1127499-56-2

Upstream product

• 771-99-3 4-phenylpiperidine 
• 1127499-07-3 4-bromo-1-(cyclopropylmethyl)-1,2-dihydropyridin-2-one 
• 1127499-35-7 4-benzyloxy-1-cyclopropylmethyl-3-trifluoromethyl-1H-pyridin-2-one 
• 1127499-32-4 4-benzyloxy-1-cyclopropylmethyl-3-iodo-1H-pyridin-2-one 
• 1127499-01-7 4-benzyloxy-1-cyclopropylmethyl-1H-pyridin-2-one 
• 1127499-38-0 1-cyclopropylmethyl-4-hydroxy-3-trifluoromethyl-1H-pyridin-2-one 
• 53937-02-3 4‐benzyloxy‐2‐hydroxy‐pyridine 

Downstream Products

• 1127498-00-3 3-chloro-1-(cyclopropylmethyl)-4-(4-phenyl-1-piperidyl)pyridin-2-one 
• 1127498-06-9 3'-bromo-1'-cyclopropylmethyl-4-phenyl-3,4,5,6-tetrahydro-2H,1'H-[1,4']bipyridinyl-2'-one 

Relevant academic research and scientific papers

Discovery of 1-butyl-3-chloro-4-(4-phenyl-1-piperidinyl)-(1 H)-pyridone (JNJ-40411813): A novel positive allosteric modulator of the metabotropic glutamate 2 receptor

We previously reported the discovery of 4-aryl-substituted pyridones with mGlu2 PAM activity starting from the HTS hit 5. In this article, we describe a different exploration from 5 that led to the discovery of a novel subseries of phenylpiperidine-substituted pyridones. The optimization strategy involved the introduction of different spacers between the pyridone core and the phenyl ring of 5. The fine tuning of metabolism and hERG followed by differentiation of advanced leads that were identified on the basis of PK profiles and in vivo potency converged on lead compound 36 (JNJ-40411813). Full in vitro and in vivo profiles indicate that 36 displayed an optimal interplay between potency, selectivity, favorable ADMET/PK and cardiovascular safety profile, and central EEG activity. Compound 36 has been investigated in the clinic for schizophrenia and anxious depression disorders.

1',3'-DISUBSTITUTED-4-PHENYL-3,4,5,6-TETRAHYDRO-2H, 1'H-[1, 4'] BIPYRIDINYL-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.