Design, synthesis and characterization of podocarpate derivatives as openers of BK channels

Yong-Mei Cui; Eriko Yasutomi; Yuko Otani; Takashi Yoshinaga; Katsutoshi Ido; Kohei Sawada; Tomohiko Ohwada

doi:10.1016/j.bmcl.2008.08.081

Design, synthesis and characterization of podocarpate derivatives as openers of BK channels

Bioorg Med Chem Lett. 2008 Oct 1;18(19):5197-200. doi: 10.1016/j.bmcl.2008.08.081. Epub 2008 Aug 28.

Authors

Yong-Mei Cui¹, Eriko Yasutomi, Yuko Otani, Takashi Yoshinaga, Katsutoshi Ido, Kohei Sawada, Tomohiko Ohwada

Affiliation

¹ Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

PMID: 18789683
DOI: 10.1016/j.bmcl.2008.08.081

Abstract

We found that the podocarpic acid structure provides a new scaffold for chemical modulators of large-conductance calcium-activated K(+) channels (BK channels). Structure-activity analysis indicates the importance of both the arrangement (i.e., location and orientation) of the carboxylic acid functionality of ring A and the hydrophobic region of ring C for expression of BK channel-opening activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abietanes / chemistry*
Abietanes / pharmacology*
Carboxylic Acids / chemistry*
Combinatorial Chemistry Techniques
Diterpenes / chemistry
Ion Channel Gating / drug effects*
Large-Conductance Calcium-Activated Potassium Channels / drug effects*
Models, Molecular
Molecular Structure
Patch-Clamp Techniques
Structure-Activity Relationship

Substances

Abietanes
Carboxylic Acids
Diterpenes
Large-Conductance Calcium-Activated Potassium Channels
maxikdiol
podocarpic acid
pimaric acid