- Enantioselective Palladium(II)-Catalyzed Oxidative Aminofluorination of Unactivated Alkenes with Et4NF?3 HF as a Fluoride Source
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The first asymmetric PdII-catalyzed aminofluorination of unactivated alkenes using chiral quinoline-oxazolines (Quox) as ligands has been developed. This reaction provides easy access to a wide array of enantiomerically enriched β-fluoropiperidines in good yields and with excellent enantioselectivity. Notably, Et4NF?3 HF as a readily accessible nucleophilic fluoride source was found to play an essential role in the enantioselective control, and CsOCF3 also acts a key additive to improve the excellent ee value of products.
- Hou, Chuanqi,Chen, Pinhong,Liu, Guosheng
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- Design, synthesis and anticancer properties of IsoCombretaQuinolines as potent tubulin assembly inhibitors
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The synthesis and evaluation of a new series of IsoCombretaQuinolines (IsoCoQuines) 2 with a 2-substituted-quinoline in place of the 3,4,5-trimethoxyphenyl ring present in isoCA-4 and CA-4 are described. Most of these compounds displayed a potent cytotoxic activity (IC50a panel of five human cancer cell lines and inhibited tubulin assembly at a micromolar level. The most potent analogue 2b, having a 3-hydroxy-4-methoxyphenyl as B-ring, led to cell cycle arrest in G2/M phase. Docking studies indicate that 2b showed a binding mode comparable to those previously observed with quinazoline analogous (IsoCoQ) and with isoCA-4 at the colchicine binding site of tubulin.
- Khelifi, Ilhem,Naret, Timothée,Renko, Dolor,Hamze, Abdallah,Bernadat, Guillaume,Bignon, Jérome,Lenoir, Christine,Dubois, Jo?lle,Brion, Jean-Daniel,Provot, Olivier,Alami, Mouad
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- Cyclic bridged analogs of isoCA-4: Design, synthesis and biological evaluation
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In this work, a series of cyclic bridged analogs of isocombretastatin A-4 (isoCA-4) with phenyl or pyridine linkers were designed and synthesized. The synthesis of the desired analogs was performed by the formation of nitro-vinyl intermediates, followed by a Cadogan cyclization. Structure activity relationship (SAR) study demonstrates the critical role of the combination of quinaldine as ring A, pyridine as the linker, and indole as ring B in the same molecule, for the cytotoxic activity. Among all tested compounds, compound 42 showed the highest antiproliferative activity against a panel of cancer cell lines with average IC50 values of 5.6 nM. Also, compound 42 showed high antiproliferative activity against the MDR1-overexpressing K562R cell line; thus, it was 1.5- and 12-fold more active than the reference compounds, isoCA-4 and CA-4, respectively. Moreover, 42 displayed a strong antiproliferative activity against the colon-carcinoma cells (HT-29), which are resistant to combretastatin A-4 and isoCA-4, and it was found to be 8000-fold more active than natural CA-4. Compound 42 also effectively inhibited tubulin polymerization both in vitro and in cells, and induced cell cycle arrest in G2/M phase. Next, we demonstrated that compound 42 dose-dependently caused caspase-induced apoptosis of K562 cells through mitochondrial dysfunction. Finally, we evaluated the effect of compound 42 in human no cancer cells compared to the reference compound. We demonstrated that 42 was 73 times less cytotoxic than isoCA-4 in quiescent peripheral blood lymphocytes (PBLs). In summary, these results suggest that compound 42 represents a promising tubulin inhibitor worthy of further investigation.
