4-Aryl-3-(hydroxyalkyl)quinolin-2-ones: novel maxi-K channel opening relaxants of corporal smooth muscle targeted for erectile dysfunction.
Novel 4-aryl-3-(hydroxyalkyl)quinoline-2-one derivatives were prepared and evaluated as openers of the cloned maxi-K channel hSlo expressed in Xenopus laevis oocytes by utilizing electrophysiological methods. The effect of these maxi-K openers on corporal smooth muscle was studied in vitro using isolated rabbit corpus cavernosum. From this study, a potent maxi-K opener was identified as an effective relaxant of rabbit corporal smooth muscle and shown to be active in an in vivo animal model of male erectile function.
Hewawasam
Piyasena
P
Department of Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 06492, USA. hewawasp@bms.com
Fan
Wenhong
W
Ding
Min
M
Flint
Kim
K
Cook
Deborah
D
Goggins
Gregory D
GD
Myers
Robert A
RA
Gribkoff
Valentin K
VK
Boissard
Christopher G
CG
Dworetzky
Steven I
SI
Starrett
John E
JE
Lodge
Nicholas J
NJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000188:drug therapy; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects*; D011312:Pressure; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship
D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D015363:Quinolones