- EFFECTS ON N,N'-BIS-(4-TRIFLUOROMETHYLPHENYL)-UREA ON ISOLATED PLANT MITOCHONDRIA AND THYLAKOID MEMBRANES
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The N,N'-bis(trifluoromethylphenyl)-urea is demonstrated to be powerful uncoupler of ATP formation in plant mitochondria and thylakoid membranes.In mitochondria, the full uncoupling effect was obtained at a concentration of 3 μM uncoupling agent in the me
- Routaboul, Jean-Marc,Mougin, Christian,Ravanel, Patrick,Tissut, Michel,MrLina, Georges,Calmon, Jean-Pierre
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- Di-tert-butyl peroxide (DTBP)-mediated synthesis of symmetrical N,N′-disubstituted urea/thiourea motifs from isothiocyanates in water
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ABATRACT: A direct approach to N,N′-disubstituted urea/thiourea from the self-condensation reactions of isothiocyanates in water has been developed. This access tolerated a wide range of functional groups on the aromatic ring, providing a practical and environment-friendly process to N,N′-disubstituted urea/thiourea in moderate to excellent yields from safe and easily available starting materials. A plausible mechanism of the desulfurization self-condensation reaction for urea was also proposed and the role of di-tert-butyl peroxide (DTBP) and copper catalyst in the present strategy was demonstrated with the help of ESI mass spectrometry of intermediate studies.
- Chen, Ling,Dong, Yibo,Wu, Yangjie,Yang, Jinchen,Zhang, Jinli
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supporting information
(2021/12/01)
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- Amide-assisted rearrangement of hydroxyarylformimidoyl chloride to diarylurea
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A novel amide-assisted rearrangement reaction of hydroxybenzimidoyl chloride has been established for the efficient synthesis of 1,3-diphenylurea derivatives. A variety of electronically and sterically different 1,3-diphenylurea derivatives can be obtained in good to excellent yields, and a proposed reaction mechanism is also presented.
- Jin, Yi,Liu, Xiaoyu,Song, Xizhong,Yu, Wei
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supporting information
(2021/11/11)
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- Urea-Catalyzed Vinyl Carbocation Formation Enables Mild Functionalization of Unactivated C-H Bonds
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Herein we report the 3,5-bistrifluoromethylphenyl urea-catalyzed functionalization of unactivated C-H bonds. In this system, the urea catalyst mediates the formation of high-energy vinyl carbocations that undergo facile C-H insertion and Friedel-Crafts re
- Bagdasarian, Alex L.,Popov, Stasik,Wigman, Benjamin,Wei, Wenjing,Lee, Woojin,Nelson, Hosea M.
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supporting information
p. 7775 - 7779
(2020/07/15)
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- Design, synthesis, and biological evaluation of novel substituted thiourea derivatives as potential anticancer agents for NSCLC by blocking K-Ras protein-effectors interactions
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Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01–TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 μM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.
- Cheng, Minghui,Meng, Xin,Tang, Haikang,Xu, Wenqing,Yang, Fujun,Zhang, Yuan
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p. 344 - 353
(2019/12/30)
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- Hydrosilane-Assisted Synthesis of Urea Derivatives from CO2and Amines
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A methodology employing CO2, amines, and phenylsilane was discussed to access aryl- or alkyl-substituted urea derivatives. This procedure was characterized by adopting hydrosilane to promote the formation of ureas directly, without the need to prepare silylamines in advance. Control reactions suggested that FeCl3 was a favorable additive for the generation of ureas, and this 1,5,7-triazabicyclo[4.4.0]dec-5-ene-catalyzed reaction might proceed through nucleophilic addition, silicon migration, and the subsequent formal substitution of silylcarbamate.
- Zhao, Yulei,Guo, Xuqiang,Si, Zhiyao,Hu, Yanan,Sun, Ying,Liu, Yunlin,Ji, Zhongyin,You, Jinmao
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p. 13347 - 13353
(2020/11/02)
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- Zinc Powder Catalysed Formylation and Urealation of Amines Using CO2 as a C1 Building Block?
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Transformation of CO2 into valuable organic compounds catalysed by cheap and biocompatible metal catalysts is one of important topics of current organic synthesis and catalysis. Herein, we report the zinc powder catalysed formylation and urealation of amines with CO2 and (EtO)3SiH under solvent free condition. Using 2 molpercent zinc powder as the catalyst, a series of secondary amines, both the aromatic ones and the aliphatic ones, can be formylated into formamides. When primary aromatic amines were used as the substrates, the reactions produce urea derivatives. The electronic and steric effects from the substrates on the formylation and urealation reactions were observed and discussed. The recovery and reusability of zinc powder were investigated, showing the zinc powder can be reused in the formylation reaction without loss of catalytic activity. The analysis on the reactants/products mixture after filtering out the zinc powder showed the zinc concentration in the mixture is low to 1 ppm. The pathways for the formylation and urealation of amines with this catalytic system were also investigated, and related to the different substrates.
