Synthesis and characterization of pyrazinamide derivative of Imidazo[2,1-b][1,3,4]thiadiazole, a potential anti-tubercolosis drug

• Main Authors: Dela Cruz, Derrick Emjae Gabriel T., Eslava, Sheilu G., Alea, Glenn V., Ajero, Michael Dominic M., Lagua, Faith Marie G.
• Format: text
• Published: Animo Repository 2019
• Subjects: Imidazoles—Derivatives; Antitubercular agents; Pyrazinamide; Chemicals and Drugs
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/11447
• Institution: De La Salle University

Despite the availability of first- and second-line drugs for the treatment of tuberculosis, the increasing prevalence of multi-drug resistance and extensively drug-resistant strains of Mycobacterium tuberculosis still poses a major threat to global health. With this, researchers are motivated to design and synthesize new molecules that possess promising anti-tubercular properties. Imidazo[2,1- b][1,3,4]thiadiazole derivatives have diverse pharmacological properties, one of which is that derivatives of this core molecule have been proven to have anti-tuberculosis properties. In this research, apyrazinamide derivative of Imidazo[2,1-b][1,3,4]thiadiazole (6) was synthesized and characterized. It was generated in four steps that involved the formation of athiadiazole derivative containing a propyl group followed by the formation of the imidazo[2,1-b][1,3,4]thiadiazole core incorporating the 4- chlorophenyl group. Finally, an aldehyde group on the 5th position generated via a Vilsmeier-Haack reaction enabled the attachment of the pyrazinamide moiety via imine bond formation with 2-pyrazinehydrazide.Compound 6 was generated as a yellow brownish solid in 66% yield. This molecule may serve as a potential anti- tuberculosis drug due to the coupling of the pyrazinamide drug moiety and an Imidazo[2,1-b][1,3,4]thiadiazole core. The identity and structure of all the precursor compound and the final compound were confirmed usingm.p., IR, GC-EI-MS, and 1H- NMR methods.