- Photoinduced intramolecular charge transfer to meta position of benzene ring in 6-aminophthalides
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Substitution of non-fluorescent phthalide (Pd) with amino group at meta (6) position in relation to the electron-accepting part of the lactone ring completely changes Pd photophysics: a new long-wavelength absorption band arises and the molecule becomes highly fluorescent. The experimental data and the analysis of vertical electronic transitions with TDDFT method indicate that the first absorption band in 6-aminophthalides (6-APds) comprises a single CT transition to the S1 state. Almost equal absorption and emission transition dipole moments indicate that S0 ? S1 transition in all 6-APds is not affected by any mixing with other electronic states, the excited-state vibrational relaxation is not accompanied by significant conformational changes and the Stokes shifts reflect mainly solvation energetics of these molecules. Excited state dipole moments obtained from solvatochromic plots and from CASSCF calculations confirm large charge displacement from amino group towards the meta position of the benzene ring upon excitation of 6-APds to S1 state. Long fluorescence lifetimes and high fluorescence quantum yields demonstrate efficient and stable excited state charge separation in 6-APds. Taken together with sensitivity of 6-APds to polarity and proticity of the environment these properties make them good candidates for fluorescent probes of long-time scale molecular dynamics. The Owner Societies 2005.
- Karpiuk, Jerzy,Svartsov, Yuriy N.,Nowacki, Jacek
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Read Online
- Selective Reduction of Nitroarenes to Arylamines by the Cooperative Action of Methylhydrazine and a Tris(N-heterocyclic thioamidate) Cobalt(III) Complex
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We report an efficient catalytic protocol that chemoselectively reduces nitroarenes to arylamines, by using methylhydrazine as a reducing agent in combination with the easily synthesized and robust catalyst tris(N-heterocyclic thioamidate) Co(III) complex [Co(κS,N-tfmp2S)3], tfmp2S = 4-(trifluoromethyl)-pyrimidine-2-thiolate. A series of arylamines and heterocyclic amines were formed in excellent yields and chemoselectivity. High conversion yields of nitroarenes into the corresponding amines were observed by using polar protic solvents, such as MeOH and iPrOH. Among several hydrogen donors that were examined, methylhydrazine demonstrated the best performance. Preliminary mechanistic investigations, supported by UV-vis and NMR spectroscopy, cyclic voltammetry, and high-resolution mass spectrometry, suggest a cooperative action of methylhydrazine and [Co(κS,N-tfmp2S)3] via a coordination activation pathway that leads to the formation of a reduced cobalt species, responsible for the catalytic transformation. In general, the corresponding N-arylhydroxylamines were identified as the sole intermediates. Nevertheless, the corresponding nitrosoarenes can also be formed as intermediates, which, however, are rapidly transformed into the desired arylamines in the presence of methylhydrazine through a noncatalytic path. On the basis of the observed high chemoselectivity and yields, and the fast and clean reaction processes, the present catalytic system [Co(κS,N-tfmp2S)3]/MeNHNH2 shows promise for the efficient synthesis of aromatic amines that could find various industrial applications.
- Ioannou, Dimitris I.,Gioftsidou, Dimitra K.,Tsina, Vasiliki E.,Kallitsakis, Michael G.,Hatzidimitriou, Antonios G.,Terzidis, Michael A.,Angaridis, Panagiotis A.,Lykakis, Ioannis N.
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p. 2895 - 2906
(2021/02/27)
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- Tandem selective reduction of nitroarenes catalyzed by palladium nanoclusters
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We report a catalytic tandem reduction of nitroarenes by sodium borohydride (NaBH4) in aqueous solution under ambient conditions, which can selectively produce five categories of nitrogen-containing compounds: anilines, N-aryl hydroxylamines, azoxy-, azo- and hydrazo-compounds. The catalyst is in situ-generated ultrasmall palladium nanoclusters (Pd NCs, diameter of 1.3 ± 0.3 nm) from the reduction of Pd(OAc)2 by NaBH4. These highly active Pd NCs are stabilized by surface-coordinated nitroarenes, which inhibit the further growth and aggregation of Pd NCs. By controlling the concentration of Pd(OAc)2 (0.1-0.5 mol% of nitroarene) and NaBH4, the water/ethanol solvent ratio and the tandem reaction sequence, each of the five categories of N-containing compounds can be obtained with excellent yields (up to 98%) in less than 30 min at room temperature. This tunable catalytic tandem reaction works efficiently with a broad range of nitroarene substrates and offers a green and sustainable method for the rapid and large-scale production of valuable N-containing chemicals.
