The Role of Chromenes in Drug Discovery and Development

Chromene Derivatives as Potassium Channel Openers or Inhibitors

Author(s): Krittika Mukherjee, Vivek Panwar, Deepak Kumar Jindal, Sandeep Kumar, Isha Dhamija, Deepak Kumar* and Ashutosh Kumar Dash * .

Pp: 235-244 (10)

DOI: 10.2174/9789815124330123010014

* (Excluding Mailing and Handling)

Abstract

This overview depicts the voltage-regulated potassium channel, which is found in the CNS, and the emerging therapeutic applications of potassium channel modulators. It also discusses the recent developments in our understanding of the mechanisms, that control the activity of a series of channels, that are selective for potassium ions. It has been long recognized that the excitability of cells is mediated by proteins, which can modulate the ability of potassium ions to travel across the cell membrane. Going back ten years, it has become increasingly clear that, potassium ion channels represent an excellent target for novel drug design. Investigating the role of potassium channels in treating human diseases continues to be a growing field of research. The ability of potassium channels to regulate membrane potential accords a central role in varied cellular processes that govern excitability, action potential characteristics, stimulus secretion coupling, cell volume regulation, and epithelial electrolyte transport. Attention from medicinal chemists to potassium channels as drug targets has grown with the realization that a variety of potassium channel openers offer significant therapeutic opportunities in cardiac, smooth muscle, neuronal, immune, and secretary systems. Progressive improvements in molecular biology have enabled regular cloning of potassium channels of interest, and defined families of these channels have facilitated a comprehensive understanding of their function. Importantly many families of increasingly selective small molecules have emerged as target validation and clinical proof of principle. Many reviews have appeared summarizing the synthesis and therapeutic potential of these channels. The scope of this report is to make you aware of potassium channel biology, which leads to a more expedient identification of agents for the treatment of CNS disorders, emphasizing developments in medicinal chemistry based on potassium channels where modulators would have considerable clinical potential. While every effort has been made to include all relevant reports in this discussion, any omission is inadvertent and we apologize for the same.

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