Bharate Sandip B, Mahajan Tushar R, Gole Yogesh R, Nambiar Mahesh, Matan T T, Kulkarni-Almeida Asha, Balachandran Sarala, Junjappa H, Balakrishnan Arun, Vishwakarma Ram A
Department of Medicinal Chemistry, Piramal Life Sciences Limited, 1, Nirlon Complex, Off Western Express Highway, Goregaon (E), Mumbai 400063, India.
Bioorg Med Chem. 2008 Aug 1;16(15):7167-76. doi: 10.1016/j.bmc.2008.06.042. Epub 2008 Jun 26.
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.
在本文中，我们采用了一种新颖的合成策略，通过5,6-二氢-4H-吡喃-3-甲醛/2-甲酰基-3,4,6-三-O-甲基-D-葡萄糖醛/色酮-3-甲醛与杂环芳胺的一锅缩合反应，合成了三种不同系列的吡唑并[3,4-b]吡啶及其结构类似物。对所有合成的化合物进行了针对肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的抗炎活性评估。在筛选的28种化合物中，40、51、52和56在10微摩尔浓度下对IL-6表现出有前景的活性，抑制率为60 - 65%。其中，51、52和56显示出强效的IL-6抑制活性，其半数抑制浓度（IC50）分别为0.2、0.3和0.16微摩尔。化合物56在浓度大于100微摩尔时对CCK-8细胞无细胞毒性。
