Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38MAPK inhibitor RO3201195 for study in Werner syndrome cells
Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38MAPK inhibitor RO3201195 for study in Werner syndrome cells
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DOI：
10.1016/j.bmcl.2008.05.037
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发表时间：
2008-07-01
影响因子：
2.7
通讯作者：
Kipling, David
中科院分区：
文献类型：
--
作者：
Bagley, Mark C.;Davis, Terence;Kipling, David
以N，N‘-二苯基甲酰胺为原料，经微波介电加热，再用肼进行杂环缩合反应，快速、高效地合成了5-氨基吡唑-4-酮。用这种方法制备的RO3201195在200 nM浓度的hTERT永生化的HCA2和WS真皮成纤维细胞中的抑制活性得到了证实，并且对p38αMAPK表现出比相关的应激激活激酶JNK更好的激酶选择性。(C)2008爱思唯尔有限公司。保留所有权利。
5-Aminopyrazol-4-yl ketones are prepared rapidly and efficiently using microwave dielectric heating from beta-ketonitriles by treatment with N, N'-diphenylformamidine followed by heterocyclocondensation by irradiation with a hydrazine. The inhibitory activity of RO3201195 prepared by this methodology was confirmed in hTERT-immortalized HCA2 and WS dermal fibroblasts at 200 nM concentration, both by ELISA and immunoblot assay, and displays excellent kinase selectivity for p38 alpha MAPK over the related stress-activated kinase JNK. (C) 2008 Elsevier Ltd. All rights reserved.