title: The synthesis and structure-activity relationships of 4-aryl-3-aminoquinolin-2-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel openers targeted for post-stroke neuroprotection.
abstract: A series of 4-aryl-3-aminoquinoline-2-one derivatives was synthesized and evaluated as activators of the cloned maxi-K channel mSlo (hSlo) expressed in Xenopus laevis oocytes using electrophysiological methods. A brain penetrable activator of maxi-K channels was identified and shown to be significantly active in the MCAO model of stroke.
authors.affiliation: Department of Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. hewawasp@bms.com
authors.forename: Piyasena
authors.initials: P
authors.lastname: Hewawasam
authors.forename: Wenhong
authors.initials: W
authors.lastname: Fan
authors.forename: Jay
authors.initials: J
authors.lastname: Knipe
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Moon
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Boissard
authors.forename: Valentin K
authors.initials: VK
authors.lastname: Gribkoff
authors.forename: John E
authors.initials: JE
authors.lastname: Starrett
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D002999:Clone Cells; D004195:Disease Models, Animal; D004594:Electrophysiology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials; D018696:Neuroprotective Agents / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism*; D015363:Quinolones / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D020521:Stroke / Q000150:complications / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D018696:Neuroprotective Agents; D024681:Potassium Channels, Calcium-Activated; D015363:Quinolones