title: Synthesis and pharmacological characterisation of 2,4-dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists.
abstract: Metabotropic glutamate receptors (mGluRs) are an unusual family of G-protein coupled receptor (GPCR), and are characterised by a large extracellular N-terminal domain that contains the glutamate binding site. We have identified a new class of non-competitive metabotropic glutamate receptor 1 (mGluR1) antagonists, 2,4-dicarboxy-pyrroles which are endowed with nanomolar potency. They interact within the 7 transmembrane (7TM) domain of the receptor and show antinociceptive properties when tested in a number of different animal models.
authors.affiliation: GlaxoSmithkline Medicine Research Centre, Via Fleming, 4-37135 Verona, Italy. fm20244@gsk.com
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Micheli
authors.forename: Romano Di
authors.initials: RD
authors.lastname: Fabio
authors.forename: Paolo
authors.initials: P
authors.lastname: Cavanni
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Rimland
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Capelli
authors.forename: Cristiano
authors.initials: C
authors.lastname: Chiamulera
authors.forename: Mauro
authors.initials: M
authors.lastname: Corsi
authors.forename: Corrado
authors.initials: C
authors.lastname: Corti
authors.forename: Daniele
authors.initials: D
authors.lastname: Donati
authors.forename: Aldo
authors.initials: A
authors.lastname: Feriani
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraguti
authors.forename: Micaela
authors.initials: M
authors.lastname: Maffeis
authors.forename: Andrea
authors.initials: A
authors.lastname: Missio
authors.forename: Emiliangelo
authors.initials: E
authors.lastname: Ratti
authors.forename: Alfredo
authors.initials: A
authors.lastname: Paio
authors.forename: Roberta
authors.initials: R
authors.lastname: Pachera
authors.forename: Mauro
authors.initials: M
authors.lastname: Quartaroli
authors.forename: Angelo
authors.initials: A
authors.lastname: Reggiani
authors.forename: Fabio Maria
authors.initials: FM
authors.lastname: Sabbatini
authors.forename: David G
authors.initials: DG
authors.lastname: Trist
authors.forename: Annarosa
authors.initials: A
authors.lastname: Ugolini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitulli
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D020128:Inhibitory Concentration 50; D010147:Pain Measurement / Q000187:drug effects; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D018712:Analgesics, Non-Narcotic; D011758:Pyrroles; D018094:Receptors, Metabotropic Glutamate; D011993:Recombinant Fusion Proteins; C104077:metabotropic glutamate receptor type 1