Initial SAR studies on apamin-displacing 2-aminothiazole blockers of calcium-activated small conductance potassium channels.
An initial SAR study on a series of apamin-displacing 2-aminothiazole K(Ca)2 channel blockers is described. Potent inhibitors such as N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (13) are disclosed, and for select members of the series, the relationship between the observed activity in a thallium flux, a binding and a whole-cell electrophysiology assay is presented.
Gentles
Robert G
RG
Research and Development, Bristol Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA. robert.gentles@bms.com
Grant-Young
Katherine
K
Hu
Shuanghua
S
Huang
Yazhong
Y
Poss
Michael A
MA
Andres
Charles
C
Fiedler
Tracey
T
Knox
Ronald
R
Lodge
Nicholas
N
Weaver
C David
CD
Harden
David G
DG
D001030:Apamin / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
C532530:N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine; D026902:Potassium Channel Blockers; D011725:Pyridines; D051640:Small-Conductance Calcium-Activated Potassium Channels; D013844:Thiazoles; D001030:Apamin