- Late-stage Pd-catalyzed Cyanations of Aryl/Heteroaryl Halides in Aqueous Micellar Media
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New technology is described that enables late stage ppm Pd-catalyzed cyanations of highly complex molecules, as well as a wide variety of aryl and heteroaryl halides possessing sensitive functional groups. These reactions are efficient in water containing nanomicelles, formed from a commercially available and inexpensive surfactant. The implications for advancing drug synthesis and discovery are apparent.
- Thakore, Ruchita R.,Takale, Balaram S.,Singhania, Vani,Gallou, Fabrice,Lipshutz, Bruce H.
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p. 212 - 216
(2020/12/01)
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- 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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- Compounds and use thereof in anti-AML drugs
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The present invention relates to the field of medicinal chemistry, discloses compounds and use thereof in anti-AML drugs, and specifically relates to imidazole ring-substituted thiophenic compounds, preparation method thereof, pharmaceutical compositions containing the compounds, and medical use of the compounds, particularly use of the compounds as an ITD mutant selective inhibitor of FMS-like tyrosine kinase 3.
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Paragraph 0152; 0195; 0196; 0197
(2018/11/04)
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- Aryl nitrile compound preparation method
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The present invention provides a preparation method of an aryl nitrile compound having a general formula I, wherein the general formula I is defined in the specification. The preparation method comprises: adopting an aryl compound having a general formula II as a substrate, wherein the general formula II is defined in the specification, n is 0-1, X1, X2, X3 and X4 are independently and respectively any one selected from N, S, O and C in chemically acceptable structures, Y is OSO2F, OTf or OTs, and R1, R2, R3 and R4 are independently and respectively any one selected from H, alkyl, aryl and halogen; and carrying out a cyanation reaction on the aryl compound and a cyanogen source under the catalysis effect of a catalyst, a reducing agent and a ligand to obtain the aryl nitrile compound. With the preparation method of the present invention, the aryl nitrile compound preparation cost can be reduced, the required reaction temperature is low, the requirements on the catalyst is low, the conversion rate is high, and the preparation method is suitable for various aryl or miscellaneous aryl substrates containing electron-rich or electron-deficient substituents.
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Paragraph 0112; 0113; 0114
(2017/06/20)
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- Mild palladium-catalyzed cyanation of (hetero)aryl halides and triflates in aqueous media
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A mild, efficient, and low-temperature palladium-catalyzed cyanation of (hetero)aryl halides and triflates is reported. Previous palladium-catalyzed cyanations of (hetero)aryl halides have required higher temperatures to achieve good catalytic activity. This current reaction allows the cyanation of a general scope of (hetero)aryl halides and triflates at 2-5 mol % catalyst loadings with temperatures ranging from rt to 40 °C. This mild method was applied to the synthesis of lersivirine, a reverse transcriptase inhibitor.
- Cohen, Daniel T.,Buchwald, Stephen L.
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supporting information
p. 202 - 205
(2015/01/30)
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- ZnO-supported Pd nanoparticle-catalyzed ligand- and additive-free cyanation of unactivated aryl halides using K4[Fe(CN)6]
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The use of a new ZnO-supported palladium(0) nanoparticle catalyst for the cyanation of aryl halides using a relatively benign cyanide source, K 4[Fe(CN)6], is described. This catalyst has been applied for the efficient cyanation of a variety of functionalized aryl bromides and activated aryl chlorides. This process circumvents the need for an additive and a ligand for the reaction and offers the advantages of high product yields, low catalyst loading (0.2 mol % Pd), and recyclability of the catalyst.
- Chatterjee, Tanmay,Dey, Raju,Ranu, Brindaban C.
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p. 5875 - 5879
(2014/07/08)
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- Palladium-Catalyzed Cyanation Reactions of Thiophene Halides
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The described method provides an efficient cyanation reaction of thiophene halides using tris(dibenzylidene-acetone)dipalladium(0), 1,1′-bis- (diphenylphosphino)ferrocene) and zinc powder as the catalyst system and Zn(CN)2 as the cyanide source
- Erker, Thomas,Nemec, Stephanie
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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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