title: Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators.
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.
authors.affiliation: Chemical & Pharmacokinetic Sciences, Lundbeck Research USA, 215 College Road, Paramus, New Jersey 07652, USA.
authors.forename: Sang-Phyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Liu
authors.forename: Gil
authors.initials: G
authors.lastname: Ma
authors.forename: Michael
authors.initials: M
authors.lastname: Sabio
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Uberti
authors.forename: Maria D
authors.initials: MD
authors.lastname: Bacolod
authors.forename: John
authors.initials: J
authors.lastname: Peterson
authors.forename: Zack Z
authors.initials: ZZ
authors.lastname: Zou
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Robichaud
authors.forename: Darío
authors.initials: D
authors.lastname: Doller
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D052176:Azulenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D008958:Models, Molecular; D010539:Permeability; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D052176:Azulenes; D002491:Central Nervous System Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006575:Heterocyclic Compounds, 3-Ring; D007191:Indazoles; D011720:Pyrazoles; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; C108823:metabotropic glutamate receptor 4