- Yan, Ziqiang,Xie, Xiaoyu,Song, Qun,Ma, Fulei,Sui, Xinyu,Huo, Ziyu,Ma, Mingming
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supporting information
p. 1301 - 1307
(2020/03/11)
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- Commercially Available CuO Catalyzed Hydrogenation of Nitroarenes Using Ammonia Borane as a Hydrogen Source
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Tandem ammonia borane dehydrogenation and nitroarenes hydrogenation has been reported as a novel strategy for the preparation of aromatic amines. However, the practical application of this strategy is subjected to the high-cost and tedious preparation of supported noble metal nanocatalysts. The commercially available CuO powder is herein demonstrated to be a robust catalyst for hydrogenation of nitroarenes using ammonia borane as a hydrogen source under mild conditions. Numerous amines (even sterically hindered, halogenated, and diamines) could be obtained through this method. This monometallic catalyst is characteristic of support-free, excellent chemoselectivity, low-cost, and high recyclability, which will favor its future utilization in preparative reduction chemistry. Mechanistic studies are also carried out to clarify that diazene and azoxybenzene are key intermediates of this heterogeneous reduction.
- Du, Jialei,Chen, Jie,Xia, Hehuan,Zhao, Yiwei,Wang, Fang,Liu, Hong,Zhou, Weijia,Wang, Bin
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p. 2426 - 2430
(2020/03/30)
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- THIENODIAZEPINE DERIVATIVES AND APPLICATION THEREOF
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The present invention relates to a class of thienodiazepine derivatives and an application thereof in the preparation of a drug for the treatment of diseases associated with bromodomain and extra-terminal (BET) Bromodomain inhibitors. Specifically, the present invention relates to compounds represented by formulas (I) and (II), as well as pharmaceutically acceptable salts thereof.
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Paragraph 0296-0298
(2020/08/09)
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- Preparation of Well-Ordered Mesoporous-Silica-Supported Ruthenium Nanoparticles for Highly Selective Reduction of Functionalized Nitroarenes through Transfer Hydrogenation
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MCM-41-type mesoporous silica (OMS-IL) was prepared by using an ionic liquid (1-hexadecyl-3-methylimidazolium bromide) as a template. The XRD and TEM results demonstrated that OMS-IL was more stable than the MCM-41 material. Ru nanoparticles were supported on OMS-IL (Ru/OMS-IL) by impregnating OMS-IL with a RuCl3 aqueous solution, and the resulting material was used for the selective reduction of nitroarenes. The effects of the components of the catalysts and the reaction conditions on the catalytic behavior of the prepared catalysts were investigated in detail. Ru/OMS-IL exhibited high catalytic activity and chemoselectivity for the reduction of various substituted nitroarenes to the corresponding aromatic amines in ethanol with hydrazine hydrate as a hydrogen donor under mild conditions. The Ru/OMS-IL catalysts were highly stable and could easily be recovered by simple filtration over at least six recycling reactions without any observable loss in catalytic performance.
- Wei, Ning,Zou, Xiujing,Huang, Haigen,Wang, Xueguang,Ding, Weizhong,Lu, Xionggang
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supporting information
p. 209 - 214
(2018/01/26)
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- N-doped graphitic carbon-improved Co-MoO3 catalysts on ordered mesoporous SBA-15 for chemoselective reduction of nitroarenes
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Metallic Co-MoO3 catalysts supported on ordered mesoporous SBA-15 were first prepared through in situ reaction of SBA-15-supported Co-Mo oxides with 1,10-phenanthroline. The resulting Co-MoO3/NC@SBA-15 catalysts with N-doped carbon (NC) exhibited high catalytic activity and chemoselectivity for selective reduction of various functionalized nitroarenes to the corresponding arylamines in ethanol with hydrazine hydrate at near room temperature (30 °C). For reduction of all tested substrates (28 examples), the catalyst could afford a conversion of >99% and arylamine selectivity of >99%. The excellent catalytic performance of the Co-MoO3/NC@SBA-15 was attributed to the Co-Nχ(C)-Mo active sites generated through the interaction between the surface Co-Nχ(C) and MoO3 species, promoting the dissociation of hydrazine molecule into the active H* species for the reduction of nitro groups. After the seventh cycle for reduction of 4-methoxylnitrobenzene, the 2%Co-MoO3/NC@SBA-15 showed little change in catalytic performance, textural properties, size and dispersion of metal species and valence states of elements, indicating high stability and recyclability.
