title: Structure-activity relationship (SAR) investigations of tetrahydroquinolines as BKCa agonists.
abstract: 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.
authors.affiliation: Department of Chemistry Research and Discovery, Amgen Inc., Thousand Oaks, CA 91320-1799, USA. vgore@amgen.com
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Gore
authors.forename: Vu V
authors.initials: VV
authors.lastname: Ma
authors.forename: Ruoyuan
authors.initials: R
authors.lastname: Yin
authors.forename: Joe
authors.initials: J
authors.lastname: Ligutti
authors.forename: David
authors.initials: D
authors.lastname: Immke
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Doherty
authors.forename: Mark H
authors.initials: MH
authors.lastname: Norman
mesh_terms: 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
chemical_list: C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D011804:Quinolines