Th. 3e cycle--Biochim.--Nancy--I.N.P.L., 1978.

The present investigation was also made with the object of preparing the vinylquinoxalines and studying their 1,4- addition reactions. The attempts to prepare vinylquinoxalines were unsuccessful. However, sodium acetylide reacted with 2,3-dichloroquinoxaline to give a new compound which (from its analysis and properties) appears to be 2,3-bis(1-hydroxyethyl) quinoxaline . This new compound should be investigated further , as it may prove to be an intermediate in the preparation of vinylquinoxalines. The preparation of 2-methylquinoxaline has become very simple by the use of the method of Jones, Kornfeld and McLaughlin^5, which consists of condensing o-phenylenediamine with pyruvic aldehyde. The condensation of chloral with 2-methylquinoxaline by the method of Jones^5 was repeated to obtain 2-(3,3,3-trichloro-1- propenyl)quinoxaline. Attempts to dehydrohalogenate the latter compound with palladium on barium sulfate as a catalyst resulted in a new compound, as yet unidentified, when triethylamine was also present. The hydrolysis of 2-(3,3,3-trichloro-1-propenyl)quinoxaline with sodium hydroxide was accomplished, giving β-(2-quinoxalyl)acrylic acid. Attempts made to decurboxylate β-(2-quinoxalyl)acrylic acid by various methods were unsuccessful; however o-phenylenodiamine was obtained using a concentrated sodium hydroxide solution for decarboxylation. The β-(2-quinoxalyl)acrylic acid was also brominated, and attempts made to decarboxylate the α,β-dibromo- (2-quinoxalyl)propionic acid were unsuccessful. Attempts to accomplish an anil addition of sodium phenylacetylide to quinoxaline and 2-methylquinoxaline were unsuccessful. A new unidentified compound was obtained on treating β-(2-quinoxalyl)acrylic acid in methanol with hydrogen chloride. The spectrophotometric data in the ultraviolet range were obtained on pyridine , α-picoline, 2-vinylpyridine, 2-methylquinoxaline, quinoxaline , and an unknown compound of quinoxaline which was proved to be 2-methylquinoxaline.

This work reported is divided into two parts: the first part deals with quinoxaline derivatives and includes the preparation and characterisation of novel linear tricyclic quinones 1,4-diazanthracen-9,10-diones, (54) and (55). The reaction of diazanaphthoquinones and 1-acetyl-1,3-butadiene are used to produce these quinones through the Diels-Alder reaction. In addition hexaazapentacyclic 5,6,7,12,13, 14-hexaazapentacene was prepared by the reaction ofbis(2-chloroquinoxalin-3-yl)sulfide with thioxamide and the reaction of the sulfide with amines was investigated. Two different approaches to 6,13-dibutyl-5,6,7,12,13,14-hexaazapentacene are given. Derivatives of the pentacyclic, 6-thia- 5,7,12,13,14-pentaazapentacene and the unsubstituted 6,13 -dihydro compound are described. The novel N-(2,5-dimethoxy-6-nitrophenyl)guanidine is used to obtain 3-amino-5,6-dimethoxy-1 ,2,4-benzotriazine-1-oxide and 4,7 -dimethoxy-1 ,2,3 -benzotriazole is shown to be second product. Second part of the work is concerned with the development of a preparative route to 2,6-diphenylpyridines substituted with different groups on the phenyl nuclei. Several approaches were attempted. Finally, success was achieved and a series of compounds having basic chains of different length on the phenyl groups was prepared. One chain in each case had a terminal primary amine. The binding constants of the primary amines and their N-acetyl derivatives with DNA were determined using fluorescence spectroscopy.

A long term research program into the chemistry of quinoxalines has been instituted at Brigham Young University. The literature of quinoxaline chemistry was reviewed and assembled in one paper. Methods of preparation of 2,3-dimethyl- and 2- methylquinoxaline were studied and improved. The bromination of 2,3-dimethylquinoxaline using N-bromosuccinimide was accomplished and an anil addition using quinoxaline and phenyllithium was achieved. Efforts to prepare vinylquinoxalines were unsuccessful. In order to pursue an investigation into the numerous reactions of the 1,4 addition type, a method of preparations of vinyl-quinoxalines must be achieved. In the present investigation, various methods of synthesis of vinyl- and propenylquinoxalines were attempted. Several new products were prepared in the course of the investigation as well as products only recently reported in the literature. Evidence was obtained that the preparation of 2-vinylquinoxaline may be achieved.

