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

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 24; pp. 8642 - 8659
• Main Authors: Cui, Yong-Mei, Yasutomi, Eriko, Otani, Yuko, Ido, Katsutoshi, Yoshinaga, Takashi, Sawada, Kohei, Ohwada, Tomohiko
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.12.2010; Elsevier
• Subjects: Animals; Biological and medical sciences; BK channels; Channel openers; CHO Cells; Cricetinae; Cricetulus; Dehydroabietic acid; Diterpenes, Abietane - chemical synthesis; Diterpenes, Abietane - chemistry; Diterpenes, Abietane - pharmacology; Drug Design; Humans; Large-Conductance Calcium-Activated Potassium Channels - agonists; Large-Conductance Calcium-Activated Potassium Channels - genetics; Medical sciences; Miscellaneous; Oximation; Oximes - chemistry; Pharmacology. Drug treatments; Podocarpic acid; Structure-Activity Relationship; Transduction, Genetic; BK channels; Dehydroabietic acid; Podocarpic acid; Channel openers; Oximation; BK potassium channel; Terpenoid; Agonist; Oxime; Ionic channel; Potassium channel agonist; Structure activity relation; Diterpene; Aromatic compound; Chemical synthesis; Resinic acid
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.09.072

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. 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.