- Methoxy and bromo scans on N-(5-methoxyphenyl) methoxybenzenesulphonamides reveal potent cytotoxic compounds, especially against the human breast adenocarcinoma MCF7 cell line
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Thirty seven N-(5-methoxyphenyl)-4-methoxybenzenesulphonamide with methoxy or/and bromo substitutions (series 1-4) and with different substituents on the sulphonamide nitrogen have been synthesised. 21 showed sub-micromolar cytotoxicity against HeLa and HT-29 human tumour cell lines, and were particularly effective against MCF7. The most potent series has 2,5-dimethoxyanilines, especially the 4-brominated compounds 23–25. The active compounds inhibit microtubular protein polymerisation at micromolar concentrations, thus pointing at tubulin as the target. Co-treatment with the MDR inhibitor verapamil suggests that they are not MDR substrates. Compound 25 showed nanomolar antiproliferative potency. It severely disrupts the microtubule network in cells and arrests cells at the G2/M cell-cycle phase, thus confirming tubulin targeting. 25 triggered apoptotic cell death, and induced autophagy. Docking studies suggest binding in a distinct way to the colchicine site. These compounds are promising new antitumor agents acting on tubulin.
- González, Myriam,Ovejero-Sánchez, María,Vicente-Blázquez, Alba,Medarde, Manuel,González-Sarmiento, Rogelio,Peláez, Rafael
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p. 1029 - 1047
(2021/06/16)
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- Method of preparing Quinoline-5,8-dione derivatives for TGase 2 inhibitor
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I Is -5,8- of the quinoline, dione derivative compound. of Formula I, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein the compound of Formula, TGase 2 has, inhibitory effects TGase 2, and thus the pharmaceutical composition may be useful for preventing or treating disorders or diseases mediated by TGase 2 or inhibiting. (by machine translation)
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Paragraph 0311; 0315-0317
(2020/04/28)
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- Quinoline-5,8-dione derivatives for TGase 2 inhibitor, and the pharmaceutical composition comprising the same
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The present invention relates to a quinolin-5,8-dione derivative compound represented by chemical formula I, an optical isomer thereof or a pharmaceutically acceptable salt thereof. The compound represented by chemical formula I of the present invention has a TGase 2 inhibitory effect, and the pharmaceutical composition comprising the same can be usefully used for preventing or treating disorders or diseases mediated by TGase 2 or response to TGase 2 inhibition.COPYRIGHT KIPO 2020
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Paragraph 0186; 0190-0192
(2019/10/29)
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- Synthesis method of 2,4,5-trimethoxybenzeneamine
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The invention discloses a synthesis method of 2,4,5-trimethoxybenzeneamine, and especially uses a palladium-carbon catalyst to synthesize 2,4,5-trimethoxybenzeneamine. The method is characterized in that a reaction mixture and hydrogen are contacted to fo
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Paragraph 0026-0030; 0031-0038; 0039-0052
(2018/07/30)
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- 2-Aroylquinoline-5,8-diones as potent anticancer agents displaying tubulin and heat shock protein 90 (HSP90) inhibition
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This study reports the synthesis of a series of 2-aroylquinoline-5,8-diones (11-23) on the basis of scaffold hopping. The presence of a methoxy group at C6 assists the highly regioselective incorporation with various amines, and simplifies the structural
- Nepali, Kunal,Kumar, Sunil,Huang, Hsiang-Ling,Kuo, Fei-Chiao,Lee, Cheng-Hsin,Kuo, Ching-Chuan,Yeh, Teng-Kuang,Li, Yu-Hsuan,Chang, Jang-Yang,Liou, Jing-Ping,Lee, Hsueh-Yun
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p. 716 - 723
(2016/01/12)
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- Total synthesis of the antitumor antibiotic (±)-streptonigrin: First- and second-generation routes for de novo pyridine formation using ring-closing metathesis
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The total synthesis of (±)-streptonigrin, a potent tetracyclic aminoquinoline-5,8-dione antitumor antibiotic that reached phase II clinical trials in the 1970s, is described. Two routes to construct a key pentasubstituted pyridine fragment are depicted, both relying on ring-closing metathesis but differing in the substitution and complexity of the precursor to cyclization. Both routes are short and high yielding, with the second-generation approach ultimately furnishing (±)-streptonigrin in 14 linear steps and 11% overall yield from inexpensive ethyl glyoxalate. This synthesis will allow for the design and creation of druglike late-stage natural product analogues to address pharmacological limitations. Furthermore, assessment of a number of chiral ligands in a challenging asymmetric Suzuki-Miyaura cross-coupling reaction has enabled enantioenriched (up to 42% ee) synthetic streptonigrin intermediates to be prepared for the first time.
- Donohoe, Timothy J.,Jones, Christopher R.,Kornahrens, Anne F.,Barbosa, Luiz C. A.,Walport, Louise J.,Tatton, Matthew R.,O'Hagan, Michael,Rathi, Akshat H.,Baker, David B.
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p. 12338 - 12350
(2014/01/17)
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- Total synthesis of (±)-streptonigrin: De novo construction of a pentasubstituted pyridine using ring-closing metathesis
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The synthesis of the potent antitumor agent (±)-streptonigrin has been achieved in 14 linear steps and 11% overall yield from ethyl glyoxalate. The synthesis features a challenging ring-closing metathesis reaction, followed by elimination and aromatization, to furnish a key pentasubstituted pyridine fragment.
- Donohoe, Timothy J.,Jones, Christopher R.,Barbosa, Luiz C. A.