A long term research program into the chemistry of quinoxalines has been instituted at Brigham Young University with the aim of preparing the vinylquinoxalines so that their 1,4-addition reactions might be studied. The literature of quinoxaline chemistry has been thoroughly reviewed and assembled. Methods of preparing 2-methyl- and 2,3-dimethylquinoxaline have been studied and improved but all attempts to prepare the vinylquinoxalines have been unsuccessful. In the course of these attempts several compounds of unknown structure were prepared. The purpose of this investigation is to study the spectra of various known quinoxaline derivatives and to attempt to identify the unknowns by an analysis of their spectra.

No description available.

A search of the literature revealed that almost nothing is known concerning the class of compounds known as decahydroquinoxalines. Since this posed a problem involving a search for a systematic synthetic method of general application as well as a method for establishing the characteristic class and individual properties, a research project under the guidance of Dr. H. Smith Broadbent was initiated. Of particular interest aside from matters of purely chemical interest was the recognition that the hydroquinoxalines possess obvious structural similarities with atropine and other well-known drugs which have valuable application as hypotensive agents, analgesics, spasmolytic agents, parasympathetic depressants, antihistaminics, bronchodilators, etc. A catalyst consisting of 5% rhodium on alumina powder was reported by Baker and Co., Inc., to have certain special activity toward nitrogen heterocycles. This catalyst was applied in hydrogenation of alcohol solutions of quinoxaline and some of its substituted derivatives. At hydrogen pressures which ranged from 2000-5500 p.s.i. and temperatures of 100-200° C it was found that a variety of quinoxalines could be reduced completely to the decahydro compounds. The following decahydroquinoxalines were synthesized, described, and identified for the first time: decahydroquinoxaline, 6-methyldecahydroquinoxaline, 2,3,5,7-tetramethyldecahydroquinoxaline, 6-methoxydecahydroquinoxaline, 2,3-dimethyl-6-methoxydecahydroquinoxaline, and 6,7-dimethoxydecahydroquinoxaline. The existence of stereoisomeric forms of the decahydroquinoxalines is indicated, and it is believed that a separation of the cis and trans forms can be successfully accomplished by a combination of fractional crystallization and solvent recrystallization. Another method of separation depending on the differences of picrate solubilities in ethyl alcohol and in water is suggested. During the course of investigation five additional new compounds not previously reported in the literature were prepared and identified by elemental analysis. These were 6-phenylquinoxaline, 2,3,5,7-tetramethylquinoxaline, 6-phenyl-1,2,3,4-tetrahydroquinoxaline, 6-amino-1,2,3,4-tetrahydroquinoxaline, and 6,7-dimethoxy-1,2,3,4-tetrahydroquinoxaline. This fundamental research has opened up a convenient synthetic route for a whole new class of compounds and has in part indicated their characteristic properties.

No abstract available. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2009.

Tikslas: Įvertinti chinoksalino darinių struktūros įtaką jų antimikrobiniam ir priešvėžiniam aktyvumui ir atrinkti perspektyviausius junginius tolimesniems tyrimams. Darbo uždaviniai: 1. Ištirti chinoksalino darinių antimikrobinį (priešgrybelinį ir antibakterinį) aktyvumą in vitro. 2. Ištirti chinoksalino darinių priešvėžinį aktyvumą in vitro. 3. Nustatyti chinoksalino darinių antimikrobinio ir priešvėžinio aktyvumo bei cheminės struktūros ryšio dėsningumus. 4. Įvertinti chinoksalino darinių toksiškumą ir farmakokinetines savybes in silico. 5. Remiantis gautais rezultatais, atrinkti perspektyviausius chinoksalino darinius. Tyrimo metodai. Antimikrobiniam aktyvumui nustatyti naudoti in vitro metodai: skiedimo standžioje ir skystoje terpėse bei difuzijos į agarą metodas. Priešvėžinis aktyvumas įvertintas tiriant ląstelių gyvybingumo slopinimą MTT metodu. Struktūros-aktyvumo ryšys įvertintas analizuojant eksperimentinius duomenis. Junginių toksiškumas ir farmakokinetinės savybės įvertintos in silico, remiantis kompiuterinės programos ACD/I-Lab duomenimis. Tyrimo rezultatai. Aktyviausi chinoksalino dariniai Bacillus ir Staphylococcus genties bakterijų augimą slopino 16 μM koncentracija, grybelio Candida albicans – 22 μM koncentracija. Aktyviausi chinoksalino dariniai žmogaus plaučių karcinomos A549 ir glioblastomos U87 ląsteles veikė 0,5-10 μM koncentracijomis. Nustatyti antimikrobinio poveikio struktūros ryšio dėsningumai: aktyviausi junginiai chinoksalino žiedo antroje padėtyje... [toliau žr. visą tekstą] / The Aim of the Research: To evaluate the structure influence on antimicrobial and anticancer activity of quinoxaline derivatives and identify the most promising compounds for the further development. Objectives: 1. To test antimicrobial (antibacterial and antifungal) activity of quinoxaline derivatives in vitro. 2. To test anticancer activity of quinoxaline derivatives in vitro. 3. To establish relationship between structure and antimicrobial, also anticancer activity. 4. To evaluate toxicity and pharmacokinetic properties of quinoxaline derivatives in silico. 5. To identify the most promising quinoxaline derivatives with reference to experimental results. Methods. Antimicrobial activity was tested in vitro using three different methods: serial dilution in agar, in liquid broth, and diffusion into agar. Anticancer activity was investigated by evaluating cell viability using MTT assay. Structure-activity relationship was evaluated from analysis of experimental data. Toxicity and pharmacokinetic properties were predicted by using ACD/I-Lab program. Results. The most promising quinoxaline derivatives inhibited growth of Bacillus and Staphylococcus genus bacteria with 16 μM concentration, fungus Candida albicans with 22 μM concentration. The most active quinoxaline derivatives were active against human lung carcinoma A549 and glioblastoma U87 cell lines with concentrations of 0.5-10 μM. Some principles of structure – antimicrobial activity relationship were established: the most... [to full text]

