Isoindoline-1,3-dione Derivatives as Prototypes for Anticonvulsant Drug Discovery.

IF 1.9 4区医学 Q3 CHEMISTRY, MEDICINAL

Medicinal Chemistry Pub Date : 2025-01-09 DOI:10.2174/0115734064336758241113180402

Rafael Consolin Chelucci, Richard Chiquetto, Diego Eidy Chiba, Cauê Benito Scarim, Chung Man Chin, Jean Leandro Dos Santos

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引用次数: 0

Abstract

Introduction: Epilepsy encompasses numerous syndromes characterized by spontaneous, intermittent, and abnormal electrical activity in the brain. Affecting about 1-2% of the population, it is estimated that approximately 30-40% of patients experience refractory epilepsy, which does not respond to traditional anticonvulsant drugs.

Aims: Therefore, developing novel, safe, and effective antiepileptic drugs remains a medical need. In this study, we synthesized a series of isoindoline-1,3-dione derivatives and evaluated their anticonvulsant effects.

Results: Compounds (2a-j) and (5) were obtained with yields ranging from 52-97%. These compounds were assessed for their protective effects on the following parameters: a) time to first seizure (seizure latency), b) seizure duration, and c) mortality rate post-seizure. The most active compound, (2a), increased seizure latency, reduced seizure duration, and lowered the mortality rate.

Conclusion: These findings indicate that compound (2a) is a promising new anticonvulsant prototype, offering an alternative to current anticonvulsant drugs.

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异吲哚-1,3-二酮衍生物作为抗惊厥药物发现的原型。

简介：癫痫包括许多以自发性、间歇性和异常脑电活动为特征的综合征。该病影响约1-2%的人口，估计约有30-40%的患者患有难治性癫痫，这对传统抗惊厥药物无反应。目的：因此，开发新型、安全、有效的抗癫痫药物仍然是一种医学需求。本研究合成了一系列异吲哚-1,3-二酮衍生物，并评价了它们的抗惊厥作用。结果：得到化合物（2a-j）和(5)，收率在52% ~ 97%之间。评估这些化合物对以下参数的保护作用：a)首次发作时间（发作潜伏期），b)发作持续时间，c)发作后死亡率。最有效的化合物（2a）增加了癫痫发作潜伏期，缩短了癫痫发作持续时间，降低了死亡率。结论：化合物（2a）是一种很有前景的新型抗惊厥药物原型，为现有的抗惊厥药物提供了一种替代方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medicinal Chemistry 医学-医药化学

CiteScore

4.30

自引率

4.30%

发文量

109

审稿时长

12 months

期刊介绍： Aims & Scope Medicinal Chemistry a peer-reviewed journal, aims to cover all the latest outstanding developments in medicinal chemistry and rational drug design. The journal publishes original research, mini-review articles and guest edited thematic issues covering recent research and developments in the field. Articles are published rapidly by taking full advantage of Internet technology for both the submission and peer review of manuscripts. Medicinal Chemistry is an essential journal for all involved in drug design and discovery.