- Modular synthesis and antiproliferative activity of new dihydro-1H-pyrazolo[1,3-b]pyridine embelin derivatives
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A set of new dihydro-1H-pyrazolo[1,3-b]pyridine and pyrazolo[1,3-b]pyridine embelin derivatives was synthesized through a multicomponent reaction from natural embelin, 3-substituted-5-aminopyrazoles and aldehydes. The synthesized compounds were evaluated against three hematologic tumor cell lines, HEL (acute erythroid leukemia), K-562 (chronic myeloid leukemia) and HL-60 (acute myeloid leukemia), and five breast cancer cell lines (SKBR3, MCF-7, MDA-MB-231, BT-549, HS-578T). The primate non-malignant kidney Vero cell line was used as the control of cytotoxicity. From the obtained results, some structure–activity relationships were out-lined. Furthermore, in silico prediction of physicochemical properties and ADME parameters were determined for the derivatives with the best antiproliferative values.
- Amesty, ángel,Estévez-Braun, Ana,Fernández-Pérez, Leandro,Guerra, Borja,Guerra-Rodríguez, Miguel,Martín-Acosta, Pedro
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- Design, synthesis and α-glucosidase inhibition study of novel embelin derivatives
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Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC50 = 4.2 μM) against α-glucosidase in this study. Then, four seri
- Chen, Wenhua,Chen, Xiaole,Gao, Min,Hong, Weiqian David,Jian, Rongchao,Li, Yuling,Sheng, Zhaojun,Tang, Xiaowen,Wu, Panpan,Zhang, Kun,Zhao, Denggao,Zheng, Xi
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p. 565 - 573
(2020/02/15)
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- Alpha-glucosidase inhibitor based on p-hydroxyquinone framework and preparation method and application of inhibitor
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The invention discloses an alpha-glucosidase inhibitor based on a p-hydroxyquinone framework and a preparation method and application of inhibitor. The glucosidase inhibitor is obtained through six-step synthesis with a natural product framework p-hydroxyquinone as an initial raw material. The compound can effectively inhibit the activity of alpha-glucosidase, the aim of controlling excessively high blood glucose is achieved by delaying absorption of the intestinal tract to glucose, and the inhibitor is used for treating diabetes and obesity and has a heart blood vessel protection function.
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Paragraph 0048-0052; 0070-0074; 0092-0096
(2019/07/16)
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- Alpha-glucosidase inhibitor, and synthesis method and application thereof
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The invention discloses an alpha-glucosidase inhibitor, and a synthesis method and application thereof. The invention aims to provide the alpha-glucosidase inhibitor with a relatively good hypoglycemic effect. The structural formula of the alpha-glucosidase inhibitor is shown in the specification, wherein R1 is selected from H or CH3, and R2 is selected from the groups shown in the specification.The invention belongs to the technical field of medicines.
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Paragraph 0048-0052
(2019/12/12)
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- Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic α-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study
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Inspired by the traditional Chinese herbal pair of Polygala tenuifolia-Acori Tatarinowii for treating epilepsy, 33 novel substituted cinnamic α-asaronol esters and analogues were designed by Combination of Traditional Chinese Medicine Molecular Chemistry (CTCMMC) strategy, synthesized and tested systematically not only for anticonvulsant activity in three mouse models but also for LDH inhibitory activity. Thereinto, 68–70 and 75 displayed excellent and broad spectra of anticonvulsant activities with modest ability in preventing neuropathic pain, as well as low neurotoxicity. The protective indices of these four compounds compared favorably with stiripentol, lacosamide, carbamazepine and valproic acid. 68–70 exhibited good LDH1 and LDH5 inhibitory activities with noncompetitive inhibition type, and were more potent than stiripentol. Notably, 70, as a representative agent, was also shown as a moderately positive allosteric modulator at human α1β2γ2 GABAA receptors (EC50 46.3 ± 7.3 μM). Thus, 68–70 were promising candidates for developing into anti-epileptic drugs, especially for treatment of refractory epilepsies such as Dravet syndrome.
