Synthesis and biological activities of conformationally restricted cyclopentenyl-glutamate analogues.
An efficient method for preparing conformationally restricted cyclopentenyl-glutamate analogues in a regioselective and diastereoselective manner has been developed using a formal [3 + 2] cycloaddition reaction of dehydroamino acids. Methods for preparing optically active versions of these compounds have also been devised. Of these compounds, (S)-2 is an agonist at the mGlu5 (EC(50) 18 microM) and mGlu2 (EC(50) 45 microM) receptors.
Ung
Alison T
AT
Department of Chemistry, University of Wollongong, Wollongong, NSW, 2522, Australia.
Schafer
Karl
K
Lindsay
Karl B
KB
Pyne
Stephen G
SG
Amornraksa
Kitti
K
Wouters
Ria
R
Van der Linden
Ilse
I
Biesmans
Ilse
I
Lesage
Anne S J
AS
Skelton
Brian W
BW
White
Allan H
AH
D000818:Animals; D016466:CHO Cells; D020013:Calcium Signaling / Q000187:drug effects; D006224:Cricetinae; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D005971:Glutamates / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D011485:Protein Binding; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014162:Transfection
D003517:Cyclopentanes; D005971:Glutamates; D018094:Receptors, Metabotropic Glutamate; D016244:Guanosine 5'-O-(3-Thiotriphosphate)