1474050-82-2

Upstream product

• 868171-66-8 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid methyl ester 
• 25991-27-9 methyl 2-oxo-2H-pyrane-3-carboxylate 
• 868171-67-9 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 
• 371-40-4 4-fluoroaniline 
• 1003-29-8 2-pyrrole aldehyde 

Relevant academic research and scientific papers

Bioisosteric replacement of an acylureido moiety attached to an indolin-2-one scaffold with a malonamido or a 2/4-pyridinoylamido moiety produces a selectively potent Aurora-B inhibitor

Bioisosteric replacement of acylureido moiety in 6-acylureido-3- pyrrolylmethylidene-2-oxoindoline derivatives resulted in a series of malonamido derivatives with indolin-2-one scaffold (11-14). Further conformational restrictions of the malonamido moiety led to 2-oxo-1,2-dihydropyridine (21-25) or a 4-oxo-1,4-dihydropyridine derivatives (31-36). 4-Oxo-1,4-dihydropyridine derivatives were more potent Aurora B inhibitors than their 2-oxo-1,2- dihydropyridine counterparts and demonstrated cytotoxicities against A549 and HepG2 cells in the submicromolar range. In A549 cells, 31h decreased phosphorylation of histone H3, triggered polyploidy, induced expression of pro-apoptotic Fas and FasL with subsequent activation of caspase 8, resulting into apoptosis. In a Huh7-xenograft mouse model, 31h demonstrated potent in vivo efficacy with a daily dose of 5 mg/kg.

INDOLIN-2-ONE DERIVATIVES AS PROTEIN KINASE INHIBITORS

A novel class of indoline-2-one derivatives are disclosed. These compounds are protein kinase inhibitors which are useful for treating hyperproliferative diseases such as cancer.