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Bioisosterically modified dipeptide excitatory amino acid receptor antagonists containing 3-oxygenated isothiazole
L Matzen1, B Ebert, T B Stensbøl
1Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Copenhagen, Denmark.
Bioorganic & Medicinal Chemistry
|August 1, 1997
Abstract:
The AMPA receptor agonist Thio-AMPA, the 3-isothiazolol analogue of AMPA was converted into the selective NMDA antagonist, 2, in which a 3-isothiazolone unit is a bioisosteric analogue of the peptide bond of the NMDA antagonist, gamma-(R)-Glu-Gly. The isomeric 3-oxygenated isothiazole amino acid, 3, and the corresponding isothiazole phosphono amino acid 4 were also synthesized, and were shown to be selective AMPA receptor antagonists. Compound 1, in which the peptide bond of gamma-(R)-Glu-Gly is replaced by an ester group, was synthesized and shown to be unstable in the test buffer system.