- CARBONYLATION OF NITROBENZENE WITH RUTHENIUM CLUSTERS
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Evidence is presented for the participation of cluster intermediates in the carbonylation of nitrobenzene.
- Basu, Amitabha,Bhaduri, Sumit,Khwaja, Hanif
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- Carbamoyl complexes as a source of isocyanates or carbamyl chlorides
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Isocyanates or carbamyl chlorides have been prepared by reaction of carbamoyl complexes of nickel and palladium with CuCl2.Isocyanates are selectively produced from the carbamoyl complexes of primary amines, , (L=2,6-bis(diphenylphosphinomethyl) pyridine; R=C6H5, p-CH3C6H4, or p-ClC6H4)) and , whereas carbamoyl complexes of secondary amines, such as , afford carbamyl chloride.As expected, the reaction of the resulting isocyanates or carbamyl chlorides in situ with alcohols or amines produces carbamates or N,N'-substituted ureas, respectively.Key words: Carbamyl chloride; Carbamate; Carboxamide; Chloroformamide; Complex; Isocyanates; Palladium; Phosphine; Synthesis
- Giannoccaro, Potenzo,Tommasi, Immacolata,Aresta, Michele
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- Preferred Binding of Carboxylates by Chiral Urea Derivatives Containing α-Phenylethyl Group
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An efficient, simple protocol for the synthesis of a new family of chiral ureas 1 – 4 is described. The binding properties of 1 – 4 toward different anion (acetate, benzoate, fluoride, and chloride) have been studied by1H-NMR titration and have been observed in the case of 4 is a selective receptor for acetate. The theoretical calculation M06/6-311+G(d,p) helped us explain the binding properties observed. The most interesting observation is that this calculated structure is consistent with expected, based on the concept of allylic 1,3-strain (A1,3strain). When chiral caboxylates were studied, urea 1 was the best in discriminating between enantiomers.
- Cortés-Hernández, Mayra,Rojas-Lima, Susana,Hernández-Rodríguez, Marcos,Cruz-Borbolla, Julián,López-Ruiz, Heraclio
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- Design, Synthesis and Biological Evaluation of a New Series of 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea Derivatives as Antiproliferative Agents
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To discover new antiproliferative agents with high efficacy and selectivity, a new series of 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea derivatives (7a–7t) were designed, synthesized and evaluated for their antiproliferative activity against A549, HCT-116 and PC-3 cancer cell lines in vitro. Most of the target compounds demonstrated significant antiproliferative effects on all the selective cancer cell lines. Among them, the target compound, 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-{4-{{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}thio}phenyl}urea (7i) was identified to be the most active one against three cell lines, which was more potent than the positive control with an IC50 value of 1.53 ± 0.46, 1.11 ± 0.34 and 1.98 ± 1.27 μM, respectively. Further cellular mechanism studies confirmed that compound 7i could induce the apoptosis of A549 cells in a concentration-dependent manner and elucidated compound 7i arrests cell cycle at G1 phase by flow cytometry analysis. Herein, the studies suggested that the 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea skeleton might be regarded as new chemotypes for designing effective antiproliferative agents.
- Zhang, Chuanming,Tan, Xiaoyu,Feng, Jian,Ding, Ning,Li, Yongpeng,Jin, Zhe,Meng, Qingguo,Liu, Xiaoping,Hu, Chun
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- Multijet oscillating disc millireactor: A novel approach for continuous flow organic synthesis
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This report discloses proof of concept and experimental results from a project involving design, development, and investigation of a novel approach for flow chemistry and the realization of equipment operating according to this new approach. This device is named multijet oscillating disk (MJOD) reactor and is dedicated to continuous flow organic synthesis in milliscale. Characteristics such as the importance of the multijet disk unit, with or without oscillating, and possible limitations, such as back-mixing, have been explored, and the flow system is benchmarked with other technologies. Several well-known reactions and syntheses usefully both in the chemical industry as well as in the research laboratory have been conducted using the new system, which have been benchmarked with batch- and microreactor protocols. In particular the Haloform reaction, the Nef reaction, nucleophilic aromatic substitution, the Paal-Knorr pyrrole synthesis, sodium borohydride reduction, O-allylation, the Suzuki cross-coupling reaction, the Hofmann rearrangement and N-acylation were performed during the study of the MJOD reactor performance. Our investigations revealed that the MJOD millireactor system can produce various organic compounds at a high rate concomitant with an excellent selectivity. A Hofmann rearrangement was conducted, a reaction that involves handling of a slurry of the substrate. This reaction was successfully conducted, achieving a quantitative conversion into the target molecule.
- Liguori, Lucia,Bjorsvik, Hans-Rene
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- CO2 conversion to phenyl isocyanates by uranium(vi) bis(imido) complexes
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Uranium(vi) trans-bis(imido) complexes [U(κ4-{(tBu2ArO)2Me2-cyclam})(NPh)(NPhR)] react with CO2 to eliminate phenyl isocyanates and afford uranium(vi) trans-[OUNR]2+ complexes, including [U(κ4-{(tBu2ArO)2Me2-cyclam})(NPh)(O)] that was crystallographically characterized. DFT studies indicate that the reaction proceeds by endergonic formation of a cycloaddition intermediate; the secondary reaction to form a dioxo uranyl complex is both thermodynamically and kinetically hindered.
- Maria, Leonor,Bandeira, Nuno A. G.,Mar?alo, Joaquim,Santos, Isabel C.,Gibson, John K.
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- The curtius rearrangement of acyl azides revisited - Formation of cyanate (R-O-CN)
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The Curtius rearrangement is a synthesis of isocyanates (R-N=C=O) by thermal or photochemical rearrangement of acyl acides and/or acylnitrenes. The photochemical rearrangement of benzoyl azide is now shown for the first time to produce a small amount of phenyl cyanate (Ph-O-CN) together with phenyl isocyanate. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Wentrup, Curt,Bornemann, Holger
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- Palladium-catalyzed reductive carbonylation of nitrobenzene for producing phenyl isocyanate
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Direct reductive carbonylation of nitrobenzene to phenyl isocyanate with carbon monoxide was performed using various types of palladium catalysts together with many types of N-donor ligands. The effect of reaction time, pressure, temperature, ligand amount, and molar ratio to establish the optimized conditions was also investigated. With this, we were able to achieve up to 100% conversion and 63.5% yield with PdCl2 and alkylimidazole system (1:3) within 2 h at 220 °C and 1400 psi of CO in toluene.
- Nguyen, Thanh Tung,Tran, Anh Vy,Lee, Hye Jin,Baek, Jayeon,Kim, Yong Jin
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- Development of tyrosinase labile protecting groups for amines
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(Chemical Equation Presented) The development of two novel protecting groups for amines is described. Thus, a range of amines have been converted to ureas, and the deprotection of these upon exposure to mushroom tyrosinase (E.C. 1.14.18.1) has been demonstrated.
- Osborn, Helen M. I.,Williams, Nana Aba O.
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- Reactivity of Carbamoyl Radicals: the First General and Convenient Free-radical Synthesis of Isocyanates
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The first free-radical synthesis of isocyanates was performed by oxidation of oxalic acid monoamides by S2O82-, catalysed by silver(I) and copper(II) salts, in a two-phase system.
- Minisci, Francesco,Coppa, Fausta,Fontana, Francesca
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- A new and efficient palladium-catalyzed synthesis of a 2,3,4,5- tetrahydro-1H-2,4-benzodiazepine-1,3-dione derivative
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The palladium-catalyzed intramolecular cyclization of 1-butyl-1(o- iodobenzyl)-3-phenylurea 1 at 80°C in the presence of carbon monoxide at atmospheric pressure gives the corresponding 2,3,4,5-tetrahydro-1H-2,4- benzodiazepine-1,3-dione derivative 2 in 91% yield. Yield and selectivity are strongly affected by the solvent.
- Bocelli, Gabriele,Catellani, Marta,Cugini, Federica,Ferraccioli, Raffaella
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- Synthesis and biological evaluation of novel 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives as potential antitumor agents
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A novel series of 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives were synthesized and evaluated against different tumor cell lines. Experiments in vitro showed that these derivatives could inhibit the proliferation of two kinds of human cancer cell lines (HepG2, HCT116) at low micromolar concentrations and the most potent analog 5q possessed broad-spectrum antiproliferative activity. Experiments in vivo demonstrated that 5q could effectively prolong the longevity of colon carcinoma-burdened mice and slow down the progression of cancer cells by suppression of angiogenesis and the induction of apoptosis and necrosis.
- Hu, Min,Meng, Nana,Xia, Yong,Xu, Youzhi,Yu, Luoting,Zeng, Xiuxiu,Zhou, Shuyan
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- Continuous Flow Synthesis of Urea-Containing Compound Libraries Based on the Piperidin-4-one Scaffold
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The advantages of performing reactions in continuous flow vs. the classic batch processes render flow chemistry a suitable technique for library synthesis. Inspired by our recent work to create fluorine-containing nitrogen heterocycles and by the potentia
- Riesco-Domínguez, Alejandra,Blanco-Ania, Daniel,Rutjes, Floris P. J. T.
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- One-pot synthesis of carbamates and thiocarbamates from Boc-protected amines
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A highly efficient one-pot procedure for the synthesis of carbamates and thiocarbamates has been described. In the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, the isocyanate intermediates were generated in situ for further reactions with alcohols and thiols to afford the desired carbamates and thiocarbamates in high yields.
- Kim, Hee-Kwon,Lee, Anna
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- Synthesis of new coumarin compounds and its hypoglycemic activity and structure-activity relationship
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Novel coumarin compounds were designed and synthesized by combining the active moieties of hypoglycemic drugs. The coumarin compounds were made by sulfanilamide with isocynate, the intermediate sulfanilamide was formed from coumarin by chlorosulfonated and aminated. These targeted compounds were characterized by FT-IR, 1H NMR and MS spectra and their hypoglycemic activities were evaluated in mice. The preliminary results showed that some compounds exhibited evident hypoglycemic effect (P > 0.01, CMC-Na as negative control). The relationship between these compounds structure with their hypoglycemic activities were studied in order to design new antidiabetic agents.
- Qi, Gang,Zhang, Wenguo
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- Matrix isolation, time-resolved IR, and computational study of the photochemistry of benzoyl azide
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It was shown recently on the basis of DFT calculations (N. P. Gritsan and E. A. Pritchina, Mendeleev Commun., 2001, 11, 94) that the singlet states of aroylnitrenes undergo tremendous stabilization due to an extra N-O bonding interaction. To test experimentally the multiplicity and the structure of the lowest state of benzoylnitrenes we performed a study of their photochemistry in Ar matrices at 12 K. Formation of two species was observed on irradiation of benzoyl azide (1b) and its 4-acetyl derivative (1c). One of these species has an IR spectrum, which is consistent with that of isocyanate (2b,c). The IR and UV spectra of the second intermediate are in very good agreement with the calculated spectra of the singlet species (3b,c), whose structure is intermediate between that of a carbonylnitrene and an oxazirene. We further examined the photochemistry of benzoyl azide in solution at ambient temperatures by nanosecond time-resolved IR methods and obtained additional evidence for the singlet ground state of benzoylnitrene as well as insight into its reactivity in acetonitrile, cyclohexane, and dichloromethane. The above experiments were accompanied by quantum chemical calculations which included also a thorough investigation of the parent species, formylnitrene, at different levels of theory.
- Pritchina, Elena A.,Gritsan, Nina P.,Maltsev, Alexander,Bally, Thomas,Autrey, Tom,Liu, Yonglin,Wang, Yuhong,Toscano, John P.
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- Preparation and photocatalytic property of hexagonal cylinder-like bipods ZnO microcrystal photocatalyst
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Single crystalline ZnO with hexagonal cylinder-like bipods morphologies were successfully synthesized via a cationic surfactant-assisted hydrothermal microemulsion route. The structure, morphologies and properties of the as-prepared samples were determined using X-ray diffraction, scanning electron microscopy, photoluminescence spectrum and Ultraviolet and Visible absorption spectroscopy. The photocatalytic activities of the obtained products were evaluated by the degradation of Reactive Brilliant Red K-2BP in aqueous solution under a variety of conditions. Under the optimum condition, approximately 99.5% decolorization efficiency within 45 min and 65.3% TOC removal efficiency within 3 h were achieved, which were higher than that by the commercial ZnO. Moreover, the degradation products were analyzed by a gas chromatography coupled with mass spectrometry system and the probable pathways for the formation of the intermediates were proposed. The photocatalytic results indicated that the as-prepared ZnO showed good photocatalytic activity and it could be considered as a promising photocatalyst for dyes wastewater treatment.
- Liu, Yumin,Hua, Lv,Li, Shuangqing,Xing, Xinyan,Xi, Guoxi
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- Kinetics of the homogeneous, unimolecular elimination reactions of ethyl oxamate, ethyl N,N-dimethyloxamate and ethyl oxanilate in the gas phase
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The gas-phase elimination kinetics of the title compounds were determined over the temperature range 350-430°C and pressure range 35-240 Torr (1 Torr = 133.3 Pa). The reactions, which were carried out in a static reactor system, seasoned with allyl bromide and in the presence of a free radical inhibitor, are homogeneous, unimolecular and obey a first-order rate law. The temperature dependences of the overall rate coefficients are given by the following Arrhenius equations: for ethyl oxamate, log [k1 (s-1)] = (13.28±0.20)-(203.7±2.5)kJ mol-1 (2.303RT) -1, for ethyl N,N-dimethyloxamate, log [k1(s -1)] = (13.06±0.34)-(206.8±4.4)kJ mol -1(2.303RT)-1, and for ethyl oxanilate, log [k1 (s-1)] = (13.86±0.12)-(207.4±1.5)kJ mol -1(2.303RT)-1. The overall rates, the partial rates and the kinetic and thermodynamic parameters of these eliminations are presented and discussed. These reactions appear to proceed through moderately polar cyclic transition states. Copyright
- Chacin, Esker V.,Tosta, Maria,Herize, Armando,Dominguez, Rosa M.,Alvarado, Ysaias,Chuchani, Gabriel
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- Photoinduced Cascade Reaction of Tertiary Amines with Sulfonyl Azides: Synthesis of Amidine Derivatives
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A metal-free cascade reaction of tertiary amines with sulfonyl azides promoted by acridinium salts under blue light irradiation was developed and provided amidine derivatives in moderate to good yields. Enamine was generated from tertiary amine via single-electron transfer promoted by acridinium salts, and the following [3+2] cyclization with sulfonyl azide and CH2N2 release afforded the desired products. (Figure presented.).
- Ding, Rui,Chen, Hui,Xu, Yan-Li,Tang, Hai-Tao,Chen, Yan-Yan,Pan, Ying-Ming
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- Design, synthesis and structure-activity relationships of novel diaryl urea derivatives as potential EGFR inhibitors
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Two novel series of diaryl urea derivatives 5a-i and 13a-l were synthesized and evaluated for their cytotoxicity against H-460, HT-29, A549, and MDA-MB-231 cancer cell lines in vitro. Therein, 4-aminoquinazolinyl-diaryl urea derivatives 5a-i demonstrated significant activity, and seven of them are more active than sorafenib, with IC50 values ranging from 0.089 to 5.46 μM. Especially, compound 5a exhibited the most active potency both in cellular (IC50 = 0.15, 0.089, 0.36, and 0.75 μM, respectively) and enzymatic assay (IC50 = 56 nM against EGFR), representing a promising lead for further optimization.
- Jiang, Nan,Bu, Yanxin,Wang, Yu,Nie, Minhua,Zhang, Dajun,Zhai, Xin
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- Synthesis and Crystal Structure of , a Ruthenium Cluster with a Phenyl Isocyanate Ligand
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The ruthenium cluster = (Ph3P)2N> has been synthesised by intramolecular nucleophilic attack on CO and characterised by X-ray structure determination.
- Bhaduri, Sumit,Khwaja, Hanif,Jones, Peter G.
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- Palladium nitrosoarene complexes in reductive carbonylation of nitroarenes
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The reactions of carbon monoxide with the palladium nitrosoarene complexes Pd2(μ-OCOR)2(-CH2C6H 4NO)2 (1, R = Me, CF3, But, or Ph) and Pd2(μ-OCOR)2(PhNC6H4NO) 2 (2, R = Me, CF3, But, or Ph) were studied. Complexes 1 contain the o-nitrosotoluene molecule metallated at the methyl group. In complexes 2, the phenyl-o-nitrosophenylamide ligand coordinated via two nitrogen atoms can be considered as a nitrosobenzene derivative bearing the NPh group in the ortho position of the Ph ring. It all cases, carbonylation of the complexes afforded the corresponding aryl isocyanates Ar-N=C=O or the products of their further transformations. The mechanism of reductive carbonylation of nitroarenes catalyzed by palladium compounds and the role of palladium nitrosoarene complexes as possible intermediates in this process are discussed.
- Stromnova,Orlova
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- Aminolysis of phenyl N-phenylcarbamate via an isocyanate intermediate: Theory and experiment
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A comprehensive examination of the mechanism of the uncatalyzed and base-catalyzed aminolysis of phenyl N-phenylcarbamate by theoretical quantum mechanical methods at M06-2X/6-311+G(2d,2p) and B3LYP-D3/6-31G(d,p) levels, combined with an IR spectroscopic study of the reaction, was carried out. Three alternative reaction channels were theoretically characterized: concerted, stepwise via a tetrahedral intermediate, and stepwise involving an isocyanate intermediate. In contrast to dominating views, the theoretical results revealed that the reaction pathway through the isocyanate intermediate (E1cB) is energetically favored. These conclusions were supported by an IR spectroscopic investigation of the interactions of phenyl N-phenylcarbamate with several amines possessing varying basicities and nucleophilicities: n-butylamine, diethylamine, triethylamine, N-methylpyrrolidine, and trimethylamine. The reactivity of substituted phenyl N-phenylcarbamates in the aminolysis reaction was rationalized using theoretical and experimental reactivity indexes: electrostatic potential at nuclei (EPN), Hirshfeld and NBO atomic charges, and Hammett constants. The obtained quantitative relationships between these property descriptors and experimental kinetic constants reported in the literature emphasize the usefulness of theoretical parameters (EPN, atomic charges) in characterizing chemical reactivity.
- Ilieva, Sonia,Nalbantova, Didi,Hadjieva, Boriana,Galabov, Boris
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- Hypervalent Iodine Reagent-Promoted Hofmann-Type Rearrangement/Carboxylation of Primary Amides
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A novel transformation of primary amides to secondary amides promoted by hypervalent iodine reagents was developed. The hypervalent iodine reagent-mediated Hofmann-type rearrangement generated an isocyanate intermediate, which was subsequently trapped by an in situ generated carboxylic acid from the hypervalent iodine reagent to provide the corresponding secondary amides. This method provided a facile and efficient route for the synthesis of secondary amides from primary amides and also revealed novel reactivities of hypervalent iodine reagents.
- Wang, Xia,Yang, Peng,Hu, Bo,Zhang, Qian,Li, Dong
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supporting information
p. 2820 - 2826
(2021/02/01)
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- Crystal form substance of plant growth regulator, and preparation method thereof
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The invention relates to a crystal form substance of a plant growth regulator, and a preparation method thereof. The crystal form substance comprises the following cell parameters: alpha = 90 DEG, beta = 90 DEG and gamma = 90 DEG. The preparation method of the crystal form substance comprises the following steps: 1) purifying a crude product of the plant growth regulator to obtain a purified substance; and 2) culturing crystals from the purified product in a mixed solvent. The crystal form substance of the plant growth regulator provided by the invention is a single crystal type compound, and due to the single crystal form, the stability is high, and the bioavailability is more obvious than a polycrystal effect; and the preparation method breaks through the technical bottleneck that technicians in the field cannot obtain the single crystal substance added with the plant growth regulator at the present stage, and the method is simple and easy to obtain.
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Paragraph 0046; 0048-0050
(2021/06/23)
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- Discovery of Potent EGFR Inhibitors With 6-Arylureido-4-anilinoquinazoline Derivatives
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According to the classical pharmacophore fusion strategy, a series of 6-arylureido-4-anilinoquinazoline derivatives (Compounds 7a–t) were designed, synthesized, and biologically evaluated by the standard CCK-8 method and enzyme inhibition assay. Among the title compounds, Compounds 7a, 7c, 7d, 7f, 7i, 7o, 7p, and 7q exhibited promising anti-proliferative bioactivities, especially Compound 7i, which had excellent antitumor activity against the A549, HT-29, and MCF-7 cell lines (IC50 = 2.25, 1.72, and 2.81?μM, respectively) compared with gefitinib, erlotinib, and sorafenib. In addition, the enzyme activity inhibition assay indicated that the synthesized compounds had sub-micromolar inhibitory levels (IC50, 11.66–867.1?nM), which was consistent with the results of the tumor cell line growth inhibition tests. By comparing the binding mechanisms of Compound 7i (17.32?nM), gefitinib (25.42?nM), and erlotinib (33.25?nM) to the EGFR, it was found that Compound 7i could extend into the effective region with a similar action conformation to that of gefitinib and interact with residues L85, D86, and R127, increasing the binding affinity of Compound 7i to the EGFR. Based on the molecular hybridization strategy, 14 compounds with EGFR inhibitory activity were designed and synthesized, and the action mechanism was explored through computational approaches, providing valuable clues for the research of antitumor agents based on EGFR inhibitors.
- Li, Meng,Xue, Na,Liu, Xingang,Wang, Qiaoyun,Yan, Hongyi,Liu, Yifan,Wang, Lei,Shi, Xiaowei,Cao, Deying,Zhang, Kai,Zhang, Yang
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- METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION
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Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.
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Paragraph 0530
(2021/11/20)
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- Practical one-pot amidation of N -Alloc-, N -Boc-, and N -Cbz protected amines under mild conditions
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A facile one-pot synthesis of amides from N-Alloc-, N-Boc-, and N-Cbz-protected amines has been described. The reactions involve the use of isocyanate intermediates, which are generated in situ in the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, to react with Grignard reagents to produce the corresponding amides. Using this reaction protocol, a variety of N-Alloc-, N-Boc-, and N-Cbz-protected aliphatic amines and aryl amines were efficiently converted to amides with high yields. This method is highly effective for the synthesis of amides and offers a promising approach for facile amidation.
- Hong, Wan Pyo,Tran, Van Hieu,Kim, Hee-Kwon
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p. 15890 - 15895
(2021/05/19)
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- Anti-tumor compound, pharmaceutically acceptable salt, preparation method and application thereof
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The invention provides an anti-tumor compound and the pharmaceutically acceptable salt thereof, which have good anti-breast cancer activity, are excellent anti-breast cancer lead compounds, and have broad prospects in preparation of drugs for preventing or treating breast cancer. The preparation method is simple and convenient for industrial production.
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Paragraph 0019-0022
(2021/03/13)
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- METHOD FOR PRODUCING ISOCYANATES
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The invention relates to a method for producing an isocyanate, wherein a carbamate or thiolcarbomate is converted, in the presence of a catalyst, with separation of an alcohol or thioalcohol, at a temperature of at least 150° C., to the corresponding isocyanate, wherein a compound of the general formula (X)(Y)(Z—H) is used as a catalyst, in particular characterized in that the compound has both a proton donor function and a proton acceptor function. In the catalysts according to the invention, a separable proton is bound to a heteroatom, which is more electronegative than carbon. Said heteroatom is either identical to Z or a component thereof. In the catalysts according to the invention, there is additionally a proton acceptor function which is either identical to X or a component thereof. According to the invention, the proton donator and proton acceptor function are connected to each other by the bridge Y.
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Paragraph 0147-0150
(2020/12/04)
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- Heterogeneous photocatalysis of azides: Extending nitrene photochemistry to longer wavelengths
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The photodecomposition of azides to generate nitrenes usually requires wavelengths in the 300 nm region. In this study, we show that this reaction can be readily performed in the UVA region (368 nm) when catalyzed by Pd-decorated TiO2. In aqueous medium the reaction leads to amines, with water acting as the H source; however, in non-protic and non-nucleophilic media, such as acetonitrile, nitrenes recombine to yield azo compounds, while azirine-mediated trapping occurs in the presence of nucleophiles. The heterogeneous process facilitates catalyst separation while showing great chemoselectivity and high yields.
- Argüello, Juan E.,Lanterna, Anabel E.,Lemir, Ignacio D.,Scaiano, Juan C.
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supporting information
p. 10239 - 10242
(2020/10/02)
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- Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus
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Parasitic roundworms (nematodes) are significant pathogens of humans and animals and cause substantive socioeconomic losses due to the diseases that they cause. The control of nematodes in livestock animals relies heavily on the use of anthelmintic drugs. However, their extensive use has led to a widespread problem of drug resistance in these worms. Thus, the discovery and development of novel chemical entities for the treatment of parasitic worms of humans and animals is needed. Herein, we describe our medicinal chemistry optimization efforts of a phenotypic hit against Haemonchus contortus based on a pyrrolidine-oxadiazole scaffold. This led to the identification of compounds with potent inhibitory activities (IC50 = 0.78–22.4 μM) on the motility and development of parasitic stages of H. contortus, and which were found to be highly selective in a mammalian cell counter-screen. These compounds could be used as suitable chemical tools for drug target identification or as lead compounds for further optimization.
- Ruan, Banfeng,Zhang, Yuezhou,Tadesse, Solomon,Preston, Sarah,Taki, Aya C.,Jabbar, Abdul,Hofmann, Andreas,Jiao, Yaqing,Garcia-Bustos, Jose,Harjani, Jitendra,Le, Thuy Giang,Varghese, Swapna,Teguh, Silvia,Xie, Yiyue,Odiba, Jephthah,Hu, Min,Gasser, Robin B.,Baell, Jonathan
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supporting information
(2020/02/04)
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- Heterocyclic amide compound, pharmaceutical composition containing heterocyclic amide compound, preparation method of heterocyclic amide compound and application of heterocyclic amide compound
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The invention relates to a heterocyclic amide compound, a pharmaceutical composition containing the heterocyclic amide compound, a preparation method of the heterocyclic amide compound and an application of the heterocyclic amide compound serving as an agonist of stimulator of interferon gene (STING). More specifically, the invention relates to the heterocyclic amide compound; the heterocyclic amide compound is capable of stimulating the production of interferon, thereby being used as an immunomodulator for treatment of STING-mediated diseases or disease conditions such as cancer, infectious diseases, inflammation, immune-related diseases and the like.
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Paragraph 0352-0355
(2020/04/17)
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- Design, synthesis and antitumor assessment of phenylureas bearing 5-fluoroindolin-2-one moiety
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Background: The development of novel antineoplastic agents remains highly desirable. Objective: This study focuses on the design, synthesis, and antitumor evaluation of phenyl ureas bearing 5-fluoroindolin-2-one moiety. Methods: Three sets of phenylureas were designed and synthesized and their antiproliferative abil-ity was measured against four human carcinoma cell lines (Hela, Eca-109, A549, and MCF-7) via MTT assay. In vivo anticancer activity was further evaluated in xenograft models of human breast cancer (MCF-7). Results: A total of twenty-one new compounds were synthesized and characterized by means of1 H and13 C NMR as well as HR-MS. Three sets of compounds (1a?1c, 2a?2c, and 3a?3c) were ini-tially constructed, and preliminary antiproliferative activities of these molecules were evaluated against Hela, Eca-109, A549 and MCF-7, highlighting the meta-substituted phenylureas (1a?1c) as the most cytotoxic set. A series of meta-substituted phenylureas derivatives (1d?1o) were then designed and synthesized for structure-activity relationship study. Most of the new compounds showed desirable cytotoxicity, among which compound 1g exhibited the most remarkable cyto-toxic effects against the tested human cancer cells with IC50 values ranging from 1.47 to 6.79 μM. Further studies showed that compound 1g suppressed tumor growth in human breast cancer (MCF-7) xenograft models without affecting the body weight of its recipients. Conclusion: In this study, twenty-one new compounds, containing the privileged structures of phenylurea and 5-fluoroindolin-2-one, were designed and synthesized. Subsequent structure-activity studies showed that 1g was the most bioactive antitumor agent among all tested com-pounds, hence a potentially promising lead compound once given further optimization.
