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1
Barr, Stephen Alexander. "Quinoline alkaloids : synthesis and stereochemistry." Thesis, Queen's University Belfast, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333796.
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Klaas, Phindile Jonathan. "Novel approaches to the synthesis of quinoline derivatives." Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1004751.
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The investigation has been concerned with the application of the Baylis-Hillman methodology to the synthesis of quinoline derivatives. An extensive range of novel Baylis-Hillman products has been prepared, typically in moderate to excellent yields, by condensing 2-nitrobenzaldehyde derivatives with various vinyl ketones and acrylic esters in the presence of diazabicyclo[2.2.2]octane (DABCO). Reduction of the nitro group in the Baylis-Hillman products was effected by catalytic hydrogenation in ethanol using a 10% palladium-on-carbon catalyst to afford quinoline, quinoline-N-oxide and quinolone derivatives. In all cases, it is apparent that cyclisation involves exclusive attack of nucleophilic nitrogen at the carbonyl centre, with acrylic ester derivatives affording quinolones and vinyl ketone derivatives affording quinolines and the corresponding quinoline-N-oxides. No products arising from a conjugate addition pathway were observed. The use of stannous chloride as an alternative reagent to effect reductive cyclisation of the Baylis-Hillman products has been explored, and found to favour the formation of 1,2- dihydroquinoline derivatives, with cyclisation occurring via a conjugate addition pathway. Isolation of the products, following work-up of the stannous chloride reactions, however, presented some difficulty. All compounds were characterised by spectroscopic (NMR and IR) and, where appropriate, elemental (high-resolution MS) analysis. Interconversion of the quinoline and quinoline-N-oxide derivatives has been explored and finally achieved in quantitative yields. Reduction of 2,3-dimethylquinoline-N-oxide to the corresponding quinoline was effected using phosphorus tribromide in DMF, and the reverse transformation with meta-chloroperbenzoic acid (MCPBA) in CHCl₃. Application of these methods to mixtures of 2,3-dimethylquinoline and its N-oxide has afforded, selectively, either the quinoline derivative or the corresponding N-oxide.KMBT_363
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3
Neville, Charles Frederick. "The synthesis and biosynthesis of quinoline alkaloids." Thesis, University of Ulster, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.481119.
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4
Velioglu, Ozlem. "Synthesis Of Ferrocenyl Substituted Quinolines." Master's thesis, METU, 2008. http://etd.lib.metu.edu.tr/upload/3/12609785/index.pdf.
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Quinolines have been studied for over a century as an important class of heterocyclic compounds and continue to attract considerable interest due to the broad range of biological activities they possess. The incorporation of the essential
structural features of quinolines with a ferrocene moiety could provide new derivatives with unexpected and/or enhanced biological activities since several ferrocene derivatives have already been shown to be active against a number of
tumors. For this reason, we investigated the synthesis of ferrocenyl-substituted quinolines, such as 2-ferrocenylquinoline, by employing the molecular iodine catalyzed reaction between enolizable aldehydes and ferrocenyl imines, which were prepared by the condensation reactions of ferrocenecarboxaldehyde with aniline derivatives. As anticipated, these reactions produced 2-ferrocenylquinoline derivatives. By employing this ethodology, we synthesized 2-ferrocenylquinoline, 6-chloro-2-ferrocenylquinoline, 6-bromo-2-ferrocenyl-quinoline, 2-ferrocenyl-7-methylquinoline and 2-ferrocenyl-3,7-dimethylquinoline. Due to the ready availability of ferrocenylimines and aldehydes, this practical onepot
method represents a versatile synthesis of ferrocenyl-substituted quinolines.
5
Haddad, Jalal. "Synthesis and chemistry of some quinoline-5,8-diones." Virtual Press, 1994. http://liblink.bsu.edu/uhtbin/catkey/917048.
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The synthesis of several 7-substituted analogs of 2-methylquinoline-5,8-dione and their chemistry are described. In this investigation the following compounds were prepared.5,7-Diformamido-8-hydroxy-2-methylquinoline (207), 7-formamido-2methylquinoline-5,8-dione (199), 7-acetamido-2-methylquinoline-5,8-dione (6), 7-isobutyramido-2-methylquinoline-5,8-dione (200), 7-amino-2-methylquinoline-5,8-dione (210), 7-amino-6-chloro-2-methylquinoline-5,8-dione (213), 7-methoxy-2-methylquinoline5,8-dione (214), 7-ethoxy-2-methylquinoline-5,8-dione (215), 7-isopropyloxy-2methylquinoline-5,8-dione (216), 7-amino-5-ethyl-5-hydroxy-2-methylquinoline-8-one (218), 7-acetamido-5-ethyl-5-hydroxy-2-methylquinoline-8-one (220), and 7-chloro-2methylquinoline-5,8-dione (222).Trimetylacetic formic anhydride (206) was prepared according to McGarvy,s 68 method from treatment of sodium formate (204) and trimethylacetyl chloride (203) in the presence of poly (4-vinylpyridine-N-oxide) (205) as catalyst. 7-Formamido-2methylquinoline-5,8-dione (199) was prepared according to the following general procedure. 8-Hydroxy-2-mehylquinoline (5) was reacted with a 70% mixture of HNO3/H2SO4 to produce 5,7-dinitro-8-hydroxy-2-methylquinoline (18). Compound 18 was reduced by H2/Pd-C in the presence of HCl and then the resulting 5,7-diamino-8-hydroxy-2 methylquinolin-5,8-dione hydrochloride salt (198) reacted with trimethylacetic formic anhydride to produce 5,7-diformamido-8-hydroxy-2-methylquinoline-5,8-dione (207). Compound 207 was treated with a solution of potassium dichromate in acetic acid-water mixture to give product 199.7-Acetamido-2-methylquinoline-5,8-dione (6) was prepared from reaction of a solution of 198 with acetic anhydride in the presence of sodium acetate and sodium sulfite followed by oxidation with potassium dichromate in acetic acid-water solution. 7-Isobutyramido-2methylquinoline-5,8-dione (200) was prepared according to following procedure. Treatment of a solution of 198 with isobutyric anhydride in the presence of sodium acetate and sodium sulfite afforded 5,7-diisobutyramido-8-isobutyroxy-2-methylquinoline (212). Partial hydrolysis of 212 in boiling methanol-water mixture gave 5,7-diisobutyramido-8-hydroxy-2methylquinoline (211). Oxidation of 211 by a solution of potassium dichromate in acetic acid-water mixture afforded product 200.7-amino-2-methylquinoline-5,8-dione (210) was prepared from alcoholysis of 7-acylamino-2-methylquinoline-5,8-diones 6, 199,and 200 with methanol and sulfuric acid. 7-Alkoxy-2-methylquinoline-5,8-diones 214, 215, and 216 were prepared from reaction of 7-acetamido compound 6 with alcohols in the presence of sulfuric acid. Reaction of 7-acylamino compounds 6, 199, and 200 with methanol in the presence of hydrogen chloride gas at 60°C afforded 7-amino-6-chloro-2-methylquinoline-5,8-dione (213).Reaction of compound 210 with diethylaluminum cyanide gave 7-amino-5-ethyl-5hydroxy-2-methylquinoline-8-one (218). The same reaction was carried out on compound 6 to give 7-acetamido-5-ethyl-5-hydroxy-2-methylquinoline-8-one (220).1-[(tert-Butyldimethylsilyl)oxy]-2-methyl-l-aza-1,3-butadiene (4) was prepared from treatment of methyl vinyl ketone (210) and t-butylmethylsilylhydroxylamine (202) in dichloromethane in the presence of molecular sieves. Cycloaddition reaction of a solution of 4 in dichloromethane with 2,6-dichloro-1,4-benzoquinone (221) in sealed tube afforded 7-chloro-2-methylquinoline-5,8-dione (222).Department of Chemistry
6
Watters, William Henry. "Studies towards the synthesis of hemiterpenoid quinoline alkaloids." Thesis, University of Ulster, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241684.
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Mazzanti, Stefano. "A novel atroposelective strategy for the synthesis of quinoline substrates." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2018. http://amslaurea.unibo.it/16660/.
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Among heterocyclic compounds, quinoline scaffold has become an important motif for the development of new pharmacological active compounds. Since the discovery of their antimalarial properties, a large variety of quinolines was found to have interesting physiological activities and displayed attractive applications for pharmaceutical industries. In accordance to the above-mentioned features, a number of methods were developed for their synthesis but enantioselective versions are still lacking in the literature. In the past decades, this question has become even more complex, with the emergence of the less common axial chirality. Within the growing number of articles about atropisomers, the discovery of new synthetic pathways for the synthesis of enantioenriched atropisomers and their use in drug discovery has become a challenging topic in the organic chemistry scenario. In this work, the development of a novel atroposelective strategy for the synthesis of quinoline substrates has been achieved, and in order to obtain high values of enantioselectivity and yields a screening of the reaction conditions has been performed. The design of such strategy has been developed combining an already established methodology for the synthesis of heteroaromatic compounds such as a well-known Friedländer-type quinoline synthesis with chiral Brønsted acid catalysis to obtain the C-C bond formation in an enantioselective fashion.
8
Hamilton, Lynne. "Synthesis, stereochemistry and reactions of quinoline, isoquinoline and acridine metabolites." Thesis, Queen's University Belfast, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334710.
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Loke, P. L. "Chemoenzymatic and chemical synthesis of enantiopure quinoline derivatives and alkaloids." Thesis, Queen's University Belfast, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273295.
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Rahman, Adrian. "The synthesis of new tricyclic beta lactams based upon quinoline." Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366356.
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Bar, GreÌgory L. J. "Manganese(III) acetate-mediated radical reactions in organic synthesis." Thesis, University of York, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274499.
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Shi, Aibin. "Synthesis and bioactivities of substituted quinolines and nanogels." Diss., Manhattan, Kan. : Kansas State University, 2009. http://hdl.handle.net/2097/1638.
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13
Melis, Diana. "Quinoline-triazole half-sandwich iridium(III) complexes: Synthesis, antiplasmodial activity and preliminary transfer hydrogenation studies." Master's thesis, Faculty of Science, 2020. http://hdl.handle.net/11427/32414.