- Huang, Haigen,Liang, Xiangcheng,Wang, Xueguang,Sheng, Yao,Chen, Chenju,Zou, Xiujing,Lu, Xionggang
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p. 127 - 137
(2018/05/04)
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- Synthesis and antitumor activity of novel phenylhydrazonopyrazolone derivatives and molecular dynamics simulations
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SHP2 is a new promising target for anti-cancer drug discovery. A series of novel phenylhydrazonopyrazolone derivatives was synthesized by a more convenient method, and their chemical structures were characterized by various spectroscopic methods. The inhibitory effects of these compounds on SHP2 enzyme and SHP2-dependent cancer cell H1975 were evaluated. The compound 11f with IC50 value of 3.38?μmol/L exhibited more potent antitumor activity against H1975 cell than GS-493 (IC50 = 20.92?μmol/L). Molecular dynamics simulation of compound 11f displayed a possible mode of interaction between this compound and SHP2 enzyme.
- Hu, Xia-min,Cui, Zhi-wen,Dong, Wei,Zhu, Yue,Gao, Cheng-zhi,Xu, Shi-qiang,Yuan, Qiong,Yu, Zhi-jun,Min, Zhen-li
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p. 5107 - 5122
(2018/04/05)
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- Controllable Synthesis of Mesoporous Iron Oxide Nanoparticle Assemblies for Chemoselective Catalytic Reduction of Nitroarenes
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Iron(III) oxide is a low-cost material with applications ranging from electronics to magnetism, and catalysis. Recent efforts have targeted new nanostructured forms of Fe2O3 with high surface area-to-volume ratio and large pore volume. Herein, the synthesis of 3D mesoporous networks consisting of 4-5 nm γ-Fe2O3 nanoparticles by a polymer-assisted aggregating self-assembly method is reported. Iron oxide assemblies obtained from the hybrid networks after heat treatment have an open-pore structure with high surface area (up to 167 m2 g-1) and uniform pores (ca. 6.3 nm). The constituent iron oxide nanocrystals can undergo controllable phase transition from γ-Fe2O3 to α-Fe2O3 and to Fe3O4 under different annealing conditions while maintaining the 3D structure and open porosity. These new ensemble structures exhibit high catalytic activity and stability for the selective reduction of aryl and alkyl nitro compounds to the corresponding aryl amines and oximes, even in large-scale synthesis.
- Papadas, Ioannis T.,Fountoulaki, Stella,Lykakis, Ioannis N.,Armatas, Gerasimos S.
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p. 4600 - 4607
(2016/03/22)
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- Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase B inhibitors in Parkinson's disease
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The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins. Among them, 13 exhibited remarkable and balanced neuroprotective potency. The protective effects of 13 against neurotoxins-induced apoptosis were confirmed with flow cytometry and staining methods. Furthermore, 13 also showed good BBB permeability and low toxicity according to in vitro BBB prediction and in vivo acute toxicity test. The results indicated that 13 is an effective and promising candidate to be further developed as disease-modifying drug for Parkinson's disease therapy.
- Wang, Zhimin,Wu, Jiajia,Yang, Xuelian,Cai, Pei,Liu, Qiaohong,Wang, Kelvin D.G.,Kong, Lingyi,Wang, Xiaobing
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supporting information
p. 5929 - 5940
(2016/11/09)
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- SULFONAMIDE DERIVATIVE AND MEDICINAL USE THEREOF
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Provided are sulfonamide derivatives of a specific chemical structure in which a sulfonamide group having, as a substituent, a phenyl group or a heterocyclic group having a hetero atom(s) as a constituent element(s) is present at its terminal, and pharmaceutically acceptable salts thereof. These compounds are novel compounds having excellent α4 integrin-inhibitory action.
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Paragraph 1325-1326
(2015/02/25)
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- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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Paragraph 1264
(2015/09/22)
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- Indium(III)-Catalyzed Reduction of Nitrobenzenes to Anilines: Scope and Limitations
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We have demonstrated that a combination of indium(III) iodide and 1,1,3,3-tetramethyldisiloxane (TMDS) effectively catalyzes the chemoselective reduction of nitrobenzenes with a variety of functional groups (halogens, alkyl, alkoxy, hydroxy, ester, amino, amide, cyanide, thiol, and an alkene moiety), producing the corresponding aniline derivatives.
