PMID

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Discovery of dual positive allosteric modulators (PAMs) of the metabotropic glutamate 2 receptor and CysLT1 antagonists for treating migraine headache.

Eli Lilly

Novel bicyclo[3.1.0]hexane analogs as antagonists of metabotropic glutamate 2/3 receptors for the treatment of depression.

Eli Lilly

N-Alkylpyrido[1',2':1,5]pyrazolo-[4,3-d]pyrimidin-4-amines: A new series of negative allosteric modulators of mGlu1/5 with CNS exposure in rodents.

Vanderbilt University Medical Center

Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 3. Engineering plasma stability by discovery and optimization of isoindolinone analogs.

Vanderbilt University Medical Center

Lead optimization of the VU0486321 series of mGlu(1) PAMs. Part 2: SAR of alternative 3-methyl heterocycles and progress towards an in vivo tool.

Vanderbilt University Medical Center

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.

Janssen Pharmaceutica

Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 1: SAR of modifications to the central aryl core.

Vanderbilt University Medical Center

Acyl dihydropyrazolo[1,5-a]pyrimidinones as metabotropic glutamate receptor 5 positive allosteric modulators.

Vanderbilt University Medical Center

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

Vanderbilt University

Synthesis and Pharmacological Characterization of C4-(Thiotriazolyl)-substituted-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1R,2S,4R,5R,6R)-2-Amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2812223), a Highly Potent, Functionally Selective

Eli Lilly

Re-exploring the N-phenylpicolinamide derivatives to develop mGlu4 ligands with improved affinity and in vitro microsomal stability.

Massachusetts General Hospital

GPCR crystal structures: Medicinal chemistry in the pocket.

Friedrich-Alexander University

Discovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain.

Korea Institute of Science and Technology

Discovery and SAR of novel series of imidazopyrimidinones and dihydroimidazopyrimidinones as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5).

Janssen Pharmaceutica

Novel thienopyrimidinones as mGluR1 antagonists.

Yonsei University

Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator.

Pfizer

Dihydrothiazolopyridone derivatives as a novel family of positive allosteric modulators of the metabotropic glutamate 5 (mGlu5) receptor.

Janssen Pharmaceutica

Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1.

Vanderbilt University Medical Center

Discovery, synthesis, and structure-activity relationships of 2-aminoquinazoline derivatives as a novel class of metabotropic glutamate receptor 5 negative allosteric modulators.

Merz Pharmaceuticals

N-Acyl-N'-arylpiperazines as negative allosteric modulators of mGlu1: identification of VU0469650, a potent and selective tool compound with CNS exposure in rats.

Vanderbilt University Medical Center

Discovery of (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3-(2-methyl-2H-indazol-5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide, a potent and orally efficacious mGlu5 receptor negative allosteric modulator.

Eli Lilly

13C bis-labeled pyrroles: a tool for the identification of the rat metabolism of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester.

Glaxosmithkline

A novel series of positive modulators of the AMPA receptor: structure-based lead optimization.

Merck Research Laboratories

The identification of structurally novel, selective, orally bioavailable positive modulators of mGluR2.

Glaxosmithkline

Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain.

Merck Research Laboratories

Synopsis of some recent tactical application of bioisosteres in drug design.

Bristol-Myers Squibb Pharmaceutical Research and Development

Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover.

Vanderbilt University Medical Center

Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery.

Vanderbilt University Medical Center

3-Phenyl-5-isothiazole carboxamides with potent mGluR1 antagonist activity.

Eli Lilly

Syntheses of 2-amino and 2-halothiazole derivatives as high-affinity metabotropic glutamate receptor subtype 5 ligands and potential radioligands for in vivo imaging.

National Institute of Mental Health

Design, synthesis and biological evaluation of novel bicyclo[1.1.1]pentane-based omega-acidic amino acids as glutamate receptors ligands.

Universit£

Prospects for metabotropic glutamate 1 receptor antagonists in the treatment of neuropathic pain.

Eli Lilly

Synthesis, molecular modeling studies, and preliminary pharmacological characterization of all possible 2-(2'-sulfonocyclopropyl)glycine stereoisomers as conformationally constrained L-homocysteic acid analogs.

