- Preparation method of benzofuran -2-(3H)- ketone (by machine translation)
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The preparation method of the benzofuran, 2-(3H)- ketone takes the phenol, as the raw material, and the α - chloroacetyl chloride in the esterification reaction to react itself to form benzofuran - Friedel - Crafts, 2 (Benzofuran-2.(3H)-one. The method greatly shortens, the reaction conditions of the reaction path which is reported in, the art and the chloroacetyl chloride . The method does, not need to add, highly toxic compound sodium cyanide to form benzofuran-2-(-(H)-one in a, simple, and easily available raw. material. The invention greatly shortens the reaction cost and has high industrial application value in the synthesis step. (by machine translation)
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Paragraph 0021-0023; 0026-0028; 0031-0033; 0036-0038; 0041-
(2020/03/06)
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- Flavone inspired discovery of benzylidenebenzofuran-3(2H)-ones (aurones) as potent inhibitors of human protein kinase CK2
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In this work, we describe the design, synthesis and SAR studies of 2-benzylidenebenzofuran-3-ones (aurones), a new family of potent inhibitors of CK2. A series of aurones have been synthesized. These compounds are structurally related to the synthetic flavones and showed nanomolar activities towards CK2. Biochemical tests revealed that 20 newly synthesized compounds inhibited CK2 with IC50 values in the nanomolar range. Further property-based optimization of aurones was performed, yielding a series of CK2 inhibitors with enhanced lipophilic efficiency. The most potent compound 12m (BFO13) has CLipE = 4.94 (CLogP = 3.5; IC50 = 3.6 nM) commensurable with the best known inhibitors of CK2.
- Bdzhola, V. G.,Bilokin, Y. V.,Borysenko, I. P.,Lukashov, S. S.,Protopopov, M. V.,Prykhod'ko, A. O.,Starosyla, S. A.,Vdovin, V. S.,Yarmoluk, S. M.
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- Novel N-4-Piperazinyl Ciprofloxacin-Ester Hybrids: Synthesis, Biological Evaluation, and Molecular Docking Studies
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Abstract: A series of novel N-4-piperazinylciprofloxacin-ester hybrids has been synthesized and the structures confirmed by1H and 13C NMR, FT-IRspectral data, and elemental analysis. The products have been tested in vitro for their antibacterial activity againstsix bacterial strains (MRSA, Staphylococcusepidermidis, Bacillussubtilis, Escherichia coli,Salmonella enterica, and Klebsiella pneumoniae) and have demonstrated goodantibacterial activity with MIC values range 6.25–200 μg/mL. Antifungal andcytotoxic activities of the products have been tested against Candida kefyr and human leukemia K562 cell line,respectively. All compounds inhibit growth of K562 cells more efficiently thanthe parent ciprofoxacin in a dose- and duration-dependent way. Molecular dockingstudies performed for the compound 3i indicatesthat similarly to ciprofloxacin it can act as an inhibitor of S. aureus DNA gyrase.
- Mahdavi, M.,Mostafavi, H.,Shahbazi, A.,Zarrini, G.
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p. 1558 - 1565
(2020/09/21)
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- An Intramolecular Wittig Approach toward Heteroarenes: Synthesis of Pyrazoles, Isoxazoles, and Chromenone-oximes
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α-Halohydrazones/ketoximes are transformed into trisubstituted pyrazoles/disubstituted isoxazoles by treatment with phosphine, acyl chloride, and a base. Mechanistic investigations revealed the in situ formation of azo/nitroso olefin intermediates which underwent a tandem phospha-Michael/N- or O-acylation/intramolecular Wittig reaction to afford the heteroarenes in moderate to good yields. Further, proper functionalization of α-haloketoximes and a change of conditions allowed the chemoselective synthesis of chromenone-oximes as well as rearranged isoxazoles, thereby realizing a diversity-oriented synthesis.
- Khairnar, Pankaj V.,Lung, Tsai-Hui,Lin, Yi-Jung,Wu, Chi-Yi,Koppolu, Srinivasa Rao,Edukondalu, Athukuri,Karanam, Praneeth,Lin, Wenwei
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supporting information
p. 4219 - 4223
(2019/06/17)
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- Substituted phenyl[(5-benzyl-1,3,4-oxadiazol-2-yl)sulfanyl]acetates/acetamides as alkaline phosphatase inhibitors: Synthesis, computational studies, enzyme inhibitory kinetics and DNA binding studies
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Substituted phenyl[(5-benzyl-1,3,4-oxadiazol-2-yl)sulfanyl]acetates/acetamides 9a-j were synthesized as alkaline phosphatase inhibitors. Phenyl acetic acid 1 through a series of reactions was converted into 5-benzyl-1,3,4-oxadiazole-2-thione 4. The intermediate oxadiazole 4 was then reacted with chloroacetyl derivatives of phenols 6a-f and anilines derivatives 8a-d to afford the title oxadiazole derivatives 9a-j. All of the title compounds 9a-j were evaluated for their inhibitory activity against human alkaline phosphatise (ALP). It was found that compounds 9a-j exhibited good to excellent alkaline phosphatase inhibitory activity especially 9h displayed potent activity with IC50 value 0.420 ± 0.012 μM while IC50 value of standard (KH2PO4) was 2.80 μM. The enzyme inhibitory kinetics of most potent inhibitor 9h was determined by Line-weaever Burk plots showing non-competitive mode of binding with enzyme. Molecular docking studies were performed against alkaline phosphatase enzyme (1EW2) to check the binding affinity of the synthesized compounds 9a-j against target protein. The compound 9h exhibited excellent binding affinity having binding energy value (?7.90 kcal/mol) compared to other derivatives. The brine shrimp viability assay results proved that derivative 9h was non-toxic at concentration used for enzyme assay. The lead compound 9h showed LD50 106.71 μM while the standard potassium dichromate showed LD50 0.891 μM. The DNA binding interactions of the synthesized compound 9h was also determined experimentally by spectrophotometric and electrochemical methods. The compound 9h was found to bind with grooves of DNA as depicted by both UV–Vis spectroscopy and cyclic voltammetry with binding constant values 7.83 × 103 and 7.95 × 103 M?1 respectively revealing significant strength of 9h-DNA complex. As dry lab and wet lab results concise each other it was concluded that synthesized compounds, especially compound 9h may serve as lead compound to design most potent inhibitors of human ALP.
- Iqbal,Ashraf,Hassan, Mubashir,Abbas,Jabeen, Erum
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- Design, synthesis, biological evaluation and molecular modeling study of new thieno[2,3-d]pyrimidines with anti-proliferative activity on pancreatic cancer cell lines
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Pancreatic cancer is one of the most challenging diseases with seven months only as median survival time due to its poor prognosis. Several enzymes are blamed for the progress of pancreatic cancer especially, platelet-derived growth factor receptors (PDGFRs), this in turn makes them promising targets for its treatment. In this study, twenty eight new compounds based on thieno[2,3-d]pyrimidine scaffold were synthesized as anti-pancreatic cancer agents mimicking the benzofuro[3,2-d]pyrimidine derivative, amuvatinib. Various linkers including amides, esters, ketones, urea and thiourea derivatives were utilized to study their effect on the anti-proliferative activity of these compounds. Most of the tested compounds revealed good cytotoxic activities against pancreatic carcinoma cell line PANC-1. Compound 9d showed the highest cytotoxicity with an IC50 value of 5.4 μM. Furthermore, 9d showed excellent platelet derived growth factor receptor (PDGFR-α) inhibitory activity, with IC50 value 0.155 μM. Docking study was carried out into PDGFR-α active site which showed comparable binding mode to that of FDA approved PDGFR-α inhibitor, imatinib. 3D-Quantitative structure activity relationship (QSAR) model was built up with five-featured pharmacophore which could be implemented for emerging effective lead structures. These compounds could serve as a new chemotype for discovering new agents for pancreatic cancer therapy.
- Salem, Mohamed S.H.,Abdel Aziz, Yasmine M.,Elgawish, Mohamed S.,Said, Mohamed M.,Abouzid, Khaled A.M.
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- Synthesis and antibacterial activity of 3-benzylamide derivatives as FtsZ inhibitors
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The emergence and spread of multidrug-resistant strains of the human pathological bacteria are generating a threat to public health worldwide. In the current study, a series of PC190723 derivatives was synthesized and investigated for their antimicrobial activity. The compounds exhibited good activity against several Gram-positive bacteria as determined by comparison of diameters of the zone of inhibition of test compounds and standard antibiotics. Compound 9 with a fluorine substitution on the phenyl ring showed the best antibacterial activity in the series against M. smegmatis with the zone ratio of 0.62, and against S. aureus with the zone ratio of 0.44. The results from this study indicate that based on the unique 3-methoxybenzamide pharmacophore, compound 9 may represent a promising lead candidate against Gram-positive bacteria that are worthy of further investigation
- Hu, Zhongping,Zhang, Shasha,Zhou, Weicheng,Ma, Xiang,Xiang, Guangya
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supporting information
p. 1854 - 1858
(2017/04/04)
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- METHOD FOR PRODUCING CARBONATE COMPOUND AND METHOD FOR PRODUCING AROMATIC POLYCARBONATE
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The present invention relates to a method for producing a carbonate compound containing: a first step of reacting a compound represented by the following Formula (1) with a compound represented by the following Formula (21) or a compound represented by the following Formula (22) to obtain a reaction mixture containing a carbonate compound, and a second step of bringing the reaction mixture containing a carbonate compound into contact with a strongly basic compound, in which R1 represents a monovalent organic group, and R2 represents a divalent organic group.
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Paragraph 0193-0195
(2015/06/10)
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- Synthesis of fused piperidinones through a radical-ionic cascade
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(Chemical Equation Presented) Azabicyclo[4.3.0]nonanes were assembled, from chiral allylsilanes possessing an oxime moiety, using a stereocontrolled formal [2 + 2 + 2] radical-ionic process. The cascade involves the addition of an α-iodoester to the less substituted end of the enoxime which is then followed by a 5-exo-trig cyclization onto the aldoxime function, producing an alkoxyaminyl radical species which finally lactamizes to afford the titled piperidinone. High levels of stereoinduction were observed, demonstrating the ability of a silicon group located at the allylic position to efficiently control the stereochemistry of the two newly created stereogenic centers. When the radical cascade was extended to ketoximes, the resulting sterically hindered alkoxyaminyl radical did not react further with the initiator Et3B to produce the expected nucleophilic amidoborane complex. In sharp contrast, this long-lived radical recombined with the initial α-stabilized ester radical to produce a cyclopentane incorporating two ester fragments.
- Godineau, Edouard,Schenk, Kurt,Landais, Yannick
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supporting information; experimental part
p. 6983 - 6993
(2009/05/09)
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- Synthesis of substituted 3-arylpiperidines and 3-arylpyrrolidines by radical 1,4 and 1,2-aryl migrations
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A route to 3-arylpiperidines and 3-arylpyrrolidines involving radical 1,4- and 1,2-aryl migrations has been explored. For the piperidines, the first route requires a xanthate addition to an N-allylarylsulfonamide, followed by acetylation and treatment with lauroyl peroxide to give the corresponding 1,4-aryl transfer product. This compound can be converted into the desired piperidine derivative following acidic hydrolysis. For the second approach to piperidines, addition of an α-keto xanthate to olefins of type 14 causes 1,2-aryl migration leading to an α,β-unsaturated ester, which can be converted into a piperidine by the action of ammonia or a primary amine and sodium cyanoborohydride. Substituted 3-arylpyrrolidines can be obtained by simply starting with an α-amido substituted xanthate.
- Gheorghe, Alexandru,Quiclet-Sire, Béatrice,Vila, Xavier,Zard, Samir Z.
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p. 7187 - 7212
(2008/02/07)
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- A stereocontrolled access to ring-fused piperidines through a formal [2+2+2] process
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(Chemical Equation Presented) A formal [2+2+2] process has been devised that allows the stereocontrolled formation of ring-fused piperidines from allylsilanes possessing an oxime moiety. The cascade involves an intermolecular radical addition of an α-iodoacetate onto an allylsilane double bond, which is followed by a 5-exo-trig cyclization onto an oxime and is completed by the formation of the amide bond by nucleophilic attack of the amine onto the ester function.
- Godineau, Edouard,Schaefer, Christian,Landais, Yannick
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p. 4871 - 4874
(2007/10/03)
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- Electron-withdrawing substituents decrease the electrophilicity of the carbonyl carbon. An investigation with the aid of 13C NMR chemical shifts, v(C=O) frequency values, charge densities, and isodesmic reactions to interprete substituent effects on reactivity
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13C NMR chemical shifts and v(C=O) frequencies have been measured for several series of phenyl-or acyl-substituted phenyl acetates and for acyl-substituted methyl acetates to investigate the substituent-induced changes in the electrophilic character of the carbonyl carbon. Charge density, bond order, and energy calculations have also been performed. The spectroscopic and charge density results indicate that opposite to the conventional thinking, electron-withdrawing substituents do not increase the electrophilicity of the carbonyl carbon but instead decrease it. On the other hand, reaction energies of the isodesmic reactions designed show that electron-withdrawing substituents destabilize the carbonyl derivatives investigated. So, a significant ground-state destabilization of carboxylic acid esters, and carbonyl compounds in general, due to the decreased resonance stabilization, is proposed as a novel concept to explain both the increase in their reactivity and the changes in the chemical shifts and carbonyl frequencies induced by electron-withdrawing substituents.
