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

Bioorg Med Chem

Department of Medicinal Chemistry, Piramal Life Sciences Limited, 1, Nirlon Complex, Off Western Express Highway, Goregaon (E), Mumbai 400063, India.

Published: August 2008

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2008.06.042DOI Listing

Publication Analysis

Top Keywords

pyrazolo[34-b]pyridines structural
8
structural analogues
8
tnf-alpha il-6
8
synthesis evaluation
4
evaluation pyrazolo[34-b]pyridines
4
analogues tnf-alpha
4
il-6
4
il-6 inhibitors
4
inhibitors article
4
article synthesized
4

Similar Publications

Pim-1 kinase targeted recently has proved an essential goal of breast cancer therapy. We report the design, synthesis with full characterization analysis of pyrazolo[3,4-b]pyridine scaffold-based derivatives targeting Pim-1 kinase as anti-breast cancer agents. All the newly synthesized compounds were screened for their in vitro cytotoxic activity against two breast cancer cell lines MCF-7 and MDA-MB-231, and non-cancerous MCF-10A cells.

View Article and Find Full Text PDF

Synthesis and discovery of pyrazolo-pyridine analogs as inflammation medications through pro- and anti-inflammatory cytokine and COX-2 inhibition assessments.

Bioorg Chem

January 2020

Research and Development Centre, Bharathiar University, Coimbatore 641046, India; Department of Chemistry, Adhiyamaan College of Engineering, Hosur 635109, India. Electronic address:

This article briefs about the efforts taken to synthesis, characterize and develop (E)-5-methyl-2-phenyl-3-(thiophen-2-yl)-7-(thiophen-2-ylmethylene)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine and their analogs. In the two-step reaction, the first step is the synthesis of (3Z,5E)-1-methyl-3,5-bis(thiophen-2-ylmethylene)piperidin-4-one derivatives (3a-l) by stirring the mixture of 1-methylpiperidin-4-one and substituted thiophene-carbaldehydes in presence of methanol. In the second and final step, compounds 3a-l were refluxed with phenyl-hydrazine to achieve the target compounds (E)-5-methyl-2-phenyl-3-(thiophen-2-yl)-7-(thiophen-2-ylmethylene)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine and their analogs (5a-l) in good yield.

View Article and Find Full Text PDF

A number of 4-aminopyrazolo[3,4-b]pyridines 5-carboxylic acid esters (2-8) were synthesized and evaluated for their binding affinity at the A1, A2A, and A3 adenosine receptors (AR), in bovine cortical membranes, as well as for their affinity toward human A1AR (hA1AR). Some of the new compounds were characterized by a high affinity and selectivity toward the A1 receptor subtype, showing a significant improvement in comparison with other pyrazolo-pyridines previously reported in the literature. In particular the methyl ester 2h as well as the isopropyl ester 5h, both of them bearing a p-methoxyphenylethylamino side chain at the position 4, presented Ki values of 6 and 7 nM, respectively.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!