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Malaria is a devastating and pervasive infectious disease and continues to be a major global health issue, with over half the world's population being at risk of transmission. In the absence of a suitable vaccine, efforts to eradicate the disease rely heavily on clinically available drugs. Plasmodium falciparum, the deadliest species of malaria, has however become resistant to most conventional antimalarial treatments, resulting in the worldwide search for new, effective drugs. Amongst other requirements, these drugs should target resistant parasitic strains in an attempt to curb the escalation of the disease. In this regard, the incorporation of a metal into the organic framework of a biologically active compound has become an increasingly popular method of enhancing antiplasmodial activity in the drug-resistant parasite strains. Two series of 7-chloroquinoline-1,2,3-triazole ligands, one with the direct attachment of the triazole to the quinoline and one where the two entities are separated by an aminopropyl linker, were synthesised. Coordination of selected ligands with [IrCl(μ-Cl)(Cp*)]₂ yielded six neutral, cyclometallated and two cationic,N,N-chelated iridium complexes. Computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming an unstable kinetic product that, upon heating over time, forms the stable, cyclometallated, thermodynamic product. All of the compounds were fully characterised using an array of spectroscopic (¹H, ¹³C{¹H}, ¹⁹F{¹H}, ³¹P{¹H} NMR and FT-IR spectroscopy) and analytical (mass spectrometry and melting point analysis) techniques. Single crystal X-ray diffraction confirmed the proposed molecular structure and a pseudo-tetrahedral geometry around the metal centre for the cyclometallated and monodentate, quinoline nitrogen-coordinated complexes. The ligand series containing the propyl chain linker displayed superior in vitro antiplasmodial activity against the chloroquine-sensitive NF54 strain of P. falciparum in comparison with the series having thetriazole directly attached to the quinoline moiety. Upon complexation with iridium, the activity of selected ligands is significantly enhanced (0.247< IC₅₀ (μM)< 2.34), with some complexes being over one hundred times more active than their respective ligands. For most of these compounds, their antiplasmodial activity is lower in the chloroquine-resistant K1 strain, however, their calculated RI values suggest that they likely only experience mild cross-resistance, not to the same extent of chloroquine. Selected complexes were tested against the healthy, mammalian Chinese Hamster Ovarian (CHO) cell line and were found not to be cytotoxic. They were also determined to be more selective towards the parasite than healthy cells. An “IC₅₀ speed assay” using the three most active complexes against the chloroquine-sensitive NF54 strain found the two neutral, cyclometallated complexes to be fast-acting compounds which reach their lowest IC₅₀ values within 24 hours, while the active cationic complex was determined to be slow-acting, only reaching its lowest IC₅₀ value after 48 hours. To gain insight into the possible mechanisms of action of these compounds, selected ligands and complexes were tested for their ability to inhibit the formation β-haematin(the synthetic form of haemozoin), sinceone of the mechanisms of 7-chloroquinoline-containing compounds is the inhibition of haemozo information. All five of the tested compounds were found to inhibit β-haematin formation to some extent but were, in general, less effective β-haematin inhibitors than chloroquine itself. Interestingly, the aminopropyl-containing cationic complex which displayed the lowest antiplasmodial activity exhibited far greater β-haematin inhibitory activity (IC₅₀ 9.65 μM) than chloroquine(IC₅₀ 65.3 μM).Finally, three of the most active complexes were evaluated for their ability to facilitate transfer hydrogenation, by reducing β-nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of hydrogen source, sodium formate. Through preliminary qualitative and quantitative cell-free experiments, it was found that the two most active neutral, cyclometallated complexes tested may be capable of acting as transfer hydrogenation catalysts while the active, cationic complex tested did not indicate reduction of NAD+ to NADH over 4 hours.
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Pretorius, Izak Stefanus. "Synthesis, characterisation and antimalarial activity of quinoline–pyrimidine hybrids / Izak Stefanus Pretorius." Thesis, North-West University, 2012. http://hdl.handle.net/10394/8105.
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The world suffers under the immense threat of malaria with about 1 million people dying and
a further 500 million people getting infected and debilitated by the disease each year. It has a
negative effect on the economic growth in developing countries that already battles with
political unrest, civil wars, famine and the effect of diseases like tuberculosis and HIV/AIDS.
Resistance against the first line drugs such as the quinolines and the antifolate combination
drugs makes the fight against malaria increasingly difficult and has prompted studies into
alternative chemotherapeutic treatments of the disease. An efficient strategy to develop an
effective and cheaper antimalarial compound appears to be the re–design of existing drugs
and the exploitation of known parasite–specific targets.
In our search for novel drugs with improved antimalarial properties compared to the existing
ones, we applied an emerging strategy in medicinal chemistry called hybridisation. This is the
combination of two or more active ingredients into a single chemical entity to form a hybrid
drug. The hybrid drug strategy has the potential advantage of restoring the effectiveness in
antimalaria drugs such as the quinolines and the antifolate drugs. Artemisinin based and
quinoline based hybrid drugs are demonstrative examples of the validity of such an
approach.
Chloroquine used to be the first–choice drug in malaria treatment and prophylaxis ever since
its discovery, but drug resistance has rendered it almost completely useless in treating
Plasmodium falciparum. Today, it is still widely used in treating Plasmodium vivax malaria in
resistance free areas. The historical success of the aminoquinoline antimalarial drugs
supported our decision to include the quinoline pharmacophore in our study.
Pyrimethamine has been the most widely used antimalarial antifolate drug. It is used in
malaria prophylaxis in combination with sulphonamides. Point mutations in the parasite’s dhfr
domain of the dhfr gene are severely compromising its antimalarial effectiveness.
The pharmacophores of chloroquine and pyrimethamine are a quinoline and a pyrimidine
moiety, respectively. Through hybridisation of these two pharmacophores we hoped to bring
about molecules with potent antimalarial properties and, thus restoring their antimalarial
usefulness.
In this study we aimed to synthesise a series of quinoline–pyrimidine hybrids, determine their
physicochemical properties and evaluate their antimalarial activity in comparison to that of
chloroquine and pyrimethamine.
We successfully synthesised ten quinoline–pyrimidine hybrids by connecting a quinoline and
a pyrimidine moiety via different linkers. The structures of the prepared hybrids were
confirmed by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS).
The experimental aqueous solubility of the compounds was determined to be higher at pH
5.5 than at pH 7.4 although no structure–physicochemical property could be drawn from this
investigation.
The quinoline–pyrimidine hybrids were screened in vitro alongside chloroquine and
pyrimethamine against the chloroquine–sensitive D10 strain of Plasmodium falciparum. The
ether–linked hybrids tended to be more potent than the amine–linked ones. Compound 21,
exhibited the best antimalarial activity (IC50 = 0.08 uM) of all, and possessed activity similar to
that of pyrimethamine (IC50 = 0.11 uM). None of the compounds proved to be as effective as
chloroquine (IC50 = 0.03 uM).Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2012.
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Vlok, Martha Carolina. "Artemisinin-quinoline hybrids :|bdesign, synthesis and antimalarial activity / Martha Carolina (Marli) Vlok." Thesis, North-West University, 2013. http://hdl.handle.net/10394/9543.
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Introduction -
Malaria is a major global health problem, with more than 500 million reported cases and at least 1 million deaths each year. The main problem with malaria control is the emerging drug resistance. Plasmodium falciparum (P. falciparum) developed widespread resistance to antimalarial drugs such as chloroquine (CQ) and mefloquine, but not to the artemisinins. The World Health Organization (WHO) recommended artemisinin combination therapy (ACT) for the treatment of uncomplicated malaria in all chloroquine resistance areas. However, P. falciparum has recently started to display resistance to these ACTs, highlighting the need for new chemotherapeutic approaches for the treatment of P. falciparum infections.
Aims -
The aims of this study were: (i) to design and synthesise a new series of antimalarial hybrid drugs, consisting of dihydroartemisinin (DHA) and aminoquinoline moieties bound covalently through different, very distinctive linkers; (ii) to determine the in vitro antiplasmodial activity and cytotoxicity of the synthesised series; (iii) to ascertain whether the in vitro antiplasmodial activity of the promising compounds would be carried over in vivo against Plasmodium vinckei (P. vinckei); and, (iv) to obtain an indication of the pharmacokinetic properties of this class of antimalarial drugs by performing snapshot pharmacokinetic analysis.
Methods -
DHA was coupled via an aminoethylether bond to various aminoquinolines to give hybrids and hybrid-dimers. CQ-susceptible (D10 and 3D7) and CQ-resistant (Dd2) strains of P. falciparum were used to determine the in vitro antiplasmodial activity. In vitro cytotoxicity was assessed using a mammalian cell-line (Chinese Hamster Ovarian, CHO). The antiproliferative activity of the hybrid-dimers was tested against three cell lines; renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62). P. vinckei-infected mice were treated with the hybrid drugs for four days at a dosage of 0.8 mg/kg, 2.5 mg/kg, 7.5 mg/kg or 15 mg/kg intraperitoneally (ip) or orally (po), with 2.7 mg/kg, 8.3 mg/kg, 25 mg/kg or 50 mg/kg, in order to determine their antimalarial activity. A snapshot oral and intravenous (IV) pharmacokinetic study was performed.
Results -
All compounds were obtained as the 10-β-isomers and were isolated as the oxalate salts. Low nanomolar in vitro antiplasmodial activities were displayed by several compounds in this series, with IC50 values ranging from 5.15 to 29.5 nM, in comparison with the values of 2.09–5.11 nM and 21.54–157.90 nM for each of DHA and CQ respectively. All compounds displayed good selectivity towards P. falciparum in vitro (selectivity index (SI) ≥ 20). Two of the hybrids, featuring non-methylated and methylated two-carbon diaminoalkyl linkers, exerted potent in vivo antimalarial activities, with ED50 values of 1.1 and 1.4 mg/kg by ip route and 12 and 16 mg/kg po, respectively. Long-term monitoring of parasitaemia showed a complete cure of mice (without recrudescence) at 15 mg/kg ip and at 50 mg/kg po for these two hybrids, whereas artesunate was able to provide a complete cure only at 30 mg/kg ip and 80 mg/kg po.
