N-{4-Chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide (CPPHA) Acts through a Novel Site as a Positive Allosteric Modulator of Group 1 Metabotropic Glutamate Receptors

No abstract is available for this paper.

• Publication year

  2008

• Venue

  Molecular Pharmacology

• Publication date

  2008-03-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1124/mol.107.040097PMID 18056795
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Interaction of Novel Positive Allosteric Modulators of Metabotropic Glutamate Receptor 5 with the Negative Allosteric Antagonist Site Is Required for Potentiation of Receptor Responses

  2007cited by this paper
• Substituent effects of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat cortical astrocytes.

  2006cited by this paper
• A NOVEL CLASS OF POSITIVE ALLOSTERIC MODULATORS OF mGluR1 INTERACT WITH A SITE DISTINCT FROM THAT OF NEGATIVE ALLOSTERIC MODULATORS

  2006cited by this paper
• Determination of key amino acids implicated in the actions of allosteric modulation by 3,3'-difluorobenzaldazine on rat mGlu5 receptors.

  2006cited by this paper
• Biphenyl-indanone A, a Positive Allosteric Modulator of the Metabotropic Glutamate Receptor Subtype 2, Has Antipsychotic- and Anxiolytic-Like Effects in Mice

  2006cited by this paper
• A Novel Class of Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 1 Interact with a Site Distinct from That of Negative Allosteric Modulators

  2006cited by this paper
• A close structural analog of MPEP acts as a neutral allosteric site ligand on metabotropic glutamate receptor subtype 5 and blocks the effects of multiple allosteric modulators

  2005cited by this paper
• Allosteric Potentiators of Metabotropic Glutamate Receptor Subtype 5 Have Differential Effects on Different Signaling Pathways in Cortical Astrocytes

  2005cited by this paper
• A Close Structural Analog of 2-Methyl-6-(phenylethynyl)-pyridine Acts as a Neutral Allosteric Site Ligand on Metabotropic Glutamate Receptor Subtype 5 and Blocks the Effects of Multiple Allosteric Modulators

  2005cited by this paper
• A Novel Selective Positive Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Has in Vivo Activity and Antipsychotic-Like Effects in Rat Behavioral Models

  2005cited by this paper
• Targeting metabotropic glutamate receptors for treatment of the cognitive symptoms of schizophrenia

  2004cited by this paper
• A Novel Selective Allosteric Modulator Potentiates the Activity of Native Metabotropic Glutamate Receptor Subtype 5 in Rat Forebrain

  2004cited by this paper
• The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates PCP-induced cognitive deficits in rats

  2004cited by this paper
• [3H]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists.

  2003cited by this paper
• Functional coupling of the human dopamine D2 receptor with G alpha i1, G alpha i2, G alpha i3 and G alpha o G proteins: evidence for agonist regulation of G protein selectivity.

  2003cited by this paper
• Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors

  2003cited by this paper
• Mutational analysis and molecular modeling of the binding pocket of the metabotropic glutamate 5 receptor negative modulator 2-methyl-6-(phenylethynyl)-pyridine.

  2003cited by this paper
• A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5.

  2003cited by this paper
• Functional coupling of the human dopamine D2 receptor with Gαi1, Gαi2, Gαi3 and Gαo G proteins: evidence for agonist regulation of G protein selectivity

  2003cited by this paper
• G Protein-Coupled Receptor Allosterism and Complexing

  2002cited by this paper
• Direct and indirect modulation of the N-methyl D-aspartate receptor.

  2002cited by this paper
• Differential regulation of metabotropic glutamate receptor 5‐mediated phosphoinositide hydrolysis and extracellular signal‐regulated kinase responses by protein kinase C in cultured astrocytes

  2002cited by this paper
• Distinct physiological roles of the Gq‐coupled metabotropic glutamate receptors co‐expressed in the same neuronal populations

  2002cited by this paper
• Book Review: Metabotropic Glutamate Receptors: Electrical and Chemical Signaling Properties

  2002cited by this paper
• Activation of Group I Metabotropic Glutamate Receptors Produces a Direct Excitation and Disinhibition of GABAergic Projection Neurons in the Substantia Nigra Pars Reticulata

  2001cited by this paper
• Positive allosteric modulators of metabotropic glutamate 1 receptor: Characterization, mechanism of action, and binding site

  2001cited by this paper
• Metabotropic Glutamate Receptor 5-Induced Phosphorylation of Extracellular Signal-Regulated Kinase in Astrocytes Depends on Transactivation of the Epidermal Growth Factor Receptor

  2001cited by this paper
• Agonist-directed trafficking of porcine alpha(2A)-adrenergic receptor signaling in Chinese hamster ovary cells: l-isoproterenol selectively activates G(s).

