Design and synthesis of Rho kinase inhibitors (I)
Design and synthesis of Rho kinase inhibitors (I)
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DOI：
10.1016/j.bmc.2004.02.025
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发表时间：
2004-05-01
影响因子：
3.5
通讯作者：
Iijima, H
中科院分区：
文献类型：
--
作者：
Takami, A;Iwakubo, M;Iijima, H
利用从高通量筛选结果获得的药效团信息和来自 Rho 激酶同源模型的结构信息，设计了几种结构上不相关的 Rho 激酶抑制剂支架。使用 Rho 激酶模型的配体结合口袋进行对接模拟有助于全面理解和预测抑制剂的构效关系。这一认识对于开发具有更高效力和选择性的新型 Rho 激酶抑制剂非常有用。我们确定了几个用于开发 Rho 激酶抑制剂的有效平台，即吡啶、1H-吲唑、异喹啉和邻苯二甲酰亚胺。 (C) 2004 Elsevier Ltd. 保留所有权利。
Several structurally unrelated scaffolds of the Rho kinase inhibitor were designed using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. A docking simulation using the ligand-binding pocket of the Rho kinase model helped to comprehensively understand and to predict the structure-activity relationship of the inhibitors. This understanding was useful for developing new Rho kinase inhibitors of higher potency and selectivity. We identified several potent platforms for developing the Rho kinase inhibitors, namely, pyridine, 1H-indazole, isoquinoline, and phthalimide. (C) 2004 Elsevier Ltd. All rights reserved.