- Photopolymerization of Disordered Solid Acetaldehyde at Crygenic Temperature
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Binary solid solutions of 5percent chlorine in acetaldehyde were formed by vapor deposition onto the surface of a CsI optical window at 77 and 10 K.Laser photolysis of the low-temperature films at 308 nm induces a chemical reaction forming acetyl chloride and oligomeric acetaldehyde as the major products.The average chain length of the oligomer is 8.1 +/- 1.1 monomer units for the 77 K experiments.Films deposited and photolyzed at 10 K exhibit smaller chain lengths which grow upon warming to temperature above 40 K.The photochemical behavior of this system parallels that of well-studied formaldehyde polymerization reaction in the solid state in which the principal barriers to chain propagation are spatial and orientational discordering of molecules in the solid lattice.
- Mansueto, Edward S.,Wight, Charles A.
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- Chemical decarbonylation of organometallic compounds
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Transition metal carbonyl acyl complexes of the type π-C5H5M(CO)nCOR (M = Fe, n = 2; M, = Mo, n = 3) can be chemically decarbonylated under mild conditions using Rh[P(C6H5)3]3Cl. The products are a mixture of the corresponding alkyl and triphenylphosphine-substituted acyl complexes. The scope and mechanism of this reaction are discussed.
- Alexander, John J.,Wojcicki, Andrew
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- 1,1-Dichloroethyl Hydroperoxide and 1,1-Dichloroethyl Peroxide Ion as Intermediates in the Ozonolysis of 2,3-Dichloro-2-butene
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On the basis of its spectroscopic and chemical properties, an unstable intermediate previously detected in the ozonolysis of trans-2,3-dichloro-2-butene (1) in inert solvents is reformulated as 1,1-dichloroethyl hydroperoxide (5).Ozonolysis of 1 in ethyl formate saturated with anhydrous HCl leads to high yields of this intermediate. 1,1-Dichloroethyl peroxide ion (10), rather then 5, is believed to be the precursor of acetyl 1,1-dichloroethyl peroxide (8), which is produced in higher yield on ozonolysis of 1 in the presence of tetraalkylammonium chloride.
- Gaeb, Siegmar,Turner, Walter V.
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- Rhodium(III)-catalyzed chemodivergent annulations between phenyloxazoles and diazos via C–H activation
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Acid-controlled, chemodivergent and redox-neutral annulations for the synthesis of isocoumarins and isoquinolinones have been realized via Rh(III)-catalyzed C[sbnd]H activation. Diazo compounds act as a carbene precursor, and coupling occurs in one-pot process, where adipic acid and trimethylacetic acid promote chemodivergent cyclizations.
- Zhang, Xueguo,Wang, Peigen,Zhu, Liangwei,Chen, Baohua
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supporting information
p. 695 - 699
(2020/06/28)
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- Benzimidazole tethered thioureas as a new entry to elastase inhibition and free radical scavenging: Synthesis, molecular docking, and enzyme inhibitory kinetics
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The porcine pancreatic elastase inhibition and free-radical scavenging play a crucial role in age progression. All the series of 10 newly synthesized benzimidazole thioureas (4a-j) were assessed for elastase inhibition and radical scavenging activity to identify the suitable anti-aging ingredient for cosmetics products. The compounds 4e, 4f, 4g, and 4h showed inhibition better than the standard, while compound 4f showed the most significant elastase inhibition with the IC50 value of 1.318 ± 0.025 μM compared with oleanic acid IC50 13.451 ± 0.014 used ±1.989 and 41.563 ± 0.824, respectively, as standard. Molecular docking studies were performed and the compound 4f showed binding energy of 7.2 kcal/mol. Kinetics studies revealed inhibition of the pancreatic elastase in a competitive manner. The relative binding energy and structure activity relationship (SAR) identified compound 4f as an effective inhibitor of porcine pancreatic elastase. Compounds 4e and 4i showed remarkable free-radical scavenging activity with SC50 values of 26.421.
- Abbas, Qamar,Ashraf, Saba,Channar, Pervaiz Ali,Hassan, Abbas,Hassan, Mubashar,Rafique, Hummera,Raza, Hussain,Rind, Mahboob Ali,Saeed, Aamer,Seo, Sung-Yum,Ujan, Rabail,Ul-Hamid, Anwar
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- Neutrophil-Selective Fluorescent Probe Development through Metabolism-Oriented Live-Cell Distinction
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Human neutrophils are the most abundant leukocytes and have been considered as the first line of defence in the innate immune system. Selective imaging of live neutrophils will facilitate the in situ study of neutrophils in infection or inflammation events as well as clinical diagnosis. However, small-molecule-based probes for the discrimination of live neutrophils among different granulocytes in human blood have yet to be reported. Herein, we report the first fluorescent probe NeutropG for the specific distinction and imaging of active neutrophils. The selective staining mechanism of NeutropG is elucidated as metabolism-oriented live-cell distinction (MOLD) through lipid droplet biogenesis with the help of ACSL and DGAT. Finally, NeutropG is applied to accurately quantify neutrophil levels in fresh blood samples by showing a high correlation with the current clinical method.
