856256-81-0Relevant articles and documents
Discovery of a Selective and CNS Penetrant Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 3 with Antidepressant and Anxiolytic Activity in Rodents
Engers, Julie L.,Rodriguez, Alice L.,Konkol, Leah C.,Morrison, Ryan D.,Thompson, Analisa D.,Byers, Frank W.,Blobaum, Anna L.,Chang, Sichen,Venable, Daryl F.,Loch, Matthew T.,Niswender, Colleen M.,Daniels, J. Scott,Jones, Carrie K.,Conn, P. Jeffrey,Lindsley, Craig W.,Emmitte, Kyle A.
, p. 7485 - 7500 (2015)
Previous preclinical work has demonstrated the therapeutic potential of antagonists of the group II metabotropic glutamate receptors (mGlus). Still, compounds that are selective for the individual group II mGlus (mGlu2 and mGlu3) hav
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
Conde-Ceide, Susana,Alcázar, Jesús,Alonso De Diego, Sergio A.,López, Silvia,Martín-Martín, María Luz,Martínez-Viturro, Carlos M.,Pena, Miguel-Angel,Tong, Han Min,Lavreysen, Hilde,MacKie, Claire,Bridges, Thomas M.,Daniels, J. Scott,Niswender, Colleen M.,Jones, Carrie K.,MacDonald, Gregor J.,Steckler, Thomas,Conn, P. Jeffrey,Stauffer, Shaun R.,Lindsley, Craig W.,Bartolomé-Nebreda, José Manuel
supporting information, p. 429 - 434 (2016/01/09)
As part of our efforts to identify a suitable back-up compound to our recently disclosed mGlu5 positive allosteric modulator (PAM) clinical candidate VU0490551/JNJ-46778212, this letter details the investigation and challenges of a novel series of 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one derivatives. From these efforts, compound 4k emerged as a potent and selective mGlu5 PAM displaying overall attractive in vitro (pharmacological and ADMET) and PK profiles combined with in vivo efficacy in preclinical models of schizophrenia. However, further advancement of the compound was precluded due to severely limiting CNS-related side-effects confirming the previously reported association between excessive mGlu5 activation and target-related toxicities.
Discovery and SAR of a novel series of metabotropic glutamate receptor 5 positive allosteric modulators with high ligand efficiency
Turlington, Mark,Noetzel, Meredith J.,Bridges, Thomas M.,Vinson, Paige N.,Steckler, Thomas,Lavreysen, Hilde,Mackie, Claire,Bartolomé-Nebreda, José M.,Conde-Ceide, Susana,Tong, Han Min,Macdonald, Gregor J.,Daniels, J. Scott,Jones, Carrie K.,Niswender, Colleen M.,Conn, P. Jeffrey,Lindsley, Craig W.,Stauffer, Shaun R.
, p. 3641 - 3646 (2014/07/22)
We report the optimization of a series of novel metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs) from a 5,6-bicyclic class of dihydropyrazolo[1,5-a]pyridin-4(5H)-ones containing a phenoxymethyl linker. Studies foc
SUBSTITUTED BICYCLIC CYCLOALKYL PYRAZOLE LACTAM ANALOGS AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
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Paragraph 00392, (2014/01/09)
In one aspect, the invention relates to substituted bicyclic cycloalkyl pyrazole lactam analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
SUBSTITUTED BICYCLIC ARALKYL PYRAZOLE LACTAM ANALOGS AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
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Paragraph 00574; 00400, (2014/01/09)
In one aspect, the invention relates to substituted bicyclic aralkyl pyrazole lactam analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
BICYCLIC PYRAZOLE COMPOUNDS AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
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Page/Page column 142, (2012/06/30)
In one aspect, the invention relates to bicyclic pyrazole compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the
BICYCLIC TRIAZOLE AND PYRAZOLE LACTAMS AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
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Page/Page column 246, (2012/06/30)
In one aspect, the invention relates to bicyclic triazole and pyrazole lactams, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for
Pyrrole and pyrazole DAAO inhibitors
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Page/Page column 22, (2008/06/13)
Methods for increasing D-Serine concentration and reducing concentration of the toxic products of D-Serine oxidation, for enhancing learning, memory and/or cognition, or for treating schizophrenia, Alzheimer's disease, ataxia or neuropathic pain, or preventing loss in neuronal function characteristic of neurodegenerative diseases involve administering to a subject in need of treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof: wherein R1 and R2 are independently selected from hydrogen, halo, nitro, alkyl, acyl, alkylaryl, and XYR5; or R1 and R2, taken together, form a 5, 6, 7 or 8-membered substituted or unsubstituted carbocyclic or heterocyclic group; X and Y are independently selected from O, S, NH, and (CR6R7)n; R3 is hydrogen, alkyl or M+; M is aluminum, calcium, lithium, magnesium, potassium, sodium, zinc ion or a mixture thereof; Z is N or CR4; R4 is from selected from hydrogen, halo, nitro, alkyl, alkylaryl, and XYR5; R5 is selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl; R6 and R7 are independently selected from hydrogen and alkyl; n is an integer from 1 to 6; at least one of R1, R2 and R4 is other than hydrogen; and at least one of X and Y is (CR6R7)n. D-serine or cycloserine may be coadministered along with the compound of formula I.
