Synthesis and Anticonvulsant Activities of Some Triazolothiadiazole Derivatives

Abstract

The present study describes the synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (4a-4x) and their partially dehydrogenated products 5,6-dihydro-6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (5a-5n). The bioevaluation demonstrated that most compounds in the series of 4a-4x exhibited potent anticonvulsant activity in the maximal electroshock test. Among which, 6-(4-chlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4h) emerged as the most promising candidate on the basis of its favorable ED(50) value of 23.7 mg/kg and PI value of 10.8. In addition, the potency of compound 4h against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemical-induced seizure tests suggested that compound 4h displayed broad-spectrum activity in several models, and it may exert its anticonvulsant activity through affecting the GABAergic system.

Design, Synthesis, Neuroprotective and Antibacterial Activities of 1,2,4‐Triazolo[3,4‐b]1,3,4‐thiadiazole Linked Thieno[2,3‐d]pyrimidine Derivatives and In Silico Docking Studies

“…Similarly 1,2,4‐triazoles also have immense importance in chemistry, since a large number of 1,2,4 triazoles have been incorporated into a variety of biologically active compounds possessing antimicrobial,, antiproliferative, antitubercular,, anti‐inflammatory, insecticidal, anticonvulsant, anticancer activities. Some of the existing important drugs having 1,2,4 triazole nucleus are Itraconazole, Fluconazole, Posaconazole, Ravuconazole, Voriconazole (antimicrobial drugs), Vorozole, Letrozole Anastrozole (breast cancer drugs), Ribavirin (antiviral), Alprazolam, Etizolam (antianxiolytic), these are demonstrating the importance of 1,2,4 triazole in present medicinal chemistry. Moreover, combined heterocyclic derivatives of 1,2,4 triazole and 1,3,4‐thiadiazole (i.e 1,2,4‐triazolo[3,4‐b]1,3,4‐thiadiazole) are found to have diverse biological activities including anticancer,, antitumor, anti‐inflammatory, anticonvulsant and antimicrobial (VII) activities etc.…”

Transformation of 1,2,3‐Thiadiazolyl Hydrazones as Method for Preparation of 1,2,3‐Triazolo[5,1‐b][1,3,4]thiadiazines

“…Synthesis of condensed 1,2,4‐triazoles from 4‐amino‐3‐mercapro‐1,2,4‐triazole have been reported in literature widely . Preparation of structurally related condensed 1,2,3‐triazoles from 1‐amino‐5‐mercapto‐1,2,3‐triazoles was observed only for few examples .…”

Synthesis and biological evaluation of new quinazolinone derivatives

“…It is also well established that varion derivatives of 1,3,4thiadiazole exhibit broad spectrum of pharmacological properties such as anticonvulsant [12] and liver enzymes inhibition [13].…”