Universit£

A new series of pyridinyl-alkynes as antagonists of the metabotropic glutamate receptor 5 (mGluR5).

Astrazeneca R & D M£Lndal

Synthesis, structure-activity relationship, and receptor pharmacology of a new series of quinoline derivatives acting as selective, noncompetitive mGlu1 antagonists.

Janssen-Cilag

Ligands for glutamate receptors: design and therapeutic prospects.

The Royal Danish School of Pharmacy

Synthesis and biology of the conformationally restricted ACPD analogue, 2-aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I, a potent mGluR agonist.

Georgetown University Medical Center

A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid.

Royal Danish School of Pharmacy

Metabotropic glutamate receptors: novel targets for drug development.

Cns Research

First enantiospecific synthesis of a 3,4-dihydroxy-L-glutamic acid [(3S,4S)-DHGA], a new mGluR1 agonist.

Cnrs

Synthesis and metabotropic glutamate receptor antagonist activity of N1-substituted analogs of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylic acid.

Eli Lilly

Fused tricyclic mGluR1 antagonists for the treatment of neuropathic pain.

Merck Research Laboratories

Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators.

Lundbeck Research Usa

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

Vanderbilt University Medical Center

Tricyclic thienopyridine-pyrimidones/thienopyrimidine-pyrimidones as orally efficacious mGluR1 antagonists for neuropathic pain.

Schering-Plough Research Institute

Radiosynthesis and preliminary evaluation of 4-[18F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide as a new positron emission tomography ligand for metabotropic glutamate receptor subtype 1.

National Institute of Radiological Sciences

Benzimidazoles as Potent and Orally Active mGlu5 Receptor Antagonists with an Improved PK Profile

TBA

Synthesis and evaluation of 6-[1-(2-[(18)F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline for positron emission tomography imaging of the metabotropic glutamate receptor type 1 in brain.

National Institute of Radiological Sciences

Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes: discovery of nanomolar, nonselective, and use-dependent antagonists.

University of Copenhagen

A new metabotropic glutamate receptor agonist with in vivo anti-allodynic activity.

The University of Adelaide

Carbamoyloximes as novel non-competitive mGlu5 receptor antagonists.

Gedeon Richter

A-ring modifications on the triazafluorenone core structure and their mGluR1 antagonist properties.

Merck Research Laboratories

Piperidyl amides as novel, potent and orally active mGlu5 receptor antagonists with anxiolytic-like activity.

Novartis Institutes For Biomedical Research

Discovery and biological profile of isoindolinone derivatives as novel metabotropic glutamate receptor 1 antagonists: a potential treatment for psychotic disorders.

Tsukuba Research Institute

Discovery and in vitro and in vivo profiles of 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide as novel class of an orally active metabotropic glutamate receptor 1 (mGluR1) antagonist.

Tsukuba Research Institute

Synergism of virtual screening and medicinal chemistry: identification and optimization of allosteric antagonists of metabotropic glutamate receptor 1.

Merz Pharmaceuticals

 

(+)-2-Methyl-4-carboxyphenylglycine (LY367385) selectively antagonises metabotropic glutamate mGluR1 receptors

TBA

 

A novel class of antagonists for metabotropic glutamate receptors, 7-(Hydroxyimino)cyclopropa[b]chromen-1a-carboxylates

TBA

 

Synthesis and biology of the rigidified glutamate analogue, trans-2-carboxyazetidine-3-acetic acid (t-CAA)

TBA

 

Synthesis of conformationally-constrained stereospecific analogs of glutamic acid as antagonists of metabotropic receptors

TBA

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.

Vanderbilt University Medical Center

In vitro and in vivo SAR of pyrido[3,4-d]pyramid-4-ylamine based mGluR1 antagonists.

Medical Research Council Technology

Discovery and biological profile of 4-(1-aryltriazol-4-yl)-tetrahydropyridines as an orally active new class of metabotropic glutamate receptor 1 antagonist.

Tsukuba Research Institute

Discovery of orally efficacious tetracyclic metabotropic glutamate receptor 1 (mGluR1) antagonists for the treatment of chronic pain.