- Bai, Yajun,He, Xirui,Bai, Yujun,Sun, Ying,Zhao, Zefeng,Chen, Xufei,Li, Bin,Xie, Jing,Li, Yang,Jia, Pu,Meng, Xue,Zhao, Ye,Ding, Yanrui,Xiao, Chaoni,Wang, Shixiang,Yu, Jie,Liao, Sha,Zhang, Yajun,Zhu, Zhiling,Zhang, Qiang,Zhao, Yuhui,Qin, Fanggang,Zhang, Yi,Wei, Xiaoyang,Zeng, Min,Liang, Jing,Cuan, Ye,Shan, Guangzhi,Fan, Tai-Ping,Wu, Biao,Zheng, Xiaohui
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- New tetralactam hosts for squaraine dyes
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The photophysical properties of a deep-red fluorescent squaraine dye can be improved by encapsulating it within a tetralactam macrocycle. Three new tetralactams are described with different substituents (methyl, methoxy, methylenedioxy) on the macrocycle aromatic sidewalls. The capability of each tetralactam to encapsulate a squaraine dye in chloroform solution was determined experimentally using absorption, fluorescence, and NMR spectroscopy. Two of the tetralactams were found to thread a squaraine dye with association constants on the order of 106 M-1, while a third macrocycle exhibited no squaraine affinity. An X-ray crystal structure of the third tetralactam showed that the substituents sterically blocked squaraine association. Of the two tetralactams that encapsulate a squaraine, one induces an increase in squaraine fluorescence quantum yield, while the other quenches the squaraine fluorescence. The results suggest that these new squaraine binding systems will be useful for biological imaging and diagnostics applications.
- Dempsey, Janel M.,Zhang, Qi-Wei,Oliver, Allen G.,Smith, Bradley D.
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p. 8976 - 8983
(2018/12/10)
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- A new family of densely functionalized fused-benzoquinones as potent human protein kinase CK2 inhibitors
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A new series of 2-amino-4-phenyl-6-hydroxy-7-alkyl-pyranobenzoquinones was synthesized as ATP-competitive CK2 inhibitors. They were readily synthesized through a three-component Knoevenagel condensation-Michael addition-heterocyclization reaction from ald
- Martín-Acosta, Pedro,Haider, Samer,Amesty, ángel,Aichele, Dagmar,Jose, Joachim,Estévez-Braun, Ana
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p. 410 - 423
(2018/01/01)
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- Tetramethoxybenzene is a good building block for molecular wires: Insights from photoinduced electron transfer
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Two donor bridge-acceptor molecules with terminal triarylamine and Ru(bpy)32+ (bpy = 2,2′-bipyridine) redox partners were synthesized and investigated by cyclic voltammetry, optical absorption, luminescence, and transient absorption spectroscopy. The two dyads differ only by the central bridging unit, which was tetramethoxybenzene (tmb) in one case and unsubstituted phenylene (ph) in the other case. Photoirradiation of the Ru(bpy)32+ complex of the two dyads triggers intramolecular electron transfer from the triarylamine to the 3MLCT-excited metal complex, and this process occurs with time constants of 1.5 and 6.8 ns for the tmb- and ph-bridged dyads, respectively. Thermal electron transfer in the reverse direction then leads to disappearance of the photoproduct with a time constant of 10 ns in both dyads. The faster rate of photoinduced charge transfer in the tmb-bridged dyad can be understood in the framework of a hole-tunneling model in which the electron-rich tmb bridge imposes a more shallow barrier than the less electron-rich ph spacer. Until now tmb-based molecular wires have received very little attention, and alkoxy substituents have been mostly used for improving the solubility of oligo-p-phenylene vinylene (OPV) and oligo-p-phenylene ethynylene (OPE) wires. Our study illustrates how four alkoxy-substituents on a phenylene backbone can have a significant influence on the charge-transfer properties of a molecular wire, and this is relevant in the greater context of a future molecular electronics technology.
- Heinz, Luisa G.,Yushchenko, Oleksandr,Neuburger, Markus,Vauthey, Eric,Wenger, Oliver S.
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p. 5676 - 5684
(2015/06/16)
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- Design, synthesis, and SAR of embelin analogues as the inhibitors of PAI-1 (plasminogen activator inhibitor-1)
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The natural product embelin was found to have PAI-1 inhibitory activity with the IC50 value of 4.94 μM. Based on the structure of embelin, a series of analogues were designed, synthesized, and evaluated for their ability to inhibit PAI-1. The SAR study on these compounds disclosed that the inhibitory potency largely depended on the hydroxyl groups at C2 and C5, and the length of the alkyl chains at C3 and C6. Compound 11 displayed the best PAI-1 inhibitory potency with the IC50 value of 0.18 μM.
