- Substituted diarylurea derivative as well as preparation method and application thereof
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The invention relates to a substituted diarylurea derivative as well as preparation and application thereof. Specifically, the invention discloses a compound with a formula (I) or an optical isomer, a cis-trans-isomer or a pharmaceutically acceptable salt thereof, and a preparation method thereof, wherein the definition of each substituent group in the general formula is described in the specification and claims. The invention further discloses a composition containing the compound and application of the composition. The compound disclosed by the invention has excellent anti-cancer activity on HepG2 liver cancer cells, MGC 803 gastric cancer cells, MCF 7 breast cancer cells and the like, and has a good inhibition effect on the growth of human umbilical vein endothelial cells (HUVEC).
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Paragraph 0157-0158; 0160
(2021/08/19)
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- Microballs Containing Ni(0)Pd(0) Nanoparticles for Highly Selective Micellar Catalysis in Water
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Both Ni(0) complexes and nanoparticles (NPs) are unstable in water, which poses a significant hindrance to their application in aqueous synthetic catalysis. To overcome these barriers, ligated Ni(0) nanoparticles (diameter 1 nm) containing a minimum amount of Pd(0) in the microballs formed of amphiphile PS-750-M are developed and applied in the highly selective carbamate cleavage. Selectivity and functional group tolerance are thoroughly investigated. Control experiments revealed the importance of an individual component of the nanocatalyst. Use of our proline-based amphiphile PS-750-M is critical for achieving microball architecture, the stability of nanoparticles, and desired catalytic activity. Once formed, microballs can be isolated and stored at ambient temperature. Catalyst is thoroughly characterized by X-ray photoelectron spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, thermogravimetric analysis, infrared, and cyclic voltammetry. For selective catalysis, zero oxidation state of both Ni and Pd is crucial. On the basis of catalyst characterization and control experiments, the plausible reaction mechanism is proposed.
- Bihani, Manisha,Bora, Pranjal P.,Nachtegaal, Maarten,Jasinski, Jacek B.,Plummer, Scott,Gallou, Fabrice,Handa, Sachin
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p. 7520 - 7526
(2019/08/15)
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- A preparation method of the m-aminophenol
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The invention belongs to organic synthesis and chemical raw material preparation technology field, in particular to m-aminophenol of preparation method and its intermediate, m-aminophenol of the preparation method, comprises the steps of: (1) dinitrobenzene substituted with benzyl alcohol produced by the reaction of 1 - benzyloxy - 3 - nitrophenyl; (2) 1 - benzyloxy - 3 - nitrobenzene for filtering of the alkaline inorganic salt the substitution reaction of the liquid catalytic hydrogenation generating m-aminophenol; or, 1 - benzyloxy - 3 - nitrophenyl replace alkaline inorganic salt and filtered out of the reaction solution after the recovery of the solvent is soluble in the organic solvent and then re-dissolved in the solution of the, generated by the catalytic hydrogenation of m-aminophenol. Without intermediate separation and purification processes, direct catalytic hydrogenation "one-pot" process for preparing m-aminophenol; then the re-crystallization or reduced pressure distillation purification of m-aminophenol. The method is simple, mild reaction conditions, equipment strength requirement is low, not generate intermediate waste, environment-friendly, high yield, is suitable for industrial generation.
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- Novel Deazaflavin Analogues Potently Inhibited Tyrosyl DNA Phosphodiesterase 2 (TDP2) and Strongly Sensitized Cancer Cells toward Treatment with Topoisomerase II (TOP2) Poison Etoposide
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Topoisomerase II (TOP2) poisons as anticancer drugs work by trapping TOP2 cleavage complexes (TOP2cc) to generate DNA damage. Repair of such damage by tyrosyl DNA phosphodiesterase 2 (TDP2) could render cancer cells resistant to TOP2 poisons. Inhibiting TDP2, thus, represents an attractive mechanism-based chemosensitization approach. Currently known TDP2 inhibitors lack cellular potency and/or permeability. We report herein two novel subtypes of the deazaflavin TDP2 inhibitor core. By introducing an additional phenyl ring to the N-10 phenyl ring (subtype 11) or to the N-3 site of the deazaflavin scaffold (subtype 12), we have generated novel analogues with considerably improved biochemical potency and/or permeability. Importantly, many analogues of both subtypes, particularly compounds 11a, 11e, 12a, 12b, and 12h, exhibited much stronger cancer cell sensitizing effect than the best previous analogue 4a toward the treatment with etoposide, suggesting that these analogues could serve as effective cellular probes.
