Exploring chemical space with organometallics: Ruthenium complexes as protein kinase inhibitors
Exploring chemical space with organometallics: Ruthenium complexes as protein kinase inhibitors
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DOI：
10.1055/s-2007-973893
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发表时间：
2007-05-16
期刊：
影响因子：
2
通讯作者：
Williams, Douglas S.
中科院分区：
文献类型：
--
作者：
Meggers, Eric;Atilla-Gokcumen, G. Ekin;Williams, Douglas S.
用金属中心补充有机元素为构建具有独特且明确形状的三维结构提供了新的机会。这种对未探索的化学空间的访问可能会导致具有前所未有的特性的分子的发现。沿着这些思路，这篇报道文章描述了我们通过使用吲哚并咔唑生物碱类作为先导结构，成功设计了针对蛋白激酶 GSK-3 和 Pim-1 的高效、选择性钌基抑制剂。所描述的钌配合物是动力学惰性支架，其中钌具有组织有机配体在三维空间中的方向的功能。
Complementing organic elements with a metal center provides new opportunities for building three-dimensional structures with unique and defined shapes. Such access to unexplored chemical space may lead to the discovery of molecules with unprecedented properties. Along these tines, this account article describes our successful design of highly potent and selective ruthenium-based inhibitors for the protein kinases GSK-3 and Pim-1 by using the class of indolocarbazole alkaloids as a lead structure. The described ruthenium complexes are kinetically inert scaffolds in which the ruthenium has the function to organize the orientation of the organic ligands in the three-dimensional space.