Synthesis and Biological Activity Evaluation of Some New Coumarin Derivatives as Potent Anticonvulsant and CNS-Depressant Agents

Abstract

Triazolo-thiadiazines 4a–f and triazolo-tetrazines 8g–l were prepared from reaction of 3-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)-2H-chromen-2-one with the respective hydrazonoyl halides 2a–f and 2g–l. Moreover, the reaction of the aminomercaptotriazole derivative with phenacyl bromide and ethyl 2-chloro-3-oxobutanoate followed by the coupling reaction of the products with benzenediazonium chloride yielded the corresponding products 4f and 8g, respectively. All of the newly prepared heterocyclic derivatives were determined using spectral data, elemental analysis, and alternate methods. The in-vivo anticonvulsant and CNS-depressant activities of all the prepared derivatives were tested using the maximal electroshock method and showed excellent activities, especially triazolo[4,3-b]tetrazine derivatives 8j, 8k, and 8l. Additionally, their structure–activity relationship was proven clearly, demonstrating that electron-releasing groups increase activities while electron-withdrawing groups lower them.

Keywords:

• Anticonvulsant
• CNS-depressant activities
• epilepsy
• hydrazonoyl halides
• 1,2,4-triazolylchoumarins
• triazolotetrazines
• triazolothiadiazines

Additional information

Funding

Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2022R24), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.