- Du, Chongyang,Chen, Yaofeng
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p. 1057 - 1064
(2020/06/30)
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- Simple preparation method of N-acyl compound
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The invention relates to a simple preparation method of an N-acyl compound. The simple preparation method comprises the specific steps that an amine compound and R-OCF3 are mixed in a solvent and react for 1 min-48 h at -80-100 DEG C, after the reaction is completed, water is added for quenching, and column separation and purification or recrystallization and purification are carried out to obtainthe N-acyl compound. According to the simple preparation method of the N-acyl compound, the characteristic that a substance containing trifluorooxygen groups can be decomposed in situ to produce fluorophosgene is utilized, and the substance directly reacts with the amine compound to achieve rapid N-carbonylation of an amines substrate and efficiently prepare a urea derivative and a carbamyl fluoride compound. The simple preparation method of the N-acyl compound has the advantages that the operation is simple, the reaction time is short, the application range of the substrate is wide, no catalysts or additives need to be used, the raw materials are easy to obtain, the product yield is high, the purification is easy, and the required compound can be obtained by using a column chromatographyisolation method or recrystallization.
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Paragraph 0040-0042
(2019/07/04)
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- Concise and Additive-Free Click Reactions between Amines and CF3SO3CF3
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Trifluoromethyl trifluoromethanesulfonate has proved to be an excellent reservoir of difluorophosgene and a promising click ligation for amines in the preparation of urea derivatives, heterocycles, and carbamoyl fluorides under metal- and additive-free conditions. The reactions are rapid, efficient, selective, and versatile, and can be performed in benign solvents, giving products in excellent yields with minimal efforts for purification. The characteristics of the reactions meet the requirements of a click reaction. The use of trifluoromethyl trifluoromethanesulfonate as a click reagent is advantageous over other “CO” sources (e.g., TsOCF3, PhCO2CF3, CsOCF3, AgOCF3, and triphosgene) because this reagent is readily accessible; easy to scale up; and highly reactive, even under metal- and additive-free conditions. It is anticipated that CF3SO3CF3 will be increasingly as important as SO2F2 as a click agent in future drug design and development.
- Song, Hai-Xia,Han, Zhou-Zhou,Zhang, Cheng-Pan
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supporting information
p. 10907 - 10912
(2019/08/02)
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- Compound comprising urea and thiourea structures and synthesis method and application of compound
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The invention relates to an organic small molecular compound comprising urea and thiourea structures in a formula I and a synthesis method and application of the compound. According to in-vitro antitumor activity tests, the compound has high antitumor act
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Paragraph 0105-0107
(2019/08/07)
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- The: Trans / cis photoisomerization in hydrogen bonded complexes with stability controlled by substituent effects: 3-(6-aminopyridin-3-yl)acrylate case study
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The association of aminopyridine-based acrylic acid and its salt was studied by NMR titration experiments. The AA (acceptor, acceptor) hydrogen-bonding pattern present in the salt forms a complex readily with a DD (donor, donor) hydrogen-bonding pattern of the substituted ureas even in polar and competitive environment. The double carbon-carbon bond in the acrylic acid derivative is subjected to photoisomerization. This is dependent on the association with substituted urea derivatives. The substituent in ureas influences the trans/cis isomerization kinetics and position of the photostationary state. Two mechanisms that influence the photoisomerization were proposed. To the best of our knowledge, the trans/cis photoisomerization influenced by the substituent in such a hydrogen-bonding pattern has not observed previously. It was shown that interaction with urea derivatives causes lowering of the trans-to-cis photoreaction rates.
- Kwiatkowski, Adam,J?drzejewska, Beata,Józefowicz, Marek,Grela, Izabela,O?mia?owski, Borys
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p. 23698 - 23710
(2018/07/13)
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- Effective approach to ureas through organocatalyzed one-pot process
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An efficient approach to N, N′-unsymmetrically substituted ureas 9 has been developed through the ammonolysis process of N-Boc protected anilines 7 with amines prompted by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). Moreover, a convenient protocol for the
- Wang, Mingliang,Han, Jilai,Si, Xiaojia,Hu, Yimin,Zhu, Jidong,Sun, Xun
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supporting information
p. 1614 - 1618
(2018/03/28)
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- Hydrogen-Bonded Homoleptic Fluoride-Diarylurea Complexes: Structure, Reactivity, and Coordinating Power
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Hydrogen bonding with fluoride is a key interaction encountered when analyzing the mode of action of 5′-fluoro-5′-deoxyadenosine synthase, the only known enzyme capable of catalyzing the formation of a C-F bond from F-. Further understanding of the effect of hydrogen bonding on the structure and reactivity of complexed fluoride is therefore important for catalysis and numerous other applications, such as anion supramolecular chemistry. Herein we disclose a detailed study examining the structure of 18 novel urea-fluoride complexes in the solid state, by X-ray and neutron diffraction, and in solution phase and explore the reactivity of these complexes as a fluoride source in SN2 chemistry. Experimental data show that the structure, coordination strength, and reactivity of the urea-fluoride complexes are tunable by modifying substituents on the urea receptor. Hammett analysis of aryl groups on the urea indicates that fluoride binding is dependent on σp and σm parameters with stronger binding being observed for electron-deficient urea ligands. For the first time, defined urea-fluoride complexes are used as fluoride-binding reagents for the nucleophilic substitution of a model alkyl bromide. The reaction is slower in comparison with known alcohol-fluoride complexes, but SN2 is largely favored over E2, at a ratio surpassing all hydrogen-bonded complexes documented in the literature for the model alkyl bromide employed. Increased second-order rate constants at higher dilution support the hypothesis that the reactive species is a 1:1 urea-fluoride complex of type [UF]- (U = urea) resulting from partial dissociation of the parent compound [U2F]-. The dissociation processes can be quantified through a combination of UV and NMR assays, including DOSY and HOESY analyses that illuminate the complexation state and H-bonding in solution.