- Gao, Min,Lee, Sun Hyeok,Park, Sang Hyuk,Ciaramicoli, Larissa Miasiro,Kwon, Haw-Young,Cho, Heewon,Jeong, Joseph,Chang, Young-Tae
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supporting information
p. 23743 - 23749
(2021/10/14)
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- Design and synthesis of novel N-[3-(benzimidazol-2-ylamino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives as potential anticancer agents
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In this contribution, we report the design, synthesis and cytotoxicity studies of a series of N-[3-(benzimidazol-2-yl-amino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives. In vitro cytotoxicity assay of 26 selected compounds was carried out at National Cancer Institute (NCI), USA. Out of them, compounds 10e (NSC D-762842/1) and 11s (NSC D-764942/1) have shown remarkable cytotoxicity with GI50 values ranging between “0.589–14.3?μM” and “0.276–12.3?μM,” respectively, in the representative nine subpanels of human tumor cell lines. Further, flow cytometry analysis demonstrated that compound 10e exerted cell cycle arrest at G2/M phase and showed dose-dependent enhancement in apoptosis in K-562 leukemia cancer cells.
- Kumar, Honnavalli Yogish,Murumkar, Prashant R.,Pawar, Vijay,Srinivasan, B. P.,Yadav, M. R.
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- Conformation, and Charge Tunneling through Molecules in SAMs
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This paper demonstrates that the molecular conformation (in addition to the composition and structure) of molecules making up self-assembled monolayers (SAMs) influences the rates of charge tunneling (CT) through them, in molecular junctions of the form AuTS/S(CH2)2CONR1R2//Ga2O3/EGaIn, where R1 and R2 are alkyl chains of different length. The lengths of chains R1 and R2 were selected to influence the conformations and conformational homogeneity of the molecules in the monolayer. The conformations of the molecules influence the thickness of the monolayer (i.e. tunneling barrier width) and their rectification ratios at ±1.0 V. When R1 = H, the molecules are well ordered and exist predominantly in trans-extended conformations. When R1 is an alkyl group (e.g., R1 H), however, their conformations can no longer be all-trans-extended, and the molecules adopt more gauche dihedral angles. This change in the type of conformation decreases the conformational order and influences the rates of tunneling. When R1 = R2, the rates of CT decrease (up to 6.3×), relative to rates of CT observed through SAMs having the same total chain lengths, or thicknesses, when R1 = H. When R1 H R2, there is a weaker correlation (relative to that when R1 = H or R1 = R2) between current density and chain length or monolayer thickness, and in some cases the rates of CT through SAMs made from molecules with different R2 groups are different, even when the thicknesses of the SAMs (as determined by XPS) are the same. These results indicate that the thickness of a monolayer composed of insulating, amide-containing alkanethiols does not solely determine the rate of CT, and rates of charge tunneling are influenced by the conformation of the molecules making up the junction.
- Belding, Lee,Root, Samuel E.,Li, Yuan,Park, Junwoo,Baghbanzadeh, Mostafa,Rojas, Edwin,Pieters, Priscilla F.,Yoon, Hyo Jae,Whitesides, George M.
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supporting information
p. 3481 - 3493
(2021/03/08)
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- Synthesis, inhibition studies against AChE and BChE, drug-like profiling, kinetic analysis and molecular docking studies of N-(4-phenyl-3-aroyl-2(3H)-ylidene) substituted acetamides
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Halogenated and non-halogenated N-(4-phenyl-3-aroyl-2(3H)-ylidene) substituted acetamides were prepared by base-catalyzed cyclization of corresponding acetyl thioureas with phenacyl bromide. The synthesized compounds were structurally characterized by 1H NMR and 13C NMR spectroscopy and were screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibition activities. Molecular docking studies, drug-like profiling and kinetic analysis were performed to further investigate the inhibition mechanism of the compounds. This study provided useful insights into the design and development of novel dual inhibitors, in addition to understanding the mechanism by which such drugs interact with targets and exert their biochemical action. All the compounds showed superior inhibition profile compared to the standards possessing sub-micromolar and micromolar IC50 values for AChE and BChE, respectively. Docking simulations revealed that the compound 6g showed strong binding inside the active site gorges of both AChE and BChE. An excellent agreement was obtained as the best docