Structure-activity relationship (SAR) investigations of tetrahydroquinolines as BKCa agonists

Vijay K Gore; Vu V Ma; Ruoyuan Yin; Joe Ligutti; David Immke; Elizabeth M Doherty; Mark H Norman

doi:10.1016/j.bmcl.2010.04.125

Structure-activity relationship (SAR) investigations of tetrahydroquinolines as BKCa agonists

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3573-8. doi: 10.1016/j.bmcl.2010.04.125. Epub 2010 May 20.

Authors

Vijay K Gore¹, Vu V Ma, Ruoyuan Yin, Joe Ligutti, David Immke, Elizabeth M Doherty, Mark H Norman

Affiliation

¹ Department of Chemistry Research and Discovery, Amgen Inc., Thousand Oaks, CA 91320-1799, USA. [email protected]

PMID: 20493696
DOI: 10.1016/j.bmcl.2010.04.125

Abstract

The membrane bound large-conductance, calcium-activated potassium channel (BKCa) is an important regulator of neuronal activity. Here we describe the identification and structure-activity relationship of a novel class of potent tetrahydroquinoline BKCa agonists. An example from this class of BKCa agonists was shown to depress the spontaneous neuronal discharges in an electrophysiological model of migraine.

MeSH terms

Animals
CHO Cells
Cricetinae
Cricetulus
Electrophysiological Phenomena / drug effects
Humans
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / agonists*
Migraine Disorders / drug therapy
Migraine Disorders / pathology
Models, Biological
Neurons / drug effects*
Quinolines / chemistry*
Quinolines / pharmacology*
Rats
Structure-Activity Relationship
Trigeminal Nuclei / cytology

Substances

KCNMA1 protein, human
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Quinolines