- Kankanala, Jayakanth,Ribeiro, Carlos J. A.,Kiselev, Evgeny,Ravji, Azhar,Williams, Jessica,Xie, Jiashu,Aihara, Hideki,Pommier, Yves,Wang, Zhengqiang
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supporting information
p. 4669 - 4682
(2019/05/17)
-
- Enantioselective Visible-Light-Mediated Formation of 3-Cyclopropylquinolones by Triplet-Sensitized Deracemization
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3-Allyl-substituted quinolones undergo a triplet-sensitized di-π-methane rearrangement reaction to the corresponding 3-cyclopropylquinolones upon irradiation with visible light (λ=420 nm). A chiral hydrogen-bonding sensitizer (10 mol %) was shown to promote the reaction enantioselectively (88–96 % yield, 32–55 % ee). Surprisingly, it was found that the enantiodifferentiation does not occur at the state of initial product formation but that it is the result of a deracemization event. The individual parameters that control the distribution of enantiomers in the photostationary state have been identified.
- Tr?ster, Andreas,Bauer, Andreas,Jandl, Christian,Bach, Thorsten
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supporting information
p. 3538 - 3541
(2019/02/01)
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- Quinolone-based compounds, formulations, and uses thereof
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Provided herein are quinolone-based compounds that can be used for treatment and/or prevention of malaria and formulations thereof. Also provided herein are methods of treating and/or preventing malaria in a subject by administering a quinolone-based compound or formulation thereof provided herein.
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Page/Page column 103; 104
(2018/07/02)
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- AMINATION AND HYDROXYLATION OF ARYLMETAL COMPOUNDS
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In one aspect, the present disclosure provides methods of preparing a primary or secondary amine and hydroxylated aromatic compounds. In some embodiments, the aromatic compound may be unsubstituted, substituted, or contain one or more heteroatoms within the rings of the aromatic compound. The methods described herein may be carried out without the need for transition metal catalysts or harsh reaction conditions.
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Paragraph 0098; 0134; 0135; 0169
(2018/03/25)
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- Dibenzothiophene Sulfoximine as an NH3 Surrogate in the Synthesis of Primary Amines by Copper-Catalyzed C?X and C?H Bond Amination
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Readily accessible dibenzothiophene sulfoximine is an NH3 surrogate allowing the preparation of free anilines by copper-catalyzed cross-coupling reactions with aryl iodides or amides followed by radical S?N bond cleavage. The one-pot/two-step r
- Li, Zhen,Yu, Hao,Bolm, Carsten
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supporting information
p. 9532 - 9535
(2017/08/01)
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- Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)-N-phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors
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Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such as cell cycle regulation, autophagy, immune and inflammatory responses. Dysregulation of SIRT2 was considered as a main aspect contributing to several human diseases, including cancer. Development of new potent and selective SIRT2 inhibitors is currently desirable, which may provide a new strategy for treatment of related diseases. Herein, a structure-based optimization approach led to new 2-((4,6-dimethylpyrimidin-2-yl)thio)-N-phenylacetamide derivatives as SIRT2 inhibitors. SAR analyses with new synthesized derivatives revealed a number of new potent SIRT2 inhibitors, among which 28e is the most potent inhibitor with an IC50 value of 42?nM. The selectivity analyses found that 28e has a very good selectivity to SIRT2 over SIRT1 and SIRT3. In cellular assays, 28e showed a potent ability to inhibit human breast cancer cell line MCF-7 and increase the acetylation of α-tubulin in a dose-dependent manner. This study will aid further efforts to develop highly potent and selective SIRT2 inhibitors for the treatment of cancer and other related diseases.