Conclusions -
These compounds may provide a lead into a new class of antimalarial drugs so badly needed for treatment of resistant strains. Despite shorter half-lives and moderate oral bioavailability in comparison with DHA, two of the compounds of this series were able to cure malaria in mice at very low dosages, implicating extremely active metabolites. The optimum linker length for antimalarial activity was found to be a diaminoalkyl linker consisting of two carbon atoms, either unmethylated or bearing a single methyl group.Thesis (PhD (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2013
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Ngororabanga, Jean Marie Vianney. "Synthesis of fluorescent polymers with pendant triazole-quinoline groups via raft polymerization." Thesis, Nelson Mandela Metropolitan University, 2014. http://hdl.handle.net/10948/d1020798.
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In this study, fluorescent polymers with pendant quinoline groups were synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) from a fluorescent quinoline-based vinyl monomer, synthesized in multiple steps from p-nitroaniline and crotonaldehyde. The structures of the synthesized vinyl monomer and polymers were confirmed by NMR and FT-IR spectroscopy, X-ray studies and modeling stdies. The photophysical properties of the synthesized quinoline compounds and resulting polymers were investigated. In order to evaluate the binding potential of our quinoline-based polymer in the presence of transition metal ions, preliminary studies on a complexation of quinoline-based polymers with Zn, Cd, Hg, Fe, and Ni were carried out. The investigation of fluorescence properties of the complexes showed fluorescence quenching for Fe(II), and fluorescence enhancement for the remaining ions [Zn(II), Cd(II), Hg(II), and Ni(II)].
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Zehr, Peter S. "Synthesis of novel alkaloids using squaric acid esters." Morgantown, W. Va. : [West Virginia University Libraries], 2005. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=4411.
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Thesis (Ph. D.)--West Virginia University, 2005.Title from document title page. Document formatted into pages; contains xvii, 207 p. : ill. Includes abstract. Includes bibliographical references (p. 97-101).
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Banini, Serge R. "Palladium-catalyzed syntheses of indoles, pyrroloindoles, quinolines a base-mediated formation of N-alkoxyindoles, and progress toward the first total synthesis of echinosulfone A /." Morgantown, W. Va. : [West Virginia University Libraries], 2008. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=5710.
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Thesis (Ph. D.)--West Virginia University, 2008.Title from document title page. Document formatted into pages; contains xv, 275 p. : ill. Includes abstract. Includes bibliographical references (p. 107-113).
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Kerry, Mark Anthony. "The design and synthesis of novel topoisomerase I poisons." Thesis, University of Sunderland, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245780.
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Nsumiwa, Samkele. "Synthesis and investigation of quinoline based ß-haematin formation inhibitors as potential antimalarials." Doctoral thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/12176.
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Includes abstract.Includes bibliograhical references.
The question of whether or not replacing the 7-chloro group in the 4-aminoquinoline moiety with an electron withdrawing and hydrophilic substituent results in retention of antiplasmodial activity in the 4-aminoquinoline class of compounds was investigated...
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Kgokong, Joseph Lebese. "Trifluoromethyl-substituted quinoline and tetrazole derivatives :design, synthesis, antimalarial activity and cytotoxicity / Joseph L. Kgokong." Thesis, North-West University, 2008. http://hdl.handle.net/10394/3732.
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Malaria is a complex parasitic disease caused by the Plasmodium falciparum. It has been found to be responsible for the death of many people particularly in under-developed and developing countries. For many years chloroquine and quinine have been the mainstay of therapy for this disease. The research on new therapies against malaria have been hampered by factors such as the development of resistance against these and some of the new drugs or combinations thereof, the lack of adequate knowledge on the exact causes and mechanisms of resistance to the drugs and their mode of action, together with the fact that the disease occurs predominantly in poor countries where there is no adequate funding and monitoring facilities. Residual insecticides where they have been tried are not appropriate because of technical constraints and the vaccine development is still in infancy stage. Of the more than 200 000 compounds developed by Antimalarial Drug Development program of the Walter Reed Army Institute of Research (WRAIR) since its inception in the early 1960s, only 3% have been found to be active in the primary screening tests. Very few of these have reached the Phase III clinical trials.
The successes gained in the use of mefloquine and halofantrine in the treatment of resistant malaria has aroused considerable interest in the contribution made by the trifluoromethyl group as a substituent on antimalarial activity of many molecules. The objective of the current studies was to design, synthesise and evaluate the antimalarial activity of a group of compounds
containing the quinoline, triazine and tetrazole as basic structures but with either one or two trifluoromethyl groups as substituents in addition to other groups. These new compounds were evaluated for activity against the chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. The assessments made it possible to construct possible structure-activity relationship profiles.
The new compounds included a series of 2- and 8-trifluoromethyl- and 2,8-jb/s(trifluoromethyl)quinolines and those of trifluoromethyl substituted triazine and tetrazine derivatives with other substituents to form compounds containing the 4-(pyrimidine-5-yl)methanone and 2-(1-ethyl-5-nitro-1H-imidazol-4-yl)ethan-1-one moieties, the N,N-/}/s(trifluoromethyl)quinolin-4-yl)diamino alkyl derivatives and 1,2,4-triazine-[5,6b]indole and the 5H-1,2,4-triazolo[1',5',2,3]-1,2,4-triazino[5,6b]indole derivatives. All the compounds were characterised by elemental analysis, 1H and 13C NMR, mass and infrared spectrometric determinations. Comparative activities of the compounds were assessed using the chloroquine-sensitive and chloroquine-resistant strains of P. falciparum and cytotoxicity was evaluated using the human promyelocytic leukaemia (HL-60) and Chinese Hamster Ovarian (CHO) cell lines against normal human cells.
In each series of the new compounds, a trifluoromethyl group has been found to enhance antimalarial activity. Except for the tetrazoles, the presence of the two trifluoromethyl groups appears to be essential for activity against the chloroquine-resistant strains of P. falciparum. The 2,8-/}/s(trifluoromethyl)-
quinolin-4-yl]-2-(1-ethyl-5-nitro-1/-/-imidazol-4-yl)ethan-1-one also exhibit inhibition of the leukemia cell growth. The N,N-b/s(trifluoromethylqumolin-4-yl)diaminoalkane series have a high selectivity index. The ferriprotoporphyrin IX-drug complexation and DNA-drug intercalation and binding studies do not provide a convincing support for the actual mode of action of these new compounds.Thesis (Ph.D. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2009.
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Duffey, John. "Chemical and enzyme catalysed hydroxylation pathways in the synthesis of arene oxides and quinoline alkaloids." Thesis, Queen's University Belfast, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295411.
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Horn, Mark A. "Studies toward the synthesis of the A-B ring system of lavendamycin methyl ester." Virtual Press, 1987. http://liblink.bsu.edu/uhtbin/catkey/515490.
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The synthesis of 7-amino-2-methylquinoline-5-8-dione (17) and 7-amino-3-methylquinoline-5,8-dione (157) are described.7-Amino-3-methylquinoline-5,8-dione (157) was prepared via alkaline hydrolysis of 7-acetamido-3-methylquinoline5,8-dione (149). 7-Acetamido-3-methylquinoline-5,8-dione (149) was prepared via the Diels-Alder reaction of 2-acetamido-6-bromo-1,4-benzoquinone (6) and 2-methyl-2propenal dimethylhydrazone (110).7-Amino-2-methylquinoline-5,8-dione (17) was prepared by the acid hydrolysis of 7-(triphenylphosphineimino)-2methylquinoline-5,8-dione (16). 7-(Triphenylphosphineimino)2-methylquinoline-5,8-dione (16) was prepared by tie treatment of 7-azido-2-methylquinoline-5,3-dione (15) with triphenylphosphine. 7-Azido-2-methylquinoline-5,8-dione (15) was prepared by treating 7-bromo-2-methylquinoline-5,8-dione (14) with sodium azide. The structures of the new compounds 15, 16, 17,149 and 157 were confirmed using MP, NMR, IR, MS and HRMS data. NMR, IR and MS data for known compounds 10, 11, 12, 13 and 14 are included for future reference.Ball State UniversityMuncie, IN 47306
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Li, Xuesong. "Synthesis and physical properties of helical nanosized quinoline-based foldamers : structure, dynamics and photoinduced electron transport." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0013/document.
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Ce travail présente la synthèse, la caractérisation et l’utilisation (transfert électronique photo-induit) de foldamères de taille nanométriques constitués d’unité quinolines. Grâce a une stratégie de synthèse de doublement de segment une grande variété d’oligomères (jusqu’à 96 unités) ont pu être préparé à partir du synthon 8 aminoquinoline-2-carboxylate.Leurs propriétés dynamiques de ces objets ont été étudiées en solution et en phase gazeuse. La spectrométrie de masse de mobilité ionique a permis de déterminer leur conformation en phase gazeuse. Les expériences de RMN DOSY et d’anisotropie de Fluorescence ont permis de déterminer leurs propriétés de diffusion (transrationnelle et rotationnelle). Ces résultats ont révélés qui ces foldamères sont rigides et que leur architecture hélicoïdale est conservée.Le transport électronique photo-induit à travers ces foldamères de taille nanométrique ont été étudié et le mécanisme de transfert ainsi que son efficacité ont été déterminé pour une série de composés de tailles variablesHerein, synthesis, characterization and application (photoinduced electron transport) of nanosized quinoline-based foldamers have been explored. With double segment strategy, a variety of helical nanosized foldamers (up to 96 quinoline units) were successfully prepared based on 8-aminoquinoline-2-carboxylic acid monomer.The dynamic properties in gas phase and solution were investigated. Ion mobility mass spectrometry afforded access to the conformation state of foldamers ingas phase; DOSY and fluorescence anisotropy assessed the diffusion (translational and rotational, respectively) of foldamers in solution. All of these techniques revealed that quinoline-based foldamers are rigid and that helical conformation is conserved. Photoinduced electron transport through nanosized foldamer was also studied and the mechanism and the transport ratios were revealed
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Devaux, Floriane. "Synthesis and AFM-based single-molecule force spectroscopy of helical aromatic oligoamide foldamers." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0346.
