G. N. Novoselova

Synthesis and biological activity of 3-aroylmethylene-substituted 1-methyl(phenyl)-piperazin-2-ones

It was demonstrated that 3-aroylmethylenepiperazin-2ones exhibit antiinflammatory, anticonvulsive, and analgetic activity on a background of rather low toxicity [1 ]. It was established that one of the factors determining the activity is the character of acylmethylene derivative in position 3 of the piperazinone cycle. At the same time, arylamides ofaroylpyroracemic acids (noncyclic analogs of piperazinones) are known to exhibit antimicrobial effect with respect to Staphylococcus aureus [2]. In this connection, it was of interest to study the effect of substituents in position 1 of the piperazinone cycle on the biological activity. To this end, we have synthesized lmethyl(phenyl)-3-aroylmethylenepiperazin-2-ones and characterized their biological activity. The target products were obtained by interaction Of methyl esters of 4-aryl-2-hydroxy4-oxo-2-butenoic acids (1) with N-methyland Nphenylethylenediamines (II, III). It was reported that the ester of aroylpyroracemic acid (a ketone form of I) reacts with amines at the a-ketone carbonyl [4, 5]. In the case of nonsymmetric ethylenediamines, the reaction may lead to two products (A and B, see the scheme below). Taking into account the electronic effects of the methyl group and benzene ring, we may expect that the reactions of N-methylethytenediamine and N-phenylethylenediamine would lead to compounds of the B and A type, respectively. However, the steric effect of the methyl group in N-methylethylenediamines also favors the formation of compound A. The reaction proceeds smoothly with a good yield in an alcohol medium (boiling for I 1.5 h) in the presence of catalytic amounts of glacial acetic acid [2].

Interaction of 5-aryl-2,3-dihydrofuran-2,3-diones with 4-amino-3-R-1,2,4,-(4H)-triazoles and antimicrobial activity of the reaction products

As is known, aroylpyruvic acid amides formed upon decyclization of 5-aryl-2,3-dihydrofuran-2,3-diones under the action of aliphatic and aromatic amines [1] and heterylamines [2], or as a result of hydrolysis of N-substituted 2-imino-5aryl-2,3-dihydrofuran-3-ones [3], exhibit spasmolytic [4 6], analgetic, antiflammatory [7], and antimicrobial[8] activity, while being extremely low-toxicity compounds. In order to obtain new promising biologically active heterylamines of aroylpyruvic acids, we have studied the interaction of 5-aryl-2,3-dihydrofuran-2,3-diones with 4-amino3-R-1,2,4,-(4H)-triazole [9]. It is known that acylated derivatives of the latter compounds exhibit high antiflammatory and analgetie activity [10, 11], and their furfurylidene derivatives also offer bactericidal activity [12]. We have established that 5-aryl-2,3-dihydrofuran-2,3diones react at room temperature with 4-amino-l,2,4-(4H)triazoles in the course of 6 h with the formation of N-[4-1,2,4(4H)-triazolyl]amides ofaroylpyruvic acids (I IV, Table 1). The synthesized amides appear as white, creamy-tinted substances, which develop a cherry-red color on adding a FeCI3 solution in ethanol as a result of ct-carbonyl enolization [13]. The IH NMlK spectra of compounds I IV show, besides the signals of substituents in the aromatic core and the aromatic protons, a singlet due to the methyl proton of aroylpyruvoyl fragment at 7 .087.11 ppm (indicative of ct-carbonyl enolization in I IV similarly to other aroylpyruvic acid amides [1, 2, 7, 14]) and a singlet due to the two methine protons of the triazole fragment at 8.68 8.71 ppm. The signal of the proton of the amino group is not observed, probably because of the strong broadening caused by the proton exchange with solvent. The IiK absorption spectra show bands due to the stretching vibrations of N-H bonds (3100 3150 cm1), am_

SYNTHESIS AND BACTERIOSTATIC ACTIVITY OF 3-DIAZO-2-OXOPROPANOIC ACID DERIVATIVES

It is known that aliphatic diazo compounds, in particular ct-diazo ketones, exhibit different types of biological activity [5]. At the same time, the amides of carboxylic acids are widely known to be effective drugs. The combination of a biologically active amide and diazocarbonyl fragments based on such a natural metabolite as pyruvic acid seems promising in the search for novel biologically active compounds. In the search for novel compounds possessing biological activity, we synthesized a number of 3-diazo-2-oxopropanoic acid derivatives according to the scheme

Biological activity of 7-aryl-3-methyl-1-phenyl-1H,6H-pyrazolo[5,4-b]-[1,4]diazepine-5-carboxylic acids and their derivatives

The recently performed search for biologically active substances among 1,4-diazepine derivatives enabled compounds with a series of useful properties to be found [1, 3, 8, 10]. However, there is no information in the literature on the biological activity of derivatives of pyrazolo [5,4-b] [ 1,4] diazepines. In this connection, the 7-aryl-3-methyl1-phenyl1H,6H-pyrazolo[5,4b] [1,4]diazepine-5-carboxylic acids (I)-(III), their methyl esters (IV)-(VII), and the sodium salt (IX), which we synthesized, were subjected to tests for the presence of antimicrobial, neurotropic, anticonvulsant, and antiinflammatory activity.

Amides and hydrazides of aroylpyruvic acids. 2. Synthesis and biological activity of some arylidenehydrazides of aroylpyruvic acids

As shown in the previous communication [12], substituted amides and/3-acylhydrazides of aroylpyruvic acids are characterized by a wide spectrum of biological activity. These compounds possess antimicrobial [6, 12], antiviral [12], antiinflammatory, analgetic [4, 12], and antispasmodic [7] activity, and also may be used in the synthesis of dyestuffs, pesticides, and a variety of nitrogen-containing biologically active compounds [5]. While amides [2, 3] and acylhydrazides of the aroylpyruvic acids [12, 14] are sufficiently well known, the structurally-related methylenehydrazides have practically not been studied. We are aware of only a limited number of works [9, 11, 15, 20] containing fragmentary information on the synthesis of some compounds of this series. Biological activity of the methylenehydrazides of aroylpyruvic acids has not been reported before. In a search for biologically active compounds among the substituted hydrazides of the aroylpyrivic acids, we prepared the arylidenehydrazides of aroylpyrivic acids (I-XII) by the reaction of 5-aryl-2,3-dihydro-2,3-furandiones with the hydrazones of aromatic aldehydes and ketones in tetrahydrofuran or dioxane at room temperature. The constants and spectral characteristics of compounds I-XII are given in Table 1. Judging by the presence in the IR spectra of I-XII of a low-frequency band at 1590-1636 cm- 1, corresponding to the carbonyl groups of the/3-diketone fragment, these compounds exist in the form of the H-chelate with the stable intramolecularly hydrogen bond (IHB) of the type OH-.-O=C [18]. This fact agrees well with literature data indicating that/3-aroylhydrazides of aroylpyruvic acids are found in the enol chelate form of the carbonyl in position 2 [12, 14, 15].