95629-02-0Relevant articles and documents
Further optimization of the mGlu5 PAM clinical candidate VU0409551/JNJ-46778212: Progress and challenges towards a back-up compound
Zhou, Ya,Malosh, Chrysa,Conde-Ceide, Susana,Martínez-Viturro, Carlos Manuel,Alcázar, Jesus,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.,Bartolomé-Nebreda, José Manuel,Lindsley, Craig W.
, p. 3515 - 3519 (2015/08/06)
This Letter describes the progress and challenges in the continued optimization of the mGlu5 positive allosteric modulator (PAM) clinical candidate VU0490551/JNJ-46778212. While many analogs addressed key areas for improvement, no one compound possessed the amalgamation of improvements needed within the (2(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridine-5(4H)-yl(aryl)methanone scaffold to advance as a back-up clinical candidate. However, many analogs displayed excellent solubility and physiochemical properties, and were active in the amphetamine-induced hyperlocomotion (AHL) model. Moreover, the SAR was robust for this series of PAMs, and both polar and hydrogen-bond donors were found to be tolerated, leading to analogs with overall attractive profiles and good ligand efficiencies. Graphical abstract
BICYCLIC OXAZOLE AND THIAZOLE COMPOUNDS AND THEIR USE AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
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Page/Page column 124, (2012/03/26)
In one aspect, the invention relates to novel bicyclic oxazole and thiazole compounds which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 ("mGluR5"); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions; and methods for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. 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 SULFONAMIDE DERIVATIVES
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Page/Page column 143, (2009/11/29)
The invention relates to substituted sulfonamide derivatives, processes for the preparation thereof, medicaments containing these compounds and the use of substituted sulfonamide derivatives for the preparation of medicaments.
Dynamic kinetic resolution allows a highly enantioselective synthesis of cis-α-aminocycloalkanols by ruthenium-catalyzed asymmetric hydrogenation
Liu, Sheng,Xie, Jian-Hua,Wang, Li-Xin,Zhou, Qi-Lin
, p. 7506 - 7508 (2008/09/17)
(Chemical Equation Presented) Resolutely dynamic hydrogenation: A highly efficient asymmetric hydrogenation of racemic N,N-disubstituted α-aminocycloalkanones involving dynamic kinetic resolution in the presence of a ruthenium catalyst gives chiral α-aminocycloalkanols with excellent enantioselectivities and cis diastereoselectivities (see scheme). A synthesis of optically pure U-(-)-50488 based on this reaction is reported.
N-acylamino acid amide compounds and intermediates for preparation thereof
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, (2008/06/13)
The present invention discloses the compound represented by the formula (I): wherein A represents the following formula (a-1) or the following formula (a-2): B represents the following formula (b): (wherein the symbols are each as defined in the specification) or a pharmaceutically acceptable salts thereof, and intermediates for the preparation thereof, which have excellent platelet aggregation inhibitory activity and other properties and useful as prophylactic or therapeutic agents for diseases associated with a fibrinogen receptor, thrombosis, infarction and the like.
Novel N-(3-hydroxy-4-piperidinyl)benzamide derivatives
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, (2008/06/13)
Novel N-(3-hydroxy-4-piperidinyl)benzamides and derivatives thereof, said compounds being useful as stimulators of the motility of the gastro-intestinal system.