  2000cited by this paper
• Agonist-Directed Trafficking of Porcine α2A-Adrenergic Receptor Signaling in Chinese Hamster Ovary Cells: l-Isoproterenol Selectively Activates Gs

  2000cited by this paper
• The Non-competitive Antagonists 2-Methyl-6-(phenylethynyl)pyridine and 7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic Acid Ethyl Ester Interact with Overlapping Binding Pockets in the Transmembrane Region of Group I Metabotropic Glutamate Receptors*

  2000cited by this paper
• CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding.

  1999cited by this paper
• Metabotropic glutamate receptors: electrophysiological properties and role in plasticity.

  1999cited by this paper
• Pharmacological agents acting at subtypes of metabotropic glutamate receptors.

  1999cited by this paper
• 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist.

  1999cited by this paper
• SIB-1757 and SIB-1893: selective, noncompetitive antagonists of metabotropic glutamate receptor type 5.

  1999cited by this paper
• Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus.

  1998cited by this paper
• Pharmacology and functions of metabotropic glutamate receptors.

  1997cited by this paper
• Opposite influence of the metabotropic glutamate receptor subtypes mGlu3 and ‐5 on astrocyte proliferation in culture

  1997cited by this paper

• Unveiling the molecular mechanism of Gi protein biased activation at mGlu2–mGlu4 heterodimers through Gaussian accelerated molecular dynamics simulations

  2025cites this paper
• Pharmacological characterisation of allosteric modulators at human mGlu5.

  2025cites this paper
• TRPC6 knockdown-mediated ERK1/2 inactivation alleviates podocyte injury in minimal change disease via upregulating Lon peptidase 1

  2024cites this paper
• Homology modeling and molecular docking study of metabotropic glutamate receptor 5 variant F: an attempt to develop drugs for treating CNS diseases

  2024cites this paper
• Post-stress social interaction and 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide treatment attenuate depressive-like behavior induced by repeated social defeat stress.

  2023cites this paper
• Rigorous Characterization of Allosteric Modulation of the Human Metabotropic Glutamate Receptor 1 Reveals Probe- and Assay-Dependent Pharmacology

  2023cites this paper
• SCA44- and SCAR13-associated GRM1 mutations affect metabotropic glutamate receptor 1 function through distinct mechanisms

  2023cites this paper
• mGluR5 PAMs rescue cortical and behavioural defects in a mouse model of CDKL5 deficiency disorder

  2022cites this paper
• Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism

  2021cites this paper
• The evidence for and consequences of metabotropic glutamate receptor heterodimerization.

  2021cites this paper
• Allosteric Molecular Switches in Metabotropic Glutamate Receptors

  2020cites this paper
• Structure-based discovery and development of metabotropic glutamate receptor 5 negative allosteric modulators.

  2020cites this paper
• Identification of novel allosteric modulators of mGlu5 acting at site distinct from MPEP binding.

  2019cites this paper
• Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors

  2019cites this paper
• Imaging metabotropic glutamate receptor system: Application of positron emission tomography technology in drug development

  2019cites this paper
• In Vitro to in Vivo Translation of Allosteric Modulator Concentration-Effect Relationships: Implications for Drug Discovery.

  2019cites this paper
• Negative allosteric modulators of the human calcium‐sensing receptor bind to overlapping and distinct sites within the 7‐transmembrane domain

  2019cites this paper
• “Selective” Class C G Protein-Coupled Receptor Modulators Are Neutral or Biased mGlu5 Allosteric Ligands

  2018cites this paper
• Biased agonism and allosteric modulation of metabotropic glutamate receptor 5.

  2018cites this paper
• Modulation of Metabotropic Glutamate Receptors by Orthosteric, Allosteric, and Light-Operated Ligands

  2018cites this paper
• Drugs to Tune Up Glutamatergic Systems: Modulators of Glutamate Metabotropic Receptors

  2018cites this paper
• Effects of the Positive Allosteric Modulator of Metabotropic Glutamate Receptor 5, VU-29, on Impairment of Novel Object Recognition Induced by Acute Ethanol and Ethanol Withdrawal in Rats

  2018influential citation
• The metabotropic glutamate receptor 5 radioligand [11C]AZD9272 identifies unique binding sites in primate brain

  2018cites this paper
• Molecular insights into allosteric modulation of Class C G protein-coupled receptors.

  2017cites this paper
• Glutamatergic regulation of cognition and functional brain connectivity: insights from pharmacological, genetic and translational schizophrenia research

  2017cites this paper
• Structural biology of GABAB receptor

  2017cites this paper
• Synthesis of both enantiomers of 1,2,3,4-tetrahydroisoquinoline derivative IPPAM-1 and enantio-dependency of its positive allosteric modulation of prostacyclin receptor.

