Design, Synthesis and Cancer Cell Line Activities of Pyrazolo[3,4-<i>b</i>]pyridine Derivatives  

作　　者：Mosaad Sayed Mohamed Yara Essam El-Deen Awad Salwa M. El-Hallouty Moustafa El-Araby 

机构地区：[1]Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt [2]Pharmacognosy Department, National Research Centre, Giza, Egypt

出　　处：《Open Journal of Medicinal Chemistry》2012年第3期78-88,共11页药物化学期刊（英文）

摘　　要：Starting from 4,6-dimethyl-2-oxo-(1H)-3-pyridinecarbonitrile 1 and 3-aminopyrazolopyridine 4, a series of cyanopyri- dine derivatives 3a-i, Schiff bases 5a-f, urea and thiourea derivatives 6a-b, amide derivatives 7a-h, pyridopyra- zolopy-rimidine 8a-b and pyridopyrazolotriazine 10a-b were synthesized. Activities of eleven representative compounds were evaluated against A-549 (lung), HEPG2 (liver) and HCT-116 (colon) cancer cell lines. The findings revealed that some of the synthesized compounds showed remarkable anticancer activities, especially 8b which displayed the highest activity among the tested compounds with IC50 equal to 2.9, 2.6 and 2.3 μmol. In addition to synthesis and biological activities, we present discussion about the rationale of the design and activity of the potent compound 8b using struc- ture-based modeling tools.Starting from 4,6-dimethyl-2-oxo-(1H)-3-pyridinecarbonitrile 1 and 3-aminopyrazolopyridine 4, a series of cyanopyri- dine derivatives 3a-i, Schiff bases 5a-f, urea and thiourea derivatives 6a-b, amide derivatives 7a-h, pyridopyra- zolopy-rimidine 8a-b and pyridopyrazolotriazine 10a-b were synthesized. Activities of eleven representative compounds were evaluated against A-549 (lung), HEPG2 (liver) and HCT-116 (colon) cancer cell lines. The findings revealed that some of the synthesized compounds showed remarkable anticancer activities, especially 8b which displayed the highest activity among the tested compounds with IC50 equal to 2.9, 2.6 and 2.3 μmol. In addition to synthesis and biological activities, we present discussion about the rationale of the design and activity of the potent compound 8b using struc- ture-based modeling tools.

关 键 词：PYRIDINE PYRAZOLOPYRIDINE ANTICANCER Activity CDK Inhibitors Kinase Inhibitor 

分 类 号：R73[医药卫生—肿瘤]