发现钠通道小分子阻断剂的新趋势

Title:Recent Trends in the Discovery of Small Molecule Blockers of Sodium Channels

Volume: 23 Issue: 22

Author(s): Roberta Gualdani, Maria Maddalena Cavalluzzi, Giovanni Lentini

Affiliation:

关键词: 生物物理学；离子通道；化学类型；药物发现；效率指标；电生理；铅化合物；支架。

摘要: Voltage-gated sodium channels (VGSC) are responsible for the selective influx of sodium ions in excitable cells. A number of physiological phenomena such as muscle contraction, pain sensation, processing of neuronal information in the brain as well as neuronal regulation of peripheral tissues rely on the activity of these channels. On the other hand, abnormal activity of VGSC are implicated in several pathological processes (e.g., cardiac arrhythmias, epilepsy, and chronic pain) which in some cases (e.g., channelopathies such as myotonias) are linked to specific gene mutations. As a result, VGSC have never stopped attracting the attention of medicinal chemists and the quest for novel drugs to treat these ion channels-associated diseases continues. In this review, VGSC blocking agents reported in the last lustrum are scrutinised with the aim to give a medicinal chemistry perspective on the most interesting compounds classified on the basis of (i) potential therapeutic application, (ii) targeted VGSC isoforms, and (iii) chemical scaffolds. Finally, the clinical potential of selected drug candidates from each chemotype is evaluated by comparing their ligand efficiency metrics. Possible routes for improvement of these preclinical candidates are also discussed.

Cite this article as:

Roberta Gualdani, Maria Maddalena Cavalluzzi, Giovanni Lentini , Recent Trends in the Discovery of Small Molecule Blockers of Sodium Channels, Current Medicinal Chemistry 2016; 23 (22) . https://dx.doi.org/10.2174/0929867323666160517121458