Structure-activity relationship (SAR) investigations of tetrahydroquinolines as BKCa agonists.
The membrane bound large-conductance, calcium-activated potassium channel (BKCa) is an important regulator of neuronal activity. Here we describe the identification and structure-activity relationship of a novel class of potent tetrahydroquinoline BKCa agonists. An example from this class of BKCa agonists was shown to depress the spontaneous neuronal discharges in an electrophysiological model of migraine.
Gore
Vijay K
VK
Department of Chemistry Research and Discovery, Amgen Inc., Thousand Oaks, CA 91320-1799, USA. vgore@amgen.com
Ma
Vu V
VV
Yin
Ruoyuan
R
Ligutti
Joe
J
Immke
David
D
Doherty
Elizabeth M
EM
Norman
Mark H
MH
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000819:agonists*; D008881:Migraine Disorders / Q000188:drug therapy / Q000473:pathology; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects*; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014278:Trigeminal Nuclei / Q000166:cytology
C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D011804:Quinolines