Synthesis and biological activities of conformationally restricted cyclopentenyl-glutamate analogues

Alison T Ung; Karl Schafer; Karl B Lindsay; Stephen G Pyne; Kitti Amornraksa; Ria Wouters; Ilse Van der Linden; Ilse Biesmans; Anne S J Lesage; Brian W Skelton; Allan H White

doi:10.1021/jo010864i

Synthesis and biological activities of conformationally restricted cyclopentenyl-glutamate analogues

J Org Chem. 2002 Jan 11;67(1):227-33. doi: 10.1021/jo010864i.

Authors

Alison T Ung¹, Karl Schafer, Karl B Lindsay, Stephen G Pyne, Kitti Amornraksa, Ria Wouters, Ilse Van der Linden, Ilse Biesmans, Anne S J Lesage, Brian W Skelton, Allan H White

Affiliation

¹ Department of Chemistry, University of Wollongong, Wollongong, NSW, 2522, Australia.

PMID: 11777464
DOI: 10.1021/jo010864i

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CHO Cells
Calcium Signaling / drug effects
Cricetinae
Cyclopentanes / chemical synthesis
Cyclopentanes / metabolism
Cyclopentanes / pharmacology
Glutamates / chemical synthesis*
Glutamates / metabolism
Glutamates / pharmacology*
Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
Humans
Molecular Conformation
Protein Binding
Rats
Receptors, Metabotropic Glutamate / agonists*
Stereoisomerism
Structure-Activity Relationship
Transfection

Substances

Cyclopentanes
Glutamates
Receptors, Metabotropic Glutamate
Guanosine 5'-O-(3-Thiotriphosphate)