Synthesis and biological evaluation of (2S)- and (2R)-2-(3'-phosphonobicyclo[1.1.1]pentyl)glycines as novel group III selective metabotropic glutamate receptor ligands.
The synthesis of (2S)- and (2R)-2-(3'-phosphonobicyclo[1.1.1]pentyl)glycine isomers (10 and 11), characterized by the bioisosteric replacement of the distal carboxylic group of 2-(3'-carboxybicyclo[1.1.1]pent-1-yl)glycine by the phosphonate moiety, was accomplished by a stereoselective Ugi condensation. The two isomers were tested for their activity against an array of metabotropic glutamate receptors, and the S-isomer (10) turned out to be a moderately potent and selective mGluR4 agonist.
Filosa
Rosanna
R
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo, 1- 06123 Perugia, Italy.
Marinozzi
Maura
M
Costantino
Gabriele
G
Hermit
Mette Brunsgaard
MB
Thomsen
Christian
C
Pellicciari
Roberto
R
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C512322:(2R)-2-(3'-phosphonobicyclo(1.1.1)pentyl)glycine; D001643:Bridged Bicyclo Compounds; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; D005998:Glycine