Multi-substituted 8-aminoimidazo[1,2-a]pyrazines by Groebke-Blackburn-Bienayme reaction and their Hsp90 inhibitory activity
Multi-substituted 8-aminoimidazo[1,2-a]pyrazines by Groebke-Blackburn-Bienayme reaction and their Hsp90 inhibitory activity
复制标题
DOI：
10.1039/c4ob01865f
复制
发表时间：
2015-01-01
影响因子：
3.2
通讯作者：
Shen, Jingkang
中科院分区：
文献类型：
--
作者：
Ren, Jing;Yang, Min;Shen, Jingkang
以2，3-二氨基吡嗪为底物，三氟甲磺酸钇为催化剂，通过Groebke-Blackburn-Bienayme MCR反应，高效地合成了各种2-烷基和芳基取代的3，8-二氨基咪唑并[1，2-a]吡嗪。特别是，一种新的2-胡椒基3，8-二氨基咪唑并[1，2-a]吡嗪结构专门用这种新方法制备，并被发现具有适度的Hsp 90抑制活性。此外，还得到了一种新的Hsp 90抑制剂与Hsp 90 N-末端ATP结构域的晶体复合物，以阐明2-胡椒基-3，8-二氨基咪唑并[1，2-a]吡嗪类化合物的活性来源。
Using a 2,3-diamino pyrazine substrate and yttrium triflate catalyst, various 2-alkyl and aryl substituted 3,8-diaminoimidazo[1,2-a]pyrazines were efficiently prepared through Groebke-Blackburn-Bienayme MCR. In particular, a novel 2-piperonyl 3,8-diaminoimidazo[1,2-a]pyrazine structure was prepared exclusively with this new method and was found to have moderate Hsp90 inhibitory activity. A crystalline complex with N-terminus ATP domain of Hsp90 and one of the new Hsp90 inhibitors was also obtained to elucidate the origin of activity of 2-piperonyl 3,8-diaminoimidazo[1,2-a]pyrazines.