Novel substituted 5-hydroxy-2-aminomethyl-1H-indole-3-carboxylic acids and their derivatives were synthesized. The antiviral properties of these compounds were investigated in relation to bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV), and influenza A/Aichi/2/69 (H3N2) virus. Of the compounds synthesized here, only the 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-pyridin-3-yl- and 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-fluoro-1H-indole-3-carboxylic acid ethyl ester hydrochlorides had significant activity against these viruses, these agents not only suppressing the replication of influenza A/Aichi/2/69 (H3N2) virus in cell cultures at micromolar concentrations, but also demonstrating high efficacy, greater than that of Arbidol, in a model of influenza pneumonia in mice infected with influenza A/Aichi/2/69 (H3N2) virus, when given at a dose of 25 mg/kg/day.
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References
A. N. Grinev, E. K. Panisheva, A. A. Cherkasova, et al., Khim.-Farm. Zh., 17(8), 940 – 946 (1983); Pharm. Chem. J., 17(8), 564 – 570 (1983).
A. N. Grinev, E. K. Panisheva, A. A. Cherkasova, et al., Khim.-Farm. Zh., 21(1), 52 – 55 (1987); Pharm. Chem. J., 21(1), 48 – 51 (1987).
A. N. Grinev, E. K. Panisheva, I. S. Nikolaeva, et al., Khim.-Farm. Zh., 21(5), 575 – 577 (1987); Pharm. Chem. J., 21(5), 347 – 350 (1987).
A. V. Ivashchenko, P. M. Yamanushkin, O. D. Mit’kin, et al., Khim.-Farm. Zh., 47(12), 13 – 28 (2013); Pharm. Chem. J., 47(12), 636 – 650 (2013).
F. A. Trofimov, N. G. Tsishkova, S. A. Zotova, A. N. Grinev, Khim.-Farm. Zh., 27(1), 70 – 71 (1993); Pharm. Chem. J., 27(1), 75 – 76 (1993).
R. Littel, G. R. Allen Jr., J. Org. Chem., 33(5), 2064 – 2069 (1968).
A. N. Grinev, V. I. Shvedov, A. K. Chizhov, T. F. Vlasova, Khim. Geterotsikl. Soedin., 9, 1250 – 1253 (1975).
E. K. Panisheva, A. N. Fomina, I. S. Nikolaeva, et al., Khim.-Farm. Zh., 22(5), 565 – 569 (1988); Pharm. Chem. J., 22(5), 383 – 387 (1988).
R. G. Glushkov, Drugs of the Future, 17(12), 1079 – 1081 (1992).
M. R. Romero, M. A. Serrano, M. Vallejo, et al., Planta Med., 72(13), 1169 – 1174 (2006).
R. Bartenschlager, T. Pietschmann, Proc. Natl. Acad. Sci. USA, 102(28), 9739 – 9740 (2005).
J. Zhong, P. Gastaminza, G. Cheng, et al., Proc. Natl. Acad. Sci. USA, 102, 9294 – 9299 (2005).
A. P. Wilson, “Cytotoxicity and Viability Assays,” in: Animal Cell Culture: A Practical Approach, Masters J. R.W. (ed.), Oxford University Press, Oxford (2000), Vol. 1, pp. 175 – 219.
C. A. Zotova, T. M. Korneeva, V. I. Shvedov, et al., Khim.-Farm. Zh., 29(1), 51 – 53 (1995); Pharm. Chem. J., 29(1), 57 – 59 (1995).
Handbook for the Conduction of Preclinical Studies of Drugs [in Russian], A. N. Mironov, N. D. Bunatyan, et al. (eds., Grif i K., Moscow (2012).
D. R. Hwang, Y. S. Wu, C. W. Chang, et al., Bioorg. Med. Chem., 14(1), 83 – 91 (2006).
T. Kato, T. Date, M. Miyamoto, et al., Gastroenterology, 125, 1808 – 1817 (2003).
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 49, No. 3, pp. 7 – 19, March, 2015.
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Ivachtchenko, A.V., Yamanushkin, P.M., Mitkin, O.D. et al. Synthesis and Antiviral Activity of Substituted Ethyl-2-Aminomethyl-5-Hydroxy-1H-Indole-3-Carboxylic Acids and Their Derivatives. Pharm Chem J 49, 151–162 (2015). https://doi.org/10.1007/s11094-015-1244-6
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DOI: https://doi.org/10.1007/s11094-015-1244-6