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Les foldamères sont des architectures moléculaires synthétiques repliées, inspirées par les structures et les fonctions des biopolymères naturels. Le repliement est un processus sélectionné par la nature pour contrôler la conformation de sa machinerie moléculaire afin de réaliser des tâches chimiques ou mécaniques. Durant les dix dernières années de recherche sur les foldamères, des oligomères synthétiques, capables d'adopter des conformations repliées bien définies et prévisibles, comme des hélices, ont été proposés. Les progrès récents ont montré que la synthèse chimique par étapes et le design moléculaire basé sur un squelette oligoamide aromatique permettaient de produire des architectures moléculaires repliées de manière hélicoïdale. La forme du squelette et sa rigidité, des préférences conformationnelles locales, des interactions spécifiques entre monomères éloignés dans une séquence, ainsi que l'action de paramètres externes comme le solvant, ou la présence d'ions peuvent être combinés pour induire une tendance au repliement. Ces architectures sont remarquables car elles peuvent donner lieu à des motifs de repliement qui n'ont pas d'équivalent dans les structures des biopolymères naturels. Par exemple, des hélices dont le diamètre varie le long de la séquence, ou des hélices possédant un centre d'inversion du pas, des hélices en chevrons,... ont été rapportées. Alors que les structures de ces molécules hélicoïdales ont été abondamment caractérisées à l'état solide par cristallographie des rayons X, leur comportement en solution, et surtout le comportement dynamique, est très peu connu. Leurs propriétés mécano-chimiques sont quant à elles inconnues à ce jour. L'objectif du projet est de synthétiser différentes molécules synthétiques hélicoïdales de type oligoamide aromatique et d'obtenir une description détaillée de leur conformation dynamique en solution, ainsi que de leurs propriétés mécano-chimiques, par spectroscopie de force sur molécule unique basée sur l'AFMFoldamers are artificial folded molecular architectures inspired by the structures and functions of natural biopolymers. Folding is the process selected by nature to control the conformation of its molecular machinery to carry out chemical functions and mechanical tasks, such as en-zyme catalysis, duplication in nucleic acids, force generation,... During the last decade of research on foldamers, synthetic oligomers able to adopt well- defined and predictable folded conformations, such as helices, have been proposed. Recent progress has shown that stepwise chemical synthesis and molecular design based on aromatic oligoamide backbones enable to produce large helically folded molecular architectures. The shape and stiffness of the backbone, local conformational preferences, specific interactions between distant monomers in sequences, as well as the action of external parameters such as the solvent or the presence of ions, can be combine to induce folding tendency. A remarkable aspect of these architectures is that they can give rise to folded patterns that have no in natural counterparts biopolymer structures. For instance, helices whose diameter varies along the se-quence, helices possessing a handedness inversion centre, herringbone helices have been reported. While the structures of these helical molecules have been well characterized in the solid state by X-ray crystallography, much less is known about their dynamic behavior in solution. Their mechanochemical properties are unknown. The objective of the project is to synthesize various helical nanorchitectures based on an oli-goamide aromatic backbone and to obtain a detailed picture of their dynamical conformation in solution, as well as, their mechanochemical properties, by AFM-based single molecule force spectroscopy
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Voûte, Nicholas. "Rearrangements in the indolo[2,3-b]quinoline system : a novel approach to the synthesis of perophoramidine and the communesins /." Thesis, St Andrews, 2008. http://hdl.handle.net/10023/486.
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Tukulula, Matshawandile. "The design and synthesis of novel HIV-1 protease inhibitors." Thesis, Rhodes University, 2009. http://eprints.ru.ac.za/1563/.
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Meola, Alain. "Les quinolones : étude chimique et pharmacologique, synthèse." Bordeaux 2, 1991. http://www.theses.fr/1991BOR2P090.
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Colomb, Julie. "Synthèse et radiomarquage de ligands des récepteurs sérotoninergiques 5-HT6 et 5-HT7 pour la tomographie par émission de positons." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10173/document.
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Le développement de radiotraceurs (18F) des récepteurs de la sérotonine 5-HT6 et 5-HT7 pour l'imagerie TEP (tomographie par émission de positons) permettrait d'étudier la fonction et l'implication de ces récepteurs dans des maladies neurodégénératives telles que la schizophrénie ou la maladie d'Alzheimer. A partir des structures et pharmacophores déjà décrits dans la littérature, nous nous sommes orientés vers des dérivés pyrrolidiniques pour les récepteurs 5-HT7 et quinolines pour les récepteurs 5-HT6. 7 radioligands des récepteurs 5-HT7 marqués au fluor 18 ont pu être étudiés par autoradiographie et imagerie μTEP sur le rat et ont montrés des fixations intéressantes, mais avec une sélectivité moyenne du récepteur. 16 ligands du récepteur 5-HT6 ont été synthétisés et 4 d'entre eux ont été radiomarqués afin d'identifier le 2FNQ1P comme radioligand sélectif vis-à-vis du récepteur 5-HT2A (principal récepteur en compétition). Les premières images TEP réalisées sur le chat ont montrées un marquage sélectif dans les zones cérébrales riches en 5-HT6. La poursuite des études biologiques menées en collaboration avec le CERMEP – Imagerie du vivant permettront d'approfondir les caractéristiques de ces nouveaux radioligands synthétisésDevelopment of fluorine 18 labeled radiotracer of 5-HT6 and 5-HT7 receptors for PET imaging (positron emission tomography) allows the study of those receptors in various neurodegenerative diseases such as schizophrenia and Alzheimer disease. Description of structures and pharmacophores in literature led to pyrrolidine derivatives for 5-HT7 receptors and quinolones for 5-HT6. After their synthesis, 7 radioligands of 5-HT7 receptors have been studied by autoradiography and μPET. These radioligands have shown interesting binding on rat, with more or less selectivity for the receptor. 14 ligands of 5-HT6 receptors have been synthesized and 4 have been radiolabeled to select 2FNQ1P as a selective radioligand toward 5-HT2A. First PET images on cat have shown a selective binding in 5- HT6 rich area in brain. Pursue of biological studies, in collaboration with CERMEP – Imagerie du vivant will give more information on those new radioligands
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DeBord, Michael. "Synthesis, characterization, and anti-cancer structure-activity relationship studies of imidazolium salts." University of Akron / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=akron1489414733025495.
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Das, Hari Sankar [Verfasser], and Biprajit [Akademischer Betreuer] Sarkar. "Ruthenium complexes with non-innocent quinonoid, quinoline-5,8-dione and iminoquinone ligands : synthesis, structure, redox properties and electron distribution / Hari Sankar Das. Betreuer: Biprajit Sarkar." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2012. http://d-nb.info/102604331X/34.
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Saggadi, Hanen. "Valorisation du glycérol sous irradiation micro-ondes : synthèse de quinoléines, de l’échelle du laboratoire à l’échelle pilote." Thesis, Compiègne, 2014. http://www.theses.fr/2014COMP1909.
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Le glycérol, principal coproduit de l’industrie du biodiesel (10% massique), représente un solvant et un réactif d’un grand intérêt pour la chimie verte. La déshydratation du glycérol en acroléine est une voie intéressante pour sa valorisation. En effet, cet aldéhyde constitue une molécule plate-forme pour de nombreuses applications. En revanche, il s’agit d’un produit instable, toxique et inflammable, ce qui rend sa manipulation et sa manutention particulièrement dangereuses. Cette difficulté peut être surmontée par une transformation in-situ de l’acroléine formée par déshydratation du glycérol, telle que la réaction de Skraup pour la synthèse de la quinoléine à partir du glycérol et de l’aniline. Le noyau quinoléique se trouve dans des alcaloïdes de plantes médicinales et constitue un composant structurel essentiel de nombreux produits pharmaceutiques. Vu l’intérêt de ces molécules, la réaction de Skraup pour la synthèse des quinoléines s’avère un choix intéressant. Cependant, cette réaction a souvent lieu dans des conditions dures, notamment en utilisant l’acide sulfurique comme solvant, en présence d’un agent oxydant souvent toxique, à hautes températures (T>150°C) pendant plusieurs heures.D’autre part, le chauffage par micro-ondes représente une technologie intéressante capable d’offrir un chauffage volumique efficace du milieu réactionnel, et de réduire les dépenses énergétiques du processus dues aux pertes thermiques et au temps de réaction relativement long. Cette technologie alternative, couplée à l’axe de valorisation du glycérol, représente une voie intéressante de développement pour la chimie verte, et pour l’intensification de procédés plus surs et durables. Dans ce contexte, Le travail présenté dans ce mémoire s’intéresse à la synthèse de quinoléines via la réaction de Skraup en utilisant une technologie alternative de chauffage : les micro-ondes. Une procédure expérimentale plus «verte» est mise au point. A l’échelle du laboratoire, un processus expérimental de synthèse des quinoléines via la réaction de Skraup a été mis au point. A partir de cette étude, l’intensification du procédé à l’échelle pilote a été réalisée. Un réacteur micro-ondes fonctionnant en batch et en continu a été conçu et installé. Le pilote développé permet d’étudier la réaction de Skraup dans les conditions de température et de pression nécessairesGlycerol, the main byproduct of the biodiesel industry (10% w/w), is a solvent and a reagent of great interest for green chemistry. Glycerol dehydration to acrolein is an interesting way for its valorization. Indeed, this aldehyde is a platform molecule for many applications. However, it is an unstable, flammable and toxic product, which makes its handling and storage particularly dangerous. This difficulty can be overcome by in-situ conversion of acrolein resulting from glycerol dehydration, such as Skraup reaction for quinoline synthesis starting from glycerol and aniline. Quinoline moiety is found in alkaloids medicinal plants and is an essential structural component of many pharmaceuticals. Since the importance of these molecules, Skraup reaction for the synthesis of quinolines is an interesting choice. However, this reaction requires often harsh conditions, by using sulfuric acid as solvent, in the presence of a toxic oxidizing agent, at high temperatures (T > 150 °C) for several hours.Moreover, microwave irradiation is an interesting technology for chemistry since it can heat homogeneously and quickly a reaction mixture, which can reduce process energy costs resulting from thermal losses and relatively long reaction time. This alternative technology, coupled with glycerol valorization axis, is an interesting development way for green chemistry, and for intensification of safer sustainable processes. In this context, this thesis focuses on the quinolines synthesis via Skraup reaction using an alternative heating technology: microwaves. A greener experimental procedure was developed. At laboratory scale, a greener experimental procedure for quinolines synthesis via Skraup reaction was proposed. On the basis of this investigation, the intensification of a microwave pilot scale apparatus was studied. A microwave reactor operating in batch and continuous conditions was designed and installed. The developed device allowed us to perform the Skraup reaction in the required temperature and pressure conditions
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Fantin, Creusa Aparecida. "Síntese e caracterização dos compostos de adição entre os mono e dicloroacetatos de lantanídeos (III) e a quinolina-N-óxido (QNO)." Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/46/46134/tde-14032018-115520/.
