Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural analogues as TNF-α and IL-6 inhibitors

In the present article, we have synthesized three different series of pyrazolo[3,4-b]pyridines and their structural analogues using novel synthetic strategy involving one-pot condensation of 5,6-dihydro-4H-pyran-3-carbaldehyde/2-formyl-3,4,6-tri-O-methyl-d-glucal/chromone-3-carbaldehyde with heteroaromatic amines. All synthesized compounds were evaluated for their anti-inflammatory activity against TNF-α and IL-6. Out of 28 compounds screened, 40, 51, 52 and 56 exhibited promising activity against IL-6 with 60–65% inhibition at 10 μM concentration. Amongst these, 51, 52 and 56 showed potent IL-6 inhibitory activity with IC50’s of 0.2, 0.3 and 0.16 μM, respectively. Compound 56 was not cytotoxic in CCK-8 cells up to the concentration of >100 μM.

Three different series of pyrazolo[3,4-b]pyridines were synthesized and evaluated for their anti-inflammatory activity against TNF-α and IL-6. Several compounds showed promising IL-6 inhibitory activity, amongst which most potent analogue has IC50 0.16 μM and is not cytotoxic (IC50 >100 μM).Figure optionsDownload as PowerPoint slide