Design, synthesis, and characterization of BK channel openers based on oximation of abietane diterpene derivatives.
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 hBKα 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.
Department of Chemistry, College of Sciences, Shanghai University, 99 Shangda Road, Baoshan District, Shanghai 200444, China.
Yong-Mei
YM
Cui
Eriko
E
Yasutomi
Yuko
Y
Otani
Katsutoshi
K
Ido
Takashi
T
Yoshinaga
Kohei
K
Sawada
Tomohiko
T
Ohwada
D045784:Abietanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists* / Q000235:genetics; D010091:Oximes / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014161:Transduction, Genetic
D045784:Abietanes; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010091:Oximes