Synthesis and physical-chemical properties of 6-(5-(1Н-tetrazole-1-ylmethyl)-4-R-1,2,4-triazole-3-ylthio)pyridin-3-amines and 6-((5-(1Н-tetrazole-1-yl)methil-4-R-1,2,4-triazole-3-ylthio)pyridin-3-yl)-(alk,ar,heter)ylmethanimines
DOI:
https://doi.org/10.14739/2310-1210.2017.1.91726Keywords:
1, 2, 4-triazole, 1H-tetrazole, synthesis, physical-chemical propertiesAbstract
Over the past decade the number of publications, that contain different aspects of chemistry and use of triazoles and tetrazoles have been doubled and continues to grow. Puplications of recent years show that heterocycles with 1,2,3,4-teterazoles and 1,2,4-triazoles are biologically active compounds with a broad spectrum of action. This fact indicates the interest to these compounds as potential objects of modern pharmaceutical market, namely to those compounds which contain both heterocycles.
Purpose – synthesis and establishment of physical-chemical properties of 6-(5-(1Н-tetrazole-1-ylmethyl)-4-R-1,2,4-triazole-3-ylthio)pyridin-3-amines and 6-((5-(1Н-tetrazole-1-yl)methil-4-R-1,2,4-triazole-3-ylthio)pyridin-3-yl)-(alk,ar,heter)ylmethanimines.
Materials and methods. The melting point has been determined by capillary method. The elemental composition of compounds has been set with the help of elemental analyzer Elementar Vario L cube (CHNS). 1H NMR spectra of obtained compounds has been set with the help of Varian Mercury VX-200, solvent – DMSO-d6, internal standart – Tetramethylsilane. Chromatography-mass spectrometry studies have been conducted on gas-liquid chromatograph Agilent 1260 Infinity HPLC equipped with a mass spectrometer Agilent 6120.
5-(1H-Tetrazole-1-ylmethyl)-4-R-1,2,4-triazole-3-thioles were used as starting materials for 6-(5-(1Н-tetrazole-1-ylmethyl)-4-R-1,2,4-triazole-3-ylthio)pyridin-3-amines. Synthesis of the compounds was carried out in a medium of propyl alcohol in the presence of 5-amino-2-chloropyridine.
6-((5-(1Н-tetrazole-1-yl)methil-4-R-1,2,4-triazole-3-ylthio)pyridin-3-yl)-(alk,ar,heter)ylmethanimines were obtained reacting 6-(5-(1Н-tetrazole-1-ylmethyl)-4-R-1,2,4-triazole-3-ylthio)pyridin-3-amines with the appropriate aldehydes (acetaldehyde, m-anisaldehyde, 2-hydroxybenzaldehyde, 3-fluorobenzaldehyde, 4-fluorobenzaldehyde, 4-diethylaminobenzaldehyd, hydroxynaphthalene) in the acetic acid medium.
Results. 11 New compounds, which have not been described previously, were obtained during the synthetic studies. The computer prediction was performed using PASS online service, it was found that the synthesized 6-(5-(1Н-tetrazole-1-ylmethyl)-4-R-1,2,4-triazole-3-ylthio)pyridin-3-amines and 6-((5-(1Н-tetrazole-1-yl)methil-4-R-1,2,4-triazole-3-ylthio)pyridin-3-yl)-(alk,ar,heter)ylmethanimines are low-toxic compounds and exhibit a wide range of biological actions, which corresponds to literature data.
Conclusions. The results of our work have confirmed the structure of the synthesized compounds, which indicates the possibility of their further use in biological studies.
References
Shcherbak, M. O. (2015) Doslidzhennia syntetychnykh, fizyko-khimichnykh i biolohichnykh vlastyvostei 4-amino-5-(2-, 3-, 4-nitrofenil)-1,2,4-triazol-3-tioniv ta yikh N- i S-zamishchenykh (Dis…kand. farm. nauk). [Research synthetic, physical, chemical and biological properties of 4-amino-5-(2-,3-,4-nitrophenyl)-1,2,4-triazole-3-thiones and their N- and S-substituted. Dr. farm. sci. diss.]. Zaporizhzhia. [in Ukrainian].
