesis*
  • Furans / metabolism
  • Molecular Structure
  • Muscimol / metabolism
  • Rats
  • Receptors, GABA-A / metabolism*
  • Synaptic Membranes / metabolism
  • Thiophenes / chemical synthesis*
  • Thiophenes / metabolism
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / chemical synthesis
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Furans
  • Receptors, GABA-A
  • Thiophenes
  • 4-amino-3-(5-methyl-2-thienyl)butyric acid
  • 4-amino-3-(5-chloro-2-thienyl)butyric acid
  • Muscimol
  • gamma-Aminobutyric Acid
  • Baclofen