A combinatorial scaffold approach toward kinase-directed heterocycle libraries
A combinatorial scaffold approach toward kinase-directed heterocycle libraries
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DOI：
10.1021/ja0170302
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发表时间：
2002-02-27
影响因子：
15
通讯作者：
Schultz, PG
中科院分区：
文献类型：
--
作者：
Ding, S;Gray, NS;Schultz, PG
描述了一种有效合成各种取代杂环作为激酶导向组合文库的新策略。一般方案涉及将各种二氯杂环捕获到固体支持物上，并通过在升高的温度下用胺或通过苯胺、硼酸和苯酚经由钯催化的交叉偶联反应进行芳族取代来进一步阐述，因此支架本身被转化为组合方案内的多样性元素。目前正在各种基于细胞和蛋白质的测定中评估由用这些化学物质构建的离散和高度多样化的杂环小分子组成的文库。
A novel strategy for efficient synthesis of various substituted heterocycles as kinase-directed combinatorial libraries is described. The general scheme involves capture of various dichloroheterocycles onto solid support and further elaborations by aromatic substitution with amines at elevated temperature or by anilines, boronic acids, and phenols via palladium-catalyzed cross-coupling reactions, thus the scaffold itself is transformed into a diversity element within the combinatorial scheme. Libraries consisting of discrete and highly diverse heterocyclic small molecules constructed with these chemistries are currently being evaluated in a variety of cell and protein-based assays.