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Este trabalho descreve a síntese e caracterização dos compostos de adição obtidos pela reação entre os monocloroacetatos (CA) e dicloroacetatos (DCA) de lantanídeos (III) com a quinolina-N-óxido (QNO), na presença de etanol e ortoformiato de trietila. Os compostos foram obtidos na forma sólida e caracterizados por análise elementar, testes de solubilidade, medidas de condutância eletrolítica, difração de raios X (método do pó), espectros de absorção na região do infravermelho, espectros de absorção na região do visível dos compostos de Nd, espectros de emissão dos compostos de Eu e análise térmica. Os experimentos de análise térmica permitiram estudar o comportamento térmico dos compostos. A associação dos resultados de análise elementar e termogravimétrica permitiu sugerir as seguintes fórmulas mínimas: a) Ln(DCA)3.yQNO.wEtOH onde, y = w = 8/9 para Ln= La; y = w = 1 para Ln= Ce; y = 1 e w =¾ para Ln= Pr, Nd e Sm; y = 1 e w = O para Ln= Eu ao Lu e Y. b) Ln(CA)3.QNO, onde Ln= La ao Ho e Y. Os compostos não são higroscópicos, e possuem coloração bege, em sua grande maioria. São solúveis em DMF, DMSO, HMPA e água, e insolúveis em hexano, ciclohexano, dimetoxipropano, benzeno, clorofórmio, cloreto de metileno, tolueno, acetonitrila e acetona. As medidas de condutância, em solução de DMF, revelaram que os compostos se comportam como não eletrólitos, indicando que os ânions CA e DCA estão coordenados ao íon Ln3+. Os difratogramas de raios X ( método do pó) mostraram que os compostos de adição de dicloroacetatos possuem três séries isomorfas. Os espectros de absorção no infravermelho indicaram que a coordenção da QNO e dos ânions CA e DCA ocorre através do átomo de oxigênio, mas não permitiram evidenciar a coordenção do EtOH nos compostos de adição de dicloroacetatos, porém os resultados de análise térmica confirmaram a presença do etanol para os compostos de La ao Sm. As associações das técnicas auxiliaram na definição da estequiometria e existência das séries isomorfas. Os espectros de absorção dos compostos de Nd mostraram que as interações Nd3+- ligantes são de caráter eletrostático. Baseando-se nas transições 4I9/2 → 4G5/2, 2G7/2 foi possível determinar o parâmetro nefelauxético [β = 0,990 (CA) e β = 0,993 (DCA)], o fator de covalência [b1/2 = 0,070 (CA) e b1/2 = 0,0502 (DCA)] e o parâmetro de Sinha [δ = 1,01 (CA) e δ = 0,705 (DCA)]. Os espectros de emissão dos compostos de Eu, registrados a 77 K, sugeriram a simetria C3v para o composto de Eu(CA)3.QNO e C2v para o composto Eu(DCA)3.QNO. As curvas termoanalíticas evidenciaram que o processo de decomposição térmica ocorre em multi-etapas e que o produto final é o respectivo óxido.This work describes the synthesis and characterization of the addition compounds obtained between lanthanide (III) mono and dichloroacetates with Quinoline-N-oxide (QNO) in the presence of ethanol and triethyl orthoformate. These compounds were obtained in the solid form and characterized by elemental analysis, solubility tests, electrolytic condutance measures, X-ray diffraction (powder method), infrared absorption spectroscopy, visible absorption spectroscopy of the Nd compounds, emission spectroscopy of the Eu compounds and thermal analysis. The thermal analysis experiments allowed studying the thermal behavior of the compounds. The association of the results of elemental analysis and thermogravimetry allowed to suggest the minimum formule: a) Ln(DCA)3.yQNO.wEtOH, where y = w = 8/9 when Ln = La; y = w = 1 when Ln = Ce; y = 1 and w = 3/4 when Ln = Pr, Nd and Sm; y = 1 and w = 0 when Ln = Eu to Lu and Y. b) Ln(CA)3.QNO, where Ln= La -Ho e Y. The compounds are not hygroscopic and are beige coloration. They are soluble in DMF, DMSO, HMPA and water, but they are insoluble in hexane, ciclohexane, dimetoxipropane, benzene, chloroform, methylene chloride, toluene, acetonitrile and acetone. In DMF solution, the conductance measurements revealed that the compouds behave as non-electrolytes, indicating that CA and DCA ions are coordinated to the ion Ln3+. X-ray patterns suggest that the addition compounds of dichloroacetates and monochloroacetates have, respectively, three and four isomorphous series. The infrared spectra indicated that ligand and anions coordination to Ln3+ occurs through the oxygen atom, but they did not confirm the EtOH coordination in the addition compounds of dichloroacetates, however the results of thermal analysis confirmed the alcohol presence in the La to Sm complexes. The techniques association support in stoichiometry definition and isomorphic series. The absorption spectra of the Nd compounds suggest that the Nd3+-ligand interactions are of electrostatic character. Based in the 4I9/2 → 4G5/2, 2G5/2 transitions was possible to determine the spectroscopic parameters: nephelauxetic parameter [β = 0,990 (CA) and β = 0,993 (DCA)], covalency factor [bl/2 = 0,070 (CA) and b1/2 = 0,0502 (DCA)] and Sinha\'s parameter [δ = 1,01 (CA) and δ = 0,705 (DCA)]. The emission spectra of the Eu compounds, at 77 K, suggest that the symmetry for the Eu3+ ions is C3v for Eu(CA)3.QNO and C2v for Eu(DCA)3.QNO. The thermoanalytical curves evidenced that the thermal decomposition process occurs in multi-stages and that the final product is the respective oxide.
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LE, GOFF-BEVIERE CORINNE. "Pharmacomodulations de quinolones a structure benzo-ij-quinolizine : synthese et activite antibacterienne." Orléans, 1995. http://www.theses.fr/1995ORLE2019.
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L'objectif principal de notre travail sur la pharmacomodulation de quinolones nous a amenes a mettre au point de nouvelles strategies de synthese dans le domaine des quinoleines, a partir d'un synthon unique, la 6-fluoro-2-methylquinoleine conduisant aux precurseurs necessaires a la realisation des quinolones a structure benzoi,jquinolizine. Ainsi, l'utilisation des tetrahydroquinoleines-n-formylees nous a permis par des fonctionnalisations regioselectives d'atteindre des pharmacomodulations donnant acces aux heterocycles imidazo, thiazolo et oxazolo en position 4,5-g sur le noyau quinoleique. Le developpement des reactions de reduction selective par le complexe triethylamine-acide formique du noyau pyridinique des systemes polycycliques possedant differents heterocycles, ainsi que la separation a l'echelle preparative des diastereoisomeres obtenus offrent des possibilites nouvelles quant a l'etude des relations structure-activite necessaires aujourd'hui dans le domaine du medicament. La mise au point de nouvelles strategies d'obtention des heterocycles sur les structures quinoleiques, utilisation de la triphenylphosphine en presence de tamis moleculaire pour les imidazoles ou du complexe tribromure de bore-dimethylsulfure pour les oxazoles, nous a permis de developper et de generaliser les methodes de synthese de ces heterocycles. Les tentatives de fonctionnalisation de l'heterocycle des fluorotetrahydroquinoleines que nous avons realisees ont constitue une voie d'acces a de nouveaux synthons, actuellement en cours de developpement dans differents domaines de la chimie therapeuthique
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Aribi, Fallia. "Development and biological evaluation of novel fluorinated ingredients for modern crop protection." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF020.
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Ce doctorat a permis la conception de nouvelles molécules destinées aux développements de futurs produits phytosanitaires. Tout d’abord, la synthèse d’alpha,alpha-difluoro-beta-hydroxy cétones a été réalisée. Motif déjà reconnu dans le domaine pharmaceutique, nous voulions étendre son champ d’application à l’agrochimie. Une série de composés possédant une activité biologique en tant qu’agonistes des récepteurs GABA a été synthétisée. Ils ont été obtenus à l’issu d’une synthèse convergente nécessitant une réaction de couplage entre un aldéhyde aromatique et un intermédiaire alpha,alpha-difluoro-beta-trifluoromethyldihydroxy cétone. L’analyse biologique de nos produits a fait ressortir un type de famille spécifique. Une approche prodrug a débuté afin d’en affiner la structure et d’en faire ressortir un hit. Dans un second temps, le développement d’une série de quinoléines substituées par des groupements fluorés en position 2 et 4 a été conduit. Ces molécules peu décrites dans la littérature fûrent synthétisées dans des conditions douces avec de bons rendements et une complète régiosélectivité, inspirée par les réactions de Combes et de Meth-Cohn utilisant un Réactif Fluoroalkyl Amine (FARs). La post-fonctionnalisation en position 3 et 8 a permis l’exemplification de ces composés. Une étude physico-chimique réalisée sur une série homogène a apporté des informations complémentaires sur leurs propriétés électroniques. Bien qu’aucune molécule n’ait montré d’activité biologique, nous avons pu lors de ce projet réaliser la synthèse de nouvelles quinoléines et évaluer des FARs dans la synthèse de molécules inconnues de la littérature jusqu’à ce jourThis PhD thesis allowed the conception of new molecules for the development of novel phytosanitary ingredients. First, the synthesis of alpha,alpha-difluoro-betahydroxy ketones was performed. Since this motif is already known in the pharmaceutical field, we decided to extend their application to the agrochemical field. A series of compounds with biological activities as GABA agonist receptors was synthesized. They were obtained by a convergent method after a coupling reaction between benzaldehydes and alpha,alpha-difluoro-beta-trifluoromethyldihydroxy ketone intermediates. Biological analysis highlighted a specific family of compounds. A prodrug approach was applied to tune the structure and allowed the discovery of a hit. Second, the development of a series of 2,4-(fluoroalkyl)-substituted quinoline derivatives was conducted. Scarcely described in literature, these molecules were obtained under smooth conditions, with good yields and a complete regioselectivity, inspired by Combes and Meth- Cohn reactions using Fluoroalkyl Amino Reagents (FARs). Post-functionalization in position 3 and 8 allowed us to increase the scope of the reaction. A physico-chemical study gave complementary informations on their electronical properties. Although none of these molecules have shown biological activity, we have during this project realized the synthesis of new quinolines and evaluated the use of FARs in the synthesis of unknown fluorinated molecules
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Murphy, Steven Michael. "Novel aspects of the Wittig reaction." Thesis, Northumbria University, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245286.
