Insights into the interaction of negative allosteric modulators with the metabotropic glutamate receptor 5: Discovery and computational modeling of a new series of ligands with nanomolar affinity

Bioorganic and Medicinal Chemistry

Volumn 23, Issue 13, 2015, Pages 3040-3058

  Anighoro, Andrew ^a   Graziani, Davide ^b   Bettinelli, Ilaria ^b   Cilia, Antonio ^b   De Toma, Carlo ^b   Longhi, Matteo ^b   Mangiarotti, Fabio ^b   Menegon, Sergio ^b   Pirona, Lorenza ^b   Poggesi, Elena ^b   Riva, Carlo ^b   Rastelli, Giulio ^a  

^a UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^b Recordati SpA   (Italy)

Author keywords

Docking; Homology modeling; Metabotropic glutamate receptor 5; Negative allosteric modulators

Indexed keywords

1 (3 NITROPYRIDIN 2 YL) 4 (3 PHENYLPROP 2 YN 1 YL)PIPERAZINE; 1 CHLORO 4 TRIMETHYLSILYLBUT 3 YN 2 ONE; 1 [4 (2 NITROPHENYL)PIPERAZIN 1 YL] 3 PHENYLPROP 2 YN 1 ONE; 1 [4 (3 NITROPYRIDIN 2 YL)PIPERAZIN 1 YL] 3 PHENYLPROP 2 YN 1 ONE; 1 [4 (6 ETHENYL 3 NITROPYRIDIN 2 YL)PIPERAZIN 1 YL] 3 PHENYLPROP 2 YN 1 ONE; 2 CHLORO 5 [(2 METHYL 1,3 THIAZOL 4 YL)ETHYNYL]PYRIDINE; 2 METHYL 4 [(TRIMETHYLSILYL)ETHYNYL] 1,3 THIAZOLE; 2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 2 METHYL 6 [3 (1 PHENYLPIPERIDIN 4 YLIDENE)PROP 1 YN 1 YL]PYRIDINE; 2 METHYL 6 [3 [1 (2 NITROPHENYL)PIPERIDIN 4 YLIDENE]PROP 1 YN 1 YL]PYRIDINE; 2 [4 [3 (3 CHLOROPHENYL)PROP 2 YNYLIDENE] 1 PIPERIDYL] 3 NITROPYRIDINE; 2 [4 [3 (3 METHYLPHENYL)PROP 2 YN 1 YLIDENE]PIPERIDIN 1 YL] 3 NITROPYRIDINE; 2 [4 [3 (6 METHYL 2 PYRIDYL)PROP 2 YNYLIDENE] 1 PIPERIDYL] 5 PHENYL PYRIDINE 3 CARBONITRILE; 2 [4 [3 (6 METHYLPYRIDIN 2 YL)PROP 2 YN 1 YLIDENE]PIPERIDIN 1 YL] 3 NITROPYRIDINE; 3 CHLORO 5 [3 [1 (3 NITRO 2 PYRIDYL) 4 PIPERIDYLIDENE]PROP 1 YNYL]BENZONITRILE; 3 NITRO 2 [4 (3 PHENYLPROP 2 YN 1 YLIDENE)PIPERIDIN 1 YL]PYRIDINE; 3 NITRO 2 [4 [3 (PYRIDIN 2 YL)PROP 2 YN 1 YLIDENE]PIPERIDIN 1 YL]PYRIDINE; 3,3 DIMETHYL 1 [4 [3 [1 (3 NITROPYRIDIN 2 YL)PIPERIDIN 4 YLIDENE]PROP 1 YN 1 YL]PHENYL]AZETIDIN 2 ONE; 5 [(2 METHYL 1,3 THIAZOL 4 YL)ETHYNYL] 2,3' BIPYRIDINE; 6 METHYL 2 [3 [3 (6 METHYLPYRIDIN 2 YL)PROP 2 YN 1 YLIDENE]PIPERIDIN 1 YL] 3 NITROPYRIDINE; 6 [3 [1 (6 METHYL 3 NITRO 2 PYRIDYL) 4 PIPERIDYLIDENE]PROP 1 YNYL]PYRIDINE 3 CARBONITRILE; FENOBAM; METABOTROPIC GLUTAMATE RECEPTOR 5 NEGATIVE ALLOSTERIC MODULATOR; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG; UNINDEXED DRUG; [4 (3 NITRO 2 PYRIDYL)PIPERAZIN 1 YL] (2 PHENYLPHENYL)METHANONE; [4 (3 NITRO 2 PYRIDYL)PIPERAZIN 1 YL] (4 PHENYLPHENYL)METHANONE; [4 (3 NITRO 2 PYRIDYL)PIPERAZIN 1 YL]QUINOXALIN 2 YL METHANONE; [4 (6 METHYL 3 NITRO 2 PYRIDYL)PIPERAZIN 1 YL] (3 PHENYLPHENYL)METHANONE; 6-METHYL-2-(PHENYLETHYNYL)PYRIDINE; IMIDAZOLE DERIVATIVE; LIGAND; METABOTROPIC GLUTAMATE RECEPTOR TYPE 1; METABOTROPIC RECEPTOR; NEUROLEPTIC AGENT; PROTEIN BINDING; PYRIDINE DERIVATIVE;

ALLOSTERISM; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; IN VITRO STUDY; MALE; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MUTAGENESIS; NANOMOLAR AFFINITY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; BINDING SITE; CHEMISTRY; DRUG DEVELOPMENT; KINETICS; PROTEIN TERTIARY STRUCTURE; STRUCTURAL HOMOLOGY; SYNTHESIS;

ALLOSTERIC REGULATION; ALLOSTERIC SITE; ANTIPSYCHOTIC AGENTS; DRUG DISCOVERY; HUMANS; IMIDAZOLES; KINETICS; LIGANDS; MOLECULAR DOCKING SIMULATION; MOLECULAR DYNAMICS SIMULATION; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; PYRIDINES; RECEPTOR, METABOTROPIC GLUTAMATE 5; RECEPTORS, METABOTROPIC GLUTAMATE; STRUCTURAL HOMOLOGY, PROTEIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84937423867     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2015.05.008     Document Type: Article

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