455-94-7Relevant academic research and scientific papers
Identification of Diarylurea Inhibitors of the Cardiac-Specific Kinase TNNI3K by Designing Selectivity against VEGFR2, p38α, and B-Raf
Cheung, Mui,Desai, Tina A.,Fries, Harvey,Gatto, Gregory J.,Graves, Alan P.,Holt, Dennis A.,Kallander, Lara S.,Patterson, Jaclyn R.,Shewchuk, Lisa,Stoy, Patrick,Totoritis, Rachel,Wang, Liping
, p. 15651 - 15670 (2021/11/16)
A series of diarylurea inhibitors of the cardiac-specific kinase TNNI3K were developed to elucidate the biological function of TNNI3K and evaluate TNNI3K as a therapeutic target for the treatment of cardiovascular diseases. Utilizing a structure-based design, enhancements in kinase selectivity were engineered into the series, capitalizing on the established X-ray crystal structures of TNNI3K, VEGFR2, p38α, and B-Raf. Our efforts culminated in the discovery of an in vivo tool compound 47 (GSK329), which exhibited desirable TNNI3K potency and rat pharmacokinetic properties as well as promising kinase selectivity against VEGFR2 (40-fold), p38α (80-fold), and B-Raf (>200-fold). Compound 47 demonstrated positive cardioprotective outcomes in a mouse model of ischemia/reperfusion cardiac injury, indicating that optimized exemplars from this series, such as 47, are favorable leads for discovering novel medicines for cardiac diseases.
Denitrogenative hydrofluorination of aromatic aldehyde hydrazones using (difluoroiodo)toluene
Kulkarni, Kaivalya G.,Miokovic, Boris,Sauder, Matthew,Murphy, Graham K.
, p. 9907 - 9911 (2016/10/31)
An operationally simple conversion of aromatic aldehyde hydrazones to monofluoromethylated arenes is reported. The hypervalent iodine reagent TolIF2 serves as an oxidant, converting the hydrazone to the corresponding diazo compounds. The by-product of the oxidation process, HF, is consumed in situ by a denitrogenative hydrofluorination reaction of the diazo group.
Transition-metal-free C-H oxidative activation: Persulfate-promoted selective benzylic mono- and difluorination
Ma, Jing-Jing,Yi, Wen-Bin,Lu, Guo-Ping,Cai, Chun
supporting information, p. 2890 - 2894 (2015/04/27)
An operationally simple and selective method for the direct conversion of benzylic C-H to C-F to obtain mono- and difluoromethylated arenes using Selectfluor as a fluorine source is developed. Persulfate can be used to selectively activate benzylic hydrogen atoms toward C-F bond formation without the aid of transition metal catalysts.
Efficient SN2 fluorination of primary and secondary alkyl bromides by copper(I) fluoride complexes
Liu, Yanpin,Chen, Chaohuang,Li, Huaifeng,Huang, Kuo-Wei,Tan, Jianwei,Weng, Zhiqiang
, p. 6587 - 6592 (2013/12/04)
Copper(I) fluoride complexes ligated by phenanthroline derivatives have been synthesized and structurally characterized by X-ray crystallography. These complexes adopt as either ionic or neutral forms in the solid state, depending on the steric bulkiness of the substituent groups on the phenanthroline ligands. These complexes react with primary and secondary alkyl bromides to produce the corresponding alkyl fluorides in modest to good yields. This new method is compatible with a variety of important functional groups such as ether, thioether, amide, nitrile, methoxyl, hydroxyl, ketone, ester, and heterocycle moieties.
HEPATITIS B ANTIVIRAL AGENTS
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Page/Page column 225, (2013/07/05)
The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.
Practical and general method for direct synthesis of alkyl fluorides from alcohols under mild conditions
Bandgar, Babasaheb P.,Kamble, Vinod T.,Biradar, Ankush V.
, p. 1579 - 1582 (2007/10/03)
A variety of alcohols were treated with Ph 3P and KF in CCl 4-DMF at room temperature to afford the corresponding fluorides in very good yields. Springer-Verlag 2005.
Selective electrolytic fluorinations in 70% HF/30% pyridine
Lee, Sarah M.,Roseman, Jamie M.,Zartman, C. Blair,Morrison, Eamonn P.,Harrison, Sean J.,Stankiewicz, Corrie A.,Middleton
, p. 65 - 70 (2007/10/03)
The selective fluorination of compounds containing benzylic hydrogen atoms was accomplished by electrolysis in a mixture of 70% HF and 30% pyridine (Olah's reagent) using a square wave alternating current (1.76-2.75 V, 0.02-0.05 Hz) and Pt electrodes. This method can be used in the laboratory to prepare conveniently gram-size quantities of monofluorinated products. An ion radical mechanism has been proposed.
Novel Synthesis of 2,2,2-Trifluoroethyl Compounds from Homoallylic Alcohols: A Copper(I) Iodide-initiated Trifluoromethyl-Dehydroxylation Process
Duan, Jian-Xing,Chen, Quing-Yun
, p. 725 - 730 (2007/10/02)
Benzyl, prop-2-enyl and allyl chlorodifluoroacetates 3a, bromodifluoroacetates 3b or fluorosulfonyldifluoroacetates 3c, when decomposed in the presence of 1 equivalent of copper(I) iodide at an appropriate temperature in dimethylformamide, gave the corresponding trifluoromethyl derivatives in good to excellent yields.The products can also be obtained directly by ester exchange of XCF2CO2Et (X = FSO2, Cl, Br) 6 and the corresponding alcohols in the presence of KF and CuI.A trifluoromethylation-dehydroxylation mechanism, initiated by CuI, is proposed.
REACTIONS OF NITRO ALCOHOLS WITH N,N-DIETHYL-1,1,2,3,3,3-HEHAXFUOROPROPYLAMINE
Watanabe, S.,Fujita, T.,Sakamoto, M.,Endo, H.
, p. 243 - 248 (2007/10/02)
Fluorination of nitro alcohols with N,N-diethyl-1,1,2,3,3,3-hexafluoropropylamine (PPDA) was investigated. 3-Nitrobenzyl fluoride (II) was obtained from the reaction of PPDA and 3-nitrobenzyl alcohol (I) (yield 66 percent).The reaction of 2-methyl-2-nitro