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Lu, Jianyu. "Syntheses of quinolines as neural protective reagents and progress towards total synthesis of (+) - myriceric acid A." Diss., Kansas State University, 2014. http://hdl.handle.net/2097/27652.
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Doctor of PhilosophyDepartment of Chemistry
Duy H. Hua
The first chapter of this dissertation introduces and discusses the syntheses of a series of substituted quinolines as glycogen synthase kinase-3[beta] (GSK-3[beta]) inhibitors. GSK-3[beta] is highly associated with Alzheimer’s disease (AD), and it is suggested that inhibition of this enzyme could alleviate the symptoms of AD. Total 16 novel substituted quinolines were designed and synthesized, and their bio-activities were evaluated on MC65 cell protection assay. Four of the most active compounds were selected to test their enzyme inhibitory activities on GSK-3[beta] and protein kinase C assays. Among these compounds, 4-{[6-methoxy-4-methyl-5-(3-(trifluoromethyl)phenoxy)quinolin-8-ylamino]methyl} phenol (1.5) shows the highest MC65 cell protection and GSK-3[beta] enzyme inhibitory activities and potential enzyme specificity. Structure-activity relationship (SAR) was built as well, and the binding mode was simulated via computational method to interpret the observed SAR. Although additional bio-evaluation is needed, compound 1.5 is a promising lead compound for the development of more active and less toxic drug for the conteraction of AD. The second chapter introduces the progress on the total synthesis of myriceric acid A. Myriceric acid A is a triterpene-type natural product which was isolated from the young twigs of Myrica cerifera. It is a non-peptide endotheline-1 (ET-1) receptor antagonist. The total synthesis of this natural product started from the stereoselective synthesis of bicyclic intermediate (R)-5,8a-dimethyl-3,4,8,8a-tetrahydronaphthalene-1,6(2H,7H)-dione [(-)-2.28]. Then a new method was developed to enatioselectively synthesize the tricyclic intermediate (4aR,8R,8aR)-8-(tertbutyldimethylsilyloxy)-1,4a,8a-trimethyl-4,4a,4b,5,6,7,8,8a,9,10-decahydro phenanthren-2(3H)-one [(+)-2.72] which used the synthesized optically-pure (4aR,5R)-5-(tertbutyldimethylsilyloxy)-1,4a-dimethyl-4,4a,5,6,7,8-hexahydronaphthalen-2(3H)-one [(-)-2.53] derived from (-)-2.28 and [alpha]-trimethylsilylvinyl ethyl ketone via a cascade reductive Michael addition – aldol condensation reaction. After functional group inter-conversion, the desired tricyclic intermediate (4a'S,8a'R)-1',1',4a',8a'-tetramethyldecahydro-1'H-spiro[[1,3]dioxolane-2,2'-phenanthren]-8'(3'H)-one [(-)-2.33] was synthesized. An intramolecular cascade Michael addition-aldol condensation reaction was designed to construct the triterpene-skeleton of myriceric acid A, and the desired starting material for this reaction was prepared with the trimethyl{(4a'R,8a'R)-1',1',4a',8a'-tetramethyl-3',4',4a',4b',5',6',8a',9',10',10a'-decahydro-1'Hspiro[(1,3)dioxolane-2,2'-phenanthrene]-8'-yloxy}silane [(-)-2.81] and 3,3-dimethyl-7-oxooctanal (2.46) via Mukaiyama aldol condensation reaction. The resulting pentacyclic compound was further transformed to the desired ester (6a'R,8a'R,12a'S,12b'R,14b'R)-ethyl 4',4',6a',11',11',14b'-hexamethyl-8'-oxo-2',4',4a',5',6',6a',8',8a',9',10',11',12',12a',12b',13',14',14a',14b'-octadecahydro-1'H-spiro[(1,3) dioxolane - 2, 3 '- picene]-8a'-carboxylate (-)-2.106. The further investigation on total synthesis of myriceric acid A will be pursued in future.
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MacDonald, Alasdair Arthur. "Synthesis of quinolone antibiotics by Diversomer™ technology." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/11075.
Full textAbstract:
The generation of chemical diversity by the parallel synthesis of potential drug candidates has been demonstrated by Parke-Davis' DIVERSOMER Technology. This technology combines solid phase organic synthesis, (SPOS), miniaturization, automation, integration and custom equipment to generate "libraries" of discrete compounds. The research programme involved a detailed analysis of the synthesis of the quinolones, a well-known class of antibacterial agents of which over 6000 compounds are known to date. A solution phase synthesis was developed which was compatible with solid phase reaction conditions and also amenable to parallel SPOS protocols. Results of these studies and the parallel synthesis, isolation, purification and analysis of a quinolone library will be discussed. Additionally, an alternative "solid support" for the SPOS of quinolones will be discussed. Construction of the quinolones with a tetrabenzo[a,c.g.i]fluorene, (Tbf) handle enables controlled adsorption onto and off porous graphitised carbon (PGC). The Tbf/PGC system also has demonstrated utility for automated, parallel purification strategies.
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Benaissa, Tahar. "Synthèse de ligands contenant un atome de fluor et pouvant donner des complexes à applications médicales : étude de la complexation de la 5-fluoro-8-hydroxyquinoline avec des cations métalliques, par RMN du fluor." Université Joseph Fourier (Grenoble), 1996. http://www.theses.fr/1996GRE10100.
Full textAbstract:
Ce travail se place a la convergence de deux grands themes etudies au laboratoire: le marquage de molecules par un atome de fluor et l'etude de la complexation de cations metalliques par des ligands. La premiere partie concerne la preparation de deux series de ligands contenant du fluor: des biphenols et des composes contenant des groupements 2-fluoropyridines. Les biphenols substitues par deux ou quatre atomes de fluor (en position 4,4' ; 5,5' ; 4,4 ;,5,5') ont ete obtenus a partir de bromophenols par une reaction de type ullman. Leurs derives sulfones ont egalement ete prepares pour augmenter la solubilite dans l'eau. Les ligands de la seconde serie, tel la n,n,n',n' tetrakis(6-fluoro-2-pyridylmethyl)ethylenediamine, ont ete obtenus par alkylation de differentes amines avec la 2-fluoro-6-bromomethylpyridine, dans des conditions de transfert de phase. Ces ligands ont ete caracterises par rmn du #1h, #1#9f et #1#3c et des resultats interessants, concernant les constantes de couplage, ont ete observes. Ces deux familles de ligands ont ete prepares afin de permettre, par la suite, une etude de leur complexation par rmn du #1#9f, analogue a celle entreprise dans la partie suivante. La seconde partie concerne l'etude de la complexation de la 5-fluoro-8-hydroxyquinoline (fox) avec des cations metalliques (le gallium et le fer) par rmn du #1#9f et par spectroscopie uv-visible. Concernant l'etude de la complexation de ga par la fox utilisant la rmn du fluor nous avons constate que les trois complexes gafox, gafox#2 et gafox#3 ont des deplacements chimiques du fluor differents, obtenu les diagrammes de repartition des especes en fonction du ph pour differents rapports molaires c#m/c#f#o#x (c#m et c#f#o#x sont les concentrations en metal et ligand) et calcule les trois constantes de formation des complexes gafox, gafox#2 et gafox#3. Le complexe gafox#3 a egalement ete etudie seul en solvant organique (dmf-d7). Nous avons mis en evidence que dans ce complexe, qui existe presque uniquement sous la forme de l'isomere mer, les trois ligands subissent une interconversion intramoleculaire rapide
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Hodgkinson, James Thomas. "The synthesis of Pseudomonas Quinolone Signal analogues and their effects on quinolone signalling in Pseudomonas aeruginosa." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610117.
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Prasain, Keshar. "Synthesis and bioevaluation of laccase substrates and substituted quinolines." Diss., Kansas State University, 2013. http://hdl.handle.net/2097/15460.
Full textAbstract:
Doctor of PhilosophyDepartment of Chemistry
Duy H. Hua
Our research work is divided into three chapters. In the first chapter, synthesis of substituted phenolic compounds including halogenated di- and trihydroxybenzenes, aminophenols, and substituted di-tert-butylphenols, their redox potential, laccase oxidation, and mosquito anti-larval activities are discussed. The synthesized substituted phenols were found to be the substrates but not the inhibitors of laccase. An inverse correlation between the oxidation potential and the laccase oxidation efficiency of halogenated hydroxybenzenes and aminophenols was established. However, substituted di-tert-butylphenols were found to have anti-larval activities in mosquitoes resulting in the death of the larvae just before reaching pupation. Among the di-tert-butyl phenols studied, water insoluble, 2,4-di-tert-butyl-6-(3-methyl-2-butenyl)phenol (16), 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-methylpropanal oxime (14), and 6,8-di-tert-butyl-2,2-dimethyl-3,4-dihydro-2H-chromene (17) caused the mortility of 98%, 93%, and 92% of Anopheles gambiae larvae in the concentration of 182 nM, 3.4 µM, and 3.7 µM, respectively. In particular, compound 16 had similar anti-larval activities as compared to MON-0585, an anti-larval agent reported by Monsanto in the 70’s. In the second chapter, inhibition of protein kinase C (PKC) phosphorylation by substituted quinolines (PQs) is inverstigated. PQ compounds such as N-(3-aminopropyl)-6-methoxy-4-methyl-5-(3-(trifluormethyl)phenoxy)quinolin-8-amine (PQ1), N-(furan-2-ylmethyl)-6-methoxy-4-methyl)-5-(3-(trifluoromethyl)phenoxy)quinolin-8-amine (PQ11), and 6-methoxy-4-methyl-N-(quinolin-4-ylmethyl)-5-(3-(trifluoromethyl)phenoxy)quinolin-8-amine (PQ15) were found to inhibit PKC phosphorylation with IC50 values of 35 nM, 42.3 nM, and 216.3 nM respectively, among which PQ1 and PQ11 were found to be potent PKC inhibitors as comparable to that of staurosporine (IC50 = 33 nM). In chapter three, the tissue distribution of PQ1 and PQ11 in normal C57BL/6J mice and the effect of PQ1 on the normal tissues of mice were investigated. Substituted quinolines, PQ1 and PQ11 were distributed in the tissues in concentrations that were more than 40 folds of their effective dose. PQ1 and PQ11 were also found to penetrate the blood brain barrier and collect in the tissue in significant amounts. The administration of PQ1 and PQ11 had no effect in the normal behavior of the animals indicating no short term adverse effects. PQ1 was found to increase the expression of survivin, an anti-apoptotic factor and decrease the expression of cleaved caspase-3 and caspase-8, pro-apoptotic proteins. These studies suggests that PQ1 might have anti-apoptotic activities in normal cells, in contrast to the role of PQ1 in cancer cells where it has demonstrated to induce apoptosis. The study also indicated that PQ11 was better metabolized from the tissues over time as compared to PQ1.