- Neuvonen, Helmi,Neuvonen, Kari,Koch, Andreas,Kleinpeter, Erich,Pasanen, Paavo
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p. 6995 - 7003
(2007/10/03)
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- Chemistry of diazopolycarbonyl compounds: V. Synthesis, structure, and chemical characteristics of aryl diazoacetates
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Aryl diazoacetates were prepared, and basing on spectral data and quantum-chemical calculations cis-trans isomerism thereof was proved. The reactions of diazoesters with hydrochloric and sulfuric acids, triphenylphosphine, and dinitrogen tetroxide resulted respectively in aryl chloroacetates, bis(aryloxy-carbonylmethyl) sulfates, triphenylphosphoranylidenehydrazones of aryl 2-oxoethanoates, and N-oxides of diaryl 1,2,5-oxadiazole-3,4-dicarboxylates.
- Zalesov,Kataev
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p. 1666 - 1672
(2007/10/03)
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- Ortho-Coordinated Acylation on Phenol Systems
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The ortho-coordinated acylation of phenol salts reported in recent synthetic applications has been extensively investigated.The data obtained support the hypothesis that formation of an organized complex between the phenol salts and the acylating agents may strongly influence the reaction pathway, depending on the nature of the specific cation, phenol, and acyl chloride involved in the process.The structural factors which control the formation of the reacting complex 3 have been extensively investigated; the results obtained allow us to discuss the possibilities and limitations of this methodology in selective o-acylphenol synthesis.The present methodology is the procedure of choice for ortho-functionalization of phenols with electrophilic reagents such as phosgene, oxaloyl chlorides, polyunsaturated acid chlorides, phthalic dichlorides, and, in general, acid chlorides α-functionalized with an electron-withdrawing group.
- Sartori, Giovanni,Casnati, Giuseppe,Bigi, Franca
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p. 4371 - 4377
(2007/10/02)
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- Oxiranes from Methylenation of the Ester Carbonyl Group by Diazomethane
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Esters suitably substituted by electronegative groups were found to react with diazomethane with the anchimeric assistance of a ?-system or a trifluoromethyl group close to the ester oxygen to yield 2-alkoxy-2-substituted-oxiranes in good to excellent yields without catalysts.
- Strazzolini, Paolo,Verardo, Giancarlo,Giumanini, Angelo G.
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p. 3321 - 3325
(2007/10/02)
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- Simple General Acid-Base Catalysis and Virtual Transition States for Acetylcholinesterase-Catalyzed Hydrolysis of Phenyl Esters
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Acetylcholinesterase-catalyzed hydrolyses of the acetyl esters phenyl acetate and o-nitrophenyl acetate and of the chloroacetyl esters phenyl chloroacetate and p-methoxyphenyl chloroacetate have been investigated .V's are quantitatively similar for the constituents of each pair of esters, which indicates that deacylation is partly rate limiting when the enzyme is saturated by substrate.Solvent deuterium isotope effects for V/K are near unity, which is consistent with virtual acylation transition states that are prominently rate limited by nonchemical events .On the other hand, solvent deuterium isotope effects for V fall in the range 1.6-2.26 and are interpreted in terms of transition states that are stabilized by solvation catalytic proton bridges.The Eyring plot constructed from initial velocities of AChE-catalyzed hydrolysis of o-nitrophenyl acetate at 0 >> K is nonlinear downward and is interpreted in terms of prominent rate determination from both acylation and deacylation.However, the solvent isotope effect for the reaction is independent of temperature, which indicates that the solvent isotope effects for the acylation and deacylation components of V must be of comparable magnitude.Proton inventory plots of partial solvent isotope effects on initial velocities at 0 >> K vs. the atom fraction of deuterium in mixed H2O-D2O buffers are linear for the substrates phenyl chloroacetate and o-nitrophenyl acetate.Therefore, AChE behaves as a simple general acid-base catalyst for the studied ester hydrolyses. pL-rate profiles (L = H, D) for hydrolysis of o-nitrophenyl acetate are sigmoidal in shape, and nonlinear-least-squares analysis gives pKaH2O = 6.31 +/- 0.03, pKaD2O = 6.81 +/- 0.03, and D2OVi,lim = 1.82 +/- 0.02.The β-deuterium secondary isotope effect for o-nitrophenyl acetate hydrolysis is D3Vi = 0.960 +/- 0.017.These results are interpreted in terms of a virtual transition for AChE-catalyzed ester hydrolysis that is a weighted average of acylation and deacylation transition states that are each stabilized by single-proton transfers.
- Acheson, Scott A.,Dedopoulou, Dimitra,Quinn, Daniel M.
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p. 239 - 245
(2007/10/02)
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