ArticleACS medicinal chemistry letters2015
Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia.
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Article in ACS medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21citing papers in PubMed
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Who cites it
21 citing papers in PubMed.
- Article
- Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?Frontiers in pharmacology · 2022Review
- Discovery of "Molecular Switches" within a Series of mGluACS bio & med chem Au · 2021Article
- Drugs Based on NMDAR Hypofunction Hypothesis in Schizophrenia.Frontiers in neuroscience · 2021Review
- The mGluJournal of neural transmission (Vienna, Austria : 1996) · 2020Article
- Article
- Schizophrenia: synthetic strategies and recent advances in drug design.MedChemComm · 2018Review
- Role of mGluACS chemical neuroscience · 2017Article
- Design and Synthesis ofACS medicinal chemistry letters · 2017Article
- Review
- Biased allosteric agonism and modulation of metabotropic glutamate receptor 5: Implications for optimizing preclinical neuroscience drug discovery.Neuropharmacology · 2017Article
- Discovery of VU0467485/AZ13713945: An MACS medicinal chemistry letters · 2017Article
- Development of 1ACS medicinal chemistry letters · 2016Article
- Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors.Chemical reviews · 2016Review
- Metabotropic glutamate receptor 5 - a promising target in drug development and neuroimaging.European journal of nuclear medicine and molecular imaging · 2016Review
- Discovery and Preclinical Evaluation of BMS-955829, a Potent Positive Allosteric Modulator of mGluR5.ACS medicinal chemistry letters · 2016Article
- Preliminary investigation of 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one derivatives as a novel series of mGlu5 receptor positive allosteric modulators with efficacy in preclinical models of schizophrenia.Bioorganic & medicinal chemistry letters · 2016Article
- New paradigms in GPCR drug discovery.Biochemical pharmacology · 2015Review
- Acyl dihydropyrazolo[1,5-a]pyrimidinones as metabotropic glutamate receptor 5 positive allosteric modulators.Bioorganic & medicinal chemistry letters · 2015Article
- Development of Novel, CNS Penetrant Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 1 (mGlu1), Based on an N-(3-Chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide Scaffold, That Potentiate Wild Type and Mutant mGlu1 Receptors Found in Schizophrenics.Journal of medicinal chemistry · 2015Article
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Authors and funding
22 authors.
Susana Conde-CeideNeuroscience Medicinal Chemistry and Discovery Sciences Lead Discovery, Janssen Research and Development , Jarama 75A, 45007 Toledo, Spain.
Carlos M Martínez-ViturroNeuroscience Medicinal Chemistry and Discovery Sciences Lead Discovery, Janssen Research and Development , Jarama 75A, 45007 Toledo, Spain.
Jesús AlcázarNeuroscience Medicinal Chemistry and Discovery Sciences Lead Discovery, Janssen Research and Development , Jarama 75A, 45007 Toledo, Spain.
Pedro M Garcia-BarrantesDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Hilde LavreysenNeuroscience and Discovery Sciences ADME/Tox, Janssen Research and Development , Turnhoutseweg 30, B-2340 Beerse, Belgium.
Claire MackieNeuroscience and Discovery Sciences ADME/Tox, Janssen Research and Development , Turnhoutseweg 30, B-2340 Beerse, Belgium.
Paige N VinsonDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Jerri M RookDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Thomas M BridgesDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
J Scott DanielsDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Anton MegensNeuroscience and Discovery Sciences ADME/Tox, Janssen Research and Development , Turnhoutseweg 30, B-2340 Beerse, Belgium.
Xavier LangloisNeuroscience and Discovery Sciences ADME/Tox, Janssen Research and Development , Turnhoutseweg 30, B-2340 Beerse, Belgium.
Wilhelmus H DrinkenburgNeuroscience and Discovery Sciences ADME/Tox, Janssen Research and Development , Turnhoutseweg 30, B-2340 Beerse, Belgium.
Abdellah AhnaouNeuroscience and Discovery Sciences ADME/Tox, Janssen Research and Development , Turnhoutseweg 30, B-2340 Beerse, Belgium.
Colleen M NiswenderDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Carrie K JonesDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Gregor J MacdonaldNeuroscience and Discovery Sciences ADME/Tox, Janssen Research and Development , Turnhoutseweg 30, B-2340 Beerse, Belgium.
Thomas StecklerNeuroscience and Discovery Sciences ADME/Tox, Janssen Research and Development , Turnhoutseweg 30, B-2340 Beerse, Belgium.
P Jeffrey ConnDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Shaun R StaufferDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
José Manuel Bartolomé-NebredaNeuroscience Medicinal Chemistry and Discovery Sciences Lead Discovery, Janssen Research and Development , Jarama 75A, 45007 Toledo, Spain.
Craig W LindsleyDepartment of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
Funding
REGULATION OF SIGNALING BY MGLUR5R01MH062646 · NIMH · VANDERBILT UNIVERSITY · PI P Jeffrey Conn, COLLEEN M NISWENDER · 2001 to 2026
$10.9MResearch Project: Sensory and Multisensory Contributions to AutismU54HD083211 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DYKENS, ELISABETH MAY · 2015 to 2019
$7.1MFunctions of Metabotropic Glutamate Receptor SubtypesR37NS031373 · NINDS · VANDERBILT UNIVERSITY · PI CONN, P JEFFREY · 2014 to 2020
$3.5MNICHD NIH HHS U54 HD083211NIMH NIH HHS R01 MH062646NINDS NIH HHS R37 NS031373
Abstract
Herein, we report the structure-activity relationship of a novel series of (2(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridine-5(4H)-yl(aryl)methanones as potent, selective, and orally bioavailable metabotropic glutamate receptor subtype 5 (mGlu5) positive allosteric modulators (PAMs). On the basis of its robust in vitro potency and in vivo efficacy in multiple preclinical models of multiple domains of schizophrenia, coupled with a good DMPK profile and an acceptable therapeutic window, 17a (VU0409551/JNJ-46778212) was selected as a candidate for further development.
Indexed as
4,5,6,7-tetrahydrooxazolo[5,4-c]pyridineJNJ-46778212metabotropic glutamate receptor 5 (mGlu5)Positive allosteric modulator (PAM)schizophreniaVU0409551
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