Abstract
Herein we report the discovery, synthesis, and evaluation of a series of N-aryl-bicyclo[2.2.1]heptane-2-carboxamides as selective KCNQ2 (K v7.2) and KCNQ4 (K v7.4) channel openers. The best compound, 1 (ML213), has an EC 50 of 230 nM (KCNQ2) and 510 nM (KCNQ4) and is selective for KCNQ2 and KCNQ4 channels versus a large battery of related potassium channels, as well as affording modest brain levels. This represents the first report of unique selectivity profiles for KCNQ2 and KCNQ4 over the other channels (KCNQ1/3/5) and as such should prove to be a valuable tool compound for understanding these channels in regulating neuronal activity.
Original language | English (US) |
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Pages (from-to) | 572-577 |
Number of pages | 6 |
Journal | ACS Chemical Neuroscience |
Volume | 2 |
Issue number | 10 |
DOIs | |
State | Published - Oct 19 2011 |
Externally published | Yes |
Keywords
- KCNQ2
- KCNQ4
- Kv7
- ML218
- MLPCN probe
- activator
- ion channels
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Cognitive Neuroscience
- Cell Biology