Synthesis and biological activity of 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide derivatives

Abstract

The synthesis and antimicrobial evaluation of new 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide derivatives was investigated. According to the literature, there are a lot of antimicrobial agents among the pyrimidines and hydrazides, and therefore it seems promising to use 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide as a base object for synthesizing new biologically active substances. 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide was obtained by the hydrazinolysis of ethyl thioacetate, using a 3-fold molar excess of 85 % hydrazine hydrate in ethanol, at room temperature. Interaction of 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]­acetohydrazide with ketones during boiling in ethanol yielded N-ylidenehydrazides. The solid obtained by concentration was collected, and then purified by recrystallization. The new compounds were characterized by 1H, 13C NMR, IR spectroscopy and elemental analysis. The antibacterial and antifungal activities of the new compounds were analysed using agar diffusion and tenfold broth (pH 7.2 – 7.4) dilution methods, in comparison with the clinical used drugs, ceftriaxone and Pimafucin. The structure–activity studies showed that, depending on the nature of the hydrazide fragment, the newly synthesized compounds exhibited varying degrees of microbial inhibition. Within the same series the antimicrobial activity depends on the nature of the substituent attached to the benzene ring. The investigation of antibacterial screening data revealed that the compounds Nʹ-[1-(4-aminophenyl)ethylidene]-2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide, Nʹ-[1-(4-hydroxyphenyl)ethylidene]-2-[6-methyl-4-(thi­­etan­-3-yloxy)pyrimidin-2-ylthio]acetohydrazide, Nʹ-[1- (2,5-dihydroxyphenyl) ethylidene]-2-[6-methyl-4-(thietan-3-yloxy)-pyrimidin-2-ylthio]acetohydrazide were found to be more potent than the other synthesized analogues.

Synthesis and Structure of a Coordination Polymer of Ni(II) with 2-(4-Bromophenoxy)acetohydrazide

“…Drugs in the hydrazide functional group are an important category within antituberculosis, antibacterial, antifungal, and antimicrobial pharmaceuticals [1]. Hydrazides are considered key intermediates and valuable starting materials for synthesizing novel biologically active derivatives [1][2][3]. For example, hydrazide derivatives containing an aromatic fragment exhibit antibacterial and antifungal activities, the extent of which depends on the nature of the substituent attached to the benzene ring [2].…”

“…Hydrazides are considered key intermediates and valuable starting materials for synthesizing novel biologically active derivatives [1][2][3]. For example, hydrazide derivatives containing an aromatic fragment exhibit antibacterial and antifungal activities, the extent of which depends on the nature of the substituent attached to the benzene ring [2]. Benzotriazole-N-substituted acetohydrazide derivatives exhibit potent antiviral activity, characterized by their pronounced binding affinity and effective inhibition of glycoprotein B associated with Herpes Simplex Virus-I (HSV-I) [3].…”