101860-97-3Relevant articles and documents
7,7′-Diazaindirubin - A small molecule inhibitor of casein kinase 2 in vitro and in cells
Cheng, Xinlai,Merz, Karl-Heinz,Vatter, Sandra,Christ, Jochen,W?lfl, Stefan,Eisenbrand, Gerhard
, p. 247 - 255 (2014/01/17)
Aza- and diaza-bisindoles were synthesized by coupling of 7-azaisatin, 7-azaoxindol, 7-azaindoxyl acetate, and their non-aza counterparts, respectively. Whereas 7,7′-diazaindigo (10) and 7,7′-diazaisoindigo (11) did not show antiproliferative activity in several human tumor cell lines up to 100 μM, 7-azaindirubin (12) and 7′-azaindirubin (13) were more active than the parent molecule, indirubin, in LXFL529L cells (human large cell lung tumor xenograft), and 7,7′-diazaindirubin (14) was exhibiting substantially enhanced growth inhibitory activity in these cells. In the NCI 60 cell line panel, 14 displayed antiproliferative activity preferentially in certain melanoma and non-small cell lung cancer cells. In contrast to the potent serine/threonine/tyrosine kinase inhibition observed for indirubins, kinase inhibition profiling of 14 in 220 kinases revealed largely a loss of kinase inhibitory activity towards most kinases, with retained inhibitory activity for just a few kinases. At 1 μM concentration, especially casein kinases CK1γ3, CK2α, CK2α2, and SIK were inhibited by more than 50%. In cell-based assays, 14 markedly affected CK2-mediated signaling in various human tumor cells. In MCF7 cells, 14 induced cell cycle arrest at G1 and G2/M and apoptosis, whereas CK2-deficient MCF7 cells were resistant. These findings reveal a novel key mechanism of action for 14, suggesting primarily CK2 inhibition to be causally related to growth inhibition of human tumor cells.
7-azaindirubins, 7'-azaindirubins, 7-7'-diazaindirubin and the corresponding 3'-oxime ether derivates: production thereof, their production and use as a medicament
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Page/Page column 10, (2010/07/06)
The present invention relates to 7-azaindirubins (1), 7'-azaindirubins (2), and 7,7'-diaza-indirubins (3), wherein E, R1 and R2 have the meanings detailed in the description, their production and use as a medicament for treating cancer, neurodegenerative diseases, bipolar disorders, inflammatory and infectious diseases, including viral diseases. Depending on structure, these indirubins act as inhibitors of various kinases involved in tumor cell growth, and, most notably, as inhibitors of human tumor cell proliferation. As compared to indirubins bearing identical substituents but no hetero atoms in position 7 and 7', the activity of the compounds according to the present invention is increased and the propensity to get metabolized by CYP450s is reduced, resulting in improved metabolic stability.
Substituted 1-H-pyrrolopyridine-3-carboxamides
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, (2008/06/13)
Substituted 1H-pyrrolopyridine-3-carboxamides and their use in pharmaceutical compositions and in treating inflammation are disclosed.
Substituted 1,3-Dihydro-2H-pyrrolopyridin-2-ones as Potential Antiinflammatory Agents
Ting, Pauline C.,Kaminski, James J.,Sherlock, Margaret H.,Tom, Wing C.,Lee, Joe F.,et al.
, p. 2697 - 2706 (2007/10/02)
A series of analogues based on the 1,3-dihydro-2H-pyrrolopyridin-2-one ring system have been synthesized and shown to possess oral antiinflammatory activity in both the reverse passive Arthus reaction (RPAR) pleural cavity assay in rats and in the adjuvant-induced arthritic rat model (AAR).Several members of this series additionally exhibit an inhibitory effect on the in vivo production of prostaglandin- and leukotriene-derived products or arachidonic acid metabolism although these compounds exhibit no significant inhibitory activity against the cyclooxygenase and 5-lipoxygenase enzymes in vitro.Structure-activity relationships in this series are discussed.
