3-Thio-quinolinone maxi-K openers for the treatment of erectile dysfunction.
A series of Maxi-K openers for the treatment of erectile dysfunction based on the 3-thio-quinolinone core is described. Significant levels of channel opening (up to 550% of control) are seen in transfected oocytes. Functional activity in rabbit corpus cavernosum tissue strips confirms the potential to effect therapy for ED, the effect being maximal for the 3-amino-2-hydroxy thiol side chain.
Boy
Kenneth M
KM
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. boyk@bms.com
Guernon
Jason M
JM
Sit
Sing-Yuen
SY
Xie
Kai
K
Hewawasam
Piyasena
P
Boissard
Christopher G
CG
Dworetzky
Steven I
SI
Natale
Joanne
J
Gribkoff
Valentin K
VK
Lodge
Nicholas
N
Starrett
John E
JE
D000818:Animals; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010413:Penis / Q000098:blood supply; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011804:Quinolines; D013440:Sulfides; D014665:Vasodilator Agents