- Synthesis of Fluorescent Probes Targeting Tumor-Suppressor Protein FHIT and Identification of Apoptosis-Inducing FHIT Inhibitors
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For the early diagnosis of cancer, leading to a better chance of full recovery, marker genes whose expression is already altered in precancerous lesions are desirable, and the tumor-suppressor gene FHIT is one candidate. The gene product, FHIT protein, has a unique dinucleoside triphosphate hydrolase (AP3Aase) activity, and in this study, we designed and synthesized a series of FHIT fluorescent probes utilizing this activity. We optimized the probe structure for high and specific reactivity with FHIT and applied the optimized probe in a screening assay for FHIT inhibitors. Screening of a compound library with this assay identified several hits. Structural development of a hit compound afforded potent FHIT inhibitors. These inhibitors induce apoptosis in FHIT-expressing cancers via caspase activation. Our results support the idea that FHIT binders, no matter whether inhibitors or agonists of AP3Aase activity, might be promising anticancer agents.
- Kawaguchi, Mitsuyasu,Sekimoto, Eriko,Ohta, Yuhei,Ieda, Naoya,Murakami, Takashi,Nakagawa, Hidehiko
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supporting information
p. 9567 - 9576
(2021/07/19)
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- Electronic Finetuning of 8-Methoxy Psoralens by Palladium-Catalyzed Coupling: Acidochromicity and Solvatochromicity
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Differently 5-substituted 8-methoxypsoralens can be synthesized by an efficient synthetic route with various cross-coupling methodologies, such as Suzuki, Sonogashira and Heck reaction. Compared to previously synthesized psoralens, thereby promising daylight absorbing compounds as potentially active agents against certain skin diseases can be readily accessed. Extensive investigations of all synthesized psoralen derivatives reveal fluorescence in the solid state as well as several distinctly emissive derivatives in solution. Donor-substituted psoralens exhibit remarkable photophysical properties, such as high fluorescence quantum yields and pronounced emission solvatochromicity and acidochromicity, which were scrutinized by Lippert–Mataga and Stern–Volmer plots. The results indicate that the compounds exceed the limit of visible light, a significant factor for potential applications as an active agent. In addition, (TD)DFT calculations were performed to elucidate the underlying electronic structure and to assign experimentally obtained data.
- Geenen, Sarah R.,Presser, Lysander,H?lzel, Torsten,Ganter, Christian,Müller, Thomas J. J.
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supporting information
p. 8064 - 8075
(2020/06/02)
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- ALPHA, BETA-UNSATURATED AMIDE COMPOUND
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An object of the present invention is to provide an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like. The α,β-unsaturated amide compound represented by the following formula (I) or a pharmaceutically acceptable salt or the like thereof has anticancer activity and the like: [wherein, "A" represents optionally substituted heterocyclic diyl, R1 represents hydrogen atom or optionally substituted lower alkyl, R2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents -O-, -S-, -SO2-, -NRX1- (wherein, RX1 represents hydrogen atom or lower alkyl), -CHRX2- (wherein, RX2 represents hydrogen atom or hydroxy), -CH=CH-, -CO- or -NH-CO-, and n1 and n2 are the same or different, and each represents 0 or 1].
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Paragraph 0633
(2020/12/10)
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- Kolbe-Schmitt type reaction under ambient conditions mediated by an organic base
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The combined use of an organic base for resorcinols realized a Kolbe-Schmitt type reaction under ambient conditions. When resorcinols (3-hydroxyphenol derivatives) were treated with DBU under a carbon dioxide atmosphere, nucleophilic addition to carbon dioxide proceeded to afford the corresponding salicylic acid derivatives in high yields.
- Sadamitsu, Yuta,Okumura, Akira,Saito, Kodai,Yamada, Tohru
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supporting information
p. 9837 - 9840
(2019/08/20)
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- a, ? UNSATURATED AMIDE COMPOUND
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The present invention provides an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like represented by the following formula (I): [wherein, "A" represents optionally substituted heterocyclic diyl, R1 represents hydrogen atom or optionally substituted lower alkyl, R2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents -O-, -S-, -SO2-, -NRX1- (wherein, RX1 represents hydrogen atom or lower alkyl), -CHRX2- (wherein, RX2 represents hydrogen atom or hydroxy), -CH=CH-, -CO- or -NH-CO-, and n1 and n2 are the same or different, and each represents 0 or 1].
