The first representatives of the isoquino[2,3-a]quinazoline system were obtained quite recently [2, 3] and they included 5-aryl-substituted derivatives [2,4]. However, by contrast to 5-oxoisoquino[2,3-a]quinazolines, the properties of the latter were not studied. The already existing data for the biological activity of isoquinoquinazolines [5, 6] and 4-arylquinazolines condensed along the a edge [7-9] points to the potential of such an investigation.We have previously proposed [4] a method for the synthesis of the 5-aryl-7,12-dihydroisoquino-[2,3-a]quinazolinium salts 1a-c consisting of reaction of o-(bromomethyl)phenylacetonitrile with o-aminobenzophenones 2a-c and subsequent cyclization of the initially formed 2-aryl-3-imino-1,4-dihydroisoquinoline hydrobromides 3a-c in the presence of perchloric acid. In this work the reaction was subjected to closer study with the aim of optimizing the method of synthesizing the isoquinoquinazolinium salts 1 and to study the spectroscopic and chemical properties of the products.We have found that the outcome of the reaction of o-(bromomethyl)phenylacetonitrile with benzophenones 2 depends markedly on both the reaction conditions and on the nature of the substituent in reagent 2. Hence heating in acetonitrile, in some examples (2b,c) gave a mixture of the isoquinolineimine bromides 3 together with an unknown product. Addition of catalytic amounts of acetic acid to the reaction mixture virtually suppresses the formation of the side product. When the reaction is carried out in 2-propanol the unknown material is the sole product. And in the case of the benzophenone 2d gives the unknown material _______ * For Communication 28 see [1].

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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.Keywords: 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids, antiviral activity, antiinfluenza activity, influenza A/Aichi/2/69 (H3N2), BVDV, HCV.Substituted 2-and 4-aminomethyl-5-hydroxyl-1H-indole-3-carboxylic acids are known to have some degree of antiviral activity [1 -3]. In particular, 1-benzyl-2-dimethylaminomethyl-3-carbethoxy-5-acetoxy-6-bromoindole hydrochloride demonstrated antiinfluenza activity in studies using a mouse model of influenza pneumonia [3]. We have previously described the synthesis and antiviral activity of a series of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids and have shown them to have limited activity against influenza A/New Caledonia/20/99 (H1N1) virus, bovine viral diarrhea virus (BVDV), and HCV [4].We describe here the synthesis and antiviral activities of novel derivatives of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids (compounds 4 -7, 11, 16 -20, 24). Substituted ethyl esters of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids 4 -7 were prepared (scheme 1) from 1-substituted ethyl esters of 5-hydroxy-2-methyl-1H-indole-3-carboxylic acids 1a -e, which, by analogy [5] with 1,2-dimethylindole (compound 1a), were sequentially converted to 5-acetyloxy-(compounds 2a -e) and 5-acetyloxy-6-bromoindoles (compounds 3a -e). Interaction of these latter compounds with dimethylamine, pyrrolidine, and morpholine gave the corresponding 2-aminomethyl-6-bromoindoles (4a -g). 6-Bromoindoles 4b,c were hydrogenated with hydrogen on 10% Pd/C to form indoles unsubstituted at position 6 (compounds 5a, b); reaction of 6-bromoindole 4a with copper (I) cyanide in N-methylpyrrolidone (NMP) produced the corresponding 6-cyanoindole compound 6, while use of