950201-75-9

Upstream product

• 106-41-2 4-bromo-phenol 
• 3678-63-5 4-chIoro-2-methylpyridine 
• 950201-74-8 4-(4-bromophenoxy)-2-methylpyridine 
• 73183-34-3 bis(pinacol)diborane 

Downstream Products

• 1362702-70-2 1-cyclobutylmethyl-4-[4-(2-methylpyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carbonitrile 
• 1362702-68-8 1-isopentyl-4-[4-(2-methylpyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carbonitrile 
• 1128148-85-5 1-butyl-3-chloro-4-[4-(2-methylpyridin-4-yloxy)phenyl]-1H-pyridin-2-one 

Relevant academic research and scientific papers

Discovery of 1,4-disubstituted 3-cyano-2-pyridones: A new class of positive allosteric modulators of the metabotropic glutamate 2 receptor

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.

1,3-DISUBSTITUTED 4-(ARYL-X-PHENYL)-1H-PYRIDIN-2-ONES

The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I), wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors - subtype 2 ("mGluR2") which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

1,4-DISUBSTITUTED 3-CYANO-PYRIDONE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2-RECEPTORS

The present invention relates to novel compounds, in particular novel pyridinone de- rivat ives according to Formula (I) wherein all radicals are defined in the application and claims. The compounds accord- ing to the invention are positive allosteric mod