- Cai, Yunrui,Chen, Tong,Zhu, Huajian,Zou, Hongbin
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p. 958 - 968
(2020/08/19)
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- Synthesis and in vitro anti-bladder cancer activity evaluation of quinazolinyl-arylurea derivatives
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Based on the structural modification of molecular-targeted agent sorafenib, a series of quinazolinyl-arylurea derivatives were synthesized and evaluated for their anti-proliferative activities against six human cancer cell lines. Compared with other cell lines tested, T24 was more sensitive to most compounds. Compound 7j exhibited the best profile with lower IC50 value and favorable selectivity. In this study, we focused on 7j-induced death forms of T24 cells and tried to elucidate the reason for its potent proliferative inhibitory activity. Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j: (1) Lower concentrations within the initial 8 h of 7j treatment led to apoptosis-dependent death. (2) Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc?/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. (3) The above death forms were closely associated with intracellular ROS generation and decreased mitochondrial membrane potential induced by 7j. In molecular docking and structure-activity relationship analyses, 7j could bind well to the active site of the corresponding receptor glutathione peroxidase 4 (GPx4). Compound 7j could be a promising lead for molecular-targeted anti-bladder cancer agents’ discovery.
- Chen, Jia-Nian,Li, Ting,Cheng, Li,Qin, Tai-Sheng,Sun, Ye-Xiang,Chen, Chu-Ting,He, Yue-Zhen,Liu, Guang,Yao, Di,Wei, Ying,Li, Qiu-Yin,Zhang, Guang-Ji
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- Palladium-Mediated CO2 Extrusion Followed by Insertion of Isocyanates for the Synthesis of Benzamides: Translating Fundamental Mechanistic Studies to Develop a Catalytic Protocol
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Mechanistic studies of a stoichiometric palladium-mediated ExIn (ExIn = extrusion-insertion) decarboxylative amidation of aromatic carboxylic acids are presented, providing gas-phase and condensed-phase spectroscopic data, as well as theoretical computational evidence for intermediates in a proposed stepwise process. The understanding gained from these mechanistic studies directed the development of a palladium-catalyzed procedure in which benzamides are obtained in good to high yields in a one-pot 30 min microwave irradiation assisted protocol. A combination of experimental data and DFT calculations reveals that certain ligand additives favor the selective formation of benzamides rather than the undesired protodecarboxylation side product.
- Canty, Allan J.,Donnelly, Paul S.,McKay, Alasdair I.,O'Hair, Richard A. J.,Yang, Yang
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- Heterogeneous catalyst for the direct carbonylation of nitro aromatic compounds to isocyanates
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A process for preparing an aromatic isocyanate by direct carbonylation of a nitro aromatic compound by reacting the nitro aromatic compound with carbon monoxide in the presence of a catalyst, characterized in that the catalyst contains a multi metallic material comprising one or more binary intermetallic phases of the general formula AxBy wherein: A is one or more element selected from Ni, Ru, Rh, Pd, Ir, Pt and Ag, B is one or more element selected from Sn, Sb, Pb, Zn, Ga, In, Ge and As, x is in the range 0.1-10, y in is in the range 0.1-10.
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Paragraph 0203-0205; 0233-0245
(2020/04/01)
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- Design, synthesis, and biological evaluation of tetrahydroisoquinoline-based diaryl urea derivatives for suppressing VEGFR-2 signaling
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A novel structural series of tetrahydroisoquinoline-based compounds that incorporate the diaryl urea moiety was designed, synthesized, and biologically evaluated as suppressors of VEFGR-2 signaling. As a consequence, compounds 9k and 9s exhibited comparable or superior cytotoxic activity to that of gefitinib against the tested three cell lines, including A549, MCF-7, and PC-3. Importantly, both of them downregulated the expression of VEGFR-2, and inhibited VEGFR-2 phosphorylation at the concentration of 0.5 or 1.0 μmol/l. Besides, they suppressed human umbilical vein endothelial cell tube formation at the concentration of 4.0 μmol/l. Considering their capability of down-regulating VEGFR-2 expression and inhibiting VEGFR-2 phosphorylation, 9k and 9s may serve as suppressors of angiogenesis for further investigation.
- Huang, Yuanzheng,Zhang, Yang,Li, Jiaming,Ma, Xiaodong,Hu, Mengqi,Yang, Yu,Gao, Sufan
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p. 508 - 516
(2019/05/14)
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- Synthesis method of tyrosine kinase inhibitor intermediate substituted phenyl isocyanate (by machine translation)
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To the synthesis method of the tyrosine kinase inhibitor intermediate substituted phenyl isocyanate, various substituted anilines I and triphosgene are subjected to aminic oxidation in a first reaction solvent, suction filtration is carried out after reaction, the filtrate is concentrated, and the residue is distilled under reduced pressure to obtain the target compound substituted phenyl isocyanate II. To the synthesis method of the tyrosine kinase inhibitor intermediate substituted phenyl isocyanate provided by the invention, the low-toxicity solid raw material is reacted with various substituted aniline to obtain the target product substituted phenyl isocyanate. (by machine translation)
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Paragraph 0012-0016
(2019/11/20)
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- Sulfonylurea dehydroabietate compound and preparation method and application thereof
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The invention discloses a sulfonylurea dehydroabietate compound and a preparation method and application thereof. The compound has a chemical structural formula represented by a formula shown in the description, wherein R1 is 2-Br, 3-Br, 4-Br, 4-OCH3, 4-F, 2-CH3, 3-CH3, 4-CH3, 2-Cl, 3-Cl or H, and 2, 3 and 4 represent 2, 3 and 4 substituent sites on a benzene ring. The preparation method of the compound comprises the following steps synthesizing sulfonyl chloride dehydroabietate; synthesizing sulfonamide dehydroabietate; synthesizing substituted phenyl isocyanate; synthesizing N'-substituted phenyl-12-sulfonylurea dehydroabietate. The compound disclosed by the invention has better activity and low toxicity and provides a better lead compound for developing antitumor drugs.
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Paragraph 0130; 0132; 0136
(2019/02/04)
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- Design, synthesis, and biological evaluation of 2,4-imidazolinedione derivatives as hdac6 isoform-selective inhibitors
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Histone deacetylase 6 (HDAC6) has emerged as a promising drug target for various human diseases, including diverse neurodegenerative diseases and cancer. Herein, we reported a series of 2,4-imidazolinedione derivatives as novel HDAC6 isoform-selective inhibitors based on structure-based drug design. Most target compounds exhibit good profiles in a preliminary screening concerning HDAC6 inhibitory activities. Moreover, the most active compound 10c increases the acetylation level of α-tubulin with little effect on the acetylation of histone H3. Further biological evaluation suggested that potent compound 10c, which possesses good antiproliferative activity, could induce apoptosis in HL-60 cell by activating caspase 3.
- Liang, Tao,Hou, Xuben,Zhou, Yi,Yang, Xinying,Fang, Hao
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supporting information
p. 1122 - 1127
(2019/08/27)
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- 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone compounds and application thereof
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The invention belongs to the technical field of medicines and relates to 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone compounds and an application thereof. 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone derivatives comprise stereisomers and pharmaceutically applicable salts of the compounds and have the general structural formula shown in the description, wherein R is described inthe claims and description. The 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone derivatives and pharmaceutically applicable acid-added salts of the compounds can be combined with existing medicines or used separately to serve as influenza virus inhibitors to treat influenza and have better curative effects on various type-A influenza in particular.
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Paragraph 0049; 0055
(2018/04/21)
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- 3-(ureido-methyl)-4-aryl-pyridine compound, preparation method thereof and application thereof as anti-hepatoma medicament
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The invention discloses a 3-(ureido-methyl)-4-aryl-pyridine compound, a preparation method thereof and application thereof as an anti-hepatoma medicament. The invention discloses a compound shown as aformula I or a pharmacologically-acceptable salt, crystal form and solvate thereof, wherein X is O or S; n is an integer of 0 to 3; R1, R2, R3, R4 and R5 are independently selected from H, cyan, COOR11, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, trifluoromethyl, amino, nitro, hydroxyl, mercapto or halogen; R11 is selected from H or alkyl having 1 to 4 carbon atoms. Meanwhile, the invention also discloses a preparation method of the compound shown as the formula I. The compound disclosed by the invention has lower median inhibitory concentration (IC50), and a very good inhibition function on hepatoma carcinoma cells; moreover, the preparation method of the compound disclosed by the invention is simple and convenient, and has the advantages of mild reaction condition, convenience in operation and control, low energy consumption, high yield and low cost, and can be suitable for industrial production. The formula I is shown in the description.
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Paragraph 0100; 0101; 0103
(2018/03/26)
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- Derivative of Fascaplysin, preparation method and application
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The invention discloses a derivative of Fascaplysin, preparation thereof and application of derivative of Fascaplysin in drugs. The general formula of the derivative of Fascaplysin is shown in formula(I), the compound can be applied to preparation of drugs for preventing and treating diseases related to a cyclin dependent kinase CDK4 inhibitor and anti-cancer drugs. The drug action of the CDK4 inhibitor is retained, the yield of the compound is high, the compound is relatively stable in air, and water solubility is good. The derivative of Fascaplysin has the advantages of simplicity in operation, simplicity and convenience in preparation method and low production cost.
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Paragraph 0017-0019
(2018/04/28)
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- Synthesis and nematicidal activity of piperazinedione derivatives based on the natural product Barettin
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Nematodes are serious constraints of crop production worldwide. However, the traditional nematicides suffer from the side-effects, including environmental and human toxicity. Herein, more than 70 novel piperazinedione derivatives based on the natural product Barettin were synthesized and evaluated against the root-knot nematode Meloidogyne incognita (M. incognita). While most of synthesized compounds exhibited certain nematicidal activity at high concentration, the best one showed a nematicidal activity of 75% at 2.4 μmol/L.
- Sun, Haiyang,Li, Hui,Wang, Jiayi,Song, Gonghua
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p. 977 - 980
(2017/11/16)
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- Design, synthesis and structure-activity relationship of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure as multi-target inhibitors against receptor tyrosine kinase
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Inspired by that the multi-target inhibitors against receptor tyrosine kinases (RTKs) have significantly improved the effect of clinical treatment for cancer, and based on the chemical structure of Linifanib (ABT-869, Abbott), two series of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure were designed and synthesized as multi-target inhibitors against RTKs. The preliminary biological evaluation showed that several compounds exhibited comparable potency with Linifanib. Compound S21 was identified as the most potent inhibitor against Fms-like tyrosine kinase 3 (FLT-3), kinase insert domain containing receptor (KDR) and platelet-derived growth factor receptor β (PDGFR-β) with its IC50 values were 4 nM, 3 nM and 8 nM respectively, it also showed potent inhibitory activities against several cancer cells.
- Shi, Zhi-Hao,Liu, Feng-Tao,Tian, Hao-Zhong,Zhang, Yan-Min,Li, Nian-Guang,Lu, Tao
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p. 4735 - 4744
(2018/08/21)
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- Phenylquinoline transient receptor potential vanilloid 1 antagonists for the treatment of pain: Discovery of 1-(2-phenylquinoline-4-carbonyl)-N-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxamide
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Reported herein is the design, synthesis, and pharmacologic characterization of a class of TRPV1 antagonists constructed on a phenylquinoline platform that evolved from Cinchophen lead. This design composes three sections: a phenylquinoline headgroup attached to an aliphatic carboxamides, which is tethered at a phenyl tail group. Optimization of this design led to the identification of 37, comprising a pyrrolidine linker and a trifluoromethyl–phenyl tail. In the TRPV1 functional assay, using cells expressed hTRPV1, 37 antagonized capsaicin-induced Ca2+ influx, with an IC50 value of 10.2 nM. In the complete mice analgesic model, 37 exhibited better antinociceptive activity than the positive control BCTC in diverse pain models. All of these results suggested that 37 could be considered as a lead candidate for the further development of antinociceptive drugs.
- Liao, Chen,Liu, Yan,Liu, Chunxia,Zhou, Jiaqi,Li, Huilan,Wang, Nasi,Li, Jieming,Liu, Taiyu,Ghaleb, Hesham,Huang, Wenlong,Qian, Hai
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p. 845 - 854
(2018/01/10)
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- Phenyl dihydroisoquinolines TRPV1 antagonists and its preparation method and application (by machine translation)
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The invention relates to the general formula (I) compounds and salts thereof, such compounds have a strong analgesic effect, part of the compound activity is far higher than the cinchophen and BCTC, and almost no hepatotoxins, gastric mucosa injury and body temperature rise side effect, the invention also relates to the preparation method of the compound and pharmaceutical preparations containing them. The invention synthesizes a series of general formula (I) compound and its pharmaceutically acceptable salt. (by machine translation)
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Paragraph 0104; 0106; 0107
(2018/04/03)
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- Azobenzene-benzoylphenylureas as photoswitchable chitin synthesis inhibitors
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Benzoylphenylureas (BPUs) are used as synthetic insect growth regulators for inhibiting chitin synthesis. Merging insecticidal BPUs with photoswitchable azobenzene generated photoresponsive chitin synthesis inhibitors. A prepared azobenzene-benzoylphenylurea can be activated upon irradiation with UV light, and shows 6-fold and 2-fold activity difference to armyworm (Mythimna separata) and German cockroach (Blattella germanica) sulfonylurea receptors, respectively. This is the first example of a photoswitchable BPU insecticide. The generation of such a photoresponsive BPU insecticide allows for modulation of the insecticidal activity by light, and may facilitate the spatiotemporal control over the sulfonylurea receptor and the mechanistic study of this kind of insecticide.