- Sakai, Norio,Asama, Shun,Konakahara, Takeo,Ogiwara, Yohei
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p. 3179 - 3185
(2015/10/19)
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- Discovery of potent indenoisoquinoline topoisomerase i poisons lacking the 3-nitro toxicophore
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3-Nitroindenoisoquinoline human topoisomerase IB (Top1) poisons have potent antiproliferative effects on cancer cells. The undesirable nitro toxicophore could hypothetically be replaced by other functional groups that would retain the desired biological activities and minimize potential safety risks. Eleven series of indenoisoquinolines bearing 3-nitro bioisosteres were synthesized. The molecules were evaluated in the Top1-mediated DNA cleavage assay and in the National Cancer Institute's 60 cell line cytotoxicity assay. The data reveal that fluorine and chlorine may substitute for the 3-nitro group with minimal loss of Top1 poisoning activity. The new information gained from these efforts can be used to design novel indenoisoquinolines with improved safety.
- Beck, Daniel E.,Abdelmalak, Monica,Lv, Wei,Reddy, P. V. Narasimha,Tender, Gabrielle S.,O'Neill, Elizaveta,Agama, Keli,Marchand, Christophe,Pommier, Yves,Cushman, Mark
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p. 3997 - 4015
(2015/05/27)
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- Mechanistic studies of the reduction of nitroarenes by NaBH4 or hydrosilanes catalyzed by supported gold nanoparticles
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Herein, we show that mesoporous titania-supported gold nanoparticle assemblies (Au/MTA) catalyze the activation of NaBH4 and 1,1,3,3-tetramethyl disiloxane (TMDS) compounds, which act as transfer hydrogenation agents for the reduction of nitroarenes to the corresponding anilines in moderate to high yields. On the other hand, nitroalkanes are reduced to the corresponding diazo and hydrazo compounds under the studied conditions. The substantial measured primary kinetic isotope effects found here suggested that B-H bond cleavage occurs in a rate-determining step and [Au]-H active hybrids are formed, which are responsible for the reduction of nitroarenes to the corresponding amines. Formal Hammett-type kinetic analysis of a range of para-X-substituted nitroarenes lends support to this hypothesis. Nitro compounds substituted with electron-withdrawing groups were reduced faster than the corresponding compounds with electron-donating groups. The presence of water enhanced the catalytic activity of Au/MTA in aprotic solvents. Nuclear magnetic resonance studies support the formation of the corresponding hydroxylamines as the only intermediate products. On the basis of the high observed chemoselectivities and the fast and clean reaction processes, these catalytic systems, i.e., Au/MTA-NaBH4 and Au/MTA-TMDS, show promise for the efficient synthesis of aromatic amines at industrial levels.
- Fountoulaki, Stella,Daikopoulou, Vassiliki,Gkizis, Petros L.,Tamiolakis, Ioannis,Armatas, Gerasimos S.,Lykakis, Ioannis N.
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p. 3504 - 3511
(2015/02/19)
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- Iron and palladium(II) phthalocyanines as recyclable catalysts for reduction of nitroarenes
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Iron(II) and palladium(II) phthalocyanines have been established as recyclable heterogeneous catalysts for the reduction of aromatic nitro compounds to corresponding amines using diphenylsilane/sodium borohydride as hydrogen sources in ethanol. Various reducible functional groups, such as acetyl, ester, cyano, amide, sulphonamide and carboxylic acid etc. were well tolerated, and the methods were applicable up to gram scale. Mechanistic studies showed that reduction of nitro group proceed through direct (nitroso) pathway and possibly iron or palladium phthalocyanines activates nitro group for reduction. FePc and PdPc also catalyzed the generation of hydrogen from the combination of diphenylsilane/sodium borohydride and ethanol.
- Verma, Praveen Kumar,Bala, Manju,Thakur, Kavita,Sharma, Upendra,Kumar, Neeraj,Singh, Bikram
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p. 1258 - 1267
(2014/07/21)
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- A novel series of N-(azetidin-3-yl)-2-(heteroarylamino)acetamide CCR2 antagonists
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The inflammatory response associated with the activation of C-C chemokine receptor CCR2 via it's interaction with the monocyte chemoattractant protein-1 (MCP-1, CCL2) has been implicated in many disease states, including rheumatoid arthritis, multiple sclerosis, atherosclerosis, asthma and neuropathic pain. Small molecule antagonists of CCR2 have been efficacious in animal models of inflammatory disease, and have been advanced into clinical development. The necessity to attenuate hERG binding appears to be a common theme for many of the CCR2 antagonist scaffolds appearing in the literature, presumably due the basic hydrophobic motif present in all of these molecules. Following the discovery of a novel cyclohexyl azetidinylamide CCR2 antagonist scaffold, replacement of the amide bond with heterocyclic rings was explored as a strategy for reducing hERG binding and improving pharmacokinetic properties.
- Subasinghe, Nalin L.,Lanter, James,Markotan, Thomas,Opas, Evan,McKenney, Sandra,Crysler, Carl,Hou, Cuifen,O'Neill, John,Johnson, Dana,Sui, Zhihua
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p. 1063 - 1069
(2013/03/13)
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- Inhibition of monoamine oxidase by phthalide analogues
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Based on recent reports that the small molecules, isatin and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase (MAO) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues. Phthalide is structurally related to isatin and phthalimide and it is demonstrated here that substitution at C6 of the phthalide moiety yields compounds endowed with high binding affinities to both human MAO isoforms. Among the nineteen homologues evaluated, the lowest IC50 values recorded for the inhibition of MAO-A and -B were 0.096 and 0.0014 μM, respectively. In most instances, C6-substituted phthalides exhibit MAO-B specific inhibition. Among a series of 6-benzyloxyphthalides bearing substituents on the para position of the phenyl ring the general order of potency was CF3 > I > Br > Cl > F > CH3 > H. The results also show that the binding modes of representative phthalides are reversible and competitive at both MAO isoforms. Based on these data, C6-substituted phthalides may serve as leads for the development of therapies for neurodegenerative disorders such as Parkinson's disease.
- Strydom, Belinda,Bergh, Jacobus J.,Petzer, Jacobus P.
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supporting information
p. 1269 - 1273
(2013/03/14)
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- An indium-mediated allylative/transesterification DFT-directed approach to chiral C(3)-functionalized phthalides
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A one-pot synthesis of chiral C(3)-substituted phthalides via an indium-mediated allylation/transesterification reaction is described. The development of this reaction was facilitated through the applied use of DFT calculations to rationalize the stereoselection of a chiral In-mediated process. It was discovered that the enantiomeric excess of this reaction depended upon the steric size, chain length, and substitution of the aldehyde employed.
- Mirabdolbaghi, Roya,Dudding, Travis
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supporting information; scheme or table
p. 3748 - 3751
(2012/09/07)
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- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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- Structure-activity relationships (SAR) research of thiourea derivatives as dual inhibitors targeting both HIV-1 capsid and human cyclophilin A
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HIV-1 capsid (CA) and human cyclophilin A (CypA) play important roles in HIV-1 assembly and disassembly processes, which are critical in HIV-1 replication. Based on the discovery of thiourea derivatives targeting both of the two proteins and indicating effective inhibitory activities in our group, we designed and synthesized a new class of thiourea derivatives. Their abilities to bind to capsid and cyclophilin A were determined by ultraviolet spectroscopic analysis, fluorescence binding affinity, and PPIase inhibition assay. Furthermore, the newly synthesized compounds were tested for their antiviral activities and cytotoxicities using CEM cells. According to the biological evaluation and subsequent molecular docking analyses, we studied the structure-activity relationships of thiourea derivatives. Three optimal compounds (K17, K24, K25) based on the achieved structure-activity relationships would be the basis for future optimization.
- Chen, Kan,Tan, Zhiwu,He, Meizi,Li, Jiebo,Tang, Shixing,Hewlett, Indira,Yu, Fei,Jin, Yinxue,Yang, Ming
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- Synthesis of isothiocoumarin derivatives
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A method was developed for the synthesis of 1-oxo-1H-isothiochromenes from 2-benzofuran-1(3H)-one (phthalide). 3-Bromo-6-chloro- and 3,6-dibromo-2- benzofuran-1(3H)-ones were prepared by the bromination of 6-chloro- and 6-bromo-2-benzofuran-1(3H)-ones and were converted by hydrolysis into 5-chloro- or 5-bromo-2-formylbenzoic acids. The condensation of these acids with rhodanine followed by recyclization gave 7-chloro- and 7-bromo-1-oxo-1H-isothiochromene- 3-carboxylic acids.
