3-carboxy-4-phosphonocyclopentane amino acids: new metabotropic glutamate receptor ligands.
Two glutamic acid analogs (1 SR,3 RS,4 RS)- and (1 SR,3 SR,4 SR)-1-amino-4-phosphono cyclopentane-1,3-dicarboxylic acids (APCPD) have been synthesized. Pure E-(diethoxy-phosphoryl)-acrylic acid ethyl ester was obtained from ethyl propiolate, phenol and triethylphosphite. It was used as dienophile in a Diels-Alder reaction. Oxidation and cyclization afforded 3-(ethoxy-carbonyl)-4-(diethoxy-phosphoryl)-cyclopentanone. Bucherer-Bergs reaction and hydrolysis yielded APCPD-III and -IV which are inactive on mGlu1a receptor and antagonists on mGlu2 and mGlu8a receptors.
Bessis
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Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR8601-CNRS, Université René Descartes-Paris V, 45 rue des Saintes-Peres, 75270 Paris Cedex 06, France.
Vadesne
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Bourrat
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Bertho
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Pin
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JP
Acher
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FC
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D002460:Cell Line; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D003517:Cyclopentanes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate