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Anticancer screening of several 1,2,3-triazoles with heterocyclic fragments has been performed. The 1,2,3-triazole derivatives were synthesized from available starting materials according to convenient synthetic procedures. The antitumor activity of the synthesized compounds was tested in vitro by the National Cancer Institute in NCI60 cell lines. It was observed that some compounds showed slight anticancer activity. One of them possessed a moderate activity against melanoma, colon, and breast cancer. Standard COMPARE analysis was performed at the GI50 level.

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Keywords: 2-benzofuran-1(3H)-one, 1-oxo-1H-isothiochromenone, 2-formylbenzoic acid, heterocyclization, recyclization.Many derivatives of 1H-2-benzothiopyran (1H-isothiochromenes) exhibit biological activity [1][2][3][4][5]. However, due to the limited number of methods available for their synthesis the properties of these compounds have been insufficiently investigated [6]. 1H-2-Benzothiopyrans are produced by the reactions of 2-(aroylmethyl)benzoates with P 2 S 5 [7], 2-cyanomethylbenzoates with carbon disulfide [8], and lithium N,N-diethylo-toluamide with thioethers [9]. Isothiochromene-1-thione was obtained with a yield of 12% by the reaction of N-cyanomethyl-N-methyl-2-chloro-5-nitrobenzamide with NaH and carbon disulfide in DMSO [10]. A more convenient method for the synthesis of isothiocoumarins is the reaction of ortho-formylbenzoic acids with rhodanine (2-thioxo-4-thiazolidinone) followed by recyclization of the obtained 5-arylidenerhodanine in a basic medium [11,12] although the initial ortho-formylbenzoic acids are difficult to obtain. The possibilities of applying this method to the creation of combinatorial libraries of heterocyclic compounds with an isothiocoumarin fragment were demonstrated in [13]. The possibilities of the method are limited by the fact that the available starting compounds are formylbenzoic and opianic acids. During the production of substituted 2-formylbenzoic acids organometallic compounds are often used for formylation or carboxylation [14][15][16]. We note that the significant lability of the isothiocoumarin ring complicates the direct introduction of substituents by, for example, electrophilic substitution.In the present work a convenient method is proposed for the synthesis of substituted isothiocoumarins of type I suitable for further transformations and for use in combinatorial chemistry. For this purpose derivatives of phthalide III, obtained by the reduction of phthalic anhydride, were used as precursors of 2-formylbenzoic acids II.

b-Keto sulfones and b-nitrile sulfones were used as building blocks for 1,2,3-triazole synthesis in the Dimroth cyclization. It was shown, that sulfone reagents undergo base-catalyzed cyclization under mild conditions (at room temperature) to give 1,2,3-triazoles in moderate to excellent yields. This fact has confirmed the high nucleophilicity of sulfonylmethylenic compounds and allows new synthetic applications.