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异吲哚啉-1,3-二酮衍生物作为抗惊厥药物发现的原型

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

作者信息

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

机构信息

São Paulo State University - UNESP, School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil.

出版信息

Med Chem. 2025 Jan 9. doi: 10.2174/0115734064336758241113180402.

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.

摘要

引言

癫痫包括许多综合征,其特征是大脑中出现自发、间歇性和异常的电活动。据估计,癫痫影响着约1%-2%的人口,约30%-40%的患者患有难治性癫痫,对传统抗惊厥药物无反应。

目的

因此,开发新型、安全且有效的抗癫痫药物仍然是医学上的需求。在本研究中,我们合成了一系列异吲哚啉-1,3-二酮衍生物并评估了它们的抗惊厥作用。

结果

得到了化合物(2a-j)和(5),产率在52%-97%之间。评估了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,以及c)发作后的死亡率。活性最高的化合物(2a)延长了发作潜伏期,缩短了发作持续时间,并降低了死亡率。

结论

这些发现表明化合物(2a)是一种有前景的新型抗癫痫原型药物,为当前的抗癫痫药物提供了一种替代选择。

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