1H-Cyclopentapyrimidine-2,4(1H,3H)-dione-Related Ionotropic Glutamate Receptors Ligands. Structure−Activity Relationships and Identification of Potent and Selective iGluR5 Modulators

(S)-CPW399 ((S)-1) is a potent and excitotoxic AMPA receptor partial agonist. Modifying the cyclopentane ring of (S)-1, we developed two of the most potent and selective functional antagonists (5 and 7) for kainate receptor (KA-R) subunit iGluR5. Derivatives 5 and 7, with their unique pharmacologica...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2008-10, Vol.51 (20), p.6614-6618
Main Authors: Butini, Stefania, Pickering, Darryl S, Morelli, Elena, Coccone, Salvatore Sanna, Trotta, Francesco, De Angelis, Meri, Guarino, Egeria, Fiorini, Isabella, Campiani, Giuseppe, Novellino, Ettore, Schousboe, Arne, Christensen, Jeppe K, Gemma, Sandra
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Line
Electrophysiology
Excitatory Amino Acid Antagonists - chemistry
Excitatory Amino Acid Antagonists - metabolism
Excitatory Amino Acid Antagonists - pharmacology
Female
Glutamatergic system (aspartate and other excitatory aminoacids)
Humans
Ligands
Medical sciences
Molecular Structure
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Oocytes - drug effects
Oocytes - metabolism
Pharmacology. Drug treatments
Pyrimidinones - chemistry
Pyrimidinones - metabolism
Pyrimidinones - pharmacology
Rats
Receptors, Glutamate - chemistry
Receptors, Glutamate - genetics
Receptors, Glutamate - metabolism
Spodoptera
Structure-Activity Relationship
Thiophenes - chemistry
Thiophenes - metabolism
Thiophenes - pharmacology
Xenopus laevis
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Description
Summary:(S)-CPW399 ((S)-1) is a potent and excitotoxic AMPA receptor partial agonist. Modifying the cyclopentane ring of (S)-1, we developed two of the most potent and selective functional antagonists (5 and 7) for kainate receptor (KA-R) subunit iGluR5. Derivatives 5 and 7, with their unique pharmacological profile, may lead to a better understanding of the different roles and modes of action of iGluR1−5 subunits, paving the way for the synthesis of new potent, subunit selective iGluR5 modulators.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm800865a