- Yang, Lingling,Ma, Xiaobo,Yuan, Chen,He, Yanying,Li, Ling,Fang, Sha,Xia, Wei,He, Tao,Qian, Shan,Xu, Zhihong,Li, Guobo,Wang, Zhouyu
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p. 230 - 241
(2017/04/19)
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- Novel SIRT2 protein inhibitor and usage thereof in pharmacy
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The invention discloses a compound or salt, crystallographic form and solvate compounds of the compound acceptable in pharmacy, and the compound and the salt, crystallographic form, solvate compounds of the compound are shown as formula I, wherein X is selected from the formulas (please see the specifications for the formula); R1 is selected from aryl or ceteroary or substituted aryl or substituted ceteroary or from the formula (please see the specifications for the formula); R2 is selected from the formulas (please see the specifications for the formula); and R3 is selected from halogen or C1-C4 alkyl or C1-C4 alkoxy. The novel compound shown in formula I has the advantages that not only is good inhibitory activity achieved to SIRT2, but also the inhibiting effect is achieved to the tumor, and the novel compound has good pharmaceutical potentiality and provides a novel potential choice for the clinical medicament.
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- Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds
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Arylmetals are highly valuable carbon nucleophiles that are readily and inexpensively prepared from aryl halides or arenes and widely used on both laboratory and industrial scales to react directly with a wide range of electrophiles. Although C-C bond formation has been a staple of organic synthesis, the direct transfer of primary amino (-NH2) and hydroxyl (-OH) groups to arylmetals in a scalable and environmentally friendly fashion remains a formidable synthetic challenge because of the absence of suitable heteroatom-transfer reagents. Here, we demonstrate the use of bench-stable N-H and N-alkyl oxaziridines derived from readily available terpenoid scaffolds as efficient multifunctional reagents for the direct primary amination and hydroxylation of structurally diverse aryl- and heteroarylmetals. This practical and scalable method provides one-step synthetic access to primary anilines and phenols at low temperature and avoids the use of transition-metal catalysts, ligands and additives, nitrogen-protecting groups, excess reagents and harsh workup conditions.
- Gao, Hongyin,Zhou, Zhe,Kwon, Doo-Hyun,Coombs, James,Jones, Steven,Behnke, Nicole Erin,Ess, Daniel H.,Kürti, László
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p. 681 - 688
(2017/06/30)
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- Thermally Induced Denitrogenative Annulation for the Synthesis of Dihydroquinolinimines and Chroman-4-imines
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A rapid growth in synthetic methods for the preparation of diverse organic molecules using N-sulfonyl-1,2,3-triazoles is of great interest in organic synthesis. Transition metals are generally used to activate the α-imino diazo intermediates. Metal-free methods have not been studied in detail, but can be a good complement to transition metal catalysis in the mild reaction conditions. We herein report a novel method for the preparation of 2,3-dihydroquinolin-4-imine and chroman-4-imine analogs from their corresponding N-sulfonyl-1,2,3-triazoles in the absence of metal catalysts. To achieve intramolecular annulation, the introduction of an electron-donating group is required at the meta position of N-sulfonyl-1,2,3-triazole methyl anilines. The inclusion of tailored substituents on the aniline moieties and nitrogen atoms enhances the nucleophilicity of the phenyl π-electrons, thus allowing them to undergo a Friedel-Crafts-type reaction with the highly electrophilic ketenimines. This metal-free method was carefully optimized to generate a variety of dihydroquinolin-4-imines and chroman-4-imines in moderate-to-good yields.
- Chou, Chih-Hung,Chen, Ying-Yu,Rajagopal, Basker,Tu, Hsiu-Chung,Chen, Kuan-Lin,Wang, Sheng-Fu,Liang, Chien-Fu,Tyan, Yu-Chang,Lin, Po-Chiao
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supporting information
p. 757 - 765
(2016/03/09)
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- ICI 56,780 optimization: Structure-activity relationship studies of 7-(2-phenoxyethoxy)-4(1H)-quinolones with antimalarial activity
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Though malaria mortality rates are down 48% globally since 2000, reported occurrences of resistance against current therapeutics threaten to reverse that progress. Recently, antimalarials that were once considered unsuitable therapeutic agents have been revisited to improve physicochemical properties and efficacy required for selection as a drug candidate. One such compound is 4(1H)-quinolone ICI 56,780, which is known to be a causal prophylactic that also displays blood schizonticidal activity against P. berghei. Rapid induction of parasite resistance, however, stalled its further development. We have completed a full structure-activity relationship study on 4(1H)-quinolones, focusing on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2 and TM90-C2B, as well as the improvement of microsomal stability. These studies revealed several frontrunner compounds with superb in vivo antimalarial activity. The best compounds were found to be curative with all mice surviving a Plasmodium berghei infection after 30 days.
