Синтез и противовирусная активность замещенных этиловых эфиров 2,4-бис-аминометил-5-гидрокси-1 H -индол-3-карбоновых кислот и их производных

We have synthesized a series of substituted ethyl esters of 2,4-bis-aminomethyl-5-hydroxy-1 H -indole-3-carboxylic acids and 8-aminomethyl-2-methyl-2,3-dihydro-1 H ,7 H -[1,3]oxazino[5,6- e ]indole-9-carboxylis acids and previously unreported 4,5-dihydro-1 H -pyrrolo[4,3,2- de ]isoquinolin-3-ones and 1,4-dihydropyrrolo[4,3,2- de ]isoquinolin-3,6-diones. The cytotoxicity and antiviral activity of these compounds against bovine viral diarrhea (BVDV), hepatitis C virus (HCV), A/New Caledonia/20/99 (H1N1), and A/Aichi/2/69 (H3N2) viruses have been studied in vitro . Among all compounds studied, only two compounds – ethyl 5-hyroxy-2-(dimethylaminomethyl)-1-methyl-6-piridine-3-yl-1 H -indole-3-carboxylate and 5-hyroxy-2-(dimethylaminomethyl)-1-methyl-6-fluoro-1 H -indole-3-carboxylate were significantly active against influenza A/Aichi/2/69 (H3N2) virus. In particular, 2,4-bis-dimethylaminomethyl-6-pyridin-3-yl-1 H -indole (2e) not only had micromolar activity against HCV and influenza A/New Caledonia/20/99 (H1N1) and A/Aichi/2/69 (H3N2) in vitro , but was also highly active in mice infected with A/Aichi/2/69 (H3N2) influenza virus. This compound was found to be more active than arbidol, when administered at a dose of 15 – 25 mg/kg/day.