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3,6-二氨基-1H-吡唑并[3,4-b]吡啶衍生物作为蛋白激酶抑制剂的合成及生物学评价

Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors.

作者信息

Chioua Mourad, Samadi Abdelouahid, Soriano Elena, Lozach Olivier, Meijer Laurent, Marco-Contelles José

机构信息

Laboratorio de Radicales Libres y Química Computacional (IQOG, CSIC), 28006 Madrid, Spain.

出版信息

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4566-9. doi: 10.1016/j.bmcl.2009.06.099. Epub 2009 Jul 3.

Abstract

The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC(50) (microM) DYRK1A=11; CDK5=0.41; GSK-3=1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer's disease.

摘要

报道了多种不同取代的3,6-二氨基-1H-吡唑并[3,4-b]吡啶衍生物的合成及生物学评价。根据对一系列与疾病相关的蛋白激酶的抑制结果[IC(50)(μM):DYRK1A = 11;CDK5 = 0.41;GSK-3 = 1.5],我们观察到3,6-二氨基-4-苯基-1H-吡唑并[3,4-b]吡啶-5-腈(4)在寻找治疗阿尔茨海默病的药物方面构成了一种潜在的新型简单先导化合物。

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