- Maignan, Jordany R.,Lichorowic, Cynthia L.,Giarrusso, James,Blake, Lynn D.,Casandra, Debora,Mutka, Tina S.,LaCrue, Alexis N.,Burrows, Jeremy N.,Willis, Paul A.,Kyle, Dennis E.,Manetsch, Roman
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p. 6943 - 6960
(2016/08/05)
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- Safe and Selective Nitro Group Reductions Catalyzed by Sustainable and Recyclable Fe/ppm Pd Nanoparticles in Water at Room Temperature
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As a result of a unique synergy between ligand-free Fe/ppm Pd nanoparticles and PEG-containing designer surfactants, a facile and selective reduction of nitro-containing aromatics and heteroaromatics can be effected in water at room temperature in the presence of NaBH4. This new nanotechnology involves low catalyst loadings, is highly chemoselective, and tolerates a wide variety of functional groups. The process, which includes recycling of the entire aqueous medium, offers a general, environmentally responsible, and notably safe approach to highly valued reductions of nitro-containing compounds.
- Feng, Jie,Handa, Sachin,Gallou, Fabrice,Lipshutz, Bruce H.
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supporting information
p. 8979 - 8983
(2016/07/26)
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- [Cp?RhCl2]2-catalyzed alkyne hydroamination to 1,2-dihydroquinolines
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[Cp?RhCl2]2 catalyzes the formation of 1,2-dihydroquinolines from the reaction of two terminal alkynes and an aniline. This reaction is believed to proceed via an alkyne hydroamination followed by an alkyne insertion.
- Kumaran, Elumalai,Leong, Weng Kee
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p. 1779 - 1782
(2015/05/20)
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- Potent targeting of the STAT3 protein in brain cancer stem cells: A promising route for treating glioblastoma
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The STAT3 gene is abnormally active in glioblastoma (GBM) and is a critically important mediator of tumor growth and therapeutic resistance in GBM. Thus, for poorly treated brain cancers such as gliomas, astrocytomas, and glioblastomas, which harbor constitutively activated STAT3, a STAT3-targeting therapeutic will be of significant importance. Herein, we report a most potent, small molecule, nonphosphorylated STAT3 inhibitor, 31 (SH-4-54) that strongly binds to STAT3 protein (KD = 300 nM). Inhibitor 31 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. Moreover, in vivo, 31 exhibited blood-brain barrier permeability, potently controlled glioma tumor growth, and inhibited pSTAT3 in vivo. This work, for the first time, demonstrates the power of STAT3 inhibitors for the treatment of BTSCs and validates the therapeutic efficacy of a STAT3 inhibitor for GBM clinical application.
- Haftchenary, Sina,Luchman, H. Artee,Jouk, Andriana O.,Veloso, Anthony J.,Page, Brent D. G.,Cheng, Xin Ran,Dawson, Sean S.,Grinshtein, Natalie,Shahani, Vijay M.,Kerman, Kagan,Kaplan, David R.,Griffin, Carly,Aman, Ahmed M.,Al-Awar, Rima,Weiss, Samuel,Gunning, Patrick T.
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supporting information
p. 1102 - 1107
(2013/12/04)
-
- Synthesis and biological evaluation of direct thrombin inhibitors bearing 4-(piperidin-1-yl)pyridine at the P1 position with potent anticoagulant activity
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The design and synthesis of a new class of nonpeptide direct thrombin inhibitors, built on the structure of 1-(pyridin-4-yl)piperidine-4-carboxamide, are described. Starting from a strongly basic 1-amidinopiperidine derivative (6) showing poor thrombin (fIIa) and factor Xa (fXa) inhibition activities, anti-fIIa activity and artificial membrane permeability were considerably improved by optimizing the basic P1 and the X-substituted phenyl P4 binding moieties. Structure-activity relationship studies, usefully complemented with molecular modeling results, led us to identify compound 13b, which showed excellent fIIa inhibition (Ki = 6 nM), weak anti-Xa activity (K i = 5.64 μM), and remarkable selectivity over other serine proteases (e.g., trypsin). Compound 13b showed in vitro anticoagulant activity in the low micromolar range and significant membrane permeability. In mice (ex vivo), 13b demonstrated anticoagulant effects at 2 h after oral dosing (100 mg·kg-1), with a significant 43% prolongation of the activated partial thromboplastin time (aPTT), over controls (P 0.05).
