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Abstract

The 1,2,4-triazole nucleus constitutes an integral component in drug discovery. It has been incorporated into both non-bridged drugs such as anastrozole (anticancer) [1,2], ribavirin (antiviral) [1,3], fluconazole, voriconazole (antifungal agents) [4] and in biologically active N-bridged drugs like triazolam (sedative agent) [1,5], estazolam and alprazolam (anxiolytic agents) [1,6,7]. The 1,3,4-thiadiazoles have attracted more interest to the researchers due to their prominent biological properties including anticonvulsant, anti-tubercular, anti-inflammatory, antileishmanial, antioxidant [8], antimicrobial and antidepressant activities [8,9]. There are also many drugs containing the 1,3,4-thiadiazole moiety such as acetazolamide, megazol and methazolamide [10]. Interestingly, some current reports showed that the fusion of the biolabile 1,2,4-triazole with 1,3,4-thiadiazole rings affords fused bicyclic compounds with improved biological activities than their corresponding non-bridged precursors. These include some ibuprofen-based 1,2,4-triazolo[3,4-b]-1,3,4thiadiazoles with enhanced anti-inflammatory and analgesic properties than precursor ibuprofen [11-13], and some naproxen-based 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles with enhanced analgesic, ulcerogenic, anti-inflammatory, and lipid peroxidation activities than starting naproxen [14]. Furthermore, N-(heteroarylmethyl) aniline derivatives with varied potent activities such as antimicrobial [15,16], antifungal, anticancer [17,18], herbicidal [19] and analgesic [20] were also reported. Prompted by these observations and in continuation of our research for new bioactive fused heterocycles [21,22], we herein describe the synthesis of a new series of 6-arylaminomethyl-3substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles as promising antioxidant agents. Materials and Methods ChemistryThe Innovative DTC-967A apparatus was used to determine the melting points of the newly synthesized compounds and the results are uncorrected. The IR-spectra were recorded on Shimadzu FT-IR Prestige-21 spectrophotometer in KBr pellets and are expressed in cm -1 . The mass spectra were recorded on a Shimadzu LC-MS-8030 mass spectrometer operating at 70 eV. The 1 H-NMR spectra were recorded on a Bruker Avance II 400 MHz instrument in DMSO-d 6 solvent and TMS as an internal standard. All chemical shift values were reported as δ (ppm), downfield from TMS. The Systronics spectrophotometer 106 was used to record the absorbance of DPPH radical scavenging antioxidant assay. The C, H, N analysis was carried out on Vario EL III Elemental Analyzer. The completion of the reaction and the purity of the compounds were monitored by