Design, synthesis, and characterization of BK channel openers based on oximation of abietane diterpene derivatives
Design, synthesis, and characterization of BK channel openers based on oximation of abietane diterpene derivatives
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DOI：
10.1016/j.bmc.2010.09.072
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发表时间：
2010-12-15
影响因子：
3.5
通讯作者：
Ohwada, Tomohiko
中科院分区：
文献类型：
--
作者：
Cui, Yong-Mei;Yasutomi, Eriko;Ohwada, Tomohiko
合成了脱氢松香酸和罗汉果酸的芳香族C-环的未取代、二氯、三氯和一溴衍生物的苄基位置处的肟醚衍生物，并在表达hBK α通道的CHO-K1细胞的测定系统中作为BK通道开放剂进行评价。详细的SAR分析表明，肟化是特别有效的脱氢枞酸衍生物的情况下，这些肟衍生物中的一些显示出更有效的BK通道活动比标准化合物，NS 1619。本研究为开发高效BK通道开放剂提供了新的结构基础。(C)2010爱思唯尔有限公司版权所有。
Oxime ether derivatives at the benzylic position of unsubstituted, dichloro, trichloro, and monobromo derivatives of the aromatic C-ring of dehydroabietic acid and podocarpic acid were synthesized and evaluated as BK channel openers in an assay system of CHO-K1 cells expressing hBK alpha channels. Detailed SAR analysis showed that the oximation was particularly effective in the cases of dehydroabietic acid derivatives, and some of these oxime derivatives showed more potent BK channel activities than the standard compound, NS1619. The present studies provide a new structural basis for development of efficient BK channel openers. (C) 2010 Elsevier Ltd. All rights reserved.