SYNTHESIS, SPECTRAL CHARACTERISTICS, AND COMPREHENSIVE IN SILICO ANALYSIS OF A NEW METHYLTRIAZOLE DERIVATIVE

RDGDYJ

Abstract

The search for new effective and safe drugs remains a relevant task for medicinal chemistry. 1,2,4-Triazole derivatives are being actively studied as promising candidates for designing new drugs, including those with antitumor activity. This is due to the wide range of biological activity and structural diversity of compounds that structurally contain triazole heterocycles. In this work, a targeted synthesis of a new bioactive derivative based on the 1,2,4-triazole scaffold was performed via nucleophilic substitution of ethylene chlorohydrin for the nitro group in 2-methyl-3-nitro-1,2,4-triazole in the presence of a base. The interaction is shown to proceed predominantly in the specified direction to form a C3-substituted chloroethoxy derivative of 1,2,4-triazole. The structure of the new compound was reliably confirmed by ¹Н,¹³С NMR and IR spectroscopy. The comprehensive in silico assessment of the biological activity, key physicochemical parameters, pharmacokinetic profile (SwissADME), and toxicity (ProTox 3.0) of the synthesized triazole derivative was performed by computer-aided prediction methods (PASS Online). The methyl triazole framework combined with the chlorine-containing alkyl substituent provides the target compound with high (Pa = 0.868) antitumor activity against solid tumors, a favorable set of physicochemical properties, full compliance with the drug-likeness criteria (according to the rules of Lipinski, Veber, and Egan), high predicted oral bioavailability (0.55), and low toxicity (LD50 = 500 mg/kg, toxicity class 4). The findings demonstrate that the developed triazole derivative holds much promise as a candidate for further research as an orally active antitumor agent.