Features of the vegetative state and arterial pressure level in children with chronic gastroduodenal pathology
DOI:
https://doi.org/10.14739/2409-2932.2018.3.144557Keywords:
1, 2, 4-triazole, 3-methylxanthine, physical-chemical properties, molecular dockingAbstract
Introduction. Heterocyclic compounds are the foundation on which the creation of medicines is successfully carried out. One such system is 1,2,4-triazole and 3-methylxanthine. These heterocycles are characterized by wide range of biological properties, along with low toxicity.
The purpose of this work was to synthesize and investigate the properties of N-R-amides and hydrazides 2-[4-R-5-(3'-methylxanthine-7'-yl)-1,2,4-triazole-3-ylthio]acetic acid (R = CH3, C2H5, C6H5) when changing the conditions of the chemical process.Methods and results. As initial key reagents we used 7'-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)-3'-methylxanthine and ethers of 2-[4-R-5-((3'-methylxanthine-7'-yl)methyl)-1,2,4-triazole-3-ylthio]acetic acid, which were prepared according to known procedures from available raw materials. In the course of studies, it was found that when heated in ethanol the corresponding primary or secondary alkylamines (methylamine, ethylamine, monoethanolamine, diethylamine) or ammonia solution from prop-1-yl 2-[4-R-5-((3'-methylxanthine-7'-yl)methyl)-1,2,4-triazole-3-ylthio]ethanoate, then the corresponding amidated derivatives of 2-[4-R-5-((3'-methylxanthine-7'-yl)methyl)-1,2,4-triazole-3-ylthio]acetic acid are created. The corresponding amides were obtained by reacting 7'-((3-thio-4-R-4H-1,2,4-triazol-5-yl)methyl)-3'-methylxanthine with 2-chloroacetamide in a high yield sodium hydroxide medium. Hydrazides of 2-[4-R-5-((3'-methylxanthine-7'-yl)methyl)-1,2,4-triazole-3-ylthio]-ethane acid are synthesized by the interaction of the corresponding esters of 2-[4-R-5-((3'-methylxanthine-7'-yl)methyl)-1,2,4-triazole-3-ylthio]acetic acid with an aqueous hydrazine hydrate solution in ethanol. The structure of the obtained compounds is confirmed by the data of elemental analysis, 1H NMR spectroscopy, IR-spectrophotometry. Individuality was established using thin-layer chromatography and chromatography-mass spectrometry. For synthesized compounds, preliminary screening was performed using the PASS On-line® software and molecular docking.The optimal methods for the preparation hydrazides and amides of 2-[4-R-5-((3'-methylxanthine-7'-yl)methyl)-1,2,4-triazole-3-ylthio]ethane acid were developed. The production of amides in two alternative pathways using the starting thiol and the ester, derived from it, was studied: it was established that the interaction of the starting thiol with 2-chloroacetamide runs with a larger yield of the reaction product in comparison with the reaction of the corresponding ester with ammonia. The results of physical-chemical analysis of synthesized compounds was interpreted. This preliminary assessment of the possible manifestation of anti-inflammatory activity was given. The probability of manifestation of this type of activity was not high.Conclusions. 19 amides and 3 hydrazide of 2-[4-R-5-((3'-methylxanthine-7'-yl)methyl)-1,2,4-triazole-3-ylthio]ethane acid were obtained with high yields and purity, their structure was proven and properties were investigated.References
Anshul, C., & Amanpreet, K. (2014) Extensive study on microwave assisted synthesis of monocyclic heterocyclic compounds. International journal of universal pharmacy and bio sciences, 3(1), 133–135.
Bechara, W. S., Khazhieva, I. S., Rodriguez, E., & Charette, A. B. (2015) Synthesis of 3,4,5-trisubstituted 1,2,4-triazoles via the addition of hydrazides to activated secondary amides. Org. Lett., 17(5), 1184–1187. doi: 10.1021/acs.orglett.5b00128.
Chenglu, Zhang, Huan, Xi, Yuting, Sha, Xiaona, Sun, Chuanyin, Li, Jing, Wang, & Yizheng, Li. (2017) Synthesis and bioactivity of novel bis-heterocyclic amide modified sulfide derivatives. Chinese Journal of Applied Chemistry, 34(3), 308–315. doi: 10.11944/j.issn.1000-0518.2017.03.160352.
El-Wahab, H., Hamdy, A.-R. M., Gamal-Eldin, S. A., & El-Gendy, M. A. (2011) Synthesis, biological evaluation and molecular modeling study of substituted 1,2,4-triazole-3-acetic acid derivatives. Der Pharma Chemica, 3(6), 540–552.
Franklim, T. N., Freire-de-Lima, L., Diniz, J., Previato, J., Castro, R., Mendonça-Previato, L., & Lima, M. (2013) Synthesis and trypanocidal evaluation of novel 1,2,4-triazoles-3-thiones derived from natural piperine. Molecules, 18, 6366–6382. doi: 10.3390/molecules18066366.
Pachuta-Stec, A., Kosikowska, U., Chodkowska, A., Pitucha, M., Malm, & A., Jagiełło-Wójtowicz, E. (2012) Biological activity of novel N-substituted amides of endo-3-(3-methylthio-1,2,4-triazol-5-yl)bicyclo[2.2.1] hept-5-ene-2-carboxylic acid and N-substituted amides of 1-(5-methylthio-1,2,4-triazol-3-yl)cyclohexane-2-carboxylic acids. Z. Naturforsch, 67, 123–128. doi: 10.5560/ZNC.2012.67c0123.
Ruping, T., Linhong, J., Mou, C., Yin, J., Bai, S., Hu, D., et al. (2015) Synthesis, antifungal and antibacterial activity for novel amide derivatives containing a triazole moiety. Chemistry Central Journal, 7, 30. doi: 10.1186/1752-153X-7-30.
Sydorenko, L. V., Ukrainets, I. V., & Alieksieieva, T. B. (2009) Syntez ta vyvchenia antymikobakterialnoi aktyvnosti monoftorbenzylamid 1-R-4-hidroksy-2-okso-1,2-dyhidrokhinolin-3-karbonovykh kyslot [The synthesis and study of the antimycobacterial activity of monofluorobenzylamides of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids]. Visnyk farmatsii, 2(58), 12–15. [in Ukrainian]
Ukrainets, I. V., Sydorenko, L. V., Horokhova, O. V., et al. (2004) Syntez, budova ta protytuberkulozni vlastyvosti N-R-amidiv1-tsyklopropil-2-okso-4-hidroksy-1,2,5,6,7,8-heksahidrokhinolin-3-karbonovi kysloty [Synthesis, structure and anti-tuberculosis properties of N-R-amides 1-cyclopropyl-2-oxo-4-hydroxy-1,2,5,6,7,8-hexahydroquinoline-3-carboxylic acid]. Visnyk farmatsii, 2(38), 7–12. [in Ukrainian]
Ukrainets I. V., Sidorenko L. V., Horokhova O. V. (2004) Syntez, budova ta protytubercuberculozni vlastyvosti N-R-amidiv 1-tsyklopropil-2-okso-4-hidroksy-1,2,5,6,7,8-heksahidrohinolin-3-karbonovikysloty. Visnyk farmatsii, 2(38): 7-12. [in Ukrainian].
Vikas, G. R., Kiran, G., & Vinayak, D. (2014) Synthesis, characterization and study of some N-substituted aryl-2-({4-[(substituted Aryl carbamoyl)methyl]-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl}sulfanyl)acetamide. Iranian Journal of Pharmaceutical Sciences, 10(2), 21–34.
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