- Pfeifer, Lukas,Engle, Keary M.,Pidgeon, George W.,Sparkes, Hazel A.,Thompson, Amber L.,Brown, John M.,Gouverneur, Véronique
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supporting information
p. 13314 - 13325
(2016/10/22)
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- Small molecule fluoride toxicity agonists
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Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by u
- Nelson, James W.,Plummer, Mark S.,Blount, Kenneth F.,Ames, Tyler D.,Breaker, Ronald R.
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p. 527 - 534
(2015/05/05)
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- Squaramides as potent transmembrane anion transporters
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Square peg in a round ball: Squaramides are shown to be potent transmembrane anion transporters for both chloride and bicarbonate, performing better than the thiourea and urea analogues. Studies into the nature of this transport point to a mobile carrier mechanism, where the squaramide delivers the anion cargo across the lipid bilayer (see scheme, green sphere=anion). These drug-like molecules provide a platform for the development of a new generation of anion-transport systems. Copyright
- Busschaert, Nathalie,Kirby, Isabelle L.,Young, Sarah,Coles, Simon J.,Horton, Peter N.,Light, Mark E.,Gale, Philip A.
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supporting information; experimental part
p. 4426 - 4430
(2012/06/04)
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- Urea-, squaramide-, and sulfonamide-based anion receptors: A thermodynamic study
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In this work, we compare the anion-binding capabilities of receptors 1-5, characterized by similar structures, but possessing different hydrogen-bond-donor moieties (urea, squaramide, and sulfonamide). The presence of chromophoric substituents on the receptor's skeleton allowed the determination of association constants by performing UV/Vis titrations with the investigated anions on solutions of the receptors in pure acetonitrile. Additional quantitative studies of the anion-binding properties of receptors 1-5 were performed by isothermal titration calorimetry (ITC). The experimental results indicated that 1 and 2 formed 1:1 hydrogen-bonded complexes with most of the anions investigated. In the case of receptors 3-5, the formation of the 1:1 adduct was observed only with anions of low basicity (i.e., chloride, bromide, iodide, and hydrogen sulfate). With more basic anions (i.e., acetate and dihydrogen phosphate), both spectrophotometric and ITC titrations accounted for the deprotonation of the sulfonamide group, involving the formation of the conjugated base of the receptor. Copyright
- Amendola, Valeria,Fabbrizzi, Luigi,Mosca, Lorenzo,Schmidtchen, Franz-Peter
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supporting information; experimental part
p. 5972 - 5981
(2011/07/07)
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- Electrochemically controlled hydrogen bonding. O-quinones as simple redox-dependent receptors for arylureas
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9,10-Phenanthrenequinone and acenaphthenequinone are shown to act as simple redox-dependent receptors toward aromatic ureas in CH2Cl2 and DMF. Reduction of the o-quinones to their radical anions greatly increases the strength of hydr
- Ge,Miller,Ouimet,Smith
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p. 8831 - 8838
(2007/10/03)
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- REARRANGEMENT OF N-(TRIFLUOROMETHYL)ANTHRANILOYL FLUORIDE TO 2-(TRIFLUOROMETHYL)ANILINE - KINETIC AND MECHANISTIC OBSERVATIONS
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Pseudo first order rate constants for the rearrangement of N-(trifluoromethyl)anthraniloyl fluoride (2) to N-carbamoyl fluoride (3) in anhydrous HF have been determined.Increasing HF levels accelerate this process, but increasing KF concentrations retard the reaction.An ionic species has been proposed as the intermediate in the suggested mechanism.Further reaction of 3 with HF proceeded to give 2-(trifluoromethyl)aniline hydrofluoride (4) via an unprecedented expulsion of carbonyl fluoride.
- Lin, Henry C.,Cotter, Byron R.,Bieron, Joseph F.,Krishnamurti, Ramesh
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p. 107 - 116
(2007/10/02)
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