Biological Activity
KRIBB11 is an inhibitor of the transcription factor He at Shock Factor 1 (HSF1) with an IC50 value of 1.2 μM. KRIBB11 blocks induction of HSF1 downstream target proteins such as HSP27 and HSP70 by impairing the recruitment of Positive Transcription Elongation Factor b (P-TEFb) to the HSF1 transcriptional complex, preventing HSF1-mediated gene expression KRIBB11 inhibits tumor growth in vivo and acts synergistically to increase apoptosis in cancer cells treated with the HSP90 inhibitors Geldanamycin and 17-AAG.', 'KRIBB11 is capable of preventing the proliferation of cancer cells. It has the ability to stimulate apoptosis and can arrest the cell cycle at G2/M phase.
Synthesis
Example 3 Preparation of N2-(1H-indazol-5-yl)-N6-methyl-3-nitropyridine-2,6-diamine
To a reaction flask containing methanol with 40% aqueous methylamine (20 mL) was added 2-(1H-indazol-5-ylamino)-6-methoxy-3-nitropyridine (1 g) obtained by Example 1. The reaction mixture was stirred at 25°C for 1 hour. Subsequently, deionized water (20 mL) was slowly added to the reaction mixture and stirring was continued for 1 hour. After completion of the reaction, the reaction mixture was filtered and the solid product was washed with 30% aqueous methanol (5 mL). The resulting solid product was dried under vacuum at 50-60 °C to afford the target compound N2-(1H-indazol-5-yl)-N6-methyl-3-nitropyridine-2,6-diamine (0.82 g, 82% yield). Melting point: 238-240 °C. 1H-NMR (DMSO-d6, δ, ppm): 2.86 (d, 3H), 6.09 (d, 1H), 7.51 (d, 1H), 7.57 (d, 1H), 8.05 (t, 2H), 8.24 (d, 2H), 10.97 (s, 1H), 13.05 (br s, 1H).
