882974-64-3

Upstream product

• 882974-16-5 6-[2-(4-fluorophenyl)-2-oxoethyl]-2,3-dihydropyridazin-3-one 
• 107-21-1 ethylene glycol 
• 882974-10-9 2-(6-chloropyridazin-3-yl)-1-(4-fluorophenyl)ethan-1-one 
• 451-46-7 4-fluorobenzoic acid ethyl ester 
• 1121-79-5 3-chloro-6-methylpyridazine 

Downstream Products

• 928343-61-7 6-[2-(4-fluorophenyl)-6-(hydroxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one 
• 928345-68-0 6-{3-(4-fluorophenyl)-5-[(2-hydroxyethyl)amino]-1H-pyrazol-4-yl}-2-(2-methylphenyl)pyridazin-3(2H)-one 
• 1397261-96-9 6-[3-(4-fluorophenyl)-5-(3-hydroxypropoxy)-1H-pyrazol-4-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one 
• 1397261-97-0 6-[5-{[(2R)-2,3-dihydroxypropyl]amino}-3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one 
• 928345-25-9 (2S)-6-(5-{[2-(benzyloxy)-3-hydroxypropyl]amino}-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-2-(2-methylphenyl)-3(2H)-pyridazinone 
• 928345-37-3 ethyl 3-({3-(4-fluorophenyl)-4-[1-(2-methylphenyl)-6-oxo-1,6-dihydropyridazin-3-yl]-1H-pyrazol-5-yl}amino)-2-(hydroxymethyl)propanoate 
• 928344-12-1 A⁽⁴⁰⁴⁾S₁₉₇₇ 
• 928344-13-2 (S)-6-[2-(4-fluorophenyl)-6-(hydroxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-tolyl)-2,3-dihydropyridazin-3-one 
• 928343-62-8 6-[2-(4-fluorophenyl)-6-(iodomethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one 
• 928344-82-5 6-[2-(4-fluorophenyl)-6-methylene-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one 
• 882974-67-6 6-[2-(4-fluorophenyl)-2-oxoethyl]-2-(2-tolyl)-2,3-dihydropyridazin-3-one 
• 1397262-02-0 6-{5-[3-(benzyloxy)propoxy]-3-(4-fluorophenyl)-1H-pyrazol-4-yl}-2-(2-methylphenyl)pyridazin-3(2H)-one 

Relevant academic research and scientific papers

Development of a practical and scalable synthesis of a potent p38 mitogen-activated protein kinase inhibitor

Process research and development of a practical and scalable synthetic method toward a potent inhibitor of p38 mitogen-activated protein kinase 1 is described. The medicinal chemistry synthetic method had several issues in scale-up synthesis. In contrast, the synthetic method described here does not require purification by column chromatography for all steps, and the formation of impurities is suppressed well. Aminopyrazole ring formation was achieved by reaction between a new chiral amine building block 7 and bromoketone unit 4 as a key reaction. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of 1·HBr.

Identification, synthesis, and biological evaluation of 6-[(6 R)-2-(4-fluorophenyl)-6-(hydroxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a ]pyrimidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2 H)-one (AS1940477), a potent p38 MAP kinase inhibitor

Several p38 MAPK inhibitors have been shown to effectively block the production of cytokines such as IL-1β, TNFα, and IL-6. Inhibitors of p38 MAP kinase therefore have significant therapeutic potential for the treatment of autoimmune disease. Compound 2a was identified as a potent TNFα production inhibitor in vitro but suffered from poor oral bioavailability. Structural modification of 2a led to the discovery of tetrahydropyrazolopyrimidine derivatives, exemplified by compound 3, with an improved pharmacokinetic profile. We found that blocking metabolism at the methyl group of the amine and constructing the tetrahydropyrimidine core were important to obtaining compounds with good biological profiles and oral bioavailability. Pursuing the structure-activity relationships of this series led to the discovery of AS1940477 (3f), with excellent cellular activity and a favorable pharmacokinetic profile. This compound represents a highly potent inhibitor of p38 MAP kinase with regard to in vivo activity in an adjuvant-induced arthritis model.

PYRIDAZINONE DERIVATIVES USED FOR THE TREATMENT OF PAIN

A pyridazinone derivative compound shown by the following formula (I): wherein R1 is selected from hydrogen, etc.; R2 is selected from substituted or unsubstituted aryl, etc.; R3 is hydrogen, etc.;p is 0, 1 or 2; R4/

PYRIDAZINONE DERIVATIVES CYTOKINES INHIBITORS

A pyridazinone derivative shown by the following formula (I): wherein; which is useful as a medicament for cytokines mediated diseases.