1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of potent and Selective iGluR5 modulators

Stefania Butini; Darryl S Pickering; Elena Morelli; Salvatore Sanna Coccone; Francesco Trotta; Meri De Angelis; Egeria Guarino; Isabella Fiorini; Giuseppe Campiani; Ettore Novellino; Arne Schousboe; Jeppe K Christensen; Sandra Gemma

doi:10.1021/jm800865a

1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of potent and Selective iGluR5 modulators

J Med Chem. 2008 Oct 23;51(20):6614-8. doi: 10.1021/jm800865a. Epub 2008 Sep 24.

Authors

Stefania Butini¹, Darryl S Pickering, Elena Morelli, Salvatore Sanna Coccone, Francesco Trotta, Meri De Angelis, Egeria Guarino, Isabella Fiorini, Giuseppe Campiani, Ettore Novellino, Arne Schousboe, Jeppe K Christensen, Sandra Gemma

Affiliation

¹ European Research Centre for Drug Discovery and Development (NatSynDrugs), Banchi di Sotto 55, 53100 Siena, Italy.

PMID: 18811139
DOI: 10.1021/jm800865a

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Electrophysiology
Excitatory Amino Acid Antagonists / chemistry*
Excitatory Amino Acid Antagonists / metabolism*
Excitatory Amino Acid Antagonists / pharmacology
Female
Humans
Ligands
Molecular Structure
Oocytes / drug effects
Oocytes / metabolism
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

Substances

Excitatory Amino Acid Antagonists
Ligands
Pyrimidinones
Receptors, Glutamate
Thiophenes