478063-68-2

Upstream product

• 478063-65-9 methyl 4-oxo-1-[3-(trifluoromethyl)phenyl]-1,4-dihydropyridazine-3-carboxylate 
• 98-16-8 3-trifluoromethylaniline 
• 339018-16-5 methyl 3-oxo-2-{[3-(trifluoromethyl)phenyl]hydrazono}butanoate 

Downstream Products

• 1238702-03-8 N-methoxy-N-methyl-4-oxo-1-[3-(trifluoromethyl)phenyl]-1,4-dihydropyridazine-3-carboxamide 
• 1238696-25-7 3-(2-phenyl-3-furyl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one 
• 1238702-13-0 3-bromo-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one 

Relevant academic research and scientific papers

Discovery of 1-[2-Fluoro-4-(1 H -pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1 H -pyrazol-5-yl)pyridazin-4(1 H)-one (TAK-063), a highly potent, selective, and orally active phosphodiesterase 10A (PDE10A) inhibitor

A novel series of pyridazinone-based phosphodiesterase 10A (PDE10A) inhibitors were synthesized. Our optimization efforts using structure-based drug design (SBDD) techniques on the basis of the X-ray crystal structure of PDE10A in complex with hit compound 1 (IC50 = 23 nM; 110-fold selectivity over other PDEs) led to the identification of 1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (27h). Compound 27h has potent inhibitory activity (IC50 = 0.30 nM), excellent selectivity (>15000-fold selectivity over other PDEs), and favorable pharmacokinetics, including high brain penetration, in mice. Oral administration of compound 27h to mice elevated striatal 3,5-cyclic adenosine monophosphate (cAMP) and 3,5-cyclic guanosine monophosphate (cGMP) levels at 0.3 mg/kg and showed potent suppression of phencyclidine (PCP)-induced hyperlocomotion at a minimum effective dose (MED) of 0.3 mg/kg. Compound 27h (TAK-063) is currently being evaluated in clinical trials for the treatment of schizophrenia.

Pyridazinone compounds

The present invention provides a compound which has the effect of PDE inhibition, and which is useful as a medicament for preventing or treating schizophrenia or so on. A compound of formula (I0): wherein R1 represents a substituent, R2 represents a hydrogen atom, or a substituent, R3 represents a hydrogen atom, or a substituent, Ring A represents an aromatic ring which can be substituted, and Ring B represents a 5-membered heteroaromatic ring which can be substituted, or a salt thereof.