1384262-70-7Relevant academic research and scientific papers
MACROCYCLIC INHIBITORS OF PEPTIDYLARGININE DEIMINASES
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Page/Page column 259; 371-372, (2021/11/06)
The present disclosure relates to novel compounds for use in therapeutic treatement of a disease associated with peptidylarginine deiminases (PADs), such as peptidylarginine deiminase type 4 (PAD4). The present disclosure also relates to processes and intermediates for the preparation of such compounds, methods of using such compounds and pharmaceutical compositions comprising the compounds described herein.
Halogenated allyl amine type SSAO/VAP-1 inhibitor and application thereof
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, (2019/06/08)
The invention belongs to the technical field of medicine, and particularly relates to a halogenated allyl amine type compound shown as a formula I, medically acceptable salt, ester or stereo isomers thereof, wherein R1, R2, R3, R4, R5, R6, L1, Cy1, R7 and p are defined in description. The invention also relates to a medicine preparation containing the compounds, a medicine composition containing the compounds, and application of the compounds to prevention and/or treatment on diseases relevant to SSAO/VAP 1 protein or diseases caused by SSAO/VAP 1 protein mediating. The formula I is shown in the description.
Tetrahydronaphthyridine and dihydronaphthyridinone ethers as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu 5)
Turlington, Mark,Malosh, Chrysa,Jacobs, Jon,Manka, Jason T.,Noetzel, Meredith J.,Vinson, Paige N.,Jadhav, Satyawan,Herman, Elizabeth J.,Lavreysen, Hilde,Mackie, Claire,Bartolomé-Nebreda, José M.,Conde-Ceide, Susana,Martín-Martín, M. Luz,Tong, Han Min,López, Silvia,Macdonald, Gregor J.,Steckler, Thomas,Daniels, J. Scott,Weaver, C. David,Niswender, Colleen M.,Jones, Carrie K.,Conn, P. Jeffrey,Lindsley, Craig W.,Stauffer, Shaun R.
, p. 5620 - 5637 (2014/08/05)
Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) represent a promising therapeutic strategy for the treatment of schizophrenia. Starting from an acetylene-based lead from high throughput screening, an evolved bicyclic dihydronaphthyridinone was identified. We describe further refinements leading to both dihydronaphthyridinone and tetrahydronaphthyridine mGlu5 PAMs containing an alkoxy-based linkage as an acetylene replacement. Exploration of several structural features including western pyridine ring isomers, positional amides, linker connectivity/position, and combinations thereof, reveal that these bicyclic modulators generally exhibit steep SAR and within specific subseries display a propensity for pharmacological mode switching at mGlu5 as well as antagonist activity at mGlu3. Structure-activity relationships within a dihydronaphthyridinone subseries uncovered 12c (VU0405372), a selective mGlu5 PAM with good in vitro potency, low glutamate fold-shift, acceptable DMPK properties, and in vivo efficacy in an amphetamine-based model of psychosis.
NAPHTHYRIDINONE ANALOGS AS MGLUR5 POSITIVE ALLOSTERIC MODULATORS
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, (2012/07/14)
In one aspect, the invention relates to naphthyridinone 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.