- Pokhodylo,Matiychuk,Obushak
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experimental part
p. 140 - 145
(2011/08/07)
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- Highly chemo- and regioselective reduction of aromatic nitro compounds using the system silane/oxo-rhenium complexes
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(Chemical Equation Presented) The reduction of aromatic nitro compounds to the corresponding amines with silanes catalyzed by high valent oxo-rhenium complexes is reported. The catalytic systems PhMe2SiH/ReIO 2(PPh3)2 (5 mol %) and PhMe2SiH/ ReOCl3(PPh3)2 (5 mol %) reduced efficiently a series of aromatic nitro compounds in the presence of a wide range of functional groups such as ester, halo, amide, sulfone, lactone, and benzyl. This methodology also allowed the regioselective reduction of dinitrobenzenes to the corresponding nitroanilines and the reduction of an aromatic nitro group in presence of an aliphatic nitro group. 2009 American Chemical Society.
- De Noronha, Rita G.,Romao, Carlos C.,Fernandes, Ana C.
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supporting information; experimental part
p. 6960 - 6964
(2010/03/03)
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- Discovery of dual inhibitors targeting both HIV-1 capsid and human cyclophilin A to inhibit the assembly and uncoating of the viral capsid
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HIV-1 assembly and disassembly (uncoating) processes are critical for the HIV-1 replication. HIV-1 capsid (CA) and human cyclophilin A (CypA) play essential roles in these processes. We designed and synthesized a series of thiourea compounds as HIV-1 assembly and disassembly dual inhibitors targeting both HIV-1 CA protein and human CypA. The SIV-induced syncytium antiviral evaluation indicated that all of the inhibitors displayed antiviral activities in SIV-infected CEM cells at the concentration of 0.6-15.8 μM for 50% of maximum effective rate. Their abilities to bind CA and CypA were determined by ultraviolet spectroscopic analysis, fluorescence binding affinity and PPIase inhibition assay. Assembly studies in vitro demonstrated that the compounds could potently disrupt CA assembly with a dose-dependent manner. All of these molecules could bind CypA with binding affinities (Kd values) of 51.0-512.8 μM. Fifteen of the CypA binding compounds showed potent PPIase inhibitory activities (IC50 values 1 μM) while they could not bind either to HIV-1 Protease or to HIV-1 Integrase in the enzyme assays. These results suggested that 15 compounds could block HIV-1 replication by inhibiting the PPIase activity of CypA to interfere with capsid disassembly and disrupting CA assembly.
- Li, Jiebo,Tan, Zhiwu,Tang, Shixing,Hewlett, Indira,Pang, Ruifang,He, Meizi,He, Shanshan,Tian, Baohe,Chen, Kan,Yang, Ming
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scheme or table
p. 3177 - 3188
(2009/09/05)
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- Modulators of ATP-binding cassette transporters
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Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
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Page/Page column 409; 409-410
(2008/06/13)
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- Furan ring opening - Isocoumarine ring closure: A recyclization reaction of 2-carboxyaryldifurylmethanes
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A general method for the synthesis of isocoumarine derivatives has been developed. Bis(5-R-2-furyl)methylbenzoic acids (R = methyl, ethyl) underwent recyclization and subsequent cyclization into tetracyclic isochromene-1-one derivatives under treatment with hydrogen chloride in methanol. It has been shown that intermediate 4-(5-R-furan-2-yl)-3-(3-oxo-3-R-propyl)-isochromene-1- ones can be obtained selectively by varying a concentration of the hydrogen chloride and reaction times. In the case of R = tert-butyl only corresponding 4-[5-(tert-butyl)-2-furyl]-3-(4,4-dimethyl-3-oxopentyl)-1-isochromenones were isolated regardless of the reaction conditions.
- Abaev, Vladimir T.,Dmitriev, Artem S.,Gutnov, Andrey V.,Podelyakin, Sergey A.,Butin, Alexander V.
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p. 1195 - 1204
(2007/10/03)
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- WATER-SOLUBLE TRIAZOLE FUNGICIDE
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A triazole compound of the general formula (I) or a pharmacologically acceptable salt thereof: [wherein,X represents a group of formula X-OH which has antifungal activity,L represents a -(adjacently substituted C6-C10 aryl)-CH2-group and the like, andR represents a -P(=O) (OH)2 group and the like.
