V. E. Kolla

Synthesis and biological activity of amides and nitriles of 2-arylamino-5-carboxy(carbethoxy)-6-methylnicotinic acids and 1-aryl-6-carbethoxy-7-methyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines

of diester (VIII) to considerably increase the locomotive activity and to improve the preservation of CRPA in rats. Further examination of the distinct antagonism of diester (XIII) to corazole is required, which makes it possible to assume that this compound has anticonvulsive properties, possibly as a result of antagonism to Glu. We may assume that the differences in the pharmacological properties of diesters (VIII-XIII) are connected with the different rate of generating Glu from them under influence of blood enzymes.

Amides and hydrazides of aroylpyrivic acids. Part 6 Synthesis and study of antiinflammatory and analgesic activity of β-aroylpyruvoyl hydrazides of 2-methyl(phenyl)-4-quinolinecarboxylic acids

Previously we have demonstrated that 4-quinolinecarboxylic acid amides and hydrazides, substituted at position 2, exhibit pronounced antiinflammatory and analgesic activity at a quite low toxicity [1 5]. It was established that the charaeter and strength of the pharmacological action depend on the type of substituents at positions 2 and 4 of the quinoline cycle. As is known, introduction of the aroylpyruvoyl fragment into amides and hydrazides imparts to them a high antiinflammatory and analgesic activity [6, 7]. In this connection, we have synthesized cinehoninie acid hydrazides containing aroylpyruvoyl fragments at the 15-nitrogen atom. The new compounds, namely, 13-aroylpyruvoyl hydrazides of 2methyl(I) and 2-phenyl-4-quinolinecarboxylic (II) acids were obtained using a reaction of 5-aryl-2,3-dihydro-2,3furandiones with 2-methyland 2-phenyl-4-quinolinecarboxylic acids according to the scheme. Compounds I and II appear as white crystalline substances (except for Ih) poorly soluble in ethanol, benzene, chloroform, and acetonitrile, and soluble in DMSO and DMF. Their structures were established using the data of elemental analyses and the results of IR and IH NMR spectroscopic measurements. Similarly to the other pyruvic acid derivatives, the synthesized compounds provide red coloration of an ethanol solution of iron(Ill) chloride, which is evidence for the presence ofenolic hydroxyl [9, 10]. The IH NMR spectra of compounds I a Ih, IIb, and IIe contain signals attributed to the protons of methyl group (2.28-2.71 ppm), methoxy group (3.65-3.75ppm), and methine group (6.83-7.21 ppm), and a group of signals belonging to the protons of benzene ring and quinoline cycle

Synthesis and Antiinflammatory and Analgesic Activity of 2H-3,3-Dimethyl-3,4-dihydroisoquinolin-1-ones

The reactions of substituted arenes with isobutyric aldehyde and methylthiocyanate yield 1-methylthio-3,4-dihydroisoquinolines. The subsequent treatment with AcOH/AcONa yields 2H-3,3-dimethyl-3,4-dihydroisoquinolin-1-ones, some of which exhibit pronounced antiinflammatory and analgesic properties.

Synthesis, properties, and biological activity of β-aroylpyruvoyl hydrazides oF N-methyl- and N-phenylanthranilic acid

Anthranilic acid hydrazides exhibit antistaphylococcus [ I ] and antiaggregation activity with respect to blood plasma thrombocytes [2]. They also can be used for the syntheses of nitrogen-containing heterocycles exhibiting various pharmacological effects [3]. Aroylpyruvic acid hydrazides exhibit a bacteriostatic effect against Staphylococcus aureus and Escherichia coli [4], inhibit the growth of A and B influenza viruses, and exhibit an antiinflammatory effect [5]. In searching for novel biologically active compounds we synthesized 13-aroylpyruvoyl hydrazides of N-methyland Nphenylanthranilic acids ( IVXVI) and studied their antiinflammatory and antimicrobial activity. The target products were obtained by the reaction of 5aryl-2,3-dihydrofuran-2,3-diones (I) with hydrazides of Nmethyland N-phenylanthranilic acids (I1 and III) in an inert solvent at room temperature. Compounds I1 and III qualify as binucleohilic reagents. The nucleophilic centers are the !3amino group ofhydrazide moiety and the aromatic N-methyland N-phenyl amino groups. The nucleophilic properties of the hydrazide 13-amino group are most pronounced, because nucleophilicity of the aromatic amino group is reduced due to the positive mesomeric effect. In addition, the steric effects can also affect the reactivity of this group [6]. It is well known that in the case of nonequivalent nucleophilic centers the furandione ring is opened under the action of the strongest nucleophilic agent [7]. The synthesized compounds are yellow solids, almost insoluble in water, and give like other ariylpyruvic acid derivatives a cherry color when reacted with an ethanol solution of FeCI3. This indicates that the compounds exist in the enol. The previous studies have established that cc-carbonyl of aroylpyruvic moiety undergoes enolization in any case [8].

