Design, synthesis, and characterization of BK channel openers based on oximation of abietane diterpene derivatives

被引：32
作者：
Cui, Yong-Mei [1 ,2 ]
Yasutomi, Eriko [1 ]
Otani, Yuko [1 ]
Ido, Katsutoshi [3 ]
Yoshinaga, Takashi [3 ]
Sawada, Kohei [3 ]
Ohwada, Tomohiko [1 ]
机构：
[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan
[2] Shanghai Univ, Dept Chem, Coll Sci, Shanghai 200444, Peoples R China
[3] Eisai & Co Ltd, Tsukuba Res Labs, Tsukuba, Ibaraki 3002635, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 24期
基金：
日本学术振兴会;
关键词：
BK channels; Channel openers; Oximation; Dehydroabietic acid; Podocarpic acid; ACTIVATED POTASSIUM CHANNELS; LARGE-CONDUCTANCE; 12,14-DICHLORODEHYDROABIETIC ACID; OPENING ACTIVITY; MODULATORS; SUBUNIT; TONE;
D O I：
10.1016/j.bmc.2010.09.072
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：8642 / 8659
页数：18
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