- Tian, Xue,Zhang, Chao,Xu, Qi,Li, Zhong,Shao, Xusheng
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supporting information
p. 3320 - 3323
(2017/04/21)
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- Pyrido[3, 4-b]indole urea compound and use thereof as IDO inhibitor
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The invention discloses a pyrido[3, 4-b]indole urea compound. Specifically, the compound has substitution at the 9- position of pyrido[3, 4-b]indole, and the connection bridge is a urea structure. The invention also discloses a preparation method of the compound and use thereof as an IDO (indoleamine 2, 3-dioxygenase) inhibitor. The compound provided by the invention can be used for prevention and/or treatment of various diseases, like Alzheimer's disease, cataract, cell immune activation related infections, autoimmune diseases, AIDS, cancer, depression or tryptophan metabolic disorder, etc. (formula (I)).
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Paragraph 0065-0067
(2017/09/13)
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- Triazinone derivatives containing diacylhydrazine structure as well as preparation method and insecticidal and bactericidal application of triazinone derivatives
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The invention relates to triazinone derivatives (I) containing a diacylhydrazine structure as well as a preparation method and an insecticidal and bactericidal application of the triazinone derivatives. Each group in the formula is defined in the description. The triazinone derivatives containing the diacylhydrazine structure show good insecticidal activity and further have bactericidal activity. The general formula (I) is shown in the description.
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Paragraph 0064; 0065; 0066
(2017/11/16)
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- Potassium phosphate-catalyzed one-pot synthesis of 3-aryl-2-oxazolidinones from epoxides, amines, and atmospheric carbon dioxide
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Potassium phosphate was found to be a highly active catalyst in the three-component cycloaddition of amines, epoxides, and carbon dioxide in DMF at ambient temperature to form 3-aryl-2-oxazolidinones. Atmospheric CO2 and a broad range of amines were employed in this transformation. Aryl isocyanate and 1,2-aminoalcohol were generated in situ as key intermediates. This one-pot reaction is applicable to a variety of terminal epoxides and amines. The key advantages are high yields, simple work-up, inexpensive catalysts, and a practical ten gram-scale synthesis.
- Seo, Ue Ryung,Chung, Young Keun
-
supporting information
p. 803 - 808
(2017/08/15)
-
- 2-Oxo-1,2-dihydropyridinyl-3-yl amide-based GPa inhibitors: Design, synthesis and structure-activity relationship study
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Glycogen phosphorylase (GP), which plays a crucial role in the conversion of glycogen to glucose-1-phosphate, is a target for therapeutic intervention in diabetes. In this study, we report the design and synthesis of 29 new derivatives of 2-oxo-1,2-dihydro pyridin-3-yl amides, as potential inhibitors of GP. The hit rate (45%) was high with 13 compounds inhibiting GPa (between 33% at 4.40 mM and an IC50 of 1.92 μM). Two lead compounds were identified as compounds exhibiting good GPa inhibition (IC50 = 2.1 and 1.92 μM). SAR analysis of these compounds revealed sensitivity of GPa to the length of the 2-oxo-1,2-dihydro pyridin-3-yl amide derivative and a preference for inclusion of a 3,4-dichlorobenzyl moiety.
- Loughlin, Wendy A.,Jenkins, Ian D.,Karis, N. David,Schweiker, Stephanie S.,Healy, Peter C.
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supporting information
p. 1 - 14
(2016/02/18)
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- PROCESS FOR PREPARING ISOCYANATE COMPOUND
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The present invention relates to a process for the preparation of an isocyanate compound comprising the steps of: a) Reacting an amine compound A having at least one primary amino group with CO2 and an organotin compound S having at least one radical OR3 attached to the tin atom of the organotin compound, wherein R3 is a C-bound organic radical having from 1 to 30 carbon atoms, wherein 1, 2 or 3 carbon atoms may be replaced by oxygen or nitrogen, to convert at least one of the primary amino groups in the amine compound A into a carbamate group, thereby obtaining a carbamate compound C; b) cleavage of the carbamate groups in the carbamate compound C obtained in step a) to form the isocyanate compound and an alcohol R3OH, without separation of the tin compound formed in step a); c) obtaining the isocyanate compound from the reaction mixture of step b).
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Page/Page column 22
(2016/11/21)
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- 1-methyl-1-methoxy-3-phenylurea synthetic method
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The invention discloses a synthesis method of 1-methyl-1-methoxyl-3-phenylurea. The synthesis method comprises the following steps of carrying out gasification reaction of phenylamine and light in an organic solvent to obtain phenyl isocyanate; reacting an organic solvent solution of phenyl isocyanate with hydroxylamine sulphate in an alkaline aqueous solution in the presence of a catalyst A to obtain 1-hydroxyl-3-phenylurea; reacting 1-hydroxyl-3-phenylurea with dimethyl sulphate in the alkaline condition in the presence of a catalyst B to obtain 1-methyl-1-methoxyl-3-phenylurea. The synthesis method of 1-methyl-1-methoxyl-3-phenylurea has the advantages of being simple and direct in process, high in product purity, easy in control of production processes, and the like.
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Paragraph 0011-0012; 0026-0028; 0029; 0035-0037
(2016/10/07)
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- Synthesis and antibacterial activity of novel 11-[3-[(arylcarbamoyl)oxy]propylamino]-11-deoxy-6-O-methyl-3-oxoerythromycin A 11-N,12-O-cyclic carbamate derivatives
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A series of novel 11-[3-[(arylcarbamoyl)oxy]propylamino]-11-deoxy-6-O-methyl-3-oxoerythromycin A 11-N,12-O-cyclic carbamate derivatives (6a-h) were designed, synthesized and evaluated for their antibacterial activities in vitro. Most of these compounds had significant antibacterial activity against two groups of pathogens of Methicillin-sensitive Staphylococcus aureus (MIC 50 =0.031-2 μg ml -1) except 6g and Methicillin-sensitive S. epidermidis (MIC 50 =0.031-0.5 μg ml -1). MIC 90 of 6d against Methicillin-resistant S. epidermidis was at least 16-fold better than that of erythromycin (EMA), azithromycin (AZM) and ABT-773. 6d and 6e had more potent antibacterial activity against S. pneumoniae than EMA, AZM and ABT-773. In particular, compounds 6d and 6e also showed relatively potent activity against Haemophilus influenzae and Streptococcus hemolyticus.
