228728-23-2Relevant articles and documents
Conjugate Addition Routes to 2-Alkyl-2,3-dihydroquinolin-4(1H)-ones and 2-Alkyl-4-hydroxy-1,2-dihydroquinoline-3-carboxylates
Kingsbury, Alex,Brough, Steve,McCarthy, Antonio Pedrina,Lewis, William,Woodward, Simon
supporting information, p. 1011 - 1017 (2019/12/27)
Under CuBr·SMe2/PPh3 catalysis (5/10 mol-%) RMgCl (R = Me, Et, nPr, CH=CH2, nBu, iBu, nC5H11, cC6H11, Bn, CH2Bn, nC11H23) readily (–78 °C) undergo 1,4-addition to Cbz or Boc protected quinolin-4(1H)-ones to provide 2-alkyl-2,3-dihydroquinolin-4(1H)-ones (14 examples, 54–99 % yield). Asymmetric versions require AlEt3 to Boc-protected ethyl 6-substituted 4(1H)-quinolone-3-carboxylates (6-R group = all halogens, n/i/t-alkyls, CF3) and provide 61–91 % yield, 30–86 % ee; any halogen, Me, or CF3 provide the highest stereoselectivities (76–86 % ee). Additions of AlMe3 or Al(nC8H17)3 provide ≈ 45 and ≈ 75 % ee on addition to the parent (6-R = H). Ligand (S)-(BINOL)P–N(CHPh2)(cC6H11) provides the highest ee values engendering addition to the Si face of the 4(1H)-quinolone-3-carboxylate. Allylation and deprotection of a representative 1,4-addition product example confirm the facial selectivity (X-ray crystallography).
Green efficient synthesis method of quinolone compound
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Paragraph 0017; 0018, (2019/05/08)
The invention discloses a green efficient synthesis method of a quinolone compound. The method is as follows: Step 1, a dicarbonyl compound, triethyl orthoformate and an aniline compound react in theabsence of a solvent and a catalyst to obtain an enamine ester intermediate; and Step 2, the enamine ester intermediate is subjected to an intramolecular cyclization reaction under the action of a cyclization reagent diphenyl ether to obtain a quinolone parent ring compound. The purity of the product reaches up to 98.8%. the synthesis method of the invention has the following main beneficial effects: 1, the reaction in the Step 1 is efficient, and no catalyst or solvent is used so as to avoid generation of the three wastes and the yield is high; 2, the process in the step 2 is green, the cyclization reagent can be recycled and reused; and 3, the process is simple, the steps 1 and 2 can be carried out in the same reactor, and the quinolone compound is obtained after reaction and filtration.
A four-ring quinolinone alkaloid derivative and its preparation method and application (by machine translation)
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Paragraph 0155; 0184, (2018/10/27)
The invention relates to a four-ring quinolinone alkaloid derivative, or a tautomer thereof, stereo isomer, racemate, enantiomer of non-isometric mixture, geometric isomer, solvate, pharmaceutically acceptable salt or prodrug, and pharmaceutical composition containing the compound. The invention also discloses such compounds and pharmaceutical compositions thereof as a medicament, in particular as anti-virus, antibacterial and the anti-parasitic drug use. (by machine translation)
Synthesis, radiolabeling and preliminary in vivo evaluation of multimodal radiotracers for PET imaging and targeted radionuclide therapy of pigmented melanoma
Billaud, Emilie M.F.,Maisonial-Besset, Aurélie,Rbah-Vidal, Latifa,Vidal, Aurélien,Besse, Sophie,Béquignat, Jean-Baptiste,Decombat, Caroline,Degoul, Fran?oise,Audin, Laurent,Deloye, Jean-Bernard,Dollé, Frédéric,Kuhnast, Bertrand,Madelmont, Jean-Claude,Tarrit, Sébastien,Galmier, Marie-Josèphe,Borel, Michèle,Auzeloux, Philippe,Miot-Noirault, Elisabeth,Chezal, Jean-Michel
, p. 818 - 838 (2015/03/05)
Melanin pigment represents an attractive target to address specific treatment to melanoma cells, such as cytotoxic radionuclides. However, less than half of the patients have pigmented metastases. Hence, specific marker is required to stratify this patient population before proceeding with melanin-targeted radionuclide therapy. In such a context, we developed fluorinated analogues of a previously studied melanin-targeting ligand, N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide (ICF01012). These latter can be labeled either with 18F or 131I/125I for positron emission tomography imaging (melanin-positive patient selection) and targeted radionuclide therapy purposes. Here we describe the syntheses, radiosyntheses and preclinical evaluations on melanoma-bearing mice model of several iodo- and fluoro(hetero)aromatic derivatives of the ICF01012 scaffold. After preliminary planar gamma scintigraphic and positron emission tomography imaging evaluations, [125I]- and [18F]-N-[2-(diethylamino)ethyl]-4-fluoro-3-iodobenzamides ([125I]4, [18F]4) were found to be chemically and biologically stable with quite similar tumor uptakes at 1 h p.i. (9.7 ± 2.6% ID/g and 6.8 ± 1.9% ID/g, respectively).
