- Design, synthesis and study of antibacterial and antitubercular activity of quinoline hydrazone hybrids
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Emerging bacterial resistance is causing widespread problems for the treatment of various infections. Therefore, the search for antimicrobials is a never-ending task. Hydrazones and quinolines possess a wide variety of biological activities. Herewith, eleven quinoline hydrazone derivatives have been designed, synthesized, characterized and evaluated for their antibacterial activity and antitubercular potential against Mtb WT H37Rv. Compounds QH-02, QH-04 and QH-05 were found to be promising compounds with an MIC value of 4 μg/mL against Mtb WT H37Rv. Compounds QH-02, QH-04, QH-05, and QH-11 were also found to be active against bacterial strains including Acinetobacter baumanii, Escherichia coli and Staphylococcus aureus. Further, we have carried out experiments to confirm the cytotoxicity of the active compounds and found them to be non-toxic.
- Eswaran, Sumesh,Shruthi, T. G.,Subramanian, Sangeetha
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- Design, synthesis and biological evaluation of new quinoline derivatives as potential antitumor agents
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A series of new quinoline derivatives was designed, synthesized and evaluated for their antiproliferative activity. The results demonstrated that compounds 11p, 11s, 11v, 11x and 11y exhibited potent antiproliferative activity with IC50 value of lower than 10 μM against seven human tumor cell lines, and N-(3-methoxyphenyl)-7- (3-phenylpropoxy)quinolin-4-amine 11x was found to be the most potent antiproliferative agent against HCT-116, RKO, A2780 and Hela cell lines with an IC50 value of 2.56, 3.67, 3.46 and 2.71 μM, respectively. The antitumor efficacy of the representative compound 11x in mice was also evaluated, and the results showed that compound 11x effectively inhibited tumor growth and decreased tumor weight in animal models. Further investigation on mechanism of action indicated that compound 11x could inhibit colorectal cancer growth through ATG5-depenent autophagy pathway. Therefore, these quinoline derivatives are a new class of molecules that have the potential to be developed as new antitumor drugs.
- Su, Tong,Zhu, Jiongchang,Sun, Rongqin,Zhang, Huihui,Huang, Qiuhua,Zhang, Xiaodong,Du, Runlei,Qiu, Liqin,Cao, Rihui
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- Highly chemoselective deoxygenation of N-heterocyclic: N -oxides under transition metal-free conditions
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Because their site-selective C-H functionalizations are now considered one of the most useful tools for synthesizing various N-heterocyclic compounds, the highly chemoselective deoxygenation of densely functionalized N-heterocyclic N-oxides has received much attention from the synthetic chemistry community. Here, we provide a protocol for the highly chemoselective deoxygenation of various functionalized N-oxides under visible light-mediated photoredox conditions with Na2-eosin Y as an organophotocatalyst. Mechanistic studies imply that the excited state of the organophotocatalyst is reductively quenched by Hantzsch esters. This operationally simple technique tolerates a wide range of functional groups and allows high-yield, multigram-scale deoxygenation. This journal is
- Kim, Se Hyun,An, Ju Hyeon,Lee, Jun Hee
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- Design, synthesis and biological evaluation of 4-aminoquinoline-guanylthiourea derivatives as antimalarial agents
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Guanylthiourea (GTU) has been identified as an important antifolate antimalarial pharmacophore unit, whereas, 4-amino quinolones are already known for antimalarial activity. In the present work molecules carrying 4-aminoquinoline and GTU moiety have been designed using molecular docking analysis with PfDHFR enzyme and heme unit. The docking results indicated that the necessary interactions (Asp54 and Ile14) and docking score (?9.63 to ?7.36 kcal/mmol) were comparable to WR99210 (?9.89 kcal/mol). From these results nine molecules were selected for synthesis. In vitro analysis of these synthesized compounds reveal that out of the nine molecules, eight show antimalarial activity in the range of 0.61–7.55 μM for PfD6 strain and 0.43–8.04 μM for PfW2 strain. Further, molecular dynamics simulations were performed on the most active molecule to establish comparative binding interactions of these compounds and reference ligand with Plasmodium falciparum dihydrofolate reductase (PfDHFR).
