Acrylamides as potassium channel openers

Abstract

The acrylamide moiety is widely employed in medicinal chemistry for the design of bioactive molecule and, notably, it has served as a scaffold for a number of potassium channel modulators in recent years. Their synthesis has proven to be an effective approach, especially for the discovery and optimisation of small molecule openers of large-conductance calcium-activated (BK) potassium channels and KCNQ channels. This review provides an overview of the worldwide patent literature surrounding cinnamic amides, with a special focus on their potential medical use and the most salient structural and chemical features involved in the modulation of BK and KCNQ channel activity. Remarkably, such derivatives are among the most potent BK and KCNQ channel openers reported to date.

Keywords::

• BK openers
• cinnamic amides
• cinnamides
• cinnamoylamides
• KCNQ openers
• Maxi-K openers
• α,β-unsatured amides

Acknowledgements

The authors would like to thank J Demnitz (Medicinal Chemistry Department, NeuroSearch) for his insightful suggestions and comments on the manuscript.

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