Media.Player

Bicyclic Metabotropic Glutamate Receptor Ligands

技术优势

Compounds of the invention demonstrate significantly higher potency for mGluRs than (1S, 3R)-ACPD.

详细技术说明

Glutamate receptors play a role in numerous neurological,neurodegenerative, psychiatric and psychological disease states. Newderivatives of the glutamate agonist, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S, 3R)-ACPD],have been synthesized and screened for potency and biological activity.Biological data supports the activity of these compounds for a varietyof mGluRs. In-vitro studies reveal that a specific novel bicycliccompound, ABHxD-I, is between 6 to 34-fold more potent in EC50 assays for mGluRs than (1S, 3R)-ACPD.These compounds demonstrate potential as therapeutic agents inpharmaceutical compositions and can be used in research to probe mGluRfunction.

*Abstract

*Publications

Tuckmantel, W.; Kozikowski, A. P.; Wang, S.; Pshenichkin, S.;Wroblewski, J. T. Synthesis, molecular modelling, and biology of the1-benzyl derivative of APDC - an apparent mGluR6 selective ligand. Bioorg. Med. Chem. Lett. 1997, 7, 601-606.Kozikowski, A. P.; Araldi, G. L.; Tuckmantel, W.; Pshenichkin, S.;Surina, E.; Wroblewski, J. T. 1-Amino-APDC, a partial agonist of groupII metabotropic glutamate receptors with neuroprotective properties. Bioorg. Med. Chem. Lett. 1999, 9, 1721-1726.Kozikowski, A. P.; Steensma, D.; Araldi, G. L.; Tuckmantel, W.;Wang,S.; Pshenichkin, S.; Surina, E.; Wroblewski, J. T. Synthesis andbiology of the conformationally restricted ACPD analogue,2-aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I, a potent mGluRagonist. J. Med. Chem. 1998, 41, 1641-1650.Kozikowski, A. P.; Araldi, G. L.; Flippen-Anderson, J.; George, C.;Pshenichkin, S.; Surina, E.; Wroblewski, J. Synthesis and metabotropicglutamate receptor activity of a2-aminobicyclo-[3.2.0]heptane-2,5-dicarboxylic acid, a moleculepossessing an extended glutamate conformation. Bioorg. Med. Chem. Lett. 1998, 8, 925-930.Ma, D.; Tian, H.; Sun, H.; Kozikowski, A. P.; Pshenichkin, S.;Wroblewski, J. T. Synthesis and biological activity of cyclic analoguesof MPPG and MCPG as metabotropic glutamate receptor antagonists. Bioorg. Med. Chem. Lett. 1997, 7, 1195-1198.Kozikowski, A. P.; Steensma, D.; Varasi, M.; Pshenichkin, S.;Surina,E.; Wroblewski, J. T. Alpha-substituted quisqualic acid analogues: newmetabotropic glutamate receptor group II selective antagonists. Bioorg. Med. Chem. Lett. 1998, 8, 447-452.

*Stage of Development

In-vitro studies validating the potency and activity of compounds of the invention

国家/地区

美国