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 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.
Butini
Stefania
S
European Research Centre for Drug Discovery and Development (NatSynDrugs), Banchi di Sotto 55, 53100 Siena, Italy.
Pickering
Darryl S
DS
Morelli
Elena
E
Coccone
Salvatore Sanna
SS
Trotta
Francesco
F
De Angelis
Meri
M
Guarino
Egeria
E
Fiorini
Isabella
I
Campiani
Giuseppe
G
Novellino
Ettore
E
Schousboe
Arne
A
Christensen
Jeppe K
JK
Gemma
Sandra
S
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
D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D011744:Pyrimidinones; D017470:Receptors, Glutamate; D013876:Thiophenes