- Chen, Fanglei,Zhang, Guiping,Hong, Zebin,Lin, Zhonghui,Lei, Min,Huang, Mingdong,Hu, Lihong
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supporting information
p. 2379 - 2382
(2014/05/20)
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- MULTIFUNCTIONAL RADICAL QUENCHERS
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The invention provides a compound of formula (I): [insert formula (I)] wherein X, Y, and R1-R4 have any of the values defined in the specification, and salts thereof, as well as compositions comprising the compounds or salts. The compounds are useful for treating diseases associated with impaired mitochondrial function in an animal.
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- Discovery and biological evaluation of novel 1,4-benzoquinone and related resorcinol derivatives that inhibit 5-lipoxygenase
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5-Lipoxygenase (5-LO), an enzyme that catalyzes the initial steps in the biosynthesis of pro-inflammatory leukotrienes, is an attractive drug target for the pharmacotherapy of inflammatory and allergic diseases. Here, we present the discovery and biological evaluation of novel series of 1,4-benzoquinones and respective resorcinol derivatives that efficiently inhibit human 5-LO, with little effects on other human lipoxygenases. SAR analysis revealed that the potency of the compounds strongly depends on structural features of the lipophilic residues, where bulky naphthyl or dibenzofuran moieties favor 5-LO inhibition. Among the 1,4-benzoquinones, compound Ig 5-[(2-naphthyl)methyl]-2- hydroxy-2,5-cyclohexadiene-1,4-dione potently blocked 5-LO activity in cell-free assays with IC50 = 0.78 μM, and suppressed 5-LO product synthesis in polymorphonuclear leukocytes with IC50 = 2.3 mM. Molecular docking studies suggest a concrete binding site for Ig in 5-LO where select π-π interactions along with hydrogen bond interactions accomplish binding to the active site of the enzyme. Together, our study reveals novel valuable 5-LO inhibitors with potential for further preclinical assessment as anti-inflammatory compounds.
- Filosa, Rosanna,Peduto, Antonella,Aparoy, Polamarasetty,Schaible, Anja M.,Luderer, Susann,Krauth, Verena,Petronzi, Carmen,Massa, Antonio,De Rosa, Mario,Reddanna, Pallu,Werz, Oliver
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p. 269 - 279
(2013/10/01)
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- Synthesis of polyhydroxylated flavonoids bearing a lipophilic decyl tail as potential therapeutic antioxidants
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Antioxidants have potential for the treatment of stroke and neurodegeneration, and chimeric compounds that combine a flavon-3-ol head group related to myricetin and a lipophilic decyl tail are known to protect membranes from oxidative damage at least as well as vitamin E. New flavon-3-ols that are highly hydroxylated in the B ring in ways not found in natural flavon-3-ols and bearing a lipophilic decyl tail have been prepared from trimethoxy-and tetramethoxybenzoic acids accessed by lithiation-carboxylation reactions. Direct enolate acylation was preferred over Baker-Venkataraman rearrangement when there were methoxy groups at both the 2-and the 6-position of the benzoic acid derivatives.
- Caldwell, Stuart T.,McPhail, Donald B.,Duthie, Garry G.,Hartley, Richard C.
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scheme or table
p. 23 - 33
(2012/03/07)
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- A self-immolative spacer that enables tunable controlled release of phenols under neutral conditions
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A current challenge in the area of responsive materials is the design of reagents and polymers that provide controlled release of phenols in environments that are less polar than water. In these contexts, a molecular strategy that enables release of nearl
- Schmid, Kyle M.,Jensen, Lasse,Phillips, Scott T.
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experimental part
p. 4363 - 4374
(2012/06/18)
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- Accelerated hole transfer across a molecular double barrier
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We report on a dyad in which photoinduced hole transfer through a non-uniform molecular double barrier is more than one order of magnitude more rapid than hole transfer across a comparable uniform (rectangular) tunneling barrier.
- Hanss, David,Walther, Mathieu E.,Wenger, Oliver S.
