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.
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.
Hewawasam
Piyasena
P
Department of Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. hewawasp@bms.com
Fan
Wenhong
W
Knipe
Jay
J
Moon
Sandra L
SL
Boissard
Christopher G
CG
Gribkoff
Valentin K
VK
Starrett
John E
JE
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
D051036:Large-Conductance Calcium-Activated Potassium Channels; D018696:Neuroprotective Agents; D024681:Potassium Channels, Calcium-Activated; D015363:Quinolones