- De Candia, Modesto,Fiorella, Filomena,Lopopolo, Gianfranco,Carotti, Andrea,Romano, Maria Rosaria,Lograno, Marcello Diego,Martel, Sophie,Carrupt, Pierre-Alain,Belviso, Benny D.,Caliandro, Rocco,Altomare, Cosimo
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p. 8696 - 8711
(2013/12/04)
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- NEW SALICYLIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF
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The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds; or a pharmaceutically acceptable salt, solvate or prodrug thereof.
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Page/Page column 54; 65
(2014/01/07)
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- Design, synthesis, and anticonvulsant activity evaluation of 4-(3-Alkoxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-ones
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A series of 4-(3-alkoxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-ones were synthesized using the appropriate synthetic route and evaluated experimentally in the maximal electroshock test; their neurotoxicities were evaluated by the rotarod neurotoxicity test. The structures of these compounds were confirmed by IR, MS, 1H-NMR, and elementary analysis. All target compounds exhibited anticonvulsant activity to varying degrees in the maximal electroshock test. 4-(3-Benzyloxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one (4i) was the most promising compound with an ED50 value of 30.5 mg/kg and a protective index (PI) of 18.63, showing a higher safety than the standard carbamazepine (PI = 6.45). In addition, the potency of compound 4i against seizures induced by pentylenetetrazole and 3-mercaptopropionic acid suggested its broad-spectrum activity, and the mechanisms of action including inhibition of voltage-gated ion channels and modulation of GABAergic activity might be involved in its anticonvulsant activity. Copyright
- Shu, Bing,Zheng, Yan,Wang, Shi-Ben,Deng, Xian-Qing,Quan, Zhe-Shan
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p. 127 - 133
(2013/04/10)
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- Synthesis and anti-proliferative activity of substituted- anilinoquinazolines and its relation to EGFR inhibition
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4-Anilinoquinazoline is a privileged scaffold in developing small molecule inhibitors of tyrosine kinases (TK) especially epidermal growth factor receptor (EGFR). 2 series belonging to 3'-substituted-4-anilinoquinazoline scaffold were synthesized and screened in vitro on isolated and a breast cancer cell line. The research aims at exploring the activity of compounds having diverse substituents at 3' position of the aniline moiety. Generally, the meta-substituted-anilinoquinazolines exhibited significant inhibitory activity against isolated enzyme as well as MCF-7 cancer cell line. For instance, compound 10b inhibited >99% of EGFR activities at 10 M concentration. 6 of the tested compounds exhibited range of anti-proliferative activity below 10 M potency. In particular, compounds 6e and 10b displayed the highest activity among the tested compounds with IC50 values equal to 8.6 and 4.84 M, respectively. Structure-based tools were utilized to rationalize EGFR-TK binding of compound 10b since it is the most active compound in the enzyme inhibition test. Georg Thieme Verlag KG Stuttgart.New York.
- El Ella,Saleh,Hassan,Hamdy,El-Araby,Abouzid
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p. 360 - 366
(2012/10/29)
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- Synthesis of novel 5-substituted isoxazole-3-carboxamide derivatives and cytotoxicity studies on lung cancer cell line
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A series of novel 5-substituted isoxazole-3-carboxamide derivatives 6 have been prepared by coupling of 5-substituted isoxazole-3-carboxylic acids 3 with substituted-3-benzyloxyaniline 5 using DCC/HOBT as coupling agent. The products 6 have been evaluated for cytotoxicity on A549 lung cancer cell line and compounds 6a, 6b, 6e, 6j are found to show moderate proliferative activity and low cytotoxicity.
- Veeraswamy,Kurumurthy,Santhosh Kumar,Sambasiva Rao,Thelakkat, Kavya,Kotamraju, Srigiridhar,Narsaiah
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p. 1369 - 1375
(2012/11/13)
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- NOVEL CATALYSTS
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The present invention provides novel compounds and ligands that are useful in transition metal catalyzed cross-coupling reactions. For example, the compounds and ligands of the present invention are useful in palladium or gold catalyzed cross-coupling reactions.
