- MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2
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The present application provides a compound of Formula: or a pharmaceutically acceptable salt thereof, wherein ring B, L1, ring A, L2, n, R1, R2, R3, R4, and X1 are as described herein. Pharmaceutical compositions comprising the compound, as well as the methods of making and using the compound, are also provided.
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Page/Page column 76
(2021/08/06)
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- Triazolopyridine ethers as potent, orally active mGlu2positive allosteric modulators for treating schizophrenia
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Triazolopyridine ethers with mGlu2positive allosteric modulator (PAM) activity are disclosed. The synthesis, in vitro activity, and metabolic stability data for a series of analogs is provided. The effort resulted in the discovery of a potent, selective, and brain penetrant lead molecule BMT-133218 ((+)-7m). After oral administration at 10 mg/kg, BMT-133218 demonstrated full reversal of PCP-stimulated locomotor activity and prevented MK-801-induced working memory deficits in separate mouse models. Also, reversal of impairments in executive function were observed in rat set-shifting studies at 3 and 10 mg/kg (p.o.). Extensive plasma protein binding as the result of high lipophilicity likely limited activity at lower doses. Optimized triazolopyridine ethers offer utility as mGlu2PAMs for the treatment of schizophrenia and merit further preclinical investigation.
- Higgins, Mendi A.,Marcin, Lawrence R.,Christopher Zusi,Gentles, Robert,Ding, Min,Pearce, Bradley C.,Easton, Amy,Kostich, Walter A.,Seager, Matthew A.,Bourin, Clotilde,Bristow, Linda J.,Johnson, Kim A.,Miller, Regina,Hogan, John,Whiterock, Valerie,Gulianello, Michael,Ferrante, Meredith,Huang, Yanling,Hendricson, Adam,Alt, Andrew,Macor, John E.,Bronson, Joanne J.
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p. 496 - 513
(2016/12/30)
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- 1,2,4-TRIAZOLO[4,3-A]PYRIDINE COMPOUNDS AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel 1,2,4-triazolo[4,3-a]pyridine compounds of formula (I) as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor subtype 2 ("mGluR2"). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of disorders in which mGluR2 subtype of metabotropic receptors is involved.
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Page/Page column 31
(2016/07/05)
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- TRIAZOLOPYRIDINE ETHER DERIVATIVES AND THEIR USE IN NEUROLOGICAL AND PYSCHIATRIC DISORDERS
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The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds modulate the mGluR2 receptor and may be useful for the treatment of various disorders of the central nervous system.
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Page/Page column 57
(2015/04/15)
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- 1,2,4-TRIAZOLO[4,3-a]PYRIDINE COMPOUNDS AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel 1,2,4-triazolo[4,3-a]pyridine compounds of Formula (I) as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor subtype 2 ("mGluR2"). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of mGluR2 subtype disorders.
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Page/Page column 33
(2015/03/28)
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- COMBINATIONS COMPRISING POSITIVE ALLOSTERIC MODULATORS OR ORTHOSTERIC AGONISTS OF METABOTROPIC GLUTAMATERGIC RECEPTOR SUBTYPE 2 AND THEIR USE
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The present invention relates to combinations comprising a positive allosteric modulator ("PAM") of metabotropic glutamatergic receptor subtype 2 ("mGluR2") or a pharmaceutically acceptable salt or a solvate thereof, or an orthosteric agonist of metabotropic glutamatergic receptor subtype 2 compound or a pharmaceutically acceptable salt or a solvate thereof, and a synaptic vesicle protein 2A ("SV2A") ligand.
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Page/Page column 56
(2015/08/06)
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- 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 (“mGluR2”), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Paragraph 0136; 0137
(2013/10/07)
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- RADIOLABELLED mGluR2 PET LIGANDS
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The present invention relates to novel, selective, radiolabelled mGluR2 ligands which are useful for imaging and quantifying the metabotropic glutamate receptor mGluR2 in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.
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Paragraph 0166
(2013/09/12)
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- RADIOLABELLED mGLuR2 PET LIGANDS
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The present invention relates to novel, selective, radiolabelled mGluR2 ligands which are useful for imaging and quantifying the metabotropic glutamate receptor mGluR2 in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.
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Page/Page column 26-27
(2012/05/31)
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- 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2"), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Page/Page column 35
(2012/05/31)
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- 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel triazolo [4,3-a]pyridine derivatives of Formula (I), wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2"), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Page/Page column 39-40
(2012/05/31)
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- 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2"), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Page/Page column 38
(2012/05/31)
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- Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8- trifluoromethyl[1,2,4]triazolo[4,3- a ]pyridine (JNJ-42153605): A positive allosteric modulator of the metabotropic glutamate 2 receptor
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Advanced leads from a series of 1,2,4-triazolo[4,3-a]pyridines with mGlu2 receptor PAM activity are reported. By modification of the analogous imidazo[1,2-a]pyridine series, the newly reported leads have improved potency, in vitro ADMET, and hERG as well
- Cid, Jose María,Tresadern, Gary,Vega, Juan Antonio,De Lucas, Ana Isabel,Matesanz, Encarnación,Iturrino, Laura,Linares, María Lourdes,Garcia, Aránzazu,Andrés, José Ignacio,MacDonald, Gregor J.,Oehlrich, Daniel,Lavreysen, Hilde,Megens, Anton,Ahnaou, Abdellah,Drinkenburg, Wilhelmus,MacKie, Claire,Pype, Stefan,Gallacher, David,Trabanco, Andrés A.
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p. 8770 - 8789
(2013/01/15)
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- 1,2,4-TRIAZOLO[4,3-A]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2"), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Page/Page column 54
(2010/12/17)
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- 7-ARYL-1,2,4-TRIAZOLO[4,3-A]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2"), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Page/Page column 54
(2010/12/17)
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- 1,2,3-TRIAZOLO [4,3-A] PYRIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OR PREVENTION OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
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The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 ("mGluR2"), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
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Page/Page column 105-106
(2010/12/17)
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