Partial structures of ketoconazole as modulators of the large conductance calcium-activated potassium channel (BK(Ca))

Eoin C Power; C Robin Ganellin; David C H Benton

doi:10.1016/j.bmcl.2005.11.001

Partial structures of ketoconazole as modulators of the large conductance calcium-activated potassium channel (BK(Ca))

Bioorg Med Chem Lett. 2006 Feb 15;16(4):887-90. doi: 10.1016/j.bmcl.2005.11.001. Epub 2005 Dec 15.

Authors

Eoin C Power¹, C Robin Ganellin, David C H Benton

Affiliation

¹ Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK. epower@sienabiotech.it

PMID: 16359866
DOI: 10.1016/j.bmcl.2005.11.001

Abstract

A series of partial structures of ketoconazole has been synthesized and tested for activity on the large conductance calcium-activated potassium channel (BK) in bovine smooth muscle cells. This has provided openers and blockers of the channel. The results suggest that the phenyl and phenoxy moieties are important for interaction with BK, whereas the imidazole group is unimportant. The properties of the phenoxy moiety seem to determine whether the compounds act to open or block the channel.

MeSH terms

Animals
Cattle
Drug Evaluation, Preclinical
Ketoconazole / chemical synthesis
Ketoconazole / chemistry
Ketoconazole / pharmacology*
Large-Conductance Calcium-Activated Potassium Channels / drug effects*
Membrane Transport Modulators / chemical synthesis
Membrane Transport Modulators / chemistry
Membrane Transport Modulators / pharmacology*
Molecular Structure
Muscle, Smooth, Vascular / cytology
Muscle, Smooth, Vascular / drug effects
Structure-Activity Relationship

Substances

Large-Conductance Calcium-Activated Potassium Channels
Membrane Transport Modulators
Ketoconazole