Design, Synthesis And Study Of Anticonvulsant Activity Of Novel Triazole And Quinoline Derivatives

Epilepsy is a syndrome caused by multiple pathological processes in the brain. Approximately 2 million people worldwide are diagnosed with epilepsy annually, making epilepsy one of the most common of the serious neurological disorders. Current available drugs could only produce satisfactory seizure control for 60～70% of all patients, while some 30% of patients show no positive response to current therapeutic approaches at all and side effect such as sedation, neuron injury are frequently occurred. Thus, the discovery of novel antiepileptic drugs (AEDs) with improved safety, lowered toxicity and greater effectiveness is an appealing task.In this dissertation, a series of twenty-four 1,2,3-triazole derivatives was designed and synthesized based on rational drug design principles using rufinamide as the lead compound. The 1,2,3-triazole core scaffold and carboxamide subsituent of rufinamide were retained, while modifications were focused on replacing the phenyl ring with substituted aromatic heterocycles. Another series of fifteen 1,2,4-triazole derivatives was designed and synthesized adopting bioisosteric principles. Taking retigabine as the lead compound, cyclization of the 4-aniline group and replacement of the fluorobenzene moiety with different substituted heterocycles afford four 1,2,3,4-tetrahydroquinoline derivatives. A total of 43 novel compounds were synthesized and structurally confirmed by 1H NMR and MS. Synthesized 1,2,3-triazoles and 1,2,4-triazoles were tested for their anticonvulsant activities which showed that most compounds exhibited potent anticonvulsant activities with compounds 1-84,1-87,1-98,2-17,2-19,2-21,2-24,2-26 and 2-29 possessed excellent anticonvulsant activities superior to that of the lead compound. These results pave the way for further work of the design of highly effective antiepileptic drugs.