2. Academic Validation
  3. Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural analogues as TNF-alpha and IL-6 inhibitors

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

  • Bioorg Med Chem. 2008 Aug 1;16(15):7167-76. doi: 10.1016/j.bmc.2008.06.042.
Sandip B Bharate 1,  Tushar R Mahajan,  Yogesh R Gole,  Mahesh Nambiar,  T T Matan,  Asha Kulkarni-Almeida,  Sarala Balachandran,  H Junjappa,  Arun Balakrishnan,  Ram A Vishwakarma
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Piramal Life Sciences Limited, 1, Nirlon Complex, Off Western Express Highway, Goregaon (E), Mumbai 400063, India.
PMID: 18625560 DOI: 10.1016/j.bmc.2008.06.042
Abstract

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-alpha 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 microM concentration. Amongst these, 51, 52 and 56 showed potent IL-6 inhibitory activity with IC(50)'s of 0.2, 0.3 and 0.16 microM, respectively. Compound 56 was not cytotoxic in CCK-8 cells up to the concentration of >100 microM.

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