Thesis (M.Sc. (Chemistry)) -- University of Limpopo, 2020 / In an attempt to synthesise quinoxaline-ferrocene compounds with antimycobacterial activity; a series of quinoxaline alkynyl derivatives were successfully synthesised from 3- (quinoxalin-3-yl)prop-2-yn-1-ol 86A and 3-(6-chloroquinoxalin-2-yl)prop-2-yn-1-ol 86B. In this series compounds 87A – B, 90A – B, and 93A – C were intermediates obtained in an effort to synthesise quinoxaline-ferrocene compounds. Treatment of either 86A or 86B with various acid chlorides afforded quinoxaline alkynyl ester derivatives 97A - 97B. Within this series, two quinoxaline-ferrocene compounds 3-(quinoxalin-3-yl)prop-2-ynyl ferrocetate 97A-iv and 3-(6-chloroquinoxalin-2-yl)prop-2-ynyl ferrocetate 97B-iv were successfully incorporated with ferrocenoyl chloride and obtained in 42 - 43% yield. The reactions of 3-chloroquinoxaline-2-carbonyl chloride 99 with ferrocenyl alcohol and ferrocenyl amine were unsuccessful. However, 3-chloroquinoxaline-2-carbonyl ester 100A - C and amide 101A - D derivatives with various alcohols and amines were obtained. The structures of all the compounds were confirmed by spectroscopic analysis (NMR, FT-IR and HRMS). The synthesised compounds were all evaluated for preliminary in-vitro antimycobacterial activity. The results obtained exhibited compound 90B with the highest activity against Mtb H37RV strain at MIC90 of 1.13 µM, followed by 90A and 87A exhibiting MIC90 of 4.55 and 6.47 µM, respectively. The quinoxaline alkynyl ester derivatives were found to exhibit poor to good activity. Within this series, three compounds were found to exhibit antimycobacterial activity at MIC90 ˂ 20 µM with compound 97A-ii showing the highest activity at MIC90 of 16.18 µM, followed by 97A-i and 97B-iii showing MIC90 of 18.05 and 19.36 µM, respectively. From the two quixonaline-ferrocene compounds, compound 97A iv was found to exhibit antimycobacterial activity at MIC90 of 39.90 µM. However, compound 97B-iv was found to be inactive. The 3-chloroquinoxaline-2-carbonyl ester 100A - C and amide 101A - D derivatives were found to be inactive. However, compound 99-C was found to exhibit antimycobacterial activity at MIC90 of 40.66 µM. Compounds 86A, 86C, 87A and 90A were evaluated for in-vitro antiproliferative activity against cancer cell lines. The results of antiproliferative activity showed that compounds 86A and 87A exhibited excellent activity against A549 lung cancer cell lines. Compound 87A was found to be the most active against A549 cell line showing 50% viability-inhibition at 25 µM / National Research Foundation (NRF)