Synthesis and broncholytic activity of N-alkylpiperazino-substituted uracil and xanthine

Meshcheryakova, S. A.; Катаев, В. А.; Galimova, Rozalia Akramovna

doi:10.1007/s11094-013-0938-x

Cited by 3 publications

(2 citation statements)

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“…The pyrimidine fragment has been gaining special interest as it is part of many biological active compounds: vitamins, nucleotides and nucleosides. Our research group has published much research in the field of the synthesis of thietan derivatives [ 8 , 9 ] as they possess a broad spectrum of bioactivities: antimicrobial [ 10 , 11 ], hypotensive [ 12 , 13 ], broncholytic [ 14 ] and wound healing [ 15 , 16 ]. Compounds containing thietan and pyrimidine in their molecules are suitable candidates for further chemical modifications and may be pharmacologically active.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Its pyrimidine skeleton exists in many natural products such as vitamin B 1 (thiamine) and many synthetic compounds, that posses antibacterial, antifungal, antileishmanial, anticancer, anti‐inflammatory, and analgesic activities hence, they attract considerable attention in the design of biologically active molecules (Sharma, Rane, & Gurram, 2014; Agarwal, et al, 2002; Agarwal, et al, 2000; Ram, Haque, & Guru, 1992; Prachayasittikul, et al, 2017; Xie, Zhao, H., Zhao, L., Lou, & Hu, 2009; Amir, Javed, & Kumar, 2007; Sondhi, Jain, Dwivedi, Shukla, & Raghubir, 2008; Vega, Alonso, Diaz, & Junquera, 1990). Our research group investigate innovative thietan derivatives as they posses a broad spectrum of bioactivities: antimicrobial, broncholytic and wound healing (Kataev, Meshcheryakova, Lazarev, & Kuznetsov, 2013; Kataev, et al, 2018; Meshcheryakova, Kataev, Fattakhova, Nikolaeva, & Bulgakov, 2015; Meshcheryakova, Kataev, Munasipova, Shumadalova, & Bulgakov, 2017; Meshcheryakova, Kataev, & Galimova, 2013; Gabdrakhmanova, et al, 2019; Khaliullin, et al, 2021; Spasov, et al, 2017; Smirnova, et al, 2021). Structural modification of uracil by adding thietan fragment is an efficient way to get new antimicrobial compounds.…”

Section: Introductionmentioning

confidence: 99%

Innovative antimicrobial substances based on uracil S‐derivatives

et al. 2021

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The problem of antimicrobial resistance is an important global public health challenge.We propose that a development of new antibiotic compounds around known natural substances is a solution to this problem. We investigate reengineer natural products into potent antibiotics. Uracil fragment is abundant in nature and significant to treat infectious diseases due to its affection to the replication of the bacterial chromosome.12 new uracil S-derivatives were obtained and tested for their in vitro antimicrobial properties. N 3 -(thietan-3-yl)-and N 3 -(1,1-dioxothietan-3-yl)uracils derivatives were synthesized by thietanylation of 6-methyluracil with 2-chloromethylthiirane and subsequent oxidation of the thietan ring. A method of their alkylation with ethyl-2-chloroacetate was developed and acetohydrazides containing 3-(thietan-3-yl)-and 3-(1,1-dioxothietan-3-yl)uracilyls fragments in the acetyl group were obtained by hydrazinolysis of 2-(thietanyluracil-1-yl)acetic acid ethyl esters. Their interaction with β-dicarbonyl compounds, anhydride of mono-and dicarboxylic acids was studied.Antimicrobial activity was determined by the agar diffusion method on test organisms: S. aureus, E. coli, P. vulgaris, K. pneumoniae, C. diversus, E. aerogenes, P. aeruginosa, S. abosit. N-acyl-5-hydroxypyrazolines and N,N 0 -diacylhydrazines of 6-methyluracil thietanyl-and dioxothietanyl derivatives showed high antimicrobial activity, which is consistent with the results of structure activity relationship analysis (MIC 0.1-10 μg/ml).

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Three Heterocyclic Rings Fused (6-5-6)

Sączewski

Fedorowicz

2022

Comprehensive Heterocyclic Chemistry IV

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Synthesis and broncholytic activity of N-alkylpiperazino-substituted uracil and xanthine

Cited by 3 publications

References 2 publications

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

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

Innovative antimicrobial substances based on uracil S‐derivatives

Three Heterocyclic Rings Fused (6-5-6)

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