Design, synthesis and biological evaluation of novel bicyclo[1.1.1]pentane-based omega-acidic amino acids as glutamate receptors ligands.
A novel series of bicyclo[1.1.1]pentane-based omega-acidic amino acids, including (2S)- and (2R)-3-(3'-carboxybicyclo[1.1.1]pentyl)alanines (8 and 9), (2S)- and (2R)-2-(3'-carboxymethylbicyclo[1.1.1]pentyl)glycines (10 and 11), and (2S)- and (2R)-3-(3'-phosphonomethylbicyclo[1.1.1]pentyl)glycines (12 and 13), were synthesized and evaluated as glutamate receptor ligands. Among them, (2R)-3-(3'-phosphonomethylbicyclo[1.1.1]pentyl)glycine (13) showed relatively high affinity and selectivity at the NMDA receptor. The results are also discussed in light of pharmacophoric modelling studies of NMDA agonists and antagonists.
Filosa
Rosanna
R
Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte Don Melillo, Variante 11C, 84084 Fisciano, Italy.
Carmela Fulco
M
M
Marinozzi
Maura
M
Giacchè
Nicola
N
Macchiarulo
Antonio
A
Peduto
Antonella
A
Massa
Antonio
A
de Caprariis
Paolo
P
Thomsen
Christian
C
Christoffersen
Claus T
CT
Pellicciari
Roberto
R
D000409:Alanine; D024342:Amino Acids, Acidic / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis; D005998:Glycine; D006801:Humans; D008024:Ligands; D010420:Pentanes / Q000138:chemical synthesis; D011485:Protein Binding; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
D024342:Amino Acids, Acidic; D001643:Bridged Bicyclo Compounds; D008024:Ligands; D010420:Pentanes; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D000409:Alanine; D005998:Glycine