Bicyclic Metabotropic Glutamate Receptor (mGluR) Ligands
Section: For Industry
Category(ies): CNS Disorders | Small Molecules
Reference #: KOAL422406
OTC Contact: Dave Odelson, Ph.D. (Directory Information | Send a Message)
Description
L-Glutamate is one of the most abundant excitatory amino acid found in the mammalian brain. This amino acid acts on diverse glutamate receptors, including the metabotropic glutamate receptor family. Such receptors play an important role in a variety of physiological conditions such as long-term potentiation, synaptic plasticity, motor control, respiration, cardiovascular regulation, emotional states and sensory perception. Inventors at Georgetown identified a family of bicyclic compounds that are ligands for metabotropic glutamate receptors.
Applications
- Novel ligands for mGluRs
- Methods of using such ligands in neuronal degeneration, stroke and Alzheimer's disease
Advantages
Stage of Development
Inventors: Alan Kozikowski, Werner Tueckmantel,Darryl Steensma, and Gian Luca Araldi
Relevant Publications
Tuckmantel, W.; Kozikowski, A. P.; Wang, S.; Pshenichkin, S.;
Wroblewski, J. T. Synthesis, molecular modelling, and biology
of the 1-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 group II 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
and biology of the conformationally restricted ACPD
analogue, 2-aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I, a
potent mGluR agonist. 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
metabotropic glutamate receptor activity of a 2-aminobicyclo-
[3.2.0]heptane-2,5-dicarboxylic acid, a molecule possessing 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
analogues of 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: new metabotropic glutamate receptor group II
selective antagonists. Bioorg. Med. Chem. Lett. 1998, 8, 447-
452.
Patent Status
US Patents 6825211, 6376532, 6204292, 6610743
