18085-61-5Relevant academic research and scientific papers
HETEROARYL COMPOUNDS AND THEIR USE AS MER INHIBITORS
-
Paragraph 1994, (2018/04/27)
Compounds of formula (I) [Formula should be inserted here] and a pharmaceutically acceptable salt thereof, wherein A, R1, R2, R3, R4, R5, R6, R7, R24, X, L, n and p are as defined in the specification, are useful for treating or preventing Mer tyrosine kinase receptor modulated disease or conditions. Also described are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.
Discovery of 1,4-disubstituted 3-cyano-2-pyridones: A new class of positive allosteric modulators of the metabotropic glutamate 2 receptor
Cid, Jose María,Duvey, Guillaume,Tresadern, Gary,Nhem, Vanthea,Furnari, Rocco,Cluzeau, Philippe,Vega, Juan Antonio,De Lucas, Ana Isabel,Matesanz, Encarnación,Alonso, José Manuel,Linares, María Lourdes,Andrés, José Ignacio,Poli, Sonia M.,Lutjens, Robert,Himogai, Hassan,Rocher, Jean-Philippe,MacDonald, Gregor J.,Oehlrich, Daniel,Lavreysen, Hilde,Ahnaou, Abdelah,Drinkenburg, Wilhelmus,MacKie, Claire,Trabanco, Andrés A.
experimental part, p. 2388 - 2405 (2012/05/05)
The discovery and characterization of compound 48, a selective and in vivo active mGlu2 receptor positive allosteric modulator (PAM), are described. A key to the discovery was the rational exploration of the initial HTS hit 13 guided by an overlay model built with reported mGlu2 receptor PAM chemotypes. The initial weak in vitro activity of the hit 13 was quickly improved, although compounds still had suboptimal druglike properties. Subsequent modulation of the physicochemical properties resulted in compounds having a more balanced profile, combining good potency and in vivo pharmacokinetic properties. Final refinement by addressing cardiovascular safety liabilities led to the discovery of compound 48. Besides good potency, selectivity, and ADME properties, compound 48 displayed robust in vivo activity in a sleep-wake electroencephalogram (sw-EEG) assay consistent with mGlu2 receptor activation, in accordance with previous work from our laboratories.
Cognition-Activating Properties of 3-(Aryloxy)pyridines
Butler, Donald E.,Poschel, B. P. H.,Marriott, John G.
, p. 346 - 350 (2007/10/02)
A series of 3-(aryloxy)pyridines was found to possess activity in enhancing retention for passive avoidance learning in mice.This test was used to select compounds with potential therapeutic properties for the treatment of cognitive disorders.Reference drugs that gave positive results in this procedure included d-amphetamine, magnesium pemoline, methyl phenidate, picrotoxin, phenytoin, and ethosuximide.All active compounds gave inverted U-shaped doseresponse curves.The most active compounds of the 3-(aryloxy)pyridines included 3-phenoxypyridine (1), 3-(2-fluorophenoxy)pyridine (2), 3-(4-fluorophenoxy)pyridine (4), 3,3'-oxybis(pyridine) (23), and 3,3'-oxybis(pyridine) 1-oxide (24). 3-Phenoxypyridine (1) was clearly superior to all of the analogues tested in terms of the level of retention, grammometric potency, and the breadth of its inverted U-shaped dose-response curve.It was given the designation of CI-844 and after a detailed study of its pharmacological profile was submitted for preclinical toxicology.