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supporting information; experimental part
p. 16418 - 16421
(2011/11/29)
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- Synthesis of carbon-11-labeled casimiroin analogues as new potential PET agents for imaging of quinone reductase 2 and aromatase expression in breast cancer
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Carbon-11-labeled casimiroin analogues were first designed and synthesized as new potential PET agents for imaging of quinone reductase (QR) 2 and aromatase expression in breast cancer. [11C]casimiroin (6-[ 11C]methoxy-9-methyl-[1,3]dioxolo[4,5-h]quinolin-8(9H)-one, [ 11C]11) and its carbon-11-labeled analogues 5,6,8-trimethoxy-1-[ 11C]methyl-4-methylquinolin-2(1H)-one ([11C]17), 8-methoxy-1-[11C]methyl-4-methylquinolin-2(1H)-one ([ 11C]21a), 6,8-dimethoxy-1-[11C]methyl-4-methylquinolin- 2(1H)-one ([11C]21b), and 5,8-dimethoxy-1-[11C]methyl-4- methylquinolin-2(1H)-one ([11C]21c), were prepared from their corresponding precursors with [11C]methyl triflate ([ 11C]CH3OTf) under basic conditions (NaH) through either O- or N-[11C]methylation and isolated by semi-preparative HPLC method in 40-50% radiochemical yields decay corrected to end of bombardment (EOB), based on [11C]CO2, and 111-185 GBq/μmol specific activity at the end of synthesis (EOS).
- Wang, Min,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Hutchins, Gary D.,Zheng, Qi-Huang
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experimental part
p. 967 - 973
(2010/10/05)
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- Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities
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An efficient method has been developed to synthesize casimiroin (1), a component of the edible fruit of Casimiroa edulis, on a multigram scale in good overall yield. The route was versatile enough to provide an array of compound 1 analogues that were evaluated as QR2 and aromatase inhibitors. In addition, X-ray crystallography studies of QR2 in complex with compound 1 and one of its more potent analogues has provided insight into the mechanism of action of this new series of QR2 inhibitors. The initial biological investigations suggest that compound 1 and its analogues merit further investigation as potential chemopreventive or chemotherapeutic agents.
- Maiti, Arup,Reddy, P. V. Narasimha,Sturdy, Megan,Marler, Laura,Pegan, Scott D.,Mesecar, Andrew D.,Pezzuto, John M.,Cushman, Mark
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experimental part
p. 1873 - 1884
(2009/12/31)
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- Total synthesis of streptonigrone
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(Chemical Equation Presented) A total synthesis of streptonigrone, 1, is described, which incorporates a one-step synthesis of substituted pyridones devised in our laboratory. Other aspects of the synthesis that differentiate the present approach from previous ones are the use of a Conrad-Limpach reaction, rather than the customary Friedlaender methodology, to assemble the quinoline segment of 1, and the implementation of an anionic sequence for the functionalization of a key pyridone intermediate.
- Chan, Bryan K.,Ciufolini, Marco A.
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p. 8489 - 8495
(2008/02/13)
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- Synthesis of benzothiazoles via ipso substitution of ortho- methoxythiobenzamides
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An efficient route to the synthesis of benzothiazoles from orthoo-methoxythiobenzamides via the ipso substitution of an aromatic methoxy group is presented, and the mechanism of the Jacobson synthesis of benzothiazoles is further investigated.
- Downer, Nadale K.,Jackson, Yvette A.
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p. 3039 - 3043
(2007/10/03)
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- Design, synthesis, and evaluation of a radicicol and geldanamycin chimera, radamide
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(Chemical equation presented) A chimera composed of the natural products radicicol and geldanamycin has been prepared through an amide linkage connecting the resorcinol moiety of radicicol to the quinone ring of geldanamycin. The inhibitory activity of th
- Clevenger, Randell C.,Blagg, Brian S. J.
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p. 4459 - 4462
(2007/10/03)
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- 2, 4- DI (PHENYLAMINO) PYRIMIDINES USEFUL IN THE TREATMENT OF NEOPLASTIC DISEASES, INFLAMMATORY AND IMMUNE SYSTEM DISORDERS
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Novel pyrimidine derivatives of formula (I), to processes for their production, their use as pharmaceuticals in the treatment of neoplastic diseases, inflammatory and immune system disorders and to pharmaceutical compositions comprising them.
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Page 138; 144
(2010/02/08)
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- Positive allosteric modulators of the nicotinic acetylcholine receptor
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The invention provides compounds of Formula I: These compounds may be in the form of pharmaceutical salts or compositions, may be in pure enantiomeric form or racemic mixtures, and are useful in pharmaceuticals used to treat diseases or conditions in which α7 nAChR is known to be involved.
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- Multisubstituted 1-hydroxy-9-acridones with anticancer activity
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The present invention provides a compound having the structure: STR1 The present invention also provides a method for synthesizing a compound having the above-identified structure as well as the intermediate compounds produced according to that method. The present invention further provides a pharmaceutical composition comprising the above compounds. Lastly, the present invention provides a method of inhibiting growth of tumor cells.
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- N-substituted 2,4-dialkoxy benzenesulfonamides and pharmaceutical compositions
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The invention relates to new N-substituted benzenesulfonamides, the process for their preparation and their use. The compounds according to the invention correspond to the general formula (I): STR1 in which: n and m have values from 0 to 4; R3 and R4 represent in particular a lower alkyl radical; R1 and R2 represent in particular hydrogen atoms, linear or branched alkyl groups having from 1 to 4 carbon atoms; R5 represents particularly a hydrogen atom, a halogen, the NO2, NH2, or CF3 group; R6 and R7 represent in particular a hydrogen atom, an alkyl radical of 1 to 6 carbon atoms. The invention is useful in the preparation of tranquilizing or anxiolytic medicines.
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