2,3-Ethylene- and 2,3-trimethylene-bridged analogues of the group III metabotropic glutamate receptor ligand 2-amino-4-phosphonobutanoic acid

Rodney L Johnson, Kolluri S S P Rao

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The racemic trans- and cis-isomers of 1-amino-2-phosphonomethyl- cyclobutanecarboxylic acid (5 and 6) and 1-amino-2-phosphonomethyl- cyclopentanecarboxylic acid (7 and 8) were synthesized as extensions of the mGluR4 agonists trans- and cis-1-amino-2-phosphonomethyl-cyclopropanecarboxylic acid (3 and 4). Although the methylene bridge in 3 and 4 allows for retention of affinity toward the mGluR4 receptor, increasing the bridging unit to the ethylene group as in 5 and 6 or to the trimethylene group as in 7 and 8 introduces sufficient steric hindrance to eliminate affinity for the mGluR4 receptor.

Original languageEnglish (US)
Pages (from-to)57-60
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number1
DOIs
StatePublished - Jan 3 2005

Bibliographical note

Funding Information:
This work was supported in part from a grant from NIH (NS35608) and a Development Grant in Drug Design from the Department of Medicinal Chemistry, University of Minnesota. The crystallographic analysis carried out by Neil R Brooks and Victor G. Young, Jr. of the University of Minnesota X-ray Crystallographic Laboratory is gratefully acknowledged. The authors thank Dr. James Monn and Renee Emkey of Eli Lilly and Company for arranging and conducting, respectively, the biological testing.

Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.

Keywords

  • AP4
  • Conformational analogues
  • mGluR4

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