3-trifluoromethyl-4-nitro-5-arylpyrazoles are novel K(ATP) channel agonists.
This communication describes the discovery and synthesis of a series of 3-trifluoromethyl-4-nitro-5-arylpyrazoles as potent K(ATP) channel agonists. The most potent compound reported is ca. 100-fold more potent than diazoxide and exhibits selectivity for the SUR1 K(ATP) channel subtype. The 4-nitro substitutent on the pyrazole ring was required for activity, and limited SAR suggests that the de-protonated pyrazole maybe the active species.
Peat
Andrew J
AJ
GlaxoSmithKline Research & Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
Townsend
Claire
C
Craig McKay
M
M
Garrido
Dulce
D
Terry
Christopher M
CM
Wilson
Jayme L R
JL
Thomson
Stephen A
SA
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry*; D003981:Diazoxide / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis / Q000378:metabolism
D024661:Potassium Channels, Inwardly Rectifying; D011720:Pyrazoles; D003981:Diazoxide