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Page/Page column 61-62
(2012/06/01)
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- Synthesis, labelling and evaluation of hydantoin-substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the N-methyl- d -aspartate receptor
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The N-methyl- d-aspartate (NMDA) receptor as a type of ionotropic glutamatergic receptors is essential for physiological processes such as learning, memory and synaptic plasticity. A glutamate-induced overactivation of these receptors, accompanied by increased intracellular calcium concentration, causes cell injury and leads to a large number of acute or chronic neurological disorders, such as stroke, trauma, Parkinson's disease and Alzheimer's disease. In an attempt to visualise the glutamatergic neurotransmission in vivo with positron emission tomography, novel fluoroethoxy- and methoxy-substituted reference compounds based on the lead structure of a hydantoin-substituted indole-2-carboxylic acid were synthesised. The affinities towards the glycine binding site of the NMDA receptor showed Ki values between 322 and 11 nM and the lipophilicities ranged from logD values of 1.51 to 2.53. On the basis of these results, precursor compounds were synthesised containing a phenolic hydroxy moiety to obtain the radiolabelled ligands through an alkylation reaction. Radiosynthesis was achieved by labelling the precursor ethyl 4,6-dichloro-3-((3-(4-hydroxyphenyl)-2,4-dioxoimidazolidin-1-yl)methyl)- indole-2-carboxylate with 2-[18F]fluoroethyl tosylate or [ 11C]methyl iodide and subsequent cleavage of the ethyl ester moiety. This gave the final products in overall decay-corrected radiochemical yields of 5-7% and 6-9% and specific activities of 24-67 GBq/μmol and 8-26 GBq/μmol, respectively. Copyright
- Bauman,Piel,Hoehnemann,Krauss,Jansen,Solbach,Dannhardt,Roesch
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experimental part
p. 645 - 656
(2012/01/06)
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- A P,N-Ligand for palladium-catalyzed ammonia arylation: Coupling of deactivated aryl chlorides, chemoselective arylations, and room temperature reactions
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(Figure Presented) Amazing ammonia: A new air-stable P,N-ligand (Mor-DalPhos) is reported that enables the palladium-catalyzed crosscoupling of ammonia to a variety of aryl chloride and aryl tosylate substrates with high chemoselectivity and, for the first time, at room temperature (see scheme; Ad = adamantyl, Ts=para-toluenesulfonyl).
- Lundgren, Rylan J.,Peters, Brendan D.,Alsabeh, Pamela G.,Stradiotto, Mark
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supporting information; experimental part
p. 4071 - 4074
(2010/07/05)
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- PROCESS FOR PRODUCING AROMATIC AMINE HAVING ARALKYLOXY OR HETEROARALKYLOXY GROUP
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There is provided a process for producing an aromatic amine compound having an aralkyloxy or heteroaralkyloxy group, in which an aromatic nitro compound having an aralkyloxy or heteroaralkyloxy group is reacted with hydrogen under mild conditions in accordance with a simple procedure while preventing the removal of aralkyl or heteroaralkyl group and keeping stable the other substituents on the aryl group or heteroaryl group so that the substituent does not take part in the reaction, to selectively reduce only the nitro group. The present invention is directed to a process for producing an aromatic amine compound which comprises reacting an aromatic nitro compound represented by the general formula (1): wherein Ar represents an aryl group or heteroaryl group which may have a substituent, and Z represents a divalent aromatic group which may have a substituent, with hydrogen in the presence of a metal catalyst to obtain an aromatic amine compound represented by the general formula (2): wherein Ar and Z have the meaning as defined above.
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Page/Page column 6
(2009/12/07)
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- Design, synthesis, and anti-HCV activity of thiourea compounds
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A series of thiourea derivatives were synthesized and their antiviral activity was evaluated in a cell-based HCV subgenomic replicon assay. SAR studies revealed that the chain length and the position of the alkyl linker largely influenced the in vitro anti-HCV activity of this class of potent antiviral agents. Among this series of compounds synthesized, the thiourea derivative with a six-carbon alkyl linker at the meta-position of the central phenyl ring (10) was identified as the most potent anti-HCV inhibitor (EC50 = 0.047 μM) with a selectivity index of 596.
