Synthesis, antioxidant, and antitumor evaluation of certain new N-substituted-2-amino-1,3,4-thiadiazoles

Reaction of 2-amino-1,3,4-thiadiazole (1) with chloroacetyl chloride afforded the chloroacetamide 2 which used as starting compound for the synthesis of 2-thiocyanatoacetamide 3 and N-(1,3,4-thiadiazol-2-yl)acetamides 5-9 via reaction of 1 with various reagents. Treatment of 9 with 4-(piperidin-1-yl)benzaldehyde or DMF-DMA afforded the arylidenes 10 and 11, respectively. Cyclization of the later compound with hydrazine hydrate gave the pyrazole derivative 12. Furthermore, coupling of 9 with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-diazonium chloride afforded hydrazone derivative 13, which cyclized in acetic acid to afford 1,2,4-triazine derivative 14. Moreover, 1,3,4-thiadiazoles 15, 19, 22, and 23 were achieved via reaction of 1 with different nucleophiles. Finally, 1-phenyl-1H-pyrazol-5(4H)-one when subjected to react either with 15 or with diazonium salt of 1 afforded pyrazole derivative 16 or bis-1,3,4-thiadiazole derivative 18, respectively. Some of these compounds were screened for their cytotoxicity and antioxidant activities which showed promising results. In an effort to establish new candidates with improved activities, we reported herein the synthesis and antitumor and antioxidant evaluation of various series of N-substituted-2-amino-1,3,4-thiadiazoles. Newly synthesized compounds were characterized by (IR, H-1 NMR, C-13 NMR, high resolution mass spectra, and mass spectra). The representative compounds were evaluated as antitumor and antioxidant activities. Some of the prepared compounds exhibited promising activities.