AstraZeneca R&D, Lead Generation, SE-431 83 Mölndal, Sweden.
Expert Opin Ther Pat. 2011 Jan;21(1):85-101. doi: 10.1517/13543776.2011.536532. Epub 2010 Nov 19.
T-type calcium channels are transmembrane proteins that regulate calcium entry in the cell in a voltage-dependent manner. Intracellular calcium levels are the key to many physiological processes, ranging from neuron firing to cardiac pacemaking. Inhibition of T-type calcium channels is heralded as a potential treatment to peripheral and CNS disorders, including hypertension, heart failure, sleep, epilepsy, drug addiction and neuropathic pain.
A comprehensive summary of patent literature disclosing T-type calcium channels inhibitors is provided.
In all, 46 patent applications including 15 chemical structure classes are reviewed. Available in vitro, in vivo and clinical results are also discussed.
Several selective T-type calcium channels inhibitors with demonstrated in vitro and in vivo effects, including one Phase I clinical candidate, are now available. While future clinical results will be paramount to assess target validity in patients, these novel inhibitors represent excellent tools to further investigate the role of T-type channels in pathophysiological conditions.
T 型钙通道是跨膜蛋白，以电压依赖的方式调节细胞内钙离子的进入。细胞内钙离子水平是许多生理过程的关键，从神经元放电到心脏起搏。T 型钙通道的抑制被认为是治疗周围和中枢神经系统疾病的一种潜在方法，包括高血压、心力衰竭、睡眠、癫痫、药物成瘾和神经病理性疼痛。
本文提供了一份全面的专利文献综述，披露了 T 型钙通道抑制剂。
共审查了 46 项专利申请，包括 15 个化学结构类别。还讨论了现有的体外、体内和临床结果。
现在有几种具有体外和体内效果的选择性 T 型钙通道抑制剂，包括一个 I 期临床候选药物。虽然未来的临床结果对于评估患者的靶标有效性至关重要，但这些新型抑制剂是进一步研究 T 型通道在病理生理条件下作用的极好工具。
