Synthetic and anticonvulsant studies of some new pyridine derivatives

Abstract

Epilepsy is a rapidly growing neurological disorder that affects about 1% of world’s population. The present medications could able to control the seizure generation but none of the developed drugs are able to cure the disease completely. As a result, demand for new and efficient antiepileptic agents is growing day by day. In this connection, it was contemplated to synthesize new active antiepileptic agents. Based on the literature survey, new DHP and imidazo[1,2-a]pyridine derivatives carrying biologically active pharmacophores (P1-138) were designed as possible anticonvulsant agents. The newly designed compounds were later successfully synthesized following the appropriate synthetic routes. Further, their synthetic methods as well as purification techniques were established and their yields were optimized. They were later characterized by various spectral techniques such as FTIR, 1H NMR, 13C NMR, mass spectral followed by elemental analyses. Finally, the target compounds were screened for their antiepileptic studies following Maximal Electroshock Seizure (MES) and subcutaneous Pentylene Tetrazole (scPTZ) methods. Further, the neurotoxicity study of target compounds was performed by Rotarod technique, in order to establish their toxicity profile. At the end, based on the in vivo results, their Structure-Activity Relationship (SAR) was discussed. The in vivo results of preliminary anticonvulsant screening study indicated that newly synthesized DHPs carrying hydrazone and amide functionalities (P1-40) are moderately active antiepileptic agents in MES method. On the other hand, significant activity was observed for new imidazo[1,2-a]pyridines (P41-138) carrying various pharmacophores at position-2 and position-3. Particularly, those imidazo[1,2- a]pyridines carrying oxazolone, cyanopyridone, 1,2,3-triazole, 1,2,4-triazole and hydrazone groups exhibited pronounced activity. Interestingly, the Rotarod study revealed that most of the tested compounds are non-toxic, which further appreciated the choice of new derivatives as antiepileptic agents. Altogether, the suitably substituted new imidazo[1,2-a]pyridines carrying electron donor groups appeared as active templates for future development of new antiepileptic agents.