Novel BK channel openers containing dehydroabietic acid skeleton: structure-activity relationship for peripheral substituents on ring C

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

doi:10.1016/j.bmcl.2008.08.078

Novel BK channel openers containing dehydroabietic acid skeleton: structure-activity relationship for peripheral substituents on ring C

Bioorg Med Chem Lett. 2008 Oct 1;18(19):5201-5. doi: 10.1016/j.bmcl.2008.08.078. 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: 18789860
DOI: 10.1016/j.bmcl.2008.08.078

Abstract

A series of dehydroabietic acid (DHAA, 2) derivatives was synthesized and evaluated as BK channel openers in an assay system of CHO-K1 cells expressing hBKalpha channels. Systematic modifications of the peripheral functionality of ring C of DHAA showed that the introduction of a nitro or (thio)urea group in ring C greatly enhanced the BK channel-opening activity.

Publication types

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

MeSH terms

Abietanes / chemistry*
Abietanes / pharmacology*
Animals
Carboxylic Acids / chemistry*
Combinatorial Chemistry Techniques
Cricetinae
Cricetulus
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
Large-Conductance Calcium-Activated Potassium Channels
dehydroabietic acid