3-trifluoromethyl-4-nitro-5-arylpyrazoles are novel K(ATP) channel agonists

Andrew J Peat; Claire Townsend; M Craig McKay; Dulce Garrido; Christopher M Terry; Jayme L R Wilson; Stephen A Thomson

doi:10.1016/j.bmcl.2003.10.066

3-trifluoromethyl-4-nitro-5-arylpyrazoles are novel K(ATP) channel agonists

Bioorg Med Chem Lett. 2004 Feb 9;14(3):813-6. doi: 10.1016/j.bmcl.2003.10.066.

Authors

Andrew J Peat¹, Claire Townsend, M Craig McKay, Dulce Garrido, Christopher M Terry, Jayme L R Wilson, Stephen A Thomson

Affiliation

¹ GlaxoSmithKline Research & Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA.

PMID: 14741296
DOI: 10.1016/j.bmcl.2003.10.066

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.

Publication types

Comparative Study

MeSH terms

Animals
Cell Membrane / chemistry*
Diazoxide / chemistry
Diazoxide / pharmacology
Humans
Inhibitory Concentration 50
Molecular Structure
Oocytes / drug effects
Oocytes / metabolism
Patch-Clamp Techniques
Potassium Channels, Inwardly Rectifying / agonists*
Pyrazoles / chemical synthesis*
Pyrazoles / pharmacology*
Structure-Activity Relationship
Xenopus laevis / metabolism

Substances

Potassium Channels, Inwardly Rectifying
Pyrazoles
Diazoxide