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Gunn, Mary Esther. "A modular catalytic approach towards pyridine and quinolone synthesis." Thesis, University of Leeds, 2013. http://etheses.whiterose.ac.uk/4959/.
Full textAbstract:
N-Containing heterocycles such as substituted pyridines and 2-quinolones are commonly found in drugs and agrochemicals; however, classical methods towards their synthesis often lead to limited substitution patterns. We recently described the first examples of the organocatalytic intramolecular aza-Wittig reaction in the synthesis of azoles and azines from isocyanates. The work described herein is divided into three chapters detailing attempts to expand the scope of the use of isocyanates in heterocycle synthesis. The first chapter describes the development of multicomponent synthesis of substituted pyridines incorporating the intermolecular catalytic aza-Wittig and Diels–Alder reactions; in total 31 exemplar pyridines were prepared in up to 52% yield. The reaction works well for electron-poor and heteroaromatic aldehydes, electron-rich and electron-poor cinnamic acids and push-pull enamines to give a range of substitution patterns. The use of commercially available starting materials and catalytic phosphine oxide means the process offers distinct advantages over classical methods. The development of a tandem catalytic aza Wittig/electrocyclisation process towards benzothienopyridines was also investigated. To this end benzothienoimines and azatrienes were prepared, however, the electrocyclic ring closure of the azatrienes was non-trivial with low yields of the desired pyridines even under harsh conditions. The final chapter outlines the preparation of substituted 2-quinolones from readily available urea starting materials by two methods. The first is a two-pot three-step process incorporating urea-directed oxidative Heck reaction, isocyanate formation and electrocyclisation; in total 9 exemplar 2-quinolones were prepared in up to 61% overall yield. The second is a two-pot threestep process incorporating Heck reaction, isocyanate formation and electrocyclisation; 10 exemplar 2-quinolones were prepared in up to 59% overall yield. The use of the urea directinggroup in the subsequent isocyanate formation negates the necessity for acyl azides and means no further manipulation is required to remove the directing group after 2-quinolone synthesis
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Silva, Ana Cláudia Melo Pompeu da. "Planejamento, síntese e avaliação biológica de derivados quinolínicos potencialmente antimaláricos." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-26022015-173101/.
Full textAbstract:
A emergência e a disseminação de cepas resistentes aos fármacos antimaláricos disponíveis na quimioterapia têm conduzido à busca por novos agentes potencialmente ativos. Neste sentido, derivados 4-hidroxiquinolínicos e 4-cloroquinolínicos foram sintetizados e submetidos à avaliação biológica frente à cepa AJ de Plasmodium chabaudi e à avaliação toxicológica frente a macrófagos peritoneais de camundongos BALB/c. O planejamento sintético consistiu na preparação de β-cetoésteres-α-alquenilados através de reação de acetoacetato de etila e brometo de alila ou brometo de cinamila. Posteriormente, β-enaminoésteres-α-alquenilados foram obtidos através de reações de -β-cetoésteres-α-alquenilados com amina aromática (anilina). Os derivados 2-metil-3-alil- ou 2-metil-3-cinamil-4-hidroxiquinolínicos foram obtidos através de termociclização de Conrad-Limpach, utilizando-se difeniléter como solvente reacional. Por fim, a cloração dos agentes hidroxilados com oxicloreto de fósforo rendeu 2-metil-3-alil- ou 2-metil-3-cinamil-4-cloroquinolinas. Dos quatro derivados quinolínicos avaliados, 2-metil-3-[(2E)-3-fenilprop-2-enil]quinolin-4-ol (11) mostrou-se 1,13 vezes mais efetivo que sulfato de cloroquina contra as formas intraeritrocíticas do parasita, 1,69 vezes menos tóxico para os macrófagos peritoneais em relação ao fármaco padrão e valor de índice de seletividade igual a 280, enquanto sulfato de cloro quina apresentou valor de 146,84.The emergence and spread of resistance to antimalarial drugs have highlighted the need for the discovery and development of novel antimalarial molecules. To achieve this goal, 4-hydroxyquinoline and 4-chloroquinoline derivatives were prepared. Their biological activity was tested against the AJ Plasmodium chabaudi strain and their toxicity was evaluated toward BALB/c mouse peritoneal macrophages. The synthetic design was started by reacting ethyl-acetoacetate with allyl bromide or cinamyl bromide to obtain -α-alkenyl-β-ketoesters. The -α-alkenyl-β-enaminoesters were prepared by condensation of -α-alkenyl-β-ketoesters with aromatic amine (aniline). The derivatives 2-methyl-3-allyl- or 2-methyl-3-cinamyl-4-hydroxyquinolines were obtained by Conrad-Limpach ciclization in reacional solvent diphenyl ether. The 2-methyl-3-allyl- or 2-methyl-3-cinamyl-4-chloroquinoline derivatives had been prepared by chloration of hydroxyl group with phosphorous oxycloride. Among the quinoline compounds evaluated, 2-methyl-3-[(2E)-3-phenylpro-2-enyl]quinolin-4-ol (11) has shown more active than chloroquine sulphate (1, 13-fold) against the parasite intraerytrocytic stage. The compound 11 has presented less toxic than this drug (l,69-fold) to peritoneal macrophages. The selectivity index value has been 280, while the value to chloroquine sulphate has been 146,84.
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KO, DEN-YUAN, and 柯登淵. "Synthesis of Quinoline Derivatives of Curcumin." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/02939843223114971684.
Full textAbstract:
碩士中國文化大學
化學系應用化學碩士班
104
Curcumin is isolated from the rhizome of Curcuma longa. Much evidence indicated that curcumin could be used as a therapeutic agent in the treatment of Alzheimer’s disease (AD) and could reduce the symptoms, including oxidative damage, inflammation, senile plaques, neurofibrillary tangles, cell cycle dysregulation and neuron damages. AD, a complex disease with multiple etiological factors, needs a multifunctional drug forits treatment. Curcumin is one of the potential drugs in the treatment of AD. Some quinolines are known as good metal chelating agents and could also be used in potential remedy of AD. Owing to the characteristics of curcumin and quinolines, curcumin derivatives with quinoline structures may increase the metal chelating and radical scavenging abilities. Therefore, the main goal in this thesis is to synthesize the curcumin derivatives with two quinoline structures at both terminal positions. In this study, 4-amino-3-methoxybenzoic acid was used as the starting material to prepare 8-methoxy-6-quinolinecarboxylic acid by Skraup method and a curcumin derivative was synthesized by Knoevenagel condensation of acetylacetone and a compound with 6-quinolinecarbaldehyde structure.
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Teitgen, Alicen M. "Novel synthesis of quinoline-5,8-dione analogues." 2012. http://liblink.bsu.edu/uhtbin/catkey/1678996.
Full textAbstract:
The chemistry of quinonline-5,8-dione as a functional group is a developing field because of its various biological aspects. Lavendamycin and streptonigrin are known antibiotic, antitumor agents containing the quinolone-5,8-dione functional group believed to provide their antitumor properties. Most cancer cells show an elevated level of NQO1 enzyme which activates lavendamycin to act as an antitumor agent. The research goal is to explore different synthetic methods and reactions to produce novel quinolone-5,8-dione analogues with unique structural features while keeping the selective cytotoxicity. Lavendamycin contains a β-carboline and streptonigrin has a substituted pyridine connected to the 2-position of the quinolone-5,8-dione. The overall goal of this project will develop synthetic methods to create 1,2,3-triazoles and 1,2-diazoles attached to the quinoline moiety from azides and diazonium salts, respectively. In order to accomplish this, 8-hydroxyquinoline undergoes through a four step synthesis to install an azide at the two position of the quinoline ring. 8-Hydroxyquinoline was oxidized to produce 8-hydroxyquinoline-N-oxide, converted into 8-acetoxy-2-hydroxyquinoline with acetic anhydride, reacted with POCl3 to produce 2-chloro-8-hydroxyquinoline, and treated with sodium azide to form 2-azido-8-hydroxyquinoline. However it was found that the product cyclized to yield 8-hydroxy-tetrazole[1,5-a]quinoline.
In the quinoline-5,8-dione synthesis, 7-amidoquinoline-5,8-dione is prepared through a three step synthesis. 8-Hydroxquinoline was nitrated to form 8-hydroxy-5,7-dinitroquinoline, hydrogenated/acylated to give 5,7-diacetamido-8-acetoxyquinoline, and oxidized to yield 7-acetamidoquinoline-5,8-dione. In order to reach the end of this project, the four step tetrazole and the three step quinoline-5,8-dione syntheses required merging. Further research will focus on the optimization of these syntheses.Synthesis of 8-hydroxy-tetrazole [1,5-a] quinoline -- Synthesis of 7-amino-quinoline-5,8-dione -- Novel synthesis of quinoline-5,8-dione analogues.
Department of Chemistry
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Hlungwani, Isaac. "Design, synthesis and biological evaluation of novel tetrasubstituted quinoline-3-carboxamides derivatives." Diss., 2020. http://hdl.handle.net/11602/1558.
