title: Synthesis and preliminary biological evaluation of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives as group I selective metabotropic glutamate receptor ligands.
abstract: The first series of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives, (2R)- and (2S)-(2',2'-dichloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (10) and (11), and 2-(2'-chloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (12) were synthesized and evaluated as mGluR ligands. Compounds 11 and 12 were shown to be competitive group I mGluR antagonists. These results are also discussed in light of docking studies with both the active (closed) and inactive (open) conformations of mGluR1.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo, 1-06123 Perugia, Italy. rp@unipg.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Pellicciari
authors.forename: Rosanna
authors.initials: R
authors.lastname: Filosa
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Fulco
authors.forename: Maura
authors.initials: M
authors.lastname: Marinozzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
authors.forename: Clemens
authors.initials: C
authors.lastname: Novak
authors.forename: Benedetto
authors.initials: B
authors.lastname: Natalini
authors.forename: Mette Brunsgaard
authors.initials: MB
authors.lastname: Hermit
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Thomas Nikolaj
authors.initials: TN
authors.lastname: Sager
authors.forename: Tine Bryan
authors.initials: TB
authors.lastname: Stensbøl
authors.forename: Christian
authors.initials: C
authors.lastname: Thomsen
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001643:Bridged Bicyclo Compounds; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; C100726:UPF 596; D005998:Glycine