Keywords: amides, 2-hydroxy-4-oxo-4H-pyrido-[1,2-a]pyrimidine-3-carboxylic acids, tricarbonylmethane heterocyclic derivatives, diuretic activity, X-ray structural analysis.The problem of discovering novel classes of chemical substances capable of diuretic action, and particularly important, those which are highly efficient and safe diuretic medicines has not lost its urgency even over recent decades. Interesting substances investigated within this scheme are amidated 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids derivatives [2,3]. Although for a long time high diuretic activity has not been considered a characteristic of quinolone compounds, several of these materials proved extremely promising and have been subjected to broad pharmacological investigation to this time. With this in mind we have carried out the synthesis and biological screening to reveal the ability of the series of structurally related 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid N-R-amides 1-3 to increase the diuretic kidney function.It was found that the alkylamides 1a-u (Table 1) can be prepared by the reaction of ethyl 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate (4) with a two, or better three, fold excess of the corresponding alkylamine in refluxing ethanol. It was initially proposed that it was necessary to use quite a large excess of the _______ * For Communication 143 see [1].

The interaction of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid with thionyl chloride in oxygen-containing solvents leads to the formation of a significant amount of colored side products, consequently it was proposed the reaction be carried out in carbon tetrachloride. The synthesis of a series of amides was effected by the amidation of the obtained acid chloride with appropriate primary arylalkylamines. Results are presented of a study of the effect of the synthesized compounds on the urineexcreting function of the kidney.

A comparative analysis of the effect of halo-substituted anilides of 6-hydroxy-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids on the urinary function of the kidney has shown that methylation of the pyrroline ring at position 2 leads to an increased diuretic effect. As a method for improving the pharmacological properties of this class of compounds, it deserves more detailed attention [2]. The most promising substance or structural leader in the group of unmethylated derivatives was found to be the 6-hydroxy-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid 4-methoxyanilide [3]. Hence it was quite logical that the next step in our study should be examination of the corresponding alkoxy-and hydroxyanilides of 6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid 1a-j. O OH O OEt N Me O OH O N N H Me R N H 2 R 1a-j 2 1a R = 2-ОH; b R = 3-ОН; c R = 4-ОН; d R = 2-ОМе; e R = 3-ОМе; f R = 4-ОМе; g R = 2-Me-4-OMe; h R = 4-OEt; i R = 4-OPr; j R = 4-OC 6 H 13

The methyl ester of 1H-2-oxo-4-hydroxyquinoline-3-acetic acid is condensed in pyridine with salicylaldehydes to 1H-2-oxo-3-(coumarin-3-yl)-4-hydroxyquinolines. We present the results of a study of the effect of the synthesized compounds on thyroid function.Determination of the biological activity of a specific compound in'modern pracffce [2] is generally followed up by a series of papers on synthesis of numerous analogs of the parent structure. This report is part of specifically such an investigation, the goal of which is continuation of the search for potential antithyroid drugs in the series of structural analogs of 1H-2-oxo-3-(2-benzimidazolyl)-4-hydroxyquinoline [3,4] by replacing the benzimidazole ring by other heterocycles, in this case coumarins.The conventional route to obtaining coumarins (well known under the name of Knoevenagel condensation) is the reaction of methylene-active compounds with salicylaldehydes in the presence of relatively weak bases, most often piperidine, followed by spontaneous closure of the benzopyran ring [5]. The fact that such reactions proceed so easily is why synthesis of the target 1H-2-oxo-3-(coumarin-3-yl)-4-hydroxyquinolines (I) is done by condensation of salicylaldehydes (II) with the methyl ester of 1H-2-oxo-4-hydroxyquinonlin-3-acetic acid (III) as the methylene-active component. Considering the pronounced acidic properties of the 4-hydroxy groups in 2-oxo-4-hydroxyquinolines [6], we slightly modified the traditional route for synthesis of coumarins, proposing the use of catalytic amounts of piperidine [7]. However, carrying out the reaction ila piperidine as the basic catalyst and simultaneously the solvent unexpectedly led to the piperidylamide of 1H-2-oxo-4-hydroxyquinoline-3-acetic acid (IV). Direct amidation of ester III by a secondary amine is unlikely. So the result obtained obviously can be explained by cyclization of ester III under conditions of synthesis to the anhydride V, which in turn easily acylates piperidine with formation of the amide IV obtained. From this it follows that a positive result may be expected only in the case when we replace piperidine with a base, eliminating the possibility of amidation. In fact, in pyridine, ester III is condensed with salicylaldehydes to 1H-2-oxo-3-(coumarin-3-yl)-4-hydroxyquinolines I without any complications (Table 1), although we do not exclude the possibility that even in this case the reaction proceeds through a stage of formation of compound V.The effect of the synthesized compounds on thyroid function was studied by determining the thyroid hormones triiodothyronine (T3) and thyroxine (T 4) in blood serum of experimental animals. Antithyroid drugs, as we know, depending on their mechanism of action may activate or inhibit thyroid function, as a result of which sometimes it is rather complicated to evaluate and compare its condition according to individual indices. So for a more accurate evaluation of thyroid function, we also used the functional activity coefficients (the activation coefficient K a = h/d. 10 -...

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