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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
Author(s) -
Pellicciari Roberto,
Filosa Rosanna,
Fulco Maria Carmela,
Marinozzi Maura,
Macchiarulo Antonio,
Novak Clemens,
Natalini Benedetto,
Hermit Mette Brunsgaard,
Nielsen Søren,
Sager Thomas Nikolaj,
Stensbøl Tine Bryan,
Thomsen Christian
Publication year - 2006
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200500071
Subject(s) - metabotropic glutamate receptor , glycine , metabotropic glutamate receptor 1 , chemistry , stereochemistry , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 2 , glutamate receptor , nmda receptor , metabotropic receptor , amino acid , receptor , biochemistry
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.