Synthesis of heterocyclic enol ethers and their use as group 2 metabotropic glutamate receptor antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 9; no. 15; pp. 2173 - 2176
• Main Authors: Kolczewski, Sabine, Adam, Geo, Stadler, Heinz, Mutel, Vincent, Wichmann, Jürgen, Woltering, Thomas
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 02.08.1999; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cell Membrane - drug effects; Cell Membrane - metabolism; Ethers - chemical synthesis; Ethers - chemistry; Ethers - pharmacology; Excitatory Amino Acid Antagonists - chemical synthesis; Excitatory Amino Acid Antagonists - chemistry; Excitatory Amino Acid Antagonists - pharmacology; Glutamatergic system (aspartate and other excitatory aminoacids); Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Rats; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Structure-Activity Relationship; Sulfur Radioisotopes; Transfection; Rat; Nitrogen heterocycle; Rodentia; Glutamate receptor; In vitro; Vertebrata; Mammalia; Structure activity relation; Metabotropic receptor; Animal; Chlorine Organic compounds; Triazole derivatives; Antagonist; Enol ether; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00346-7

Heterocyclic enol ethers of type 1 were studied with respect to the inhibition of 1S,3R-ACPD (10μM)-stimulated GTP γ 35S binding on rat mGluR2 transfected cell membranes. The structure activity relationship with regard to the substitution pattern of the phenyl ring, the oxygen substituent and the nature of the heterocycle is discussed. Heterocyclic enol ethers of type 1 were studied with respect to the inhibition of 1S,3R-ACPD (10μM)-stimulated GTP γ 35S binding on rat mGluR2 transfected cell membranes. Structure activity relationship is discussed.