Synthesis of 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3-triazol-4-yl)-substituted pyrazolo[3,4-d]pyrimidin-4-amines via click chemistry: potential inhibitors of the Plasmodium falciparum PfPK7 protein kinase
Synthesis of 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3-triazol-4-yl)-substituted pyrazolo[3,4-d]pyrimidin-4-amines via click chemistry: potential inhibitors of the Plasmodium falciparum PfPK7 protein kinase
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DOI：
10.1039/b906482f
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发表时间：
2009-01-01
影响因子：
3.2
通讯作者：
Grotli, Morten
中科院分区：
文献类型：
--
作者：
Klein, Michael;Diner, Peter;Grotli, Morten
介绍了一锅两步法合成3-（1，2，3-三唑-1-基）-和3-（1，2，3-三唑-4-基）吡唑并[3，4-d]嘧啶-4-胺的有效路线。这两条路线可以很容易地得到两种不同的1，4-二取代三唑异构体，并且目标化合物可以从各种容易获得的芳香族和脂肪族卤化物中获得，而无需分离潜在不稳定的有机叠氮化物中间体。两种化合物显示出对恶性疟原虫PfPK 7激酶（IC 50 10-20 μ M）的活性，恶性疟原虫是导致最致命形式疟疾的生物体，并且可以被认为是可用于进一步开发为先导化合物的命中物。
Efficient routes to 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3-triazol-4-yl) pyrazolo[3,4-d]pyrimidin-4-amines using a one-pot two-step reaction are presented. The two routes give easy access to two different isomers of 1,4-disubstituted triazoles and the target compounds are obtained from a variety of readily available aromatic and aliphatic halides without isolation of potentially unstable organic azide intermediates. Two compounds show activity towards the PfPK7 kinase (IC50 10-20 mu M) of P. falciparum, the organism responsible for the most virulent form of malaria, and can be regarded as hits useful for further development into lead compounds.