The antimicrobial activity of 2,4-dioxothiazolidine-5-acetic acid amides and their 3-substituted analogs has been studied. The initial acid was obtained by an effective one-pot method using the reaction of thiourea with maleic anhydride in hydrochloric acid. The maximum anti-staphylococcal activity was exhibited by N-[5-(R-benzyl)thiazol-2-yl]-2-(2,4-dioxothiazolidin-5-yl)acetamides.Notes: Data in square brackets refer to the zones of partly inhibited growth; (-) no antimicrobial activity; none of the synthesized compounds were active with respect to Haffnia alvei and Candida albicans species.

By the reaction of acetylacetone and arylazoacetylacetones with 4-iminothiazolidin-2-one thiazolo [4,5-b]pyridines were obtained in good yields. Optimum reaction conditions were chosen and some properties of compounds obtained were studied.Five-membered heterocycles fused to the pyridine ring attract constant attention since many compounds of this class possess the biologic action. Thiazolo [4,5-b]pyridines are among the least accessible and in turn poorly understood representatives of this class of organic substances. The information on their biological activity is also insuffi cient. In particular, among this type compounds substances were found possessing fungicidal action [1], antagonists of Н3-histamine receptors [2], antagonists of metabotropic glutamate receptors 5 (mGluR5) [3] of high inhibitor activity with respect to the receptors of the epidermal growth factor [4] and a number of other enzymes [5,6].Two fundamentally different approaches exist with respect to the synthesis of the thiazolo[4,5-b]pyridine system. The fi rst one is based on the fusion of the thiazole ring to the pyridine. Here 2-aminopyridines [7], thioureas[8-10], or thiocarbamates [11] are used as initial compounds. The second procedure of the pyridine ring fusion is underlain by a three-component condensation of derivatives of 4-aminothiazoles and 4-aminoselenazoles with aromatic or aliphatic aldehydes and the Meldrum's acid [12]. At the use in the reaction with 2,4-diaminothiazoles of ethyl acetoacetate and acetylacetone 2-amino-5,7-dimethylthiazolo[4,5-b]pyridines and 2-amino-7-methyl-4Н-thiazolo[4,5-b]pyridin-5-ones were obtained respectively [13]. Examples are also known of the synthesis of 1,3-thiazolo[4,5-b]pyridine derivatives with the use of solid-phase carriers [14] and with the application of dominoreactions [15].We report here on a convenient method of preparation of 3H-thiazolo[4,5-b]pyridin-2-one derivatives. We used 4-iminothiazolidin-2-one (I) as the initial compound [16] that was reacted with acetylacetone (II). We optimized the conditions of this reaction that made it possible to obtain 5,7-dimethyl-3H-thiazolo[4,5-b]-pyridin-2-one (IV) in good yield. The best results were observed at keeping the reagents mixture in methanol in the presence of sodium methylate over 5 days. Similar procedure was described earlier in patent [17], but due to the low yield the method had no preparative value.We also studied the behavior in this reaction of acetylacetone arylazo derivatives IIIа-IIIg (Scheme 1). Under the chosen conditions the corresponding 6-arylazo-5,7-dimethyl-3H-thiazolo[4,5-b]pyridin-2-ones Vа-Vg formed in good yields. These substances were orange or red crystalline powders well soluble in DMF and DMSO, sparingly soluble in water and the other organic solvents.The structure of compounds obtained was proved by NMR spectra. For instance, the proton signals of the methyl groups of the pyridine ring are observed at 2.42-2.46 and 2.49-2.87 ppm respectively, and of NH groups, in a relatively wide range of 9.78-14.29 ppm.Some...

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Objective: The main purpose of this study was to develop a simple, precise, rapid and accurate method for the quantification of cardiazol in human plasma. Methods: Chromatography was achieved on Discovery C18, 50 × 2.1 mm, 5 μm column. Samples were chromatographed in a gradient mode (eluent A (acetonitrile-water–formic acid, 5: 95: 0.1 v/v), eluent B (acetonitrile–formic acid, 100: 0.1 v/v)). The initial content of the eluent B of 8%, which increases linearly to 1.0 min to 100%, is maintained up to 1.5 min and returned to the original 8% to 1.51 min. The mobile phase was delivered at a flow rate of 0.400 ml/min into the mass spectrometer ESI chamber. The sample volume was 300 μl. Results: The total chromatographic run time was 2.5 min and the elution of cardiazol and IS (difenoconazole) occurred at ~2.15 and 1.98 min, respectively. A linear response function was established at 1-100 ng/ml for cardiazol and difenoconazole in human plasma. The % mean recovery for cardiazol in LQC, MQC and HQC was 102.8 %, 100.3 % and 95.9 %. The lowest concentration with the RSD<20% was taken as LLOQ and was found to be 1.10 ng/ml for cardiazol. The % accuracy of LLOQ samples prepared with the different biological matrix lots was found 109.7 %, which were found within the range of 80.00-120.00 % for the seven different plasma lots. % CV for LLOQ samples was observed as 11.9 %, which are within 20.00% of the acceptance criteria. The within-run coefficients of variation ranged between 0.311 % and 0.601 % for cardiazol. The within-run percentages of nominal concentrations ranged between 99.80 % and 100.41 % for cardiazol. The between-run coefficients of variation ranged between 0.332 % and 0.615 % for cardiazol. The between-run percentages of nominal concentrations ranged between 98.18 % and 101.21 % for cardiazol. Conclusion: A rapid method was developed for simultaneous determination of cardiazol in human plasma. The method was strictly validated according to the ICH guidelines. Acquired results demonstrate that the proposed strategy can be effortlessly and advantageously applied for routine examination of cardiazol in human plasma.

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