title: 1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of potent and Selective iGluR5 modulators.
abstract: (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.
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Banchi di Sotto 55, 53100 Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Butini
authors.forename: Darryl S
authors.initials: DS
authors.lastname: Pickering
authors.forename: Elena
authors.initials: E
authors.lastname: Morelli
authors.forename: Salvatore Sanna
authors.initials: SS
authors.lastname: Coccone
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
authors.forename: Meri
authors.initials: M
authors.lastname: De Angelis
authors.forename: Egeria
authors.initials: E
authors.lastname: Guarino
authors.forename: Isabella
authors.initials: I
authors.lastname: Fiorini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Arne
authors.initials: A
authors.lastname: Schousboe
authors.forename: Jeppe K
authors.initials: JK
authors.lastname: Christensen
authors.forename: Sandra
authors.initials: S
authors.lastname: Gemma
mesh_terms: D000818:Animals; D002460:Cell Line; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011744:Pyrimidinones / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018411:Spodoptera; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D011744:Pyrimidinones; D017470:Receptors, Glutamate; D013876:Thiophenes