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supporting information; experimental part
p. 7034 - 7036
(2010/10/19)
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- A synthetic study on bauhinoxepin J: Construction of a dibenzo[bf]oxepin ring system by a DDQ-promoted oxidative dearomatization-cyclization approach
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Efforts to construct a dibenzo[b,f]oxepin ring system for a synthesis of bauhinoxepin J are described. A DDQ-promoted oxidative dearomatization-cyclization of the 2-phenoxyethyl-substituted tetramethoxybenzene was used to construct a tricyclic quinone mon
- Yoshida, Masahiro,Maeyama, Yohei,Shishido, Kozo
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experimental part
p. 623 - 629
(2010/04/27)
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- Nanoscale molecular rods with a new building block for solubility enhancement
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(Chemical Equation Presented) A new building block bearing a [1,3]dioxolo[4,5-f][1,3]benzodioxole core was developed to enhance the solubility of molecular rods by lateral alkyl chains. On incorporation in molecular rods with oligospiroketal structure, the straight geometry is retained, which was concluded from the X-ray crystal structure analysis of one of the rods. The determination of the solubility of a collection of rods bearing this building block revealed that already a butyl group efficiently hinders the aggregation of the rods and consequently causes a considerable enhancement of the solubility. Piperidine rings are located at the ends of the rods, which offer the opportunity for versatile functionalization. Thus, an N,N′-bis(azidoacetyl)-functionalized rod was prepared, which could serve as rigid linkage, initiated by a "Click" reaction.
- Wessig, Pablo,Moellnitz, Kristian
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p. 4452 - 4457
(2008/09/21)
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- Rust disease control by Aphanocladium album and/or Beauveria brongniartii
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There is disclosed a method and composition for controlling rust disease in plants. Metabolites produced by Aphanocladium album mycoparasites are recovered and applied in an effective amount to plants at risk for acquiring rust disease More specifically,
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Page/Page column 19
(2010/11/27)
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- Total synthesis and biological evaluation of the nakijiquinones
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The Her-2/Neu receptor tyrosine kinase is vastly overexpressed in about 30% of primary breast, ovary, and gastric carcinomas. The nakijiquinones are the only naturally occurring inhibitors of this important oncogene, and structural analogues of the nakijiquinones may display inhibitory properties toward other receptor tyrosine kinases involved in cell signaling and proliferation. Here, we describe the first enantioselective synthesis of the nakijiquinones. Key elements of the synthesis are (i) the reductive alkylation of a Wieland - Mieschertype enone with a tetramethoxyaryl bromide, (ii) the oxidative conversion of the aryl ring into a p-quinoid system, (iii) the regioselective saponification of one of the two vinylogous esters incorporated therein, and (iv) the selective introduction of different amino acids via nucleophilic conversion of the remaining vinylogous ester into the corresponding vinylogous amide. The correct stereochemistry and substitution patterns are completed by conversion of two keto groups into a methyl group and an endocyclic olefin via olefination/reduction and olefination/isomerization sequences, respectively. This synthesis route also gave access to analogues of nakijiquinone C with inverted configuration at C-2 or with an exocyclic instead of an endocyclic double bond. Investigation of the kinase-inhibiting properties of the synthesized derivatives revealed that the C-2 epimer 30 of nakijiquinone C is a potent and selective inhibitor of the KDR receptor, a receptor tyrosine kinase involved in tumor angiogenesis. Molecular modeling studies based on the crystal structure of KDR and a model of the ATP binding site built from a crystal structure of FGF-R revealed an insight into the structural basis for the difference in activity between the natural product nakijiquinone C and the C-2 epimer 30.
