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

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.