New substituted ethyl esters of 2,4-bis-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids, 8-aminomethyl-2-methyl-2,3-dihydro-1H,7H-[1,3]-oxazino-[5,6-e]indole-9-carboxylic acids, and members of the previously unknown 4,5-dihydro-1H-pyrrolo[4,3,2-de]isoquinolin-3-ones of 1,4-dihydropyrrolo[4,3,2-de]isoquinolin-3,6-diones were synthesized. Their cytotoxicities and antiviral activities against bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV), and A/Aichi/2/69 (H3N2) were studied in vitro. These compounds were found not to be active against these viruses. The only exceptions were the hydrochlorides of the ethyl esters of 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-pyridine-3-yl- and 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-fluoro-1H-indole-3-carboxylic acids, which at micromolar concentrations not only produced effective suppression of influenza A/Aichi/2/69 (H3N2) virus replication in cell cultures, but also showed high in vivo efficacy in a model of influenza pneumonia in mice infected with influenza A/Aichi/2/69 (H3N2) virus at a dose of 25 mg/kg/day.
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 48, No. 9, pp. 7 – 19, September, 2014.
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Ivashchenko, A.V., Yamanushkin, P.M., Mit’kin, O.D. et al. Synthesis and Antiviral Activity of Substituted 2,4-bis-aminomethyl-5-hydroxy-1H-indole-3-carboxylic Acid Ethyl Esters and their Derivatives. Pharm Chem J 48, 569–581 (2014). https://doi.org/10.1007/s11094-014-1153-0
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DOI: https://doi.org/10.1007/s11094-014-1153-0
Keywords
- 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids, 8-aminomethyl-2-methyl-1,2,3,7-tetrahydro[1,3]oxazino[5,6-e]indole-9-carboxylic acids
- 4,5-dihydro-1H-pyrrolo[4,3,2-de]isoquinolin-3-ones
- 1,4-dihydro-pyrrolo-[4,3,2-de]isoquinolin-3,6-diones
- hepatotoxicity
- antiviral activity
- antiinfluenza activity
- influenza A/Aichi/2/69 (H3N2) virus
- BVDV
- HCV