86847-66-7Relevant 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.
Chemical synthesis of azaindoles
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, (2008/06/13)
The present invention relates to a process for the preparation of azaindole derivatives of the formula STR1 wherein Q is hydrogen, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy, aryl or arylC1-4 alkyl; one of X, Y and Z is --N= and the others are --CH=; R1 is hydrogen, C1-6 alkyl, C2-6 alkenyl or C1-6 alkyl substituted by a group selected from aryl or --NR2 R3 where R2 and R3 each independently represent C1-4 alkyl, or R2 and R3, together with the nitrogen atom to which they are attached, form a 4-7 membered saturated heterocyclic ring, optionally containing in the ring an oxygen or sulphur atom or a group NR4 where R4 is C1-4 alkyl, aryl or arylC1-4 alkyl; and R5 is a hydrogen atom or a group selected from C1-6 alkyl or aryl.