Schering-Plough Research Institute

Synthesis and simple 18F-labeling of 3-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile as a high affinity radioligand for imaging monkey brain metabotropic glutamate subtype-5 receptors with positron emission tomography.

National Institute of Mental Health

Rapid hit to lead evaluation of pyrazolo[3,4-d]pyrimidin-4-one as selective and orally bioavailable mGluR1 antagonists.

Abbott Laboratories

Correlation between brain/plasma ratios and efficacy in neuropathic pain models of selective metabotropic glutamate receptor 1 antagonists.

Abbott Laboratories

Rational design and enantioselective synthesis of (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid - a novel inhibitor at human glutamate transporter subtypes 1, 2, and 3.

The Danish University of Pharmaceutical Sciences

Structure-activity relationship of triazafluorenone derivatives as potent and selective mGluR1 antagonists.

Abbott Laboratories

Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO).

The Danish University of Pharmaceutical Sciences

3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity.

Merck Research Laboratories

Discovery of 4-arylquinoline-2-carboxamides, highly potent and selective class of mGluR2 negative allosteric modulators: From HTS to activity in animal models.

Merck

Chiral resolution, pharmacological characterization, and receptor docking of the noncompetitive mGlu1 receptor antagonist (+/-)-2-hydroxyimino- 1a, 2-dihydro-1H-7-oxacyclopropa[b]naphthalene-7a-carboxylic acid ethyl ester.

Novartis Pharma

Discovery of an Orally Bioavailable and Central Nervous System (CNS) Penetrant mGlu

Vanderbilt University School of Medicine

Modeling of amino-terminal domains of group I metabotropic glutamate receptors: structural motifs affecting ligand selectivity.

Universit¿A Di Perugia

Urea Derivatives in Modern Drug Discovery and Medicinal Chemistry.

Purdue University

Surveying heterocycles as amide bioisosteres within a series of mGlu

Vanderbilt University

Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (LY354740): identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors

Eli Lilly

2,3'-disubstituted-2-(2'-carboxycyclopropyl)glycines as potent and selective antagonists of metabotropic glutamate receptors.

Eli Lilly

Synthesis and preliminary evaluation of (S)-2-(4'-carboxycubyl)glycine, a new selective mGluR1 antagonist.

Università

(2S,4S)-amino-4-(2,2-diphenylethyl)pentanedioic acid selective group 2 metabotropic glutamate receptor antagonist.

Eli Lilly

Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: new tools to discriminate between metabotropic glutamate receptor subtypes.

Université

Discovery of Novel Central Nervous System Penetrant Metabotropic Glutamate Receptor Subtype 2 (mGlu

Vanderbilt University School of Medicine

Homology modeling of metabotropic glutamate receptors. (mGluRs) structural motifs affecting binding modes and pharmacological profile of mGluR1 agonists and competitive antagonists.

Università

(S)-(+)-2-(3'-carboxybicyclo[1.1.1]pentyl)-glycine, a structurally new group I metabotropic glutamate receptor antagonist.

Università

Re-exploration of the mGlu? PAM Ro 07-11401 scaffold: Discovery of analogs with improved CNS penetration despite steep SAR.

Vanderbilt University Medical Center

Synthesis and pharmacological characterization of all sixteen stereoisomers of 2-(2'-carboxy-3'-phenylcyclopropyl)glycine. Focus on (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, a novel and selective group II metabotropic glutamate receptors antagonist.

Università

1-Aminoindan-1,5-dicarboxylic acid: a novel antagonist at phospholipase C-linked metabotropic glutamate receptors.

Università

VU6010608, a Novel mGlu

Vanderbilt University

Synthesis and Pharmacological Characterization of C4

TBA

Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.

Case Western Reserve University

Characterization of [(3)H]Quisqualate binding to recombinant rat metabotropic glutamate 1a and 5a receptors and to rat and human brain sections.

F. Hoffmann-La Roche

Pharmacology and functions of metabotropic glutamate receptors.

Emory University

The C-terminal domain of the mGluR1 metabotropic glutamate receptor affects sensitivity to agonists.

Cns Research