  2017cites this paper
• Investigating the pharmacology, dimerisation and receptor-dependent toxicology of metabotropic glutamate receptor 5

  2017cites this paper
• Organization and functions of mGlu and GABAB receptor complexes

  2016cites this paper
• VU0477573: Partial Negative Allosteric Modulator of the Subtype 5 Metabotropic Glutamate Receptor with In Vivo Efficacy

  2016cites this paper
• Structural insight to mutation effects uncover a common allosteric site in class C GPCRs

  2016cites this paper
• Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor

  2016cites this paper
• Metabotropic glutamate receptor subtype 5: molecular pharmacology, allosteric modulation and stimulus bias

  2016cites this paper
• Overview of Critical Parameters for the Design and Execution of a High‐Throughput Screen for Allosteric Ligands

  2016cites this paper
• Palladium-catalyzed highly regioselective 2-alkynylation of 2,x-dihalopyridines

  2016cites this paper
• N-Aryl-5-aminopyrazole: a versatile architecture in medicinal chemistry.

  2015cites this paper
• GPCR crystal structures: Medicinal chemistry in the pocket.

  2015cites this paper
• Selective Negative Allosteric Modulation Of Metabotropic Glutamate Receptors – A Structural Perspective of Ligands and Mutants

  2015cites this paper
• Overlapping binding sites drive allosteric agonism and positive cooperativity in type 4 metabotropic glutamate receptors

  2015cites this paper
• Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation

  2015cites this paper
• Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation s

  2015influential citation
• Novel Allosteric Modulators of G Protein-coupled Receptors*

  2015cites this paper
• Relationship between In Vivo Receptor Occupancy and Efficacy of Metabotropic Glutamate Receptor Subtype 5 Allosteric Modulators with Different In Vitro Binding Profiles

  2015cites this paper
• allosteric modulator Modulation of neuronal microcircuit activities within the medial prefrontal cortex by mGluR 5 positive

  2014cites this paper
• Activation of the mGlu5 Receptor for the Treatment of Schizophrenia and Cognitive-Deficit-Associated Disorders

  2014cites this paper
• mGluR5: Exploration of Orthosteric and Allosteric Ligand Binding Pockets and Their Applications to Drug Discovery

  2014cites this paper
• Modulation of neuronal microcircuit activities within the medial prefrontal cortex by mGluR5 positive allosteric modulator

  2014cites this paper
• Structure of a Class C GPCR Metabotropic Glutamate Receptor 1 Bound to an Allosteric Modulator

  2014cites this paper
• Progress toward advanced understanding of metabotropic glutamate receptors: structure, signaling and therapeutic indications.

  2014cites this paper
• SAR studies on mGlu5 receptor positive allosteric modulators (2003- 2013).

  2014cites this paper
• Pharmacology of metabotropic glutamate receptor allosteric modulators: structural basis and therapeutic potential for CNS disorders.

  2013cites this paper
• N-Aryl Piperazine Metabotropic Glutamate Receptor 5 Positive Allosteric Modulators Possess Efficacy in Preclinical Models of NMDA Hypofunction and Cognitive Enhancement

  2013cites this paper
• Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity.

  2013cites this paper
• Group III and subtype 4 metabotropic glutamate receptor agonists: discovery and pathophysiological applications in Parkinson's disease.

  2013cites this paper
• mGlu5 negative allosteric modulators: a patent review (2013 - 2016)

  2013cites this paper
• Author ' s personal copy Invited review Group III and subtype 4 metabotropic glutamate receptor agonists : Discovery and pathophysiological applications in Parkinson ’ s disease

  2013cites this paper
• A Novel Metabotropic Glutamate Receptor 5 Positive Allosteric Modulator Acts at a Unique Site and Confers Stimulus Bias to mGlu5 Signaling

  2013influential citation
• Allosteric modulation of metabotropic glutamate receptors

  2013cites this paper
• The new compound GET73, N-[(4-trifluoromethyl)benzyl]4-methoxybutyramide, Regulates hippocampal Aminoacidergic transmission possibly via an allosteric modulation of mGlu5 receptor. Behavioural evidence of its "anti-alcohol" and anxiolytic properties.

  2013cites this paper
• In vitro characterisation of the novel positive allosteric modulators of the mGlu₅ receptor, LSN2463359 and LSN2814617, and their effects on sleep architecture and operant responding in the rat.

