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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http://dx.doi.org/10.1016/j.bmc.2008.06.042 | DOI Listing |
Bioorg Med Chem
December 2020
Department of Chemistry, Faculty of Science, Zagazig University, Egypt.
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 PDFBioorg 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 PDFJ Med Chem
November 2005
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Aldo Moro, I-53100 Siena, Italy.
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.
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