- Pecnard, Shannon,Provot, Olivier,Levaique, Hélène,Bignon, Jérome,Askenatzis, Laurie,Saller, Francois,Borgel, Delphine,Michallet, Sophie,Laisne, Marie-Catherine,Lafanechère, Laurence,Alami, Mouad,Hamze, Abdallah
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- Hypervalent Iodine(III)-Mediated Regioselective Cyanation of Quinoline N-Oxides with Trimethylsilyl Cyanide
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A regioselective cyanation of quinoline N-oxides with trimethylsilyl cyanide was developed by using (Diacetoxyiodo) benzene (PIDA) as mediated hypervalent iodine(III) reagent under metal-free and base-free reaction conditions to obtain 2-cyanoquinolines. The efficient PIDA reagent could play the role of an activator of the substrates and an accelerator of N?O bond cleavage. The reaction system featured a wide range of substrate suitability and high yields. The procedure was enlarged gram-scale to synthesize the tuberculosis (TB) inhibitor. Finally, according to some experimental results, a plausible mechanism for the cyanation reaction is proposed. (Figure presented.).
- Xu, Feng,Li, Yuqin,Huang, Xin,Fang, Xinjie,Li, Zhuofei,Jiang, Hongshuo,Qiao, Jingyi,Chu, Wenyi,Sun, Zhizhong
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supporting information
p. 520 - 525
(2018/12/13)
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- Quinoline substituted indole compound, and preparation method and application thereof
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The invention discloses a quinoline substituted indole compound, a pharmaceutical composition containing the quinoline substituted indole compound, and a preparation method for the quinoline substituted indole compound. The invention also discloses the quinoline substituted indole compound, a pharmaceutical application for the pharmaceutical composition containing the quinoline substituted indolecompound, specifically an application of the pharmaceutical composition containing the quinoline substituted indole compound in preparation of drugs used for treatment of tumors, and an application ofthe quinoline substituted indole compound in preparation of drugs used for treatment of diseases or symptoms by inhibition of tubulin activity.
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Paragraph 0097; 0098; 0099; 0100
(2019/04/26)
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- NEW TARGETED CYTOTOXIC ISOCOMBRETAQUINOLINE DERIVATIVES AND CONJUGATES THEREOF
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The present invention is directed to novel natural product-derived combretastatin- based compounds useful as payloads in drug-conjugates constructs with cell target binding moieties (CTBM) and payload-linker compounds useful in connection with drug conjugates. The present invention further relates to new isoNH2CombretaQuinoline compositions including the aforementioned payloads, payload-linkers and drug conjugates, and methods for using these payloads, payload-linkers and drug conjugates, to treat pathological conditions including cancer.
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Paragraph 00126
(2018/10/25)
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- A simple procedure for the preparation of 2-cyano-4-chloropyridines
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Figure represented. 4-Nitro-pyridine-N-oxides are reacted with ethylchloroformate and trimethylsilyl cyanide to give 4-chloro-2-cyanopyridine.
- Veerareddy, Arava,Surendrareddy, Gogireddy,Dubey
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experimental part
p. 961 - 964
(2011/09/16)
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- On the mechanism of the palladium-catalyzed tert-butylhydroperoxide- mediated wacker-type oxidation of alkenes using quinoline-2-oxazoline ligands
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The mechanism of the tert-butylhydroperoxide-mediated, Pd(Quinox)-catalyzed Wacker-type oxidation was investigated to evaluate the hypothesis that a selective catalyst-controlled oxidation could be achieved by rendering the palladium coordinatively saturated using a bidentate amine ligand. The unique role of the Quinox ligand framework was probed via systematic ligand modifications. The modified ligands were evaluated through quantitative Hammett analysis, which supports a push-pull relationship between the electronically asymmetric quinoline and oxazoline ligand modules.
- Michel, Brian W.,Steffens, Laura D.,Sigman, Matthew S.
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supporting information; experimental part
p. 8317 - 8325
(2011/07/08)
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- NEW METHODS AND REAGENTS IN ORGANIC SYNTHESIS. 12. REACTION OF DIETHYL PHOSPHOROCYANIDATE (DEPC) WITH AROMATIC AMINE OXIDES. A MODIFIED REISSERT-HENZE REACTION
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Diethyl phosphorocyanidate (DEPC) reacts with aromatic amine oxides in the presence of triethylamine to give α-cyanated compounds; the reaction may be called a modified Reissert-Henze reaction.
- Harusawa, Shinya,Hamada, Yasumasa,Shioiri, Takayuki
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p. 981 - 984
(2007/10/02)
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