Name: AS1940477
Rating: 5 (10 reviews)

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HIT ID:HIT217590949
Cas No:928344-12-1
常用名:AS1940477
IUPAC:6-[(6R)-2-(4-fluorophenyl)-6-(hydroxymethyl)-4H,5H,6H,7H-pyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-methylphenyl)-2,3-dihydropyridazin-3-one
IUPAC:6-[(6R)-2-(4-fluorophenyl)-6-(hydroxymethyl)-4H,5H,6H,7H-pyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-methylphenyl)-2,3-dihydropyridazin-3-one
InChI key:LYHNSWOZRDSWLX-MRXNPFEDSA-N

分子式:C24H22FN5O2
分子量:431.471
氢键供体数 (HBD):
氢键受体数 (HBA):
LogP:
SMILES:Cc1ccccc1-n1nc(ccc1=O)-c1c2NC[C@@H](CO)Cn2nc1-c1ccc(F)cc1
SMILES:Cc1ccccc1-n1nc(ccc1=O)-c1c2NC[C@@H](CO)Cn2nc1-c1ccc(F)cc1

AS1940477 is p38 MAPK inhibitor. AS1940477 inhibited the enzymatic activity of recombinant p38α and β isoforms but showed no effect against other 100 protein kinases including p38γ and δ isoforms. In human peripheral blood mononuclear cells, AS1940477 inhibited lipopolysaccharide (LPS)- or phytohemagglutinin A (PHA)-induced production of proinflammatory cytokines, including TNFα, IL-1β, and IL-6 at low concentrations (LPS/TNFα, IC(50)=0.45n M; PHA/TNFα, IC(50)=0.40 nM). In addition, equivalent concentrations of AS1940477 that inhibited cytokine production also inhibited TNFα- and IL-1 β-induced production of IL-6, PGE(2), and MMP-3 in human synovial stromal cells. AS1940477 was also found to potently inhibit TNF production in whole blood (IC(50)=12 nM) and effectively inhibited TNFα production induced by systemically administered LPS in rats at less than 0.1mg/kg (ED(50)=0.053 mg/kg) with an anti-inflammatory effect lasting for 20h after oral administration. Overall, this stu......

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