1403771-21-0Relevant articles and documents
ETHYNYL DERIVATIVES AS MODULATORS OF MGLUR5 RECEPTOR ACTIVITY
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, (2014/05/07)
The present invention relates to ethynyl derivatives of formula (I) wherein Y is N or CH R1 is fluoro or chloro or to a pharmaceutically acceptable acid addition salt, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. It has now surprisingly been found that the compounds of general formula (I) are metabotropic glutamate receptor antagonists (negative allosteric modulators) for use in the treatment of anxiety and pain, depression, Fragile-X syndrom, autism spectrum disorders, Parkinson's disease, and gastroesophageal reflux disease (GERD)
SUBSTITUED 5-(PROP-1-YN-1-YL)PICOLINAMIDE ANALOGS AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
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Paragraph 00506; 00508, (2013/04/13)
In one aspect, the invention relates to substituted 5-(prop-1-yn-1-yl)picolinamide 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.
Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): Discovery of 5-((3-fluorophenyl)ethynyl)- N -(3-methyloxetan-3-yl)picolinamide (ML254)
Turlington, Mark,Noetzel, Meredith J.,Chun, Aspen,Zhou, Ya,Gogliotti, Rocco D.,Nguyen, Elizabeth D.,Gregory, Karen J.,Vinson, Paige N.,Rook, Jerri M.,Gogi, Kiran K.,Xiang, Zixiu,Bridges, Thomas M.,Daniels, J. Scott,Jones, Carrie,Niswender, Colleen M.,Meiler, Jens,Jeffrey Conn,Lindsley, Craig W.,Stauffer, Shaun R.
, p. 7976 - 7996 (2013/11/06)
Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) represent a promising therapeutic strategy for the treatment of schizophrenia. Both allosteric agonism and high glutamate fold-shift have been implicated in the neurotoxic profile of some mGlu5 PAMs; however, these hypotheses remain to be adequately addressed. To develop tool compounds to probe these hypotheses, the structure-activity relationship of allosteric agonism was examined within an acetylenic series of mGlu5 PAMs exhibiting allosteric agonism in addition to positive allosteric modulation (ago-PAMs). PAM 38t, a low glutamate fold-shift allosteric ligand (maximum fold-shift ～3.0), was selected as a potent PAM with no agonism in the in vitro system used for compound characterization and in two native electrophysiological systems using rat hippocampal slices. PAM 38t (ML254) will be useful to probe the relative contribution of cooperativity and allosteric agonism to the adverse effect liability and neurotoxicity associated with this class of mGlu5 PAMs.