  2013cites this paper
• In vitro binding of a radio‐labeled positive allosteric modulator for metabotropic glutamate receptor subtype 5

  2013cites this paper
• Probing the Metabotropic Glutamate Receptor 5 (mGlu5) Positive Allosteric Modulator (PAM) Binding Pocket: Discovery of Point Mutations That Engender a “Molecular Switch” in PAM Pharmacology

  2013influential citation
• mGlu5 negative allosteric modulators: a patent review (2010 – 2012)

  2013cites this paper
• Structure and ligand recognition of class C GPCRs

  2012cites this paper
• Metabotropic Receptors for Glutamate and GABA

  2012cites this paper
• Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover.

  2012cites this paper
• Metabotropic glutamate receptors as therapeutic targets for schizophrenia.

  2012cites this paper
• Targeting metabotropic glutamate receptors in neuroimmune communication.

  2012cites this paper
• Microsoft Word-72803376-file00

  2012cites this paper
• Pharmacological Characterization and Modeling of the Binding Sites of Novel 1,3-Bis(pyridinylethynyl)benzenes as Metabotropic Glutamate Receptor 5-Selective Negative Allosteric Modulators

  2012cites this paper
• Functional Impact of Allosteric Agonist Activity of Selective Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 in Regulating Central Nervous System Function

  2012cites this paper
• The role of metabotropic glutamate receptors in addiction: evidence from preclinical models.

  2012cites this paper
• Cinnabarinic Acid, an Endogenous Metabolite of the Kynurenine Pathway, Activates Type 4 Metabotropic Glutamate Receptors

  2012cites this paper
• Investigating Metabotropic Glutamate Receptor 5 Allosteric Modulator Cooperativity, Affinity, and Agonism: Enriching Structure-Function Studies and Structure-Activity Relationships

  2012cites this paper
• Metabotropic glutamate receptors for new treatments in schizophrenia.

  2012cites this paper
• Functional impact of allosteric agonist activity of selective positive allosteric modulators of mGlu 5 in regulating CNS function

  2011cites this paper
• Machine learning algorithms for prediction of biological activity and chemical properties

  2011cites this paper
• Regulation and Pharmacological Manipulation of the Type 5 Metabotropic Glutamate (mGlu5) Receptor

  2011cites this paper
• Preclinical profile of a novel metabotropic glutamate receptor 5 positive allosteric modulator.

  2011cites this paper
• Dimers and beyond: The functional puzzles of class C GPCRs.

  2011cites this paper
• GPCRs Revisited: New Insights Lead to Novel Drugs

  2011cites this paper
• Allosteric modulation of metabotropic glutamate receptors: structural insights and therapeutic potential.

  2011influential citation
• Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides as positive allosteric modulators of the metabotropic glutamate receptor subtype 5.

  2011cites this paper
• Quantitative Analysis Reveals Multiple Mechanisms of Allosteric Modulation of the mGlu5 Receptor in Rat Astroglia

  2011cites this paper
• Allosteric modulation of metabotropic glutamate receptors.

  2011cites this paper
• Positive Allosteric Modulators of Type 5 Metabotropic Glutamate Receptors (mGluR5) and Their Therapeutic Potential for the Treatment of CNS Disorders

  2011cites this paper
• Integrated Synthetic, Pharmacological, and Computational Investigation of cis‐2‐(3,5‐Dichlorophenylcarbamoyl)cyclohexanecarboxylic Acid Enantiomers As Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 4

  2011cites this paper
• Discovery of a Novel Chemical Class of mGlu5 Allosteric Ligands with Distinct Modes of Pharmacology

  2010cites this paper
• Screening for Allosteric Modulators of G Protein‐Coupled Receptors

  2010cites this paper
• Identification of Metabotropic Glutamate Receptor Subtype 5 Potentiators Using Virtual High-Throughput Screening

  2010cites this paper
• Discovery of N-Aryl Piperazines as Selective mGlu(5) Potentiators with Efficacy in a Rodent Model Predictive of Anti-Psychotic Activity.

  2010cites this paper
• Discovery of N-Aryl Piperazines as Selective mGluR5 Potentiators with Improved In Vivo Utility

  2010cites this paper
• Discovery of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Reveals Chemical and Functional Diversity and In Vivo Activity in Rat Behavioral Models of Anxiolytic and Antipsychotic Activity

  2010cites this paper
• Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders.

  2009cites this paper
• Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS.

  2009cites this paper
• Effects of Positive Allosteric Modulators on Single-Cell Oscillatory Ca2+ Signaling Initiated by the Type 5 Metabotropic Glutamate Receptor

  2009cites this paper
• Discovery and Characterization of Novel Allosteric Potentiators of M1 Muscarinic Receptors Reveals Multiple Modes of Activity

  2009cites this paper
• Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia.

  2009cites this paper
• Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders

  2009cites this paper
• Effects of Positive Allosteric Modulators on Single-Cell Oscillatory Ca 2 (cid:1) Signaling Initiated by the Type 5 Metabotropic Glutamate Receptor

  2009cites this paper