- Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model
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FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML.
- Heng, Hao,Wang, Zhijie,Li, Hongmei,Huang, Yatian,Lan, Qingyuan,Guo, Xiaoxing,Zhang, Liang,Zhi, Yanle,Cai, Jiongheng,Qin, Tianren,Xiang, Li,Wang, Shuxian,Chen, Yadong,Lu, Tao,Lu, Shuai
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p. 248 - 267
(2019/05/21)
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- Unexpectedly high activity of Zn(OTf)2·6H2O in catalytic Friedel-Crafts acylation reaction
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Zn(OTf)2·6H2O was used to promote Friedel-Crafts acylation of aromatics. The work describes the high activity and efficiency of Zn(OTf)2·6H2O in acylation of aromatics, and the catalyst has surpassed most metal triflates in dispensing when dried at high temperature under vacuum before use. Copyright Taylor & Francis Group, LLC.
- He, Fei,Wu, Huayue,Chen, Jiuxi,Su, Weike
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p. 255 - 264
(2008/03/17)
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- PROCESS FOR PRODUCING 2-ACYLTHIOPHENE COMPOUND
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The present invention provides a process for producing a 2-acylthiophene compound which has a low content of the 3-isomer generated as a by-product, the process comprising reacting a thiophene compound represented by formula (1) : wherein R1 is a hydrogen atom, a C1-6 alkyl group, a phenyl group, or a halogen atom, with at least one member selected from the group consisting of acid anhydrides represented by formula (2): wherein R2 is a C1-6 alkyl group or a phenyl group, and acid halides represented by formula (3): wherein R2 is as defined above and X is a halogen atom, in the presence of a solid acid catalyst at a temperature less than 75°C in the absence of solvent, thus producing a 2-acylthiophene compound represented by formula (4): wherein R1 and R2 are as defined above.
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Page/Page column 7
(2008/06/13)
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- CHEMICAL COMPOUNDS
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Compounds of formula (I):wherein variable groups are as defined within; for use in the inhibition of 11betaHSD1 are described
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Page 124-125
(2010/02/06)
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- Ytterbium(III) trifluoromethanesulfonate catalysed Friedel-Crafts acylation of substituted thiophenes
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Ytterbium(III) trifluoromethanesulfonate [Yb(OTf)3] has been used to catalyse Friedel-Crafts acylation of substituted thiophenes in different solvents to produce several intermediates of pharmaceuticals and pesticides with good yields. The amount of catalysis was discussed and Yb(OTf)3 could be reused without loss of activity.
- Su, Weike,Jin, Can
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p. 694 - 695
(2007/10/03)
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- Reevaluation of benzyltrimethylammonium dichloroiodide, previously reported to be a selective iodinating agent
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Benzyltrimethylammonium dichloroiodate, previously reported as an iodinating agent of thiophenes, appears to be a selective chlorinating agent of both thienyl and furyl derivatives containing a carbonyl group.
- D'Auria,Mauriello
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p. 248 - 250
(2007/10/02)
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- Facile synthesis of 5-substituted 2-acetylthiophenes
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5-Substituted 2-(α-alkoxyimino)ethylthiophenes 4-8 are obtained by the reaction of 2-(α-alkoxyimino)ethylthiophenes 3 and electrophilic reagents. Hydrolysis of thiophenes 4-8 produces 5-substituted 2-acetylthiophenes 9-13, respectively. Compounds 3 are easily obtained either by the reaction of 2-acetylthiophene (1) and an O-alkylhydroxylamine or by oxidation of 1 followed by O-alkylation.
- Goda,Sato,Ihara,Hirayama
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p. 849 - 851
(2007/10/02)
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- Thiophene derivatives and methods for producing the same
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Novel compounds, 2-(α-alkoxyimino)ethylthiophenes are susceptible to electrophilic substitution reactions, and the acetylation, nitration, sulfonation and halogenation of the compounds provide 5-acetyl-2-(α-alkoxyimino)ethylthiophenes, 5-nitro-2-(α-alkoxyimino)ethylthiophenes, 5-(α-alkoxyimino)ethyl-2-thiophenesulfonic acid and 5-halo-2-(α-alkoxyimino)ethylthiophenes, respectively. The hydrolysis of 5-acetyl-2-(α-alkoxyimino)ethylthiophenes readily provides a known compound, 2,5-diacetylthiophene which is an important intermediate for the production of medicines, whereas the haloform reaction provides novel compounds, 5-(α-alkoxyimino)ethyl-2-thiophenecarboxylic acids, the hydrolysis of which compounds readily provides a known compound, 5-acetyl-2-thiophenecarboxylic acids, an important intermediate for the production of medicines. The hydrolysis of 5-(α-alkoxyimino)ethyl-2-thiophenesulfonic acids and their salts provide novel 5-acetyl-2-thiophenesulfonic acid and its salts, respectively. Novel compounds, 2-(α-alkoxyimino)ethylthiophenes are obtained either by 0-alkylation of 2-acetylthiophene oxime or by directly reacting 2-acetylthiophene with an 0-alkylhydroxylamine.
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- Kinetics of the Detritiation of a Series of 4- and 5-Substituted 2-(acetyl)thiophenes
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A series of 4- and 5-substituted 2-(acetyl)thiophenes have been prepared and the kinetics of the hydroxide-catalysed detritiation studied at 25.0 deg C.The second-order detritiation rate constants parallel those observed for the corresponding meta- and para-substituted acetophenones but as the reaction constant ρ is higher (1.61) the range of reactivity is much wider than that witnessed for the acetophenones.
- Jones, John R.,Pearson, Gerd M.,Spinelli, Domenico,Consiglio, Giovanni,Arnone, Caterina
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p. 557 - 558
(2007/10/02)
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