A series of novel 4-amino-5-mercapto-3-[(3-aralkyl amido/imidoalkyl) phenyl]-1,2,4-triazoles (5a-d) were obtained by treating m-(aralkyl amido/imidoalkyl) benzoic acid hydrazides (3a-d) with carbon disulphide in alcoholic KOH and hydrazine hydrate, respectively. These triazole derivatives were employed in the synthesis of 5-[(3′-aralkyl amido/imidoalkyl) phenyl]-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (6a-d). The newly synthesized compounds were evaluated for their antiviral activity against two animal viruses, namely, Japanese encephalitis virus (JEV) strain P20778 and herpes simplex virus-1 (HSV-1) strain 753166. 1. Introduction Heterocycles bearing a symmetrical triazole or 1,2,4-triazole scaffold are the structural element of many drugs that have diverse pharmacological activity. The 1,2,4-triazole derivatives are extensively applicable in medicine, namely, alprazolam (tranquilizer), estazolam (hypnotic, sedative, and tranquilizer), rilmazafone (hypnotic, anxiolytic, used in the case of neurotic insomnia), benatradin (diuretic), trapidil (hypotensive), trazodone (antidepressant, anxiolytic), etoperidone (antidepressant), nefazodone (antidepressant, 5-HT2A-antagonist), anastrozole (antineoplastic, nonsteroidal aromatase inhibitor), letrozole (antineoplastic, aromatase inhibitor), ribavirin (antiviral), fluconazole, itraconazole, terconazole (antifungal), and so forth [1]. Furthermore, biheterocyclic compounds bearing a triazole moiety and another heterocyclic moiety combined in one molecular union are also eminent to possess broad spectrum of biological activities, one such imperative being triazolo thiadiazine derivatives [2]. Substituted 1,2,4-triazolo-1,3,4-thiadiazines are reported to possess antifungal, antibacterial, and anticancer activities [3–6]. Additional bioactivity shown by such molecules includes antitubercular, anti-inflammatory, and antimolluscicidal [7, 8]. Significant antiviral activity of such compounds has not been attained however, but the extensive range of the biological effects exhibited by them has engrossed scientists to work on their antiviral effects [9, 10]. Moreover, reports on the activity of triazolo thiadiazines on viruses such as herpes simplex virus (HSV-1) and Japanese encephalitis virus (JEV) are rare. With no established antiviral therapies available, the only way of prevention is vaccination that is in vogue since the safety of their administration is questionable in certain individuals [11]. Our current endeavor in this direction is therefore the synthesis of a series of 5-[(3′-aralkyl amido/imidoalkyl)
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