Docking and Synthesis of 2-Arylisoindoline-1,3-dione Derivatives as Anticonvulsant Agents

作者：Davood Asghar^*; Azimidoost Liela; Shafaroodi Hamed; Amini Mohsen; Iman Maryam; Ansari Abdollah; Nikbakht Ali; Rahmatpour Somaieh; Nematollahi Ali Reza

来源：Pharmaceutical Chemistry Journal, 2014, 48(3): 175-180.

DOI：10.1007/s11094-014-1073-z

• Anticonvulsant
• Arylisoindoline
• Design
• Phenytoin
• Seizure

Antiepileptic drugs are used to prevent or reduce the occurrence of epileptic seizures, but up to 30 % of patients are resistant to the available medical therapies. Ten new analogs of 2-aryl substituent of isoindoline-1,3-dione have been synthesized and evaluated for their anticonvulsant activities. The in vivo screening data acquired indicate that all the analogs have the ability to protect mice against pentylenetetrazole-induced seizures. These compounds exerted their maximal effects 30 min after administration. The most potent compound was 4-triazolyl derivative (compound VIII). Using a model of the open pore of the Na channel, we have docked compound VIII. Docking studies have revealed that this ligand (i) interacts mainly with residues II-S6 of NaV1.2 by forming hydrogen bonds and (ii) has additional hydrophobic interactions with domains I and II in the channel inner pore.

• 出版日期2014-6