G. A. Aleksandrova

Synthesis and Study of the Antibacterial and Analgesic Activity of 3-Acyl-1,2,4,5-tetrahydro-[1,2-a]quinoxaline-1,2,4-triones

As is known, derivatives of 1,2,3,4-tetrahydro-2-quinoxalones possess pronounced anticonvulsant and analgesic properties [1]. It was of interest to broaden the spectrum of pharmacological activity of compounds belonging to this class by modifying the base structure by annelation with a pyrrole cycle via the 1 – 2 bond of quinoxalone. For this purpose, we synthesized a series of 3-acyl-1,2,3,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones (X – XVIII) using reactions of 3-alkoxycarbonylmethyleneand 3-phenacylidene-1,2,3,5-tetrahydro-2-quinoxalones (I – IX) with oxalyl chloride in anhydrous chloroform conducted by the method developed in [2].

Synthesis and Antimicrobial Activity of Amines and Imines with a Cycloheptatriene Fragment

N-Benzylidene-4-(1-cyclohepta-2,4,6-trienyl)aniline (IIIa), N-(4-bromophenylmethylene)-41-(1-cyclohepta-2,4,6-trienyl)aniline (IIIb), and N-(4-methoxyphenylmethylene)-41-(1-cyclohepta-2,4,6-trienyl)aniline (IIIc) were prepared by tropylation of the corresponding imines. 4-(5-Dibenzo[a,d]cyclohepten-5-yl)aniline (V) was prepared by the reaction of aniline with dibenzosuberenole (VI); N-benzylidene-4-(5-dibenzo[a,d]cyclohepten-5-yl)aniline (IV), from benzalaniline and V. A study of the antimycobacterial activity of the synthesized compounds showed that IIIa, IIIc, and IV exhibited inhibiting activity against Staphylococcus aureus at concentrations >1000 μg/mL. Compounds IIIa and V at concentrations of 1000 μg/mL inhibited growth of E. coli and Candida albicans, respectively.

Synthesis and analgesic and antimicrobial activities of 2-(3,3-dialkyl-1,2,3,4-tetrahydroisoquinolin-1-idene)ethanoic acid ureides

A series of 2-(3,3-dialkyl-1,2,3,4-tetrahydroisoquinolin-1-idene)ethanoic acid ureides were synthesized via cyclocondensation of dialkylbenzylcarbinols and cyanoacetylurea. Experiments showed that hydrochlorides of the synthesized compounds exhibited an analgesic effect that surpassed that of metamizole sodium. It was established that four (of a total of seven) synthesized compounds possessed minimum inhibiting concentrations of about 31.2 μg/mL against Staphylococcus aureus.

Synthesis and antimicrobial activity of quaternary N-aryl-5,6-benzoquinaldinium derivatives

A series of quaternary N-aryl-5,6-benzoquinaldinium derivatives have been synthesized. Their antimicrobial activity (E. coli, S. aureus) has been tested. It was found that introduction of a new annelated benzene ring into the heterocyclic molecule (compared with quinolinium and benzoquinolinium compounds) leads to a significant increase of the antibacterial activity. Electron-withdrawing substituents in the quaternary phenyl group decrease slightly the antimicrobial effect. Since better results have been obtained for N-phenyl-5,6-benzoquinaldinium tetrafluoroborate, biological investigations were continued on the additional test cultures S. saprophyticus, Salmonella spp., Micrococcus luteus, Proteus vulgaris, Bacillus subtilis, and Candida albicans. The observation of high fungicidal activity against C. albicans was promising.

Synthesis and antifungal activity of 3-hydroxy-7,7-dialkyl-7,8-dihydroindolo[2,1-a]isoquinolinecarboxylic acid amides

Reaction of enaminoamides of the 1,2,3,4-tetrahydroisoquinoline series with p-benzoquinone yielded 3-hydroxy-7,7-dialkyl-7,8-dihydroindolo[2,1-a]-isoquinolinecarboxylic acid amides. Use of benzo[f]isoquinoline as the enamine resulted in synthesis of the relatively unknown benzo[f]indolo[2,1-a]isoquinoline system. The fungicidal activity of the compounds synthesized here was studied and the most active was the hexamethyleneimide, which was active at a concentration of 500 μg/ml.

Synthesis and antimicrobial activity of copolymers based on new diallyl monomers and sulfur dioxide

A series of copolymers of 2,2-diallyl-1,1,3,3-tetramethylguanidinium chloride and tris(diethylamino)diallylaminophosphonium chloride and tetrafluoroborate with sulfur dioxide have been obtained by free-radical polymerization reactions. The antimicrobial activity of the synthesized compunds with respect to several bacteria, spores, and fungi was determined by the method of double serial dilutions.

