Pyrrolopyridine and Isoindole as potential anticonvulsant agents: Design, synthesis and pharmacological evaluation.

Abstract

BACKGROUND AND OBJECTIVE Phthalimide as the rigid form of ameltolide exhibits a phenytoin-like profile of drug-receptor interaction and is active in the MES model and inactive in the PTZ model as anti-epileptic agent. In this research, based on the isosteric replacement, we have reported the design, preparation, and antiepileptic activity of 13 new analogs of pyrrolopyridine and isoindole. METHODS The designed compounds were prepared by condensing 3, 4-pyridine dicarboxylic anhydride or 4-fluorophthalic anhydride with different respective aryl amines. MES and PTZ induced seizure models were done to evaluate the antiepileptic effect of the prepared ligands. RESULTS The prepared ligands have significantly affect both tonic and clonic seizures. In tonic seizures, the prepared compounds decrease mortality to a significant extent and in clonic seizures showed better frequency and latency significantly. Compounds 9, 12 and 13 were the most potent ligands that were more potent than phenytoin. CONCLUSION It is concluded that the best distance between two aryl parts is two bonds and the substitution of the nitro group at the meta position of the phenyl ring is better than para position. Our research group has been investigating this concept for designing newer compounds with better anticonvulsant activity.