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Page/Page column 159
(2010/02/07)
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- Conformationally restricted analogues of remoxipride as potential antipsychotic agents
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Several conformationally restricted derivatives of (S)-3-bromo-N-((1- ethyl-2-pyrrolidinyl)methyl)-2,6-dimethoxybenzamide (remoxipride) were synthesized and evaluated in vitro for their ability to inhibit [3H]raclopride binding at the dopamine D-2 receptor. The cyclic benzamides designed to mimic the intramolecular hydrogen bonding of desmethylremoxipride (4, FLA-797) included 2,3-dihydro-4H-1,3-benzoxazin-4-ones, 2,3-dihydro-4H- 1,3-benzthiazin-4-ones, phthalimides, 1-isoindolinones, 1,2-benzisothiazol- 3(2H)-ones, and 1,2-benzisothiazol-3(2H)-one 1,1-dioxides. In this series, enhanced affinities to the dopamine D-2 receptor were not observed. The phthalimidine analogue 24b ((S)-6-chloro-2-(1-ethylpyrrolidinyl)-1- isoindolinone) exhibited the highest affinity to the dopamine D-2 receptor with an IC50 of 1.3 μM, which was equipotent to remoxipride.
- Norman,Kelley,Hollingsworth
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p. 3417 - 3423
(2007/10/02)
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- Syntheses of Triazolophthalide and Triazolodihydrocoumarin
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Triazolophthalide has been synthesized in a seven step sequence from phthalide in 24percent overall yield, and triazolodihydrocoumarin has been prepared in nine steps from dihydrocoumarin in 20percent overall yield.The 1H and 13C nmr spectra and the tautomeric equilibria of the final compounds and intermediates are discussed.
- Katritzky, Alan R.,Ji, Fu-Bao,Fan, Wei-Qiang,Beretta, Paolo,Bertoldi, M.
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p. 1519 - 1523
(2007/10/02)
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- Pyrophtalones VII. Synthese et activite anti-inflammatoire de (pyridinyl-4)-2 indanediones-1,3 substituees sur le noyau benzenique et/ou sur l'heterocycle
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Pyrophthalones VII.Synthesis and anti-inflammatory activity of 2-(4-pyridinyl)indane-1,3-diones diversely substituted on the benzene ring.Access routes to 2-(1,4-dihydro 4-pyridinylidene) indane-1,3-diones diversely substituted on the benzene ring are studied.The regiospecific attack of these β diketoenamines by alkyl iodides leads to N-substituted compounds.These derivatives may be obtained by any of three possible methods: (1) condensation of 4-methyl pyridine with ethyl phthalates in the absence of catalyst; (2) oxidative condensation of N-alkyl-pyridinium bromides with indane-1,3-diones; (3) aminolysis of 2-(4-4H-pyranylidene) indane-1,3-diones.Pharmacomodulation by the introduction of oxygen or sulfur containing functions (ether, thioether, alcohol, ketone, acid, ester, amide) on the nitrogen of the basic molecule is not very fruitful; only the acetic derivative 19 manifests marked antiinflammatory activity unaccompanied by anti-coagulant action.The presence of chloro, nitro or methoxyl groups on 5 after N-substitution by ethyl or piperidinylethyl groups appears to be more favorable.The most active compound 57 decreases prostaglandin production and leukocyte migration without affecting either cyclooxygenase or 5-lipoxygenase.Its interference, direct or indirect, with phospholipasic A2 activity may be envisaged in particular.Keywords - 2-(4-pyridinyl)indane-1,3-diones / heterocyclic β diketoenamines / partition coefficient / anti-inflammatory activity / mechanism of action
- Leblois, Danielle,Piessard, Sylvie,Baut, Guillaume Le,Kumar, Piyush,Brion, Jean-Daniel,et al.
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p. 229 - 238
(2007/10/02)
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- Herbicidal isoquinolinoxy- or isoquinolinamino-phenoxy alkane carboxylic acid derivatives
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The invention concerns novel compounds of the formula I STR1 The compounds are herbicides and in further embodiments the invention provides: processes for the preparation of compounds of formula I; intermediates useful in the preparation of compounds of formula I; compositions containing as active ingredient compounds of formula I; and processes for severely damaging or killing unwanted plants by applying to the plants or to the growth medium of the plants an effective amount of a compound of formula I.
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