- Kang, Iou-Jiun,Wang, Li-Wen,Lee, Chung-Chi,Lee, Yen-Chun,Chao, Yu-Sheng,Hsu, Tsu-An,Chern, Jyh-Haur
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scheme or table
p. 1950 - 1955
(2009/11/30)
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- Fluorinated benzyloxyphenyl piperidine-4-carboxamides with dual function against thrombosis: Inhibitors of factor xa and platelet aggregation
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A series of benzyloxy anilides of nipecotic (5, 6) and isonipecotic (7, 8) acids were synthesized and assayed in vitro as inhibitors of ADP-induced platelet aggregation and the blood coagulation enzymes factor Xa (FXa) and thrombin (Flla). An exploration of effects of the amidine group attached at the piperidine nitrogen, position and substitution (F, phenyl) of the benzyloxy group, and addition of fluorine/s on the second (distal) phenyl ring, led us to single out some promising isonipecotamide derivatives 7. Addition of meta-F and para-CF3 on the distal phenyl ring resulted in a 6-to-18-fold enhancement of the FXa potency and in 2-to- 4-fold increase of the antiplatelet potency, the last depending to a large extent upon lipophilicity. Two congeners of N-{[3-(1,1′-biphenyl-4-yl)methoxy]phenyljpiperidine-4-carboxamide (7m and 7p) proved to be potent FXa-selective inhibitors (Ki = 130 and 57 nM, respectively) and antiplatelet agents and were identified as leads for developing new dual function antithrombotic drugs.
- De Candia, Modesto,Liantonio, Francesco,Carotti, Andrea,De Cristofaro, Raimondo,Altomare, Cosimo
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experimental part
p. 1018 - 1028
(2009/12/24)
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- SOLUBLE EPOXIDE HYDROLASE INHIBITORS
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Disclosed are urea and thiourea compounds and compositions that inhibit soluble epoxide hydrolase (sEH), methods for preparing the compounds and compositions, and methods for treating patients with such compounds and compositions. The compounds, compositions, and methods are useful for treating a variety of sEH mediated diseases, including hypertensive, cardiovascular, inflammatory, and diabetic-related diseases.
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- Aromatic 2-chloroethyl urea derivatives and bioisosteres. Part 2: Cytocidal activity and effects on the nuclear translocation of thioredoxin-1, and the cell cycle progression
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Recently, a subset of N-phenyl-N′-(2-chloroethyl)ureas (CEU) was found abrogating the nuclear translocation of thioredoxin-1 and arresting the cell cycle in G0/G1 phase. Several derivatives were prepared to assess their effect on cell cycle progression and on the intracellular location of Trx-1. Compounds 1-20, 21-40, and 41-60 exhibited GI50 between 1 and 80 μM. Immunocytochemistry analysis showed compounds 4, 6, 8, 10, 11, 23, 24, 26-31, 34, 37, 41, 44, 46-51, 53, 56, and 57 inhibiting the nuclear translocation of Trx-1. Our results suggest that increasing the electrophilic character of these molecules might enhance the antiproliferative activity at the expense of the selectivity toward thioredoxin-1 and the G0/G1 phase arrest.
- Fortin, Jessica S.,Cote, Marie-France,Lacroix, Jacques,Petitclerc, Eric,C.-Gaudreault, Rene
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p. 7477 - 7488
(2008/12/22)
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- Selective palladium-catalyzed arylation of ammonia: Synthesis of anilines as well as symmetrical and unsymmetrical di- and triarylamines
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It is shown that by selection of an appropriate palladium/ligand system, temperature, concentration, and stoichiometry of reagents, ammonia may be selectively arylated to give either anilines, symmetrical di-, or triarylamines. Furthermore different aryl halides may be added sequentially to the reaction mixture, allowing the synthesis of unsymmetrical di- and triarylamines from aryl halides and ammonia in a one-pot protocol Copyright
- Surry, David S.,Buchwald, Stephen L.
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p. 10354 - 10355
(2008/03/13)
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- Fluorescent Dyes and Complexes
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A fluorescent dye comprising a xanthene-derived fluorophore having the formula (I) wherein R1, R2, R3, R4, R5 and R6 are independently selected from H, alkyl, alkoxy, alcohol, ether, alkenyl, alkenoxy, aryl, alkaryl, aralkyl and amido, except that R1, R4 and/or R5 is not H when bonded to Y, Y1 or Y2, respectively; X is either O? or S?; and at least one of Y, Y1, Y2, Y3, Y4 and Y5 is a group for covalently bonding the dye, optionally through. the use of a coupling agent, to a target molecule, and is otherwise H. The dye may be covalently attached to a target molecule to form a complex, and the dye and/or complex finds use in cell analysis techniques, particularly pH measurement and analysis of kinetics of migration.