Synthesis and antidepressant activity of acylhydrazides of 2-chloroand 2-anilino-5,6,7,8-tetrahydroquinoline-4-carboxylic acids

For this purpose we have synthesized a series of 13-(halogenoacyl)hydrazides of 2-chloroand 2-anilino-5,6,7,8-tetrahydroquinoline-4-carboxylic acids (IIa-IIc) by reactions of hydrazides Ia and Ib [2] with chloroanhydrides of the corresponding carboxylic acids in glacial acetic acid in the presence of anhydrous sodium acetate. Acylhydrazies I Ia I Ic appear as crystalline substances soluble in toluene, ethanol, and acetic acid (Table 1). The IR absorption spectrum of compound IIb shows characteristic bands in the regions of 1675 1680 and 17001705 cm -I (CO) and bands at 31453150, 3260 3275, and 34903500 cml (NH).

Synthesis and Biological Activity of Hydroxyphencyclidine Homologs

A series of phencyclidine homologs was synthesized by reductive cyclization of substituted ω-chlorine-substituted l-N-[l-(p-hydroxybenzyl)cyclohexyl]amides with LiAlH4. The synthesized compounds were characterized and tested for neurotropic activity.

1,3,4,6-tetracarbonyl compounds. part 2. 1 synthesis of biologically active 2-hydroxy-2,3-dihydro-3-pyrrolones and substituted amides of aroylpyruvic acids

As is known, CH acids such as arylmethylketones, acetoacetic, and cyanoacetic esters readily interact with 5-aryl2,3-dihydro-2,3-furandiones (I) in the presence of base catalysts with the formation of 2-aeylmethyl-2-hydroxy2,3-dihydro-3-furanones-stable products of regioselective aldol condensation at the lactone carbonyl [1 7]. It was established that these cyclic semiacetals occur in solution in equilibrium with linear oxotautomeric forms, enolyzed at the carbonyl groups in positions 3 and 4, and with 1,3,4,6-tetracarbonyl compounds [I, 3, 5 -7] . The structure of the latter compounds and the close cyclic heterofunctional derivatives, as well as their tautomeric equilibria in solutions, have been studied in sufficient detail [1, 3, 8 12].

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, anti-inflammatory and analgesic activity of alkylamides of 2-alkoxy-4,6-dimethylnicotinic acids

Among previously synthesized N-arylamides of 2-alkoxy-6-methylnicotinic acids, compounds have been observed with antispasmodic activity [1]. Accordingly, it seemed of interest to obtain structurally similar alkylamides of 2-alkoxy-4,6-dimethylnicotinic acids, and to study their antispasmodic, anti-inflammatory, and analgesic action. Alkylamides Ia – Ik (Table 1) were obtained in good yields when alkylamides of 2-chloro-4,6-dimethylnicotinic acid was reacted with sodium alcoholates in a medium of the corresponding alcohols. The structure of the compounds obtained has been confirmed by IR and H NMR spectra (Table 2).

Synthesis and pharmacological activity of substituted amides of 2-chloro- and 2-arylamino-5,6-tri(tetra)methyleneisonicotinic acids

As was demonstrated, isopropylamides of 2-arylamino5,6,7,8-tetrahydroquinoline-4-carboxylic acids possess several types of pharmacological activity [1]. In continuation of the previous investigation, we have synthesized a series of new alkyland arylamides of 2-chloro-5,6-trimethylene(5,6tetramethylene)isonicotinic acids (I lallft and 2-arylamino5,6-tetramethyleneisonicotinic acids (IIIa-IIIe) and studied their antiinflammatory, analgesic, and anticonvulsive properties.