T. A. Smirnova

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 reactions of esters of 3-cyano-2-OXO-5,6-tri(tetra)methylene-1,2-dihydroisonicotinic and 2-amino-3-Ethoxycarbonyl-5,6-tri(tetra)-methyleneisonicotinic acids

Esters of 3-cyano-2-oxo-5, 6-tri (tetra)-methylene-1, 2-dihydroisonicotinic and 2-amino-3-ethoxycarbonyl-5, 6-tri (tetra)methyleneisorticotinic acids have been obtained by the reaction of 2-oxocyclopentyl(hexyl)glyoxylic acid esters with malonic acid derivatives. Boiling the esters containing a tetramethylene ring with 75% sulfuric acid gave hydrolysis of the ester and cyano groups to carboxyl with subsequent decarboxylation at the 3 position and the formation of 2-oxo-5, 6-tetramethylene-1, 2-dihydroisonicotinic acid (2-oxo-1, 2, 5, 6, 7, 8-hexahydroquinoline-4-carboxylic acid).

Synthesis and antiinflammatory and analgesic activity of 2-oxo-1,2,5,6,7,8-hexahydroquinoline-4-carboxylic acid amides

[ H I Previously we have reported on a series ofalkyland arylamides of 1,2-dihydro-2-oxocinchoninic acid possessing antiinflammatory and analgesic activity [1, 2]. There is a group of structurally close 2-oxoi,2,5,6,7,8-hexahydroquinoline-4carboxylic acid amides which have not been studied in this respect until now. In searching for new antiinflammatory agents, we have synthesized and characterized a series of these compounds. The investigation showed that acid I interacts with amines in the presence of phosphorus oxychloride, with the formation of substituted 2-oxo-l,2,5,6,7,8-hexahydroquinoline-4-carboxylic acid amides (IIa-lie). Amides II can be readily methylated at the heterocyclic nitrogen by reaction with methyl iodide in an alkaline medium, which is demonstrated below by the synthesis of derivatives Illa and IIIb. The proposed structures were confirmed by IR and IH NMR spectroscopic data.

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.

Synthesis and antibacterial activity of 2-arylidene- and 2-(5-nitrofurfurylidene)hydrazides of 2-chloro- and 2-arylamino-5,6-trimethylene and 5,6-tetramethyleneisonicotinic acids

Previously we reported on the synthesis and characterization of a series of isopropylamides of 2-arylamino5,6,7,8-tetrahydroquinoline-4-carboxylic acids, which showed antiinflammatory and analgesic activity [1]. Another active compound of this class is 5,6,7,8-tetrahydroquinoline4-carboxylie acid hydrazide, known to possess antituberculous properties [2]. The purpose of this work was to search for compounds possessing antibacterial activity among arylideneand 5-nitrofurfurylidenehydrazides of 2-chloroand 2-arylamino-5,6tri(tetra)methyleneisonicotinic acids The initial compounds were methyl ester [2] and ethyl esters ( I a Ic ) obtained by successive reactions of 5,6trimethylene and 5,6-tetramethylene-2-hydroxyisonicotinic acids with phosphorus pentachloride and the corresponding alcohol. The previous investigation showed that halogen atoms in the esters Ib were not subject to nucleophilic displacement by arylamino groups during 4 17 h of boiling in DMF (we reported on a low mobility of 2-chloro-5,6,7,8-tetrahydroquinoline-4-carboxylic acid isopropylamides) [ 1 ]. The reaction was conducted only by boiling these esters with arylamine hydrochlorides in anhnydrous butalol for 12 h, leading to a 56 9 5 % yield of 2-arylamino-5,6,7,8-tetrahydroquinoline-4carboxylic acid esters ( I Ia IIe). Interaction of esters Ia and I I a lie with hydrazine hydrate led to hydrazides I I Ia IIIf. The latter readily enter into reaction with aromatic aldehydes and 5-nitrofurfurol to yield arylideneand 5-nitrofurfurylidenehydrazides of 2-chloro= and 2-arylamino-5,6-tfimethylene and 5,6-tetramethyleneisonicotinic acids (IVa IVh). Compounds I l i a IIIf appear as colorless crystals and compounds IVaIVh are yellow crystalline substances, both soluble in DMF and acetic acid. Physicochemical characteristics of the synthesized compounds are presented in Table 1. The proposed structures are confirmed by data of the IH NMR and IR absorption measurements (see the experimental part).

Synthesis and pharmacological activity of substituted hydrazides of 2-chloro-5,6,7,8-tetrahydroquinoline-4-carboxylic acids

Isber et al. [1] reported on the synthesis of 5,6,7,8-tetrahydroquinoline-4-carboxylic acid within the framework of the search for new tuberculostatic agents. In the preceding paper [2], we have reported on the synthesis of arylideneand 5-nitrofurfurylidenehydrazides of 2-chloroand 2-arylaminosubstituted 5,6-trimethyleneand 5,6-tetramethyleneisonicotinic acids possessing antimicrobial activity. The purpose of this work was to synthesize substituted hydrazides of 2-chloro-5,6,7,8-tetrahydroquinoline-4-carboxylic acid and characterize them with respect to antibacterial, antiinflammatory, analgesic, and anticonvulsive activity. It was found that 2-chloro-5,6,7,8-tetrahydroquinoline-4carboxylie acid hydrazide (I) readily enters into the condensation reactions with aromatic aldehydes, pyruvic acid or its ethyl ester, and isatin with the formation of substituted hydrazides I I a I l g at a yield o f50-95%. Compounds I I a I Ig appear as yellow or white crystalline substances soluble in DMF and acetic acid (Table 1). The IR absorption spectrum of compound lib shows the bands at 1655 (CO) and 3285 cm-1 (Nit), while the spectrum of compound IIf displays the bands at 1675 and 1710 cmi (two CO groups) and 3180 cm-1 (NH). The IR spectra of the other products also agree with the proposed structures. The structures were confirmed by the IH NMR spectroscopy data as well (Table 2).

Synthesis and pharmacological activity of isopropylamides of 2-arylamino-5,6,7,8-tetrahydroquinoline-4-carboxylic acids

As was demonstrated previously, 2-arylamino-5,6,7,8tetrahydroquinoline-3-carboxylic acid amides exhibit antiinflammatory and analgesic activity [1]. The same types of activity were reported for substituted amides of 2-anilinocinchoninic acid [2]. Derivatives of 5,6,7,8-tetrahydroquinoline-4-carboxylic acid, which are structurally analogous to these compounds, have not been characterized. Some data were only reported for 2-oxo-l,2,5,6,7,8-haxahydroquinoline-4-carboxylic acid (I) and a methyl ester of 2-chloro5,6,7,8-tetrahydroquinoline-4-carboxylic acid, which were used as the initial compounds in the synthesis of 5,6,7,8-tetrahydroquinoline-4-carboxylic acid hydrazides expected to possess antituberculous activity [3]. The purpose of this work was to search for new antiinflammatory, analgesic, and anticonvulsive agents among a series of isopropylamides of 2-arylamino-5,6,7,8-tetrahydroquinoline-4-carboxylic acids.