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Page/Page column 8
(2008/06/13)
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- Highly chemoselective reduction using a Rh/C-Fe(OAc)2 system: Practical synthesis of functionalized indoles
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Here, we report a highly effective and chemoselective method of preparing substituted indoles from (E)-2-nitropyrrolidinostyrenes via hydrogenation in the presence of a rhodium catalyst doped by additives such as Ni(NO 3)2·6H2O, Fe(OAc)2 or Co(acac)3. These hydrogenation conditions may also be applied to other substrates. Aromatic nitro compounds and olefins can be selectively reduced in the presence of aromatic benzyl ethers, aromatic halides and aromatic aldehydes.
- Akao, Atsushi,Sato, Kimihiko,Nonoyama, Nobuaki,Mase, Toshiaki,Yasuda, Nobuyoshi
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p. 969 - 972
(2007/10/03)
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- SUBSTITUTED ARYLTHIOUREA DERIVATIVES USEFUL AS INHIBITORS OF VIRAL REPLICATION
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Substituted arylthiourea compounds of Formula I, and the pharmaceutically acceptable salts of such compounds, useful as antiviral agents, are provided herein. Certain substituted arylthioureas disclosed herein are potent and/ or selective inhibitors of viral replication, particularly Hepatitis C virus replication. Pharmaceutical compositions containing one or more substituted arylthiourea compounds and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Such pharmaceutical compositions may contain a substituted arylthiourea as the only active agent or may contain a combination of a substituted arylthiourea derivative and one or more other pharmaceutically active agents. Methods of treating Hepatitis C viral infections in mammals are also provided herein.
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Page/Page column 35-36
(2010/02/10)
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- PROCESS FOR PRODUCING INDOLOPYRROLOCARBAZOLE DERIVATIVE
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The present invention provides a process for industrially advantageously producing a compound represented by the formula (I): or a pharmaceutically acceptable salt thereof, which is useful as an anticancer agent, and also provides a catalyst used for hydrogenation reaction in the process.
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Page/Page column 45
(2010/02/11)
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- The Nucleophilic Ring-opening of N-Benzylquinuclidinium Bromide
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N-Benzylquinuclidinium bromide was ring opened by a series of heteronucleophiles, in the presence of cesium carbonate, to yield the corresponding N-benzyl-4-(2-hetero-ethyl)piperidines. The best yields were found with thiophenol (56%), phenol (55%), and benzimidazole (38%) as nucleophiles.
- Axelsson, Oskar,Peters, Dan
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p. 461 - 463
(2007/10/03)
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- REMOTE INTRAMOLECULAR FUNCTIONALIZATION OF ARYLNITRENIUM IONS: SYNTHESIS OF AMINO-DIHYDROPHENANTHRIDINES AND BENZOCHROMANS.
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4-Aminobenzochroman (6) and 3-amino-5-acetyl-5,6-dihydrophenanthridine (9) are synthesized by intramolecular trapping of the delocalized nitrenium ions from 3-azidobenzyl phenyl ether and 3-azido-N-benzylacetanilide, respectively.On the other hand, no cyclization product is obtained from 3-azidophenyl benzyl ether, possibly owing to an ortho-effect exerted by the oxygen atom ortho to the developing ?-aryl cation.
- Abramovitch, Rudolph A.,Cooper, Melanie M.,Jeyaraman, Ramasubbu,Rusek, Grzegorz
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p. 3705 - 3708
(2007/10/02)
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- SELECTIVE REDUCTION OF AROMATIC NITRO COMPOUNDS CONTAINING O- AND N-BENZYL GROUPS WITH HYDRAZINE AND RANEY NICKEL
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The selectivity in the catalytic reduction of aromatic nitro compounds containing O-benzyl, N-benzyl or chlorine with hydrazine and Raney nickel was studied.
- Yuste, Francisco,Saldana, Manuel,Walls, Fernando
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p. 147 - 148
(2007/10/02)
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