- Bhagat, Shweta,Arfeen, Minhajul,Das, Gourav,Ramkumar, Mridula,Khan, Shabana I.,Tekwani, Babu L.,Bharatam, Prasad V.
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- Synthesis, antituberculosis studies and biological evaluation of new quinoline derivatives carrying 1,2,4-oxadiazole moiety
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Tuberculosis is the infectious disease caused by mycobacterium tuberculosis (Mtb), responsible for the utmost number of deaths annually across the world. Herein, twenty-one new substituted 1,2,4-oxadiazol-3-ylmethyl-piperazin-1-yl-quinoline derivatives were designed and synthesized through multistep synthesis followed by in vitro evaluation of their antitubercular potential against Mtb WT H37Rv. The compound QD-18 was found to be promising with MIC value of 0.5 μg/ml and QD-19 to QD-21 were also remarkable with MIC value of 0.25 μg/ml. Additionally, we have carried out experiments to confirm the metabolic stability, cytotoxicity and pharmacokinetics of these compounds along with kill kinetics of QD-18. These compounds were found to be orally bioavailable and highly effective. Altogether, these results indicate that QD-18, QD-19, QD-20 and QD-21 are promising lead compounds for the development of a novel chemical class of antitubercular drugs.
- Shruthi,Eswaran, Sumesh,Shivarudraiah, Prasad,Narayanan, Shridhar,Subramanian, Sangeetha
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- Phosphonium chloride as a non-volatile chlorinating reagent: Preparation and reaction in no solvent or ionic liquid
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Reaction of triphenylphosphine with trichloroisocyanuric acid in no solvent or an ionic liquid gave the corresponding phosphonium chloride, which can be used as a cheap and safe chlorinating reagent. Conversion of hydroxyheterocycles to chloroheterocycles, carboxylic acids to carboxylic acid chlorides, and primary amides to nitriles were accomplished by using the phosphonium chloride in excellent to good yields.
- Sugimoto, Osamu,Harada, Yukihiro,Tanji, Ken-Ichi
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- Metal-Free Deoxygenation of Amine N-Oxides: Synthetic and Mechanistic Studies
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We report herein an unprecedented combination of light and P(III)/P(V) redox cycling for the efficient deoxygenation of aromatic amine N-oxides. Moreover, we discovered that a large variety of aliphatic amine N-oxides can easily be deoxygenated by using only phenylsilane. These practically simple approaches proceed well under metal-free conditions, tolerate many functionalities and are highly chemoselective. Combined experimental and computational studies enabled a deep understanding of factors controlling the reactivity of both aromatic and aliphatic amine N-oxides.
- Lecroq, William,Schleinitz, Jules,Billoue, Mallaury,Perfetto, Anna,Gaumont, Annie-Claude,Lalevée, Jacques,Ciofini, Ilaria,Grimaud, Laurence,Lakhdar, Sami
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p. 1237 - 1242
(2021/06/01)
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- Highly Chemoselective Deoxygenation of N-Heterocyclic N-Oxides Using Hantzsch Esters as Mild Reducing Agents
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Herein, we disclose a highly chemoselective room-temperature deoxygenation method applicable to various functionalized N-heterocyclic N-oxides via visible light-mediated metallaphotoredox catalysis using Hantzsch esters as the sole stoichiometric reductant. Despite the feasibility of catalyst-free conditions, most of these deoxygenations can be completed within a few minutes using only a tiny amount of a catalyst. This technology also allows for multigram-scale reactions even with an extremely low catalyst loading of 0.01 mol %. The scope of this scalable and operationally convenient protocol encompasses a wide range of functional groups, such as amides, carbamates, esters, ketones, nitrile groups, nitro groups, and halogens, which provide access to the corresponding deoxygenated N-heterocycles in good to excellent yields (an average of an 86.8% yield for a total of 45 examples).