Full textAbstract:
MSc (Chemistry)Department of Chemistry
Quinolines are well known naturally occurring heterocyclic compounds with nitrogen as a heteroatom. Quinolines are also one of the major classes of naturally occurring compounds and the interest in their chemistry is due to the wide range of their biological activities. The objective of the project was the synthesis of novel tetra-substituted quinoline-3carboxamides and subsequent transformation to other novel derivatives and evaluation of their biological activities against malaria and cytotoxicity. In achieving the objective, 2-chloroquinoline-3-carbaldehyde analogues 54A-G were synthesised from the reaction of acetanilides 53A-G and acetic acid. Knoevenagal reaction of 2chloroquinoline-3-carbaldehydes 54A-G with thiazolidinedi-2,4-one 62 provided 2chloroquinoline-3-methylene thiazolidinedi-2,4-one 55A-G which then underwent nucleophilic substitution reaction with sodium azide and afforded (Z)-5-((tetrazolo [1,5a] quinoline-4-yl) methylene) thiazolidinedi-2,4-one 56A-F. (Z)-ethyl-2-(2-5-((7bromotetrazolo [1,5a] quinolin-4-yl) methylene-2,4-dioxothiazolidin-3-yl) acetamido) acetate 57 was synthesised from the reaction of (Z)-5-((7-bromotetrazolo [1,5a] quinoline-4-yl) methylene) thiazolidinedi-2,4-one 56D and ethyl-2-(2-chloroacetamido) acetate 65. The structures of the compounds were characterised by 1D NMR (1H, 13C, and DEPT 135), IR spectroscopy, elemental analysis and high-resolution mass spectroscopy. Novel selected synthesised quinoline compounds were evaluated of in vitro for two biological assays; namely anti-malarial activity and cytotoxicity. The anti-malaria activities of the novel quinoline compounds against 3D7 strain of the malaria parasite Plasmodium falciparum displayed that 2,6-dichloroquinoline-3-methylene thiazolidinedi-2,4-one 55C, (Z)-5-((7-fluorotetrazolo [1,5a] quinoline-4-yl) methylene) thiazolidinedi-2,4-one 56B and (Z)-5((7-ethoxytetrazolo [1,5a] quinoline-4-yl) methylene) thiazolidinedi-2,4-one 56F are potential malaria drugs since they reduced the percentage parasite viability to 25.80, 12.40 and 20.40 respectively. These results were further substantiated by their IC50 values 0.40, 0.04 and 0.50 µg/mL. Compound 56B displayed the highest cytotoxicity activity against human cervix adenocarcinoma cells displaying percentage viability of 14.22 %. Compounds 56F and 56C displayed moderate cytotoxicity activity at 56.60 and 59.81 % viability.
NRF
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Lin, Bao-Jiun, and 林保君. "Synthesis and Biological Evaluation of Furo[3,2-h]quinoline and Furo[2,3-h]quinoline Derivatives." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/61262624727227638045.
Full textAbstract:
碩士大仁科技大學
製藥科技研究所
97
Certain aniline- or phenoxy-substituted furo[3,2-h]quinolin-8-yl, furo[2,3-h]quinolin-2-yl, and 7-prop-2-ynyloxyquinolin-2-yl derivatives were synthesized and evaluated for their anti-inflammatory activities. These compounds were synthesized via alkylation of hydroxyl precursors followed by the chlorination, cyclization, and reaction with appropriate Ar-NH2 or Ar-OH. Anti- inflammatory activities of these quinoline derivatives were evaluated on the suppression of reactive oxygen species (ROS) production induced by formyl-methionyl-leucyl-phenylalanine (fMLP, 1 M) and phorbol-12-myristate-13-acetate (PMA, 0.1 M) in human neutrophils. The preliminary assays indicated that these compounds were more effective in the inhibition of ROS production induce by fMLP than that of PMA, and furo[2,3-h]quinolines were more potent than their corresponding furo[3,2-h]quinoline isomers. For the furo[2,3-h]quinolines, 1-[4-(8-methylfuro[2,3-h]quinolin-2-ylamino)phenyl]ethanone (12a) was the most potent for the inhibition of fMLP-induced ROS production with an IC50 value of 1.08 M. These compounds have the potential to be novel anti-inflammatory agents for the treatment of oxidative stress-induced disease with no significant cytotoxicity. The detail mechanisms and structure-activity relationships are active investigated now.
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Tai-Chi, Wang, and 王泰吉. "Synthesis And Biological Activity Evaluation of Quinoline And Quinolin-2(1H)-one a-Methylene-g-butyrolactones." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/87526227498769038220.
Full textAbstract:
博士高雄醫學院
藥學研究所
87
The quinoline and quinolin-2(1H)-one a-methylene-g-butyrolactones were synthesized from hydroxyquinoline and hydroxyquinolin-2(1H)-one via alkylation and Reformatsky-type condensation. The key precursors of hydroxyquinolin-2(1H)-ones were prepared from methoxyanilines and cinnamoyl chloride to give the respective methoxycinnamanilides. Their cyclization with aluminum chloride in chlorobenzene at 120°C afforded the desired intramolecular Friedel-Crafts cyclization products of hydroxy- quinolin-2(1H)-ones in good overall yield. To optimize the cyclization reaction, chlorobenzene was replaced with benzene as solvent. This led to an intermolecular addition to form 3,3-diphenylpropionanilides. The antiplatelet and antitumor activities of quinoline and quinolin-2(1H)-one a-methylene-g-butyrolactones are evaluated and the structure-activities relationships are as following. I. For antiplatelet activity: a). the potency of aryl portion is in a decreasing order of 7-substituted quinolin-2(1H)-one>6-substituted quinolin-2(1H)-one>>8-substituted quinolin-2(1H)-one>8-substituted 2-methyl- quinoline>8-substituted quinoline>2-substituted 8-hyrdoxy- quinoline. b). the potency of R-group is in a decreasing order of 4-halo- genated phenyl3phenyl>>4-methoxyphenyl>biphenyl3methyl. II. For vasorelaxing effect: a). the potency of aryl portion is in a decreasing order of 6-substituted quinolin-2(1H)-one>7-substituted quinolin-2(1H)-one>8-substituted quinoline>2-substituted 8-hyrdoxyquinoline> 8-substituted 2-methylquinoline>8-substituted quinolin-2(1H)-one. b). the potency of R-group is in a decreasing order of methyl >>phenyl>4-halogenated phenyl>4-methoxyphenyl3biphenyl. III. For anticancer activity: a). the potency of aryl portion is in a decreasing order of 8-substituted quinoline>2-substituted 8-hyrdoxyquinoline>8-substituted 2-methylquinoline. b). the potency of R-group is in a decreasing order of biphenyl 3 4-methoxyphenyl>phenyl34-halogenated phenyl>methyl. Among them, the most potent antiplatelet agent is 7-{[2-(4-fluorophenyl)-2,3,4,5-tetrahydro-4-methylene-5-oxo-2-furanyl] methoxy}quinolin-2(1H)-one with an IC50 of 0.4 mM against AA-induced platelet aggregation.
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RAHUL, SUBHASH TALEKAR. "Design,Synthesis and Biological Evaluation of Quinoline Analogues." 2006. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-0407200615584300.
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Mkhize, Zimbili. "Studies towards the synthesis of perhydropyrrolo[2,1-j]quinoline and perhydropyrido[2,1-j]quinoline ascidian alkaloids." Thesis, 2002. http://hdl.handle.net/10413/3725.
Full textAbstract:
Cylindricines A-K [1-11], lepadifonnine [12] and fasicularin [13] are tricyclic ascidian alkaloids exhibiting the perhydropyrrolo[2,1 :j]quinoline and perhydropyrido[2,1-j]quinoline ring systems. The structural features and biological activity of these alkaloids make them ideal targets for total synthesis.
The first aim of this project was to construct the azabicycles [111] and [112] that resemble the spirocyclic core of these alkaloids. The synthesis began with the C ring intact and the attempted construction of the B ring using Diels-Alder methodology. A key step was the Eschenmoser coupling reaction between thiolactams [105] and [106] to give the vinylogous
amides [107] and [108]. All attempts to convert the vinylogous amides to the corresponding dienes proved to be unsuccessful, due to the fact that the preferred site for deprotonation was ~ to nitrogen and not a to the carbonyl group. Due to time constraints we moved to our second
aim, the enantioselective synthesis of the B and C rings offasicularin [13].
Significant progress was made towards our second goal. (5S)-5-Hydroxytetrahydro2(lH)pyridinone [127], which represents the C ring of fasicularin, was successfully synthesized in 5 steps from L-glutamic acid [113]. This lactam was O-protected with tertbutyldiphenylsilyl
group to afford (5S)-5-tert-butyldiphenylsilyloxy-2-piperidinone [114].
Thionation of lactam [114] gave the thiolactam [160]. Conjugate addition of this thiolactam to methyl acrylate gave methyl 3-[(5S)-5- {[tert-butyl(diphenyl)silyl]oxy}-2-thioxotetrahydro1(2H)-pyridinyl ]propanoate [163], which underwent a Eschenmoser coupling reaction with bromoacetone to gIve methyl 3-[(5S)-5-{ [tert-butyl(diphenyl)-silyl]oxy} 2-[(£)-2oxopropylidine] tetrahydro-2(1H)-pyridinyl]propanoate [164]. Unfortunately conversion of [164] into the corresponding diene using KHMDS and TBSCI was unsuccessful. The reaction conditions caused the cleavage of the methyl acrylate protecting group on nitrogen, affording
the secondary E-vinylogous amide [167]. This constituted an important serendipitous discovery - methyl acrylate can be used to protect the nitrogen atom of enaminones and can be removed by KHMDS to access secondary E-enaminones that are otherwise difficult to synthesise. Another route pursued was to introduce the hexyl chain in the A ring of fasicularin
by means of an SN2 reaction between lactam [114] and mesylate [116]. The stereodefined (lR)1-(2-{[tert-butyl-(dimethyl)sily]oxy}ethyl)heptyl methanesulfonate [116] was successfully x synthesized in 5 steps from l-octyne [115]. Unfortunately the subsequent SN2 reaction with
lactam [114] failed when we using t-BuOK and THF and time constraints prevented us from attempting this coupling reaction using alternative conditions.Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 2002.