4,5-diphenyltriazol-3-ones: openers of large-conductance Ca(2+)-activated potassium (maxi-K) channels.
A series of diphenyl-substituted heterocycles were synthesized and evaluated by electrophysiological techniques as openers of the cloned mammalian large-conductance, Ca(2+)-activated potassium (maxi-K) channel. The series was designed from deannulation of known benzimidazolone maxi-K opener NS-004 (2) thereby providing an effective template for obtaining structure-activity-related information. The triazolone ring system was the most studied wherein 4,5-diphenyltriazol-3-one 6d (maxi-K = 158%) was identified as the optimal maxi-K channel opener.
Romine
Jeffrey L
JL
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. rominej@bms.com
Martin
Scott W
SW
Gribkoff
Valentin K
VK
Boissard
Christopher G
CG
Dworetzky
Steven I
SI
Natale
Joanne
J
Li
Yi
Y
Gao
Qi
Q
Meanwell
Nicholas A
NA
Starrett
John E
JE
D000818:Animals; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008958:Models, Molecular; D008968:Molecular Conformation; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists* / Q000502:physiology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014982:Xenopus laevis
C461201:4-(5-chloro-2-hydroxyphenyl)-5-(3,5-bis(trifluoromethyl)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D014230:Triazoles