- An, Ju Hyeon,Kim, Kyu Dong,Lee, Jun Hee
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supporting information
p. 2876 - 2894
(2021/02/01)
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- Synthesis method of 4,7-dichloroquinoline
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The invention discloses a synthesis method of 4,7-dichloroquinoline. The synthesis method is characterized by comprising the following steps: synthesizing 7-chloro-4-hydroxylquinoline-3-carboxylic acid by using a one-pot method, and carrying out decarboxylation and chlorination on the 7-chloro-4-hydroxylquinoline-3-carboxylic acid to obtain 4,7-dichloroquinoline. The step of synthesizing the 7-chloro-4-hydroxylquinoline-3-carboxylic acid by the one-pot method comprises the following sub-steps: with m-chloroaniline, triethyl orthoformate or trimethyl orthoformate and diethyl malonate as raw materials, carrying out condensation under the catalysis of anhydrous ferric trichloride to obtain diethyl 2-[[(3-chlorophenyl)amino]methylene]malonate, directly adding a condensation reaction solution into an organic solvent, carrying out heating cyclization to obtain 7-chloro-4-hydroxylquinoline-3-carboxylic acid ethyl ester, and after the cyclization reaction is completed, adding sodium hydroxidefor hydrolysis to obtain 7-chloro-4-hydroxylquinoline-3-carboxylic acid. Although the whole process comprises five reactions, intermediate products are good enough in purity and can be directly synthesized into a target product without purification, so operation is easy and convenient and industrialization is facilitated; and raw materials are easily available, and pollution is small.
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Paragraph 0020; 0027-0028; 0029; 0036-0036; 0038; 0045-0046
(2020/07/15)
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- Preparation method 4-7 -dichloroquinoline (by machine translation)
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The method comprises the steps of: adding 4 chloroaniline and ethoxymethyl diethyl malonate as raw materials, carrying out decarboxylation reaction, carrying out decarboxylation through condensation, cyclization and hydrolysis, carrying out decarboxylation reaction, adding sulfuric acid to 7 - under 3 - pressure, 4 and washing to obtain solid 7 - hydroxyl 3 - chloroquinolines. 230 - 260 °C. The method comprises the following steps: carrying out decarboxylation reaction, adding sulfuric acid to reaction completely, layering, organic layer recovery and water layer reaction till 90 - 100 °C 6.0 - 6.5 kg reaction until reaction is complete 90 - 100 °C, layering, organic layer recovery and water layer reaction; and the steps and chlorination are carried out 150 -170 °C pH4 - 5 4 -7 . Reaction conditions are mild, yield is high, and quality is good. (by machine translation)
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Paragraph 0035-0040
(2020/10/20)
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- Design and synthesis of 4(1H)-quinolone derivatives as autophagy inducing agents by targeting ATG5 protein
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Background: Quinolines have been characterized as a class of potential antitumor agents, and a large number of natural and synthetic quinolines acting as antitumor agents were reported. Methods: A series of 7-chloro-4(1H)-quinolone derivatives were synthesized. The antiproliferative effect of these compounds was evaluated by MTT assay against five human tumor cell lines. The mechanism of action of the selected compound 7h was also investigated. Results and Discussion: Most of the compounds had more potent antiproliferative activities than the lead compound 7-chloro-4(1H)-quinolone 6b. Compound 7h was found to be the most potent antiproliferative agent against human tumor cell lines. Further investigation demonstrated that compound 7h triggered ATG5-dependent autophagy of colorectal cancer cells by promoting the functions of LC3 proteins. Conclusion: These results were useful for designing and discovering more potent novel antitumor agents endowed with better pharmacological profiles.
- Jia, Yifan,Yu, Difei,Huang, Qiuhua,Zhang, Xiaodong,Qiu, Liqin,Cao, Rihui,Du, Runlei,Liu, Wenbin
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p. 884 - 890
(2020/07/10)
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- NOVEL COMPOUNDS AND THEIR METHODS OF USE THEREOF
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The present invention provides novel quinoline compounds or their pharmaceutically acceptable salts. The compounds of the invention efficacious in the treatment of Tuberculosis and other mycobacterial infections.