Synthesis, Analgesic, and Antibacterial Activity of the Products of Interaction of Hetereno[a]-dihydro-2,3-pyrrolediones with Phenylhydrazines

In continuation of our investigation into the chemical properties and pharmacological activity of hetereno[a]-dihydro-2,3-pyrrolediones [1], we have studied the interactions of these substances with phenylhydrazine and 2,4-dinitrophenylhydrazine and characterized the reaction products with respect to antibacterial and analgesic activity. Both 1-unsubstituted and 1-phenyl-5,5-dimethyl2,3,5,6-tetrahydropyrrolo[5,1-a]isoquinoline-2,3-diones react with phenylhydrazine to form the corresponding 3-hydrazones existing in the form of Z-isomers [2, 3]. In contrast to these products, 2,3-dihydro-2,3-pyrrolediones I – VII (condensed with their [a]-side exposing 2-quinoxalone and 1,4-benzoxazin-2-one cycles) react with phenylhydrazine and 2,4-dinitrophenylhydrazine to form three series of products, corresponding to the possible reaction pathways. The primary nucleophilic attack of the reagents upon a diketone molecule (I – VII) takes place either at C (see scheme, pathway a) with the formation of addition products VIII – X or at C (pathway b ) followed either by opening of the dihydropyrroledione cycle at the C – N bond with the formation of compounds XI and XII (this process takes place at room temperature) or by closing of the pyridazine cycle with the formation of compounds XIII – XVIII. Compounds VIII – X appear as white (X = O, R = Ph) or yellow (X = NH, R = C 6 H 3 (NO 2 ) 2 ) crystalline substances. These compounds melt with decomposition and show a positive reaction (cherry-red coloration) with an ethanol solution of iron(III) chloride (a test reaction for enole hydroxy groups). The solutions of compounds VIII – X in acetone and chloroform exhibit a violet color; according to [4], this fact is indicative of the reversible character of phenylhydrazine addition to diketones I – VII. The IR spectra of compounds VIII – X contain absorption bands due to the stretching vibrations of NH and OH groups (3310 – 3150 cm – ), C=O group (1710 – 1720 cm – ), aroyl carbonyl (1640 – 1650 cm – ), lactam carbonyl in compounds X and XI (1680 – 1690 cm – ), or lactone carbonyl in VIII (1760 cm – ). Compounds XI and XII appear as yellow-orange crystalline substances. These compounds melt without decomposition and exhibit no positive color reaction when tested for the presence of enole hydroxy groups. The IR spectra of compounds XI and XII display absorption bands due to the stretching vibrations of NH groups (3110 – 3340 cm – ), amide carbonyl group (1680 – 1700 cm – ), aroyl carbonyl (1610 – 1630 cm – ), a broad band of carbonyls in position 2 (1580 – 1610 cm – ), and “Amide 2” band (1530 – 1540 cm – ). The H NMR spectrum of compound XII contains signals due to the protons of aromatic substituents, a singlet of the amide NH side-chain group (8.15 ppm), and a singlet of the NH group in the heterocycle (12.75 ppm). It should be noted that, judging by the TLC data, the products of opening of the dihydropyrroledione cycle at room temperature are present in all reaction mixtures. However, these products were isolated in individual form only for compounds XI and XII. The reactions of diketones I – VII with phenylhydrazine on heating in anhydrous dioxane lead to the formation of bright-red high-melting poorly soluble crystalline compounds XIII – XVIII. The IR spectra of these compounds display absorption bands due to the stretching vibrations of NH and OH groups (3340 – 3190 cm – ), ketone carbonyl group of pyridazine cycle (1690 – 1700 cm – ), and amide carbonyl groups (1670 – 1680 cm – ). The H NMR spec-

SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF ANILINES WITH 1,3,5-CYCLOHEPTATRIENE AND 5H-DIBENZO(a,d )ANNULENE FRAGMENTS

Anilines with 1,3,5-cycloheptatriene and 5H-dibenzo[a,d]annulene fragments and antimicrobial activity were synthesized by the reaction of substituted anilines with tropylium perchlorate or 5H-dibenzo[a,d]-annulen-5-ol.

Synthesis and analgesic and antimicrobial activity of 2-aroylcyclohexanones and 3-aryl-4,5,6,7-tetrahydro-2,1-benzisoxazoles

A series of 2-aroylcyclohexanones were synthesized via acylation of 1-piperidinocyclohexene by aroylchlorides. The obtained 1,3-diketones reacted with hydroxylamine to yield 3-aryl-4,5,6,7-tetrahydro-2,1-benzisoxazoles. The starting 1,3-diketones and corresponding benzisoxazoles showed analgesic activity that exceeded that of metamizole sodium. Both groups of compounds exhibited weak activity against Candida albicans.

Synthesis and antimicrobial activity of 3-aryl-4,5,6,7-tetrahydroindazoles

Acylation of 1-piperidinocyclohexene by aroylchlorides yielded 2-aroylcyclohexanones. The obtained 1,3-diketones reacted with hydrazine hydrate to yield 3-aryl-4,5,6,7-tetrahydroindazoles, which formed stable hydrochlorides showing a high level of activity against Staphylococcus aureus and Candida albicans. The maximum activity against the bacterial strain was observed for the compound containing a 4-bromophenyl radical (the inhibition and bactericidal effects were produced at concentrations of 2 and 7.8 μg/mL, respectively). The maximum activity against the fungal strain was observed for the compound with a p-tolyl radical (the corresponding concentrations being 3.9 and 31.2 μg/mL).