ArticleJournal of medicinal chemistry2014
Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): pharmacological characterization and assessment in a rat model of cocaine dependence.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
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- mGlu2 Receptors in the Basal Ganglia: A New Frontier in Addiction Therapy.Frontiers in bioscience (Landmark edition) · 2025Review
- Radiosynthesis and preclinical evaluation of a carbon-11 labeled PET ligand for imaging metabotropic glutamate receptor 7.American journal of nuclear medicine and molecular imaging · 2024Article
- Development and use of a high-throughput screen to identify novel modulators of the corticotropin releasing factor binding protein.SLAS discovery : advancing life sciences R & D · 2022Article
- Allosteric Modulators of Metabotropic Glutamate Receptors as Novel Therapeutics for Neuropsychiatric Disease.Pharmacological reviews · 2022Review
- Identification and Development of a New Positron Emission Tomography Ligand 4-(2-Fluoro-4-[Journal of medicinal chemistry · 2020Article
- Operant self-stimulation of thalamic terminals in the dorsomedial striatum is constrained by metabotropic glutamate receptor 2.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Synthesis and preliminary studies ofTheranostics · 2020Article
- LY354740 Reduces Extracellular Glutamate Concentration, Inhibits Phosphorylation of Fyn/NMDARs, and Expression of PLK2/pS129 α-Synuclein in Mice Treated With Acute or Sub-Acute MPTP.Frontiers in pharmacology · 2020Article
- Allosteric modulation of metabotropic glutamate receptors in alcohol use disorder: Insights from preclinical investigations.Advances in pharmacology (San Diego, Calif.) · 2020Review
- Effect of Novel Allosteric Modulators of Metabotropic Glutamate Receptors on Drug Self-administration and Relapse: A Review of Preclinical Studies and Their Clinical Implications.Biological psychiatry · 2018Review
- A Combination of Flow and Batch Mode Processes for the Efficient Preparation of mGluTetrahedron · 2018Article
- Synthesis and Preliminary Studies of a Novel Negative Allosteric Modulator, 7-((2,5-Dioxopyrrolidin-1-yl)methyl)-4-(2-fluoro-4-[ACS chemical neuroscience · 2017Article
- Review
- Athina Markou's contributions to treatment development for mental illnesses: a perspective.Psychopharmacology · 2017Article
- Targeting metabotropic glutamate receptors for novel treatments of schizophrenia.Molecular brain · 2017Review
- Recent advances in the medicinal chemistry of group II and group III mGlu receptors.MedChemComm · 2017Review
- The individual and combined effects of phenmetrazine and mgluR2/3 agonist LY379268 on the motivation to self-administer cocaine.Drug and alcohol dependence · 2016Article
- Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors.Chemical reviews · 2016Review
- Optimization of Novel Aza-benzimidazolone mGluR2 PAMs with Respect to LLE and PK Properties and Mitigation of CYP TDI.ACS medicinal chemistry letters · 2016Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.