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Page/Page column 17
(2020/01/11)
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- Preparation method of 4,7-dichloroquinoline
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The invention discloses a preparation method of 4,7-dichloroquinoline, and belongs to the technical field of synthesis of antimalarial drug intermediates. According to the method, 7-chloro-4-hydroxyquinoline is used as a raw material and reacts with triphosgene under the action of a catalyst to generate the 4,7-dichloroquinoline. The synthetic method provided by the invention can effectively avoidthe use of chlorinating agents unfriendly to the environment, such as phosphorus oxychloride and thionyl chloride, reduces the pollution to the environment and the corrosion to equipment, and reducesthe production costs.
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Paragraph 0023-0026
(2020/01/12)
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- With anti-tumor activity of chlorine oxygen kui derivatives
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The invention relates to a chloroxoquinoline derivatives with anti-tumor activity and specifically relates to compounds of a formula I as shown in the specification and pharmaceutically acceptable salts, solvates and prodrugs thereof, wherein R1 is selected from hydrogen, -C1-6 alkyl, -C2-6 alkenyl, -C2-6 alkynyl and -C1-6 alkyl-phenyl, and the alkyl, the alkenyl, the alkynyl and the phenyl can be optionally substituted by halogens, nitryl, cyan, hydroxyl, -C1-6 alkoxy and phenyl; R3 is selected from hydrogen, -CONHR31 and -COOR32, the R31 and the R32 are independently selected from -C1-6 alkyl and -C1-6 alkylamino, respectively, and the amino can be optionally substituted by 1 to 2 -C1-6 alkyls; R7 is selected from halogens, -C1-6 alkoxy, morpholinyl and piperazine; the formula I is as shown in the specification.
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- For antibacterial chlorine oxygen kui derivatives
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The invention relates to an oxo-quinoline derivative with activity of resisting bacterial infection relevant diseases such as helicobacter pylori (Hp) infection disease. The invention specifically relates to a compound as shown in formula I in the specification, and a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R is selected from hydrogen, -C alkyl, -C alkenyl, -C alkynyl, or -C alkyl-phenyl, and the alkyl, alkenyl, alkynyl and phenyl can be randomly substituted by halogen, nitro, cyan, hydroxyl, -C alkoxy and phenyl; R is selected from hydrogen, -CONHR and -COOR, R and R are independently selected from -C alkyl and -C alkyl amino, and the amino is randomly substituted by one to two -C alkyls; R is selected from halogen, -C alkoxy, morpholinyl or piperazinyl.
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Paragraph 0297-0301
(2017/08/29)
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- Synthesis and Characterization of Iron-Nitrogen-Doped Graphene/Core-Shell Catalysts: Efficient Oxidative Dehydrogenation of N-Heterocycles
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An important goal for nanocatalysis is the development of flexible and efficient methods for preparing active and stable core-shell catalysts. In this respect, we present the synthesis and characterization of iron oxides surrounded by nitrogen-doped-graphene shells immobilized on carbon support (labeled FeOx@NGr-C). Active catalytic materials are obtained in a simple, scalable and two-step method via pyrolysis of iron acetate and phenanthroline and subsequent selective leaching. The optimized FeOx@NGr-C catalyst showed high activity in oxidative dehydrogenations of several N-heterocycles. The utility of this benign methodology is demonstrated by the synthesis of pharmaceutically relevant quinolines. In addition, mechanistic studies prove that the reaction progresses via superoxide radical anions (·O2-).
- Cui, Xinjiang,Li, Yuehui,Bachmann, Stephan,Scalone, Michelangelo,Surkus, Annette-Enrica,Junge, Kathrin,Topf, Christoph,Beller, Matthias
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supporting information
p. 10652 - 10658
(2015/09/28)
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- 2-(Quinolin-4-ylthio)-1,3,4-oxadiazole derivatives: Design, synthesis, antibacterial and antifungal studies
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A series of novel hybrid 2-(7-chloroquinolin-4-ylthio)-5-(substituted)-1,3, 4-oxadiazole derivatives have been designed, synthesized which contains different pharmacophores like quinoline and 1,3,4-oxadiazole linked via sulfur atom. All the newly synthesized derivatives have been characterized by IR, 1H NMR, 13C NMR spectral and elemental analysis. Further, All the final synthesized scaffolds have been subjected to in vitro antimicrobial activity against several bacteria (E.coli, P.aeruginosa, S.aureus, S.pyogenus) and fungi (C.albicans, A.niger, A.clavatus) using broth dilution technique. Among the compounds tested, compounds 3f substituted with coumarin analogue and 3b with amine group at second position of phenyl to oxadiazole moiety are found to be most potent.
