Design, Synthesis and Inhibitory Properties against Coxsackie B3/B6 of Some Novel Triazole Derivatives

Dongping Shao, Yanbing Yang, Fei Xue, Xianjin Luo, Reyila Wubulikasimu, Yuhuan Li, Rongmei Gao, Weidong Ye

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Zhejiang Medicine Co. Ltd., Xinchang Pharmaceutical Factory, Xinchang, China.

DOI: 10.4236/ijoc.2013.31A005                

Abstract

A series of 1,2,4-triazole derivatives were synthesized, and their abilities to inhibit the in vitro replication of Coxsackie B3/B6 were evaluated. Among the 1,2,4-triazole derivatives, compound 3 g displayed potent activity, with a high antiviral potency (IC₅₀ = 1.71 μM (against CVB3), 1.43 μM (against CVB6)). The structures of all the new synthesized compounds were confirmed by ¹H-NMR spectra, mass spectra and elemental analyses.

Keywords

1, 2, 4-Triazole; Anti-Enterovirus; Coxsackie B Viruses

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	A. K. Wahi and A. Singh, “Triazole: Recent Development and Biological Activities,” Asian Journal of Biochemical and Pharmaceutical Research, Vol. 2, No. 1, 2011, pp. 193-205.
[2]	I. Pibiri and S. Buscemi, “A Recent Portrait of Bioactive Triazoles,” Current Bioactive Compounds, Vol. 6, No. 4, 2010, pp. 208-242. doi:10.2174/157340710793237281
[3]	J.-H. Chern and K.-S. Shia, “Design, Synthesis, and Structure-Activity Relationships of Pyrazolo[3,4-d]Pyrimidines: A Novel Class of Potent Enterovirus Inhibitors,” Bioorganic & Medicinal Chemistry Letters, Vol. 14, No. 10, 2004, pp. 2519-2525. doi:10.1016/j.bmcl.2004.02.092
[4]	H. A. Rotbart, “Treatment of Picornavirus Infections,” Antiviral Research, Vol. 53, No. 2, 2002, pp. 83-98. doi:10.1016/S0166-3542(01)00206-6
[5]	V. A. Makarov, O. B. Riabova, et al., “Anti-Coxsackievirus B3 Activity of 2-AMINO-3-Nitropyrazolo[1,5-a]Pyrimidines and Their Ana-logs,” Bioorganic & Medicinal Chemistry Letters, Vol. 15, No. 1, 2005, pp. 37-39. doi:10.1016/j.bmcl.2004.10.043
[6]	G. Pürstinger, “Synthesis and Anti-CVB 3 Evaluation of Substituted 5-Nitro-2-Phenoxybenzonitriles,” Bioorganic & Medicinal Chemistry Letters, Vol. 18, No. 18, 2008, pp. 5123-5125. doi:10.1016/j.bmcl.2008.07.099
[7]	M. Esfandiarei and B. M. McManus, “Molecular Biology and Pathogenesis of Viral Myocarditis,” Annual Review of Pathology: Mechanisms of Disease, Vol. 3, 2008, pp. 127-155. doi:10.1146/annurev.pathmechdis.3.121806.151534
[8]	N. M. Chapman and K. S. Kim, “Persistent Coxsackievirus Infection: Enterovirus Persistence in Chronic Myocarditis and Dilated Cardiomyopathy,” Current Topics in Microbiology and Immunology, Vol. 323, 2008, pp. 275292. doi:10.1007/978-3-540-75546-3_13
[9]	J. Cheng, J. Xie and X. Luo, “Synthesis and Antiviral Activity against Coxsackie Virus B3 of Some Novel Benzimidazole Derivatives,” Bioorganic & Medicinal Chemistry Letters, Vol. 15, No. 2, 2005, pp. 267-269. doi:10.1016/j.bmcl.2004.10.087
[10]	F. Xue and X. Luo, “Inhibitory Properties of 2-Substituent1H-Benzimidazole-4-Carboxamide Derivatives against Enteroviruses,” Bioorganic & Medicinal Chemistry, Vol. 19, No. 8, 2011, pp. 2641-2649. doi:10.1016/j.bmc.2011.03.007
[11]	D. R. Guda, T. J. Wang and H. M. Cho, “Trimethylsilyl Isothiocyanate (TMSNCS): An Efficient Reagent for the One-Pot Synthesis of Mercapto-1,2,4-Triazoles,” Tetrahedron Letters, Vol. 53, No. 39, 2012, pp. 5238-5242. doi:10.1016/j.tetlet.2012.07.054
[12]	Y. Dürüst, “Synthesis of Some Novel 1,3,4and 1,2,4Thiadiazole Derivatives,” Phosphorus, Sulfur, and Silicon, Vol. 184, No. 11, 2009, pp. 2923-2935. doi:10.1080/10426500802625453
[13]	Z. L. Xin and H. Y. Zhao, “Synthesis and Structure-Activity Relationships of Isoxazole Carboxamides as Growth Hormone Secretagogue Receptor Antagonists,” Bioorganic & Medicinal Chemistry Letters, Vol. 15, No. 4, 2005, pp. 1201-1204. doi:10.1016/j.bmcl.2004.11.075
[14]	J. H. Kalin and H. K. Zhang, “Chiral Mercaptoacetamides Display Enantioselective Inhibition of Histone Deacetylase 6 and Exhibit Neuroprotection in Cortical Neuron Models of Oxidative Stress,” Chem-MedChem, Vol. 7, No. 3, 2012, pp. 425-439.
[15]	L. J. Reed and H. Muench, “A Simple Method for Estimating Fifty Percent Endpoints,” American Journal of Hygiene, Vol. 27, No. 3, 1938, pp. 493-497.