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Paragraph 0514
(2018/11/27)
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- BIARYL PHOSPHODIESTERASE 1NHIBITORS
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Novel biaryl compounds with phosphodiesterase inhibitory activity of the general formula (I), wherein R1, R2, R3, X, Y, Z1, Z2, Z3, and Z4 have the meanings defined herein, as well as their use as therapeutic agents in the treatment of inflammatory diseases and conditions
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Page/Page column 118
(2012/08/29)
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- NOVOBIOCIN ANALOGUES AND TREATMENT OF POLYCYSTIC KIDNEY DISEASE
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Novobiocin analogues are useful in methods of treating, inhibiting, and/or preventing cyst formation in autosomal dominant polycystic kidney disease (ADPKD) in a subject. The disclosure provides methods of treating ADPKD comprising administering a therapeutically effective amount of a coumarin-3-carboxamide novobiocin analogue. Accordingly, the method can include administering a novobiocin analogue in a therapeutically effective amount for reducing levels of mTOR pathway phosphoproteins P-mTOR, P-Akt and P-S6K, or combinations thereof. Further, the method can include administering a novobiocin analogue in a therapeutically effective amount for reducing levels of Hsp-90 client proteins CFTR, ErbB2, c-Raf and Cdk4, or combinations thereof.
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- Total synthesis of lespedezavirgatol
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Lespedezavirgatol, a novel 2-phenylbenzofuran compound which was isolated from Lespedeza virgata, was firstly synthesized from pyrogallic acid and 3,4-dimethoxyphenol as starting materials with 8 steps. The key steps for the total synthesis were the selective iodination at 3-position of 1,2-dimethoxy-4-methoxymethoxybenzene and the Sonogashira cross-coupling reaction between 4-iodo-2-methoxybenzene-1,3-diol and 2-ethynyl-3,4-dimethoxy-1- (methoxy-methoxy)-benzene.
- Qi, Jinping,Deng, Hongzhu,Cao, Derong
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scheme or table
p. 2547 - 2550
(2011/10/05)
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- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
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- The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity
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(Chemical Equation Presented) Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the Hsp90 C-terminus and induces degradation of Hsp90-dependent client proteins at ～700 μM in breast cancer cells (SKBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species exhibit antiproliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated to elucidate structure-activity relationships for novobiocin as an anticancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines.
- Donnelly, Alison C.,Mays, Jared R.,Burlison, Joseph A.,Nelson, John T.,Vielhauer, George,Holzbeierlein, Jeffrey,Blagg, Brian S. J.
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experimental part
p. 8901 - 8920
(2009/04/11)
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- The first direct transformation of 2,2'-dihydroxychalcones into coumestans
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Three coumestans, flemichapparin, medicagol and sophoracoumestan B, are synthesised by direct reaction of the analogous 2,2'-dihydroxychalcones with thallium (III) nitrate in methanol.
- Kamara, B. Irene,Brandt, E. Vincent,Ferreira, Daneel
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p. 861 - 868
(2007/10/03)
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- An improved process for the preparation of 5-bromo-2-methoxyresorcinol
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This invention is concerned with an improved process for metallating 2,4,6-tribromoanisole 1and reacting this intermediate lithio species with various electrophiles for example the trialkoxy borates which an example is trimethylborate, the improvement comprising carrying out the reaction under heterogenous conditions. This product is oxidatively converted to the compound 5-bromo-2-methoxy-resorcinol 2, which is in turn converted to the known 2-methoxy-resorcinol 3. The process and intermediate are useful in the synthesis of platelet activating factor antagonist thiazolium, 3-[[3-[[hydroxy[2-methoxy-3-(tetradecyloxy) phenoxy]phosphinyl]oxy]phenyl]methyl]-5-methyl-, hydroxide, inner salt CA of U. S. Patent 4983592 (1991).
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- SYNTHESIS OF KUKULKANINS A AND B - METHOXY CHALCONES FROM MIMOSA TENUFOLIA L.
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Synthesis of kalkulkanins A (1) and B (2) has been achieved starting from pyrogallol.Key words: Chalcones, Kukulkanins A and B Synthesis, Mimosa tenufolia
- Raju, Vegesna S.,Subbaraju, Gottumukkala V.,Manhas, Maghar S.,Kaluza, Zbigniew,Bose, Ajay K.
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p. 8347 - 8352
(2007/10/02)
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