- Modh, Rahul P,Shah, Dhruvin,Chikhalia, Kishor H
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p. 1318 - 1324
(2014/01/06)
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- Synthesis of 4- and 7-quinolinesulfonamides from 4,7-dichloroquinoline
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Action of sodium methanethiolate (in boiling DMF) towards 4,7-dichloroquinoline (1) or 7-chloro-1-methyl-4(1H)-quinolinone (11) occured via chlorine ipso-substitution followed by methanethiolato-S-demethylation to yield dithiolate 1A or thiolate 18A, whic
- Marciniec, Krzysztof,Maslankiewicz, Andrzej
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experimental part
p. 93 - 101
(2009/05/07)
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- C-MET MODULATORS AND METHODS OF USE
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The present invention provides compounds, which have activity for modulating protein kinase enzymatic activity and are potentially useful for modulating cellular activities such as, e.g., proliferation, differentiation, programmed cell death, migration and chemoinvasion. The present invention also provides compositions containing such compounds, and methods for producing and using such compounds and compositions.
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Page/Page column 94
(2010/11/24)
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- C-MET MODULATORS AND METHODS OF USE
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The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate and/or modulate kinase receptor, particularly c-Met, KDR, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.
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(2008/06/13)
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- Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities
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A simple two-step synthesis method was used to make 51 B-ring-substituted 4-hydroxyquinolines allowing analysis of the effect of ring substitutions on inhibition of growth of chloroquine sensitive and resistant strains of Plasmodium falciparum, the dominant cause of malaria morbidity. Substituted quinoline rings other than the 7-chloroquinoline ring found in chloroquine were found to have significant activity against the drug-resistant strain of P. falciparum W2.
- Madrid, Peter B.,Sherrill, John,Liou, Ally P.,Weisman, Jennifer L.,DeRisi, Joseph L.,Guy, R. Kiplin
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p. 1015 - 1018
(2007/10/03)
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- INHIBITORS OF FUNGAL INVASION
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This invention relates to various anti-fungall agents including agents that are inhibitors of fungal invasion.
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Drawing sheet 30
(2010/02/09)
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- A novel synthesis of substituted quinolines using ring-closing metathesis (RCM): Its application to the synthesis of key intermediates for anti-malarial agents
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A method for synthesizing substituted quinolines using ruthenium-catalyzed ring-closing metathesis as a key step has been developed. Substituted 1,2-dihydroquinolines, 4-silyloxy-1,2-dihydroquinoline and 4-methoxy-1,2- dihydroquinoline, were successfully synthesized in excellent yields via ene-ene metathesis and silyl or alkyl enol ether-ene metathesis, respectively. The synthetic intermediates of the antimalarial agents quinine, chloroquine, and PPMP-quinine hybrid were efficiently synthesized by this methodology.
- Theeraladanon, Chumpol,Arisawa, Mitsuhiro,Nishida, Atsushi,Nakagawa, Masako
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p. 3017 - 3035
(2007/10/03)
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- Antimalarials: Synthesis of 4-aminoquinolines that circumvent drug resistance in malaria parasites
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The strategies described here have permitted the synthesis of a series of 4-aminoquinoline antimalarials. Substantive improvements over previous syntheses include nucleophilic substitution with neat amine rather than in phenol, regioselective reductive alkylation to convert the terminal primary amine (12a-20a) on the diaminoalkane side chain to a diethylamino group, and purification by column chromatography with basic alumina. The 1H nmr spectra obtained after regioselective reductive alkylation with sodium borodeuteride (in comparison with sodium borohydride) demonstrated that this reductive alkylation proceeds via formation and subsequent reduction of the corresponding diamides in situ.
- De,Byers,Krogstad
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p. 315 - 320
(2007/10/03)
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