Abstract
There is an increasing amount of evidence to support that activation of the metabotropic glutamate receptor 4 (mGlu4 receptor), either with an orthosteric agonist or a positive allosteric modulator (PAM), provides impactful interventions in diseases such as Parkinson's disease, anxiety, and pain. mGlu4 PAMs may have several advantages over mGlu4 agonists for a number of reasons. As part of our efforts in identifying therapeutics for central nervous system (CNS) diseases such as Parkinson's disease, we have been focusing on metabotropic glutamate receptors. Herein we report our studies with a series of tricyclic thiazolopyrazoles as mGlu4 PAMs.
MeSH terms
-
Allosteric Regulation
-
Animals
-
Aza Compounds / chemical synthesis
-
Aza Compounds / chemistry
-
Aza Compounds / pharmacology
-
Azulenes / chemical synthesis
-
Azulenes / chemistry
-
Azulenes / pharmacology
-
Brain / metabolism
-
Cell Line
-
Central Nervous System Agents / chemical synthesis*
-
Central Nervous System Agents / chemistry
-
Central Nervous System Agents / pharmacology
-
ERG1 Potassium Channel
-
Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
-
Heterocyclic Compounds, 3-Ring / chemical synthesis*
-
Heterocyclic Compounds, 3-Ring / chemistry
-
Heterocyclic Compounds, 3-Ring / pharmacology
-
Humans
-
In Vitro Techniques
-
Indazoles / chemical synthesis
-
Indazoles / chemistry
-
Indazoles / pharmacology
-
Mice
-
Microsomes, Liver / metabolism
-
Models, Molecular
-
Permeability
-
Pyrazoles / chemical synthesis*
-
Pyrazoles / chemistry
-
Pyrazoles / pharmacology
-
Pyridines / chemical synthesis
-
Pyridines / chemistry
-
Pyridines / pharmacology
-
Rats
-
Receptors, Metabotropic Glutamate / physiology*
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
Aza Compounds
-
Azulenes
-
Central Nervous System Agents
-
ERG1 Potassium Channel
-
Ether-A-Go-Go Potassium Channels
-
Heterocyclic Compounds, 3-Ring
-
Indazoles
-
Pyrazoles
-
Pyridines
-
Receptors, Metabotropic Glutamate
-
metabotropic glutamate receptor 4