- Zheng, Zhonghui,Du, Deping,Cao, Lili,Liu, Jun,Chen, Xiaofang
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p. 811 - 817
(2016/12/07)
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- With anti-tumor effect of a quinazoline-urea derivative and its application (by machine translation)
-
The present invention relates to a of the general formula (II) anti-tumor function of said quinazoline-urea derivative and its application. The definition of the substituent in the general formula (II) in the specification. This invention, in order to SUO draw non-Buddhist nun and Geftinat compounds as the precursor, retention of SUO draw non-Buddhist nun the pharmocology-carbamido; at the same time, such as in reserved [...] EGFR-TKIs Geftinat, synthesis, and obtain a series of quinazoline-urea derivatives, by the in vitro activity tests, some compounds exhibit excellent anti-tumor activity, such derivatives have high research and utility value. (II). (by machine translation)
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Paragraph 0139-0142; 0144
(2016/11/02)
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- Phenyl [...] compound and its preparation method, pharmaceutical composition, drug use (by machine translation)
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The invention provides a phenylurea coupling quinazoline compound or a pharmaceutically acceptable salt thereof represented by formula (I), wherein R1 represents H, represents Br, Cl or F, represents -CH3, -CH2-CH3, -CH2(CH3)2 or -CF3, represents -O-CH3, -O-CH2-CH3 or -O-CH2(CH3)2, or represents -C[triple bond]CH or -C[triple bond]N; n1 is 1, 2, 3, 4 or 5; one of R2 and R3 is a group represented by formula (II); R4 represents H, represents Br, Cl or F, represents -CH3, -CH2-CH3, -CH2(CH3)2 or -CF3, represents -O-CH3, -O-CH2-CH3 or -O-CH2(CH3)2, represents -NH2, or represents -NO2; n2 is 1, 2, 3, 4 or 5; and the other one of R2 and R3 represents H, -O-CH3, -O-CH2-CH3, -O-CH2(CH3)2, or the following groups.
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Paragraph 0113; 0115; 0122; 0123
(2016/10/27)
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- Design, synthesis, and biological evaluation of novel quinazolinyl-diaryl urea derivatives as potential anticancer agents
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Through a structure-based molecular hybridization approach, a series of novel quinazolinyl-diaryl urea derivatives were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (HepG2, MGC-803, and A549). Six compounds (7g, 7m, 7o, 8e, 8g, and 8m) showed stronger activity against a certain cell line compared with the positive reference drugs sorafenib and gefitinib. Among the six compounds, 8g exhibited the strongest activity. In particular, compound 8g induced A549 apoptosis, arrested cell cycle at the G0/G1 phase, elevated intracellular reactive oxygen species level, and decreased mitochondrial membrane potential. This compound can also effectively regulate the expression of apoptosis- and cell cycle-related proteins, and influence the Raf/MEK/ERK pathway. Molecular docking and structure-activity relationship analyses revealed that it can bind well to the active site of the receptor c-Raf, which was consistent with the biological data. Therefore, compound 8g may be a potent antitumor agent, representing a promising lead for further optimization.
- Chen, Jia-Nian,Wang, Xian-Fu,Li, Ting,Wu, De-Wen,Fu, Xiao-Bo,Zhang, Guang-Ji,Shen, Xing-Can,Wang, Heng-Shan
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- Isoindole-1,3-dione derivatives as RSK2 inhibitors: Synthesis, molecular docking simulation and SAR analysis
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RSK2 (p90 ribosomal S6 kinase 2) is a serine/threonine kinase expressed in a variety of cancers. Molecular-targeted inhibition of RSK2 as a potential therapeutic strategy for human cancers has been documented. In this work, a series of isoindole-1,3-dione derivatives as novel RSK2 inhibitors were designed and synthesized from a hit discovered in our previous study. Some compounds were confirmed to be moderately potent RSK2 inhibitors with IC50 values of about 0.5 μM. Structure-activity relationship analysis and binding mode studies by molecular docking were performed.
- Zhou, Wei,Li, Shiliang,Lu, Weiqiang,Yuan, Jun,Xu, Yufang,Li, Honglin,Huang, Jin,Zhao, Zhenjiang
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supporting information
p. 292 - 296
(2016/03/01)
-
- A pressuring pyrolysis the preparation of isocyanates apparatus and method
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The invention relates to equipment and a method for preparing isocyanate through compression pyrolysis, and belongs to the technical field of preparation of isocyanate through pyrolysis. The reactor is an integrated reactor of a high pressure pyrolytic reaction kettle and a rectifying tower and comprises a pyrolytic reaction kettle and a rectifying tower; a gas rising pipeline and a liquid return pipeline are connected between the pyrolytic reaction kettle and the rectifying tower; a condenser is arranged on the upper part of the rectifying tower; liquid in the condenser can reflow by inner circulation or outer circulation; a gas outlet is arranged on the upper part for connecting a pressure adjusting system to keep the pressure of the system; and the pyrolytic reaction kettle is simultaneously connected with a liquid phase output discharge processing system. Under the compression pyrolysis condition, solvent can be effectively separated from lower alcohol generated from reaction in the reaction process through separation of the rectifying tower, so that the reaction rate is improved, and the yield of isocyanate is enhanced.
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Paragraph 0028-0030
(2017/03/28)
-
- Visible light C-H amidation of heteroarenes with benzoyl azides
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Benzoyl azides were used for the direct and atom economic C-H amidation of electron rich heteroarenes in the presence of phosphoric acid, a photocatalyst and visible light. Hetero-aromatic amides are obtained in good yields at very mild reaction conditions with dinitrogen as the only by-product. The reaction allows the use of aryl-, heteroaryl- or alkenyl acyl azides and has a wide scope for heteroarenes, including pyrroles, indole, furan, benzofuran and thiophene giving good regio-selectivities and yields.
- Brachet,Ghosh,Ghosh,K?nig
-
p. 987 - 992
(2015/02/19)
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- Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
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A series of novel imidazoisoquinolinone derivatives were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive GHA strain of Plasmodium falciparum. Compounds 2, 4, 6, 9, and 17 revealed moderate to good activities in the micromolar range. Binding interaction between these active compounds and heme were determined and correlated with antimalarial activity. A good correlation (r = 0.98) was observed between antimalarial activity and the heme dissociation constants (K d). These suggest that antimalarial mode of action of this class of compounds appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation.
- Bollini, Mariela,Casal, Juan J.,Asís, Silvia E.,Leal, Emilse S.,Bruno, Ana M.
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p. 1496 - 1503
(2015/04/27)
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- Rhenium-catalyzed C-H aminocarbonylation of azobenzenes with isocyanates
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The first C-H aminocarbonylation of azobenzenes with isocyanates is achieved by using rhenium-catalysis, which provides an expedient and atom-economical access to varied o-azobenzamides from readily available starting materials. The reaction efficiency can be enhanced by the catalytic use of sodium acetate via accelerated C-H bond activation.
- Geng, Xiaoyu,Wang, Congyang
-
supporting information
p. 7619 - 7623
(2015/07/15)
-
This product is a nationally controlled contraband, and the Lookchem platform doesn't provide relevant sales information.
