DESIGN, FACILE SYNTHESIS, AND BIOLOGICAL EVALUATION OF NOVEL 1,3-THIAZINE DERIVATIVES AS POTENTIAL ANTICONVULSANT AGENTS

摘要

Objective: Chalcones and their heterocyclic analogs represent an important class of small molecules having anticonvulsant activities. Therefore, in this study, the synthesis and anticonvulsant activity of some new chalcones and 1,3-thiazines were described. Methods: The reaction of 1-acetylnaphthalene with substituted aromatic aldehydes in the presence of aq. NaOH afforded corresponding chalcones which upon further cyclization with thiourea resulted in 1,3-thiazine derivatives. The newly synthesized compounds were tested for anticonvulsant activity by pentylenetetrazole-induced seizures method using diazepam as standard. Results: Most of the compounds showed good anticonvulsant activity but is less than diazepam. 1,3-thiazines were more potent than chalcones and among them, compound P4 containing 4-fluorophenyl substituents on the thiazine moiety was more potent as it has prolonged the onset of convulsions by 155.2 seconds. Conclusion: We described the synthesis and anticonvulsant activity of novel chalcones and 1,3-thiazine derivatives. 1,3-thiazines are more active anticonvulsant agents than chalcones and in particular compounds with electron withdrawing substituents.