Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS.

No abstract is available for this paper.

• Publication year

  2009

• Venue

  Bioorganic & Medicinal Chemistry Letters

• Publication date

  2009-12-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.bmcl.2009.10.059PMID 19875287PMCID PMC3177597
• 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.

• Discovery and SAR of novel mGluR5 non-competitive antagonists not based on an MPEP chemotype.

  2009cited by this paper
• Structure-activity relationships comparing N-(6-methylpyridin-yl)-substituted aryl amides to 2-methyl-6-(substituted-arylethynyl)pyridines or 2-methyl-4-(substituted-arylethynyl)thiazoles as novel metabotropic glutamate receptor subtype 5 antagonists.

  2009cited by this paper
• Synthesis, SAR and Unanticipated Pharmacological Profiles of Analogues of the mGluR5 Ago‐potentiator ADX‐47273

  2009cited by this paper
• Discovery of molecular switches that modulate modes of metabotropic glutamate receptor subtype 5 (mGlu5) pharmacology in vitro and in vivo within a series of functionalized, regioisomeric 2- and 5-(phenylethynyl)pyrimidines.

  2009cited by this paper
• 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

  2008cited by this paper
• Phenylethynyl-pyrrolo[1,2-a]pyrazine: a new potent and selective tool in the mGluR5 antagonists arena.

  2008cited by this paper
• Synthesis and SAR of a mGluR5 allosteric partial antagonist lead: unexpected modulation of pharmacology with slight structural modifications to a 5-(phenylethynyl)pyrimidine scaffold.

  2008cited by this paper
• Application of combinatorial chemistry science on modern drug discovery.

  2008cited by this paper
• Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA.

  2007cited by this paper
• Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists.

  2007cited by this paper
• Synthesis and SAR comparison of regioisomeric aryl naphthyridines as potent mGlu5 receptor antagonists.

  2007cited by this paper
• Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists.

  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
• Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP.

  2006cited by this paper
• Structure-activity relationships for the linker in a series of pyridinyl-alkynes that are antagonists of the metabotropic glutamate receptor 5 (mGluR5).

  2006cited by this paper
• Structure-activity relationship of thiopyrimidines as mGluR5 antagonists.

  2006cited by this paper
• Norepinephrine Induces Lipolysis in β1/β2/β3-Adrenoceptor Knockout Mice

  2005cited by this paper
• Fenobam: A Clinically Validated Nonbenzodiazepine Anxiolytic Is a Potent, Selective, and Noncompetitive mGlu5 Receptor Antagonist with Inverse Agonist Activity

  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
• Functionalization at position 3 of the phenyl ring of the potent mGluR5 noncompetitive antagonists MPEP.

  2005cited by this paper
• Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo.

  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
• Expedited SAR study of an mGluR5 antagonists: generation of a focused library using a solution-phase Suzuki coupling methodology.

  2004cited by this paper
• 5-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-2,3'-bipyridine: a highly potent, orally active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist with anxiolytic activity.

  2004cited by this paper
• Development of a custom high-throughput preparative liquid chromatography/mass spectrometer platform for the preparative purification and analytical analysis of compound libraries.

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

  2003cited 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
• Pharmacology and functions of metabotropic glutamate receptors.

  1997cited by this paper

• Structure-Based Discovery of Negative Allosteric Modulators of the Metabotropic Glutamate Receptor 5

  2022cites this paper
• An experimental and computational study of pyrimidine based bis-uracil derivatives as efficient candidates for optical, nonlinear optical, and drug discovery applications

  2020cites this paper
• Structural parameters, electronic, linear and nonlinear optical exploration of thiopyrimidine derivatives: A comparison between DFT/TDDFT and experimental study

  2020cites this paper
• Allosteric Molecular Switches in Metabotropic Glutamate Receptors

  2020cites this paper
• Discovery of VU0431316: a negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety.

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

  2014cites this paper
• Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety.

  2013cites this paper
• Substituted 1-Phenyl-3-(pyridin-2-yl)urea negative allosteric modulators of mGlu5: discovery of a new tool compound VU0463841 with activity in rat models of cocaine addiction.

  2013cites this paper
• Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

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

  2012cites this paper
• Fragile X syndrome: an update on developing treatment modalities.

  2011cites this paper
• Efficacy switching SAR of mGluR5 allosteric modulators: highly potent positive and negative modulators from one chemotype.

  2011cites this paper
• Recent advances in the design and development of novel negative allosteric modulators of mGlu(5).

  2011cites this paper
• Discovery and Characterization of Selective Negative Allosteric Modulators of Human α4β2 Neuronal Nicotinic Receptors

  2011cites this paper
• Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists.

  2011cites this paper
• (3-Cyano-5-fluorophenyl)biaryl negative allosteric modulators of mGlu(5): Discovery of a new tool compound with activity in the OSS mouse model of addiction.

  2011cites this paper
• "Molecular switches" on mGluR allosteric ligands that modulate modes of pharmacology.

  2011cites this paper
• 3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure in rats.

  2010cites this paper
• Discovery of a Novel Chemical Class of mGlu5 Allosteric Ligands with Distinct Modes of Pharmacology

  2010cites this paper