Mohammad Asif. (2014) Biological Potentials of Substituted Tetrazole Compounds. Pharmaceutical Methods, 5(2), 39–46. doi: 10.5530/phm.2014.2.1.
Vojtekhovich, S. V., Grigor'yev, Yu. V., Gaponik, P. N., & Ivashkevich, O. A (2010). Sintez proizvodnykh tetrazol-1-iluksusnoj kisloty geterociklizaciej α-aminokislot, trie´tilortoformiata i azida natriya [Synthesis of tetrazole-1-yl acetic acid heterocyclization α-amino acid, triethyl orthoformate and sodium azide]. Vestnik BGU, 2, 11–14. [in Belarus].
Parchenko, V. V. (2012). Novі S-pokhіdnі 1,2,4-trіazolu, yak potentsіinі oryhіnalnі vіtchyznianі veterynarnі lіkarskі zasoby [New s-derivatives of 1,2,4-triazoles as potential original home of veterinary pharmaceuticals]. Farmatsevtychnyi zhurnal, 3, 42–48. [in Ukrainian].
Pruglo, Ye. S., Belay, I. M., Scherbуna, R. O., Kaplaushenko, A. G., & Parchenko, V. V. (2011) Vyvchennia hipohlikemichnoi aktyvnosti pokhidnykh 1,2,4-triazolu pry eksperymentalnii hiperlipidemii [Researching of hypoglycemic activity 1,2,4-triazol derivatives at experimental hyperlipidemia]. ]. Farmatsevtychnyi zhurnal, 1, 74–78. [in Ukrainian].
Kaplaushenko, A. G. (2010) Vzaiemozv’iazok mizh hostroiu toksychnistiu i doslidzhenymy vydamy farmakolohichnoi aktyvnosti 4-mono- i 4,5-dyzamishchenykh 1,2,4-triazol-3-tionu ta yikh S-pokhidnykh [Relationships between the acute toxicity and studied types of pharmacological activity parameters of the 4-mono- and 4,5-disubstituted 1,2,4-triazole-3-thione and their thioderivatives were established]. Zaporozhskij medicinkij zhurnal, 4, 80–82. [in Ukrainian].
Parchenko, V. V., Panasenko, A. І., & Knysh, E. G. (2007) Fіziko-khіmіchnі vlastivostі ta hostra toksychnіst' pokhіdnykh 3-atsilalkіltіo-1,2,4-trіazolіv [Physicо –chemical properties and acute toxicity of 3-acylalkilthia-1,2,4-triazols derivatives]. Farmatsevtychnyi chasopys, 2(2), 41–43. [in Ukrainian].
Derzhavne pidpryiemstvo «Naukovo-ekspertnyi farmakopeinyi tsentr». (2001) Derzhavna Farmakopeia Ukrainy [The State Pharmacopoeia of Ukraine]. Kharkov: RІREG. [in Ukrainian].
Derzhavne pidpryiemstvo «Naukovo-ekspertnyi farmakopeinyi tsentr». (2004) Derzhavna Farmakopeia Ukrainy. Dopovnennia 1 [The State Pharmacopoeia of Ukraine. Vol. 1]. Kharkov: RІREG. [in Ukrainian].
Sajdov, T. V., & Sverdlova, O. V. (1980) Prakticheskoe rukovodstvo po molekulyarnoj spektroskopii [A Practical Guide to Molecular Spectroscopy]. Saint Petersburg: Izd-vo SPU. [in Russian].
Kazicyna, L. A. (1979) Primenenie UF–, IK–, YaMR– i MASS-spektroskopii v organicheskoj khimii [Application of UV, IR, NMR and mass spectroscopy in Organic Chemistry]. Moscow: Izd-vo Mosk. un-ta. [in Russian].
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