- Stahl,Kissau,Mazitschek,Huwe,Furet,Giannis,Waldmann
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p. 11586 - 11593
(2007/10/03)
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- Asymmetric synthesis of the nakijiquinones - Selective inhibitors of the Her-2/Neu protooncogene
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A Wieland-Miescher type ketone and a tetramethoxyaryl derivative are the key building blocks for the enantioselective total synthesis of nakijiquinone C (1). The nakijiquinones are the only natural products known that selectively inhibit the Her-2/Neu tyr
- Stahl, Petra,Waldmann, Herbert
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p. 3710 - 3713
(2007/10/03)
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- Total synthesis of maesanin and analogues
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An efficient total synthesis of maesanin and related quinones is reported, through direct alkylation of 1,2,4,5-tetramethoxybenzene with alkylbromides, followed by oxidation with ceric ammonium nitrate (CAN) which provokes formation of the quinone and dep
- Poigny, Stephane,Guyot, Michele,Samadi, Mohammad
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p. 14791 - 14802
(2007/10/03)
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- 2,3,5,6-Tetraalkoxy-1,4-benzoquinones and structurally related tetraalkoxy benzene derivatives: Synthesis, properties and solid state packing motifs
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A general synthesis of 2,3,5,6-tetraalkoxy-1,4-benzoquinones 1 from 1,2,4,5-tetraalkoxybenzenes 3 is reported. IR analysis (1a-e), the single crystal X-ray analysis of 2,3,5,6-tetramethoxy-1,4-benzoquinone 1a and semi-empirical calculations (AM1, 1a) show that the 1,4-benzoquinone skeleton possesses a merocyanine-type distortion. The solid state packing motifs of 1 are markedly affected by alkoxy chain length. For 1a, weak C-H ... O interactions and reduction of unfavourable dipole-dipole interactions are important for intermolecular organization, whereas for 2,3,5,6-tetradecyloxy-1, 4-benzoquinone [1e, wide angle X-ray diffraction (WAXD)] the close packing principle of the alkyl chains dominates. In both cases the results show that interplanar overlap is improved with respect to 1,4-benzoquinone 8. To deepen our insight into the effect of alkoxy chain length on solid state packing motifs, single crystal X-ray structures of methoxy and decyloxy derivatives of the structurally related compounds 1,4-diacetoxy-2,3,5,6-tetraalkoxybenzenes 2a and e, and 1,2,4,5-tetraalkoxybenzenes 3a and e were analysed. Compounds 1e, 2e and 3e, bearing decyloxy chains, possess board-like molecular structures which stack parallel along the a-axis as a result of alkyl chain interactions.
- Keegstra, Erik M. D.,Huisman, Bart-Hendrik,Paardekooper, Elizabeth M.,Hoogesteger, Frans J.,Zwikker, Jan W.,Jenneskens, Leonardus W.,Kooijman, Huub,Schouten, Arie,Veldman, Nora,Spek, Anthony L.
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p. 229 - 240
(2007/10/03)
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- Chemistry of Quinone Derivatives. Quinone Monoketals via Hydrolysis of Electrochemically Derived Quinone Bisketals
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The monohydrolysis of nine naphthoquinone bisketals and nine benzoquinone bisketals has been studied.In the acetamido, bromo, methyl, methoxy, and thiomethyl monosubstituted compounds, hydrolysis occurs at the ketal more distant from the substituent.The regiochemistry is nearly exclusive in the naphthoquinone series and is highly selective in the benzoquinone series.For disubstituted benzoquinone and naphthoquinone bisketals, the monohydrolysis is often regiospecific but substituent dependent.The origin of the regioselectivity in the reactions is briefly discussed.
- Henton, Daniel R.,Anderson, Keith,Manning, Michael J.,Swenton, John S.
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p. 3422 - 3433
(2007/10/02)
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- Oxidations with Lead Tetraacetate. II. Oxidations of 2,2-Disubstituted 1,3-Benzodioxoles
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The oxidation of 2,2-disubstituted 1,3-benzodioxoles by lead tetraacetate proceeds readily to give 5-acetoxy and 5,6-dione derivatives as main products. 5,6-Diacetoxy compuonds and 5-carboxy derivatives are found in some instances as minor products.Oxidation of benzodioxoles substituted at the 5 and 6 positions with methoxyl groups or with a second dioxole ring results in oxidative loss of the dioxole ring.Relative effects of these substitutions on reactivity have been evaluated.The mechanism of ο-quinone formation is discussed and is postulated to occur via a tetraacetoxy intermediate.The 5-acetoxy derivatives and the ο-quinones, by hydrolysis and reduction respectively, serve as sources of 5-hydroxy and 5,6-dihydroxy benzodioxoles.
- Cole, Edward R.,Crank, George,Minh, H. T. Hai
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p. 527 - 543
(2007/10/02)
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