Synthesis, Characterization and Preliminary Pharmacological Evaluation of Triazolothiadiazoles Derived from some NSAIDs and Thiocarbohydrazide

Abstract

The synthesis of new NSAIDs with improved efficacy and selectivity towards COX2, which encouraged by the various biological activities of 1,2,4-triazoles and 1,3,4-thiadiazoles. In this experiment, the production of 1,2,4-triazolothiadiazoles derivatives from Ibuprofen, Naproxen and Indomethacin. We have enhanced anti-inflammatory and analgesic activities by conventional method and microwave-assisted technique, and then compare the time consuming by reaction and yield percent of the product in both way, besides evaluation of anti-inflammatory action of the target compounds by pharmacological test with predictable selectivity towards COX-2 enzyme. Synthesis of the target compounds (P1a-3b, N1a-3b and I1a-3b) has been successfully accomplished by checking purity, characterization, also identification of the synthetic compounds which detected by estimation of physical properties, FT-IR and ¹H-NMR spectroscopy. In vivo potent anti-inflammatory activity of the ending compounds is evaluating in rats utilizing egg-white prompted edema model of inflammation. The experienced compounds (P1a-3b, N1a-3b and I1a-3b) and the reference drugs (Ibuprofen, Naproxen and Indomethacin) produced significant reduction in paw edema in compare to the effect of control group. Wholly tested compounds produced considerable decrease of paw edema in contrast to control group. However, compounds (P3b, N3b and I1b) have considerable more paw edema declining than Ibuprofen, Naproxen and Indomethacin. Intermediate and target compounds are synthesis by microwave method have better result by time and yield in compare with conventional way. The synthesized compounds (Pa1-3b and N1a-3b) may exhibit expected selectivity towards COX-2 enzyme properly due to their large size than its parent Ibuprofen, Naproxen.