Biomedical Engineering Reference
In-Depth Information
Advances in Structure-Activity Relationship
Studies on Potassium Channel Modulators
Brij K. Sharma, Prithvi Singh, and Yenamandra S. Prabhakar
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
2 QSAR and Modeling Studies ............................................................... 244
2.1 Benzodiazepine Derivatives . ......................................................... 245
2.2 Benzopyrans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
2.3 Benzothiazine Derivatives ............................................................ 251
2.4 Benzothiadiazine 1,1-Dioxide Derivatives . . . ....................................... 252
2.5 Khellinone Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
2.6 Benzotriazole, Benzimidazolone and Benzanilide Derivatives ..................... 256
2.7 hERG K
+
Modulators ................................................................. 258
3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
Abstract Ion channels are part of cell membranes. They control the influx and
efflux of ions such as sodium, potassium, calcium, or chloride, as well as ligands of
several biochemical processes. Due to this, they play important role in a variety of
diseases ranging from the cardiovascular, nervous, immune and endocrine systems
to the cancer metastasis. Moreover, a number of chemicals and genetic disorders
disrupt functioning of ion channels, which in turn can lead to aggrieved situations.
This makes ion channels as potential targets in drug discovery programs. However,
because of ion channels' ubiquitous nature and high variability even within a given
family, identification of drugs acting via them with specificity and high therapeutic
value is a challenge! With a brief introduction to the fundamental aspects of ion
channels, the review chapter explored the structure-activity advancements made
on some potassium channel modulators namely, benzodiazepines, cromakalim
analogues, benzothiadiazines, khellinone derivatives and other related chemical
