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.
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.
Pellicciari
Roberto
R
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo, 1-06123 Perugia, Italy. rp@unipg.it
Filosa
Rosanna
R
Fulco
Maria Carmela
MC
Marinozzi
Maura
M
Macchiarulo
Antonio
A
Novak
Clemens
C
Natalini
Benedetto
B
Hermit
Mette Brunsgaard
MB
Nielsen
Søren
S
Sager
Thomas Nikolaj
TN
Stensbøl
Tine Bryan
TB
Thomsen
Christian
C
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
D001643:Bridged Bicyclo Compounds; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; C100726:UPF 596; D005998:Glycine