Repurposing human PDE4 inhibitors for neglected tropical diseases. evaluation of analogs of the human PDE4 inhibitor GSK-256066 as inhibitors of pdeb1 of trypanosoma brucei
Ochiana, Stefan O.,Bland, Nicholas D.,Settimo, Luca,Campbell, Robert K.,Pollastri, Michael P.
, p. 549 - 564 (2015/04/22)
Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the prof
C-6 aryl substituted 4-quinolone-3-carboxylic acids as inhibitors of hepatitis C virus
Chen, Yue-Lei,Zacharias, Jeana,Vince, Robert,Geraghty, Robert J.,Wang, Zhengqiang
, p. 4790 - 4800 (2012/08/28)
Quinolone-3-carboxylic acid represents a highly privileged chemotype in medicinal chemistry and has been extensively explored as antibiotics and antivirals targeting human immunodeficiency virus (HIV) integrase (IN). Herein we describe the synthesis and anti-hepatitis C virus (HCV) profile of a series of C-6 aryl substituted 4-quinlone-3-carboxylic acid analogues. Significant inhibition was observed with a few analogues at low micromolar range against HCV replicon in cell culture and a reduction in replicon RNA was confirmed through an RT-qPCR assay. Interestingly, evaluation of analogues as inhibitors of NS5B in a biochemical assay yielded only modest inhibitory activities, suggesting that a different mechanism of action could operate in cell culture.
Synthesis and biological activity of 4″-O-acyl derivatives of 14- and 15-membered macrolides linked to ω-quinolone-carboxylic unit
Kugor, Maja Matanovi?,Timac, Vlado,Palej, Ivana,Lugari?, Urdjica,Paljetak, Hana Ipi?,Fili?, Darko,Modri?, Marina,Ilovi?, Ivica,Gembarovski, Dubravka,Mutak, Stjepan,Erakovi? Haber, Vesna,Holmes, David J.,Ivezi?-Schoenfeld, Zrinka,Alihodi?, Sulejman
experimental part, p. 6547 - 6558 (2010/10/03)
The synthesis and antimicrobial activity of a new class of macrolide antibiotics which consist of a macrolide scaffold and a quinolone unit covalently connected by an appropriate linker are described. Optimization of several synthetic steps and structural
HETEROCYCLIC UREA DERIVATIVES FOR THE TREATMENT OF BACTERIAL INFECTIONS
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, (2009/12/28)
Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.
Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration
Woodrow, Michael D.,Ballantine, Stuart P.,Barker, Michael D.,Clarke, Beth J.,Dawson, John,Dean, Tony W.,Delves, Christopher J.,Evans, Brian,Gough, Sharon L.,Guntrip, Steven B.,Holman, Stuart,Holmes, Duncan S.,Kranz, Michael,Lindvaal, Mika K.,Lucas, Fiona S.,Neu, Margarete,Ranshaw, Lisa E.,Solanke, Yemisi E.,Somers, Don O.,Ward, Peter,Wiseman, Joanne O.
scheme or table, p. 5261 - 5265 (2010/03/31)
Crystallography driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of quinoline-3-carboxamides as highly potent and selective inhibitors of phosphodiesterase 4B. This series has been optimized to GSK256066, a potent PDE4B inhibitor which also inhibits LPS induced production of TNF-α from isolated human peripheral blood mononuclear cells with a pIC50 of 11.1. GSK256066 also has a suitable profile for inhaled dosing.
Controlled derivatization of polyhalogenated quinolines utilizing selective cross-coupling reactions
Brad Nolt,Zhao, Zhijian,Wolkenberg, Scott E.
, p. 3137 - 3141 (2008/09/20)
Straightforward procedures for the derivatization of tri- and tetrahalogenated quinolines utilizing sequential selective Pd-catalyzed cross-coupling reactions are described. Taking advantage of intrinsic halide reactivity, substrate control, and appropria
