1380507-49-2Relevant academic research and scientific papers
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
, 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.
SUBSTITUTED BICYCLIC CYCLOALKYL PYRAZOLE LACTAM ANALOGS AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
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, (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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, (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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, (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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, (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
