Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologique, Université Paris Descartes, PRES Sorbonne Paris Cité, CNRS UMR 860, 45, rue des Saints Peres, 75006 Paris, France.
CQM-Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal.
Molecules. 2020 Jul 22;25(15):3320. doi: 10.3390/molecules25153320.
The 1,3-benzothiazole (BTZ) ring may offer a valid option for scaffold-hopping from indole derivatives. Several BTZs have clinically relevant roles, mainly as CNS medicines and diagnostic agents, with riluzole being one of the most famous examples. Riluzole is currently the only approved drug to treat amyotrophic lateral sclerosis (ALS) but its efficacy is marginal. Several clinical studies have demonstrated only limited improvements in survival, without benefits to motor function in patients with ALS. Despite significant clinical trial efforts to understand the genetic, epigenetic, and molecular pathways linked to ALS pathophysiology, therapeutic translation has remained disappointingly slow, probably due to the complexity and the heterogeneity of this disease. Many other drugs to tackle ALS have been tested for 20 years without any success. Dexpramipexole is a BTZ structural analog of riluzole and was a great hope for the treatment of ALS. In this review, as an interesting case study in the development of a new medicine to treat ALS, we present the strategy of the development of dexpramipexole, which was one of the most promising drugs against ALS.
1,3-苯并噻唑（BTZ）环可能为从吲哚衍生物中进行支架跳跃提供了一个有效的选择。有几种 BTZ 具有临床相关作用，主要作为中枢神经系统药物和诊断剂，其中利鲁唑是最著名的例子之一。利鲁唑是目前唯一被批准用于治疗肌萎缩侧索硬化症（ALS）的药物，但疗效有限。几项临床研究表明，它仅对患者的生存时间有一定的改善，对运动功能没有益处。尽管为了了解与 ALS 病理生理学相关的遗传、表观遗传和分子途径进行了大量的临床试验，但治疗的转化仍然令人失望地缓慢，这可能是由于该疾病的复杂性和异质性。为了治疗 ALS，许多其他药物已经进行了 20 年的测试，但都没有成功。Dexpramipexole 是利鲁唑的 BTZ 结构类似物，曾是治疗 ALS 的一大希望。在这篇综述中，作为治疗 ALS 的新药开发的一个有趣案例研究，我们介绍了 dexpramipexole 的开发策略，它是最有前途的 ALS 治疗药物之一。
