Schiff bases and their metal-complexes are versatile compounds exhibiting a broad range of biological activities and thus actively used in the drug development process. The aim of the present study was the synthesis and characterization of new Schiff bases and their copper (II) complexes, derived from L-tryptophan and isomeric (2-; 3-; 4-) pyridinecarboxaldehydes, as well as the assessment of their toxicity in vitro. The optimal conditions of the Schiff base synthesis resulting in up to 75-85% yield of target products were identified. The structure-activity relationship analysis indicated that the location of the carboxaldehyde group at 2-, 3- or 4-position with regard to nitrogen of the pyridine ring in aldehyde component of the L-tryptophan derivative Schiff bases and corresponding copper complexes essentially change the biological activity of the compounds. The carboxaldehyde group at 2- and 4-positions leads to the higher cytotoxic activity, than that of at 3-position, and the presence of the copper in the complexes increases the cytotoxicity. Based on toxicity classification data, the compounds with non-toxic profile were identified, which can be used as new entities in the drug development process using Schiff base scaffold.

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Fused pyrimidine derivatives R 0515 Novel Route for the Transformation of a Pyrimidine Ring Using Hydrazides. -The reaction of the pyrimidinium salt (I) with different hydrazides (II) leads to pyrazolo[1,5-a]pyrimidine derivatives (III) and (IV) rather than the previously reported triazolo[4,3-a]pyridines. -(DANAGULYAN, G. G.; TADEVOSYAN, D. A.; TAMAZYAN, R. A.; PANOSYAN, G. A.; Chem. Heterocycl.

Intermediate recyclization products were obtained in a study of the Kost-Sagitullin rearrangement of a series of 1,2-dialkylpyrimidinium iodides. The initial attack of the nucleophile leads to the formation of products of the addition of the hydroxyl group, namely, the corresponding pseudo bases. Heating one of these intermediates in ethanol or in the presence of primary amines leads to rearrangement to give a pyridone derivative. Upon heating in chloroform, the pseudo bases readily lose a water molecule and are converted to anhydro bases, namely, derivatives of 1-alkyl-1,2-dihydro-2-methylidenepyrimidine.Pseudo base 2a is formed upon the action of KOH on 2-(ethoxycarbonyl)methyl-1,4,6-trimethylpyrimidinium iodide (1a) at 0°C, which indicates initial attack of the hydroxide ion at C (2) in the pyrimidine ring [1]. The structure of 2a was indicated by 1 H NMR and IR spectroscopy, while the mass spectrum corresponded to the product of the elimination of water, namely, anhydro base 3a.We have shown in subsequent studies that brief heating of pseudo base 2a in chloroform leads to anhydro base 3a in quantitative yield, while the complete accord of the mass spectrum of 3a with the mass spectrum previously recorded in a study of 2a (discrepancies only in the peak intensities) supports our previous proposal [1] of the loss of water upon electron impact during the recording of the mass spectrum of 2a.The similar attack of the hydroxide ion at C (2) in the pyrimidine ring was also noted in the reaction of 2-(ethoxycarbonyl)methyl-1-ethyl-4,6-dimethylpyrimidinium iodide (1b) with KOH, leading to pseudo base 2b, which also loses a water molecule upon heating in chloroform.We note that the elimination of water from pseudo base 2b upon heating in chloroform proceeds very rapidly. Thus, only anhydro base 3b is recorded in the mass spectrum and also in the 1 H NMR spectrum in CDCl 3 . Products 2b and 3b differ in their physicochemical characteristics and IR spectral data, which served to establish the structure of pseudo base 2b (Table 1).Heating 2-(carbamoyl)methyl-1,4,6-trimethylpyrimidinium iodide (1c) with an equivalent of KOH in absolute ethanol for 1 min leads to anhydro base 3c, probably also through the intermediate formation of pseudo base 2c. Anhydro base 3c was isolated by chloroform extraction. By analogy with the previous examples, this transformation also involves water elimination. The chloroform extraction was carried out to avoid side reactions occurring when using polar solvents since the intermediates of the transformation of iodide 1c do not dissolve in nonpolar solvents.