title: 3-trifluoromethyl-4-nitro-5-arylpyrazoles are novel K(ATP) channel agonists.
abstract: 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.
authors.affiliation: GlaxoSmithKline Research & Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Peat
authors.forename: Claire
authors.initials: C
authors.lastname: Townsend
authors.forename: M
authors.initials: M
authors.lastname: Craig McKay
authors.forename: Dulce
authors.initials: D
authors.lastname: Garrido
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Terry
authors.forename: Jayme L R
authors.initials: JL
authors.lastname: Wilson
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Thomson
mesh_terms: 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
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D011720:Pyrazoles; D003981:Diazoxide