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.
Cui
Yong-Mei
YM
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Yasutomi
Eriko
E
Otani
Yuko
Y
Yoshinaga
Takashi
T
Ido
Katsutoshi
K
Sawada
Kohei
K
Ohwada
Tomohiko
T
D045784:Abietanes / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D004224:Diterpenes / Q000737:chemistry; D015640:Ion Channel Gating / Q000187:drug effects*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D018408:Patch-Clamp Techniques; D013329:Structure-Activity Relationship
D045784:Abietanes; D002264:Carboxylic Acids; D004224:Diterpenes; D051036:Large-Conductance Calcium-Activated Potassium Channels; C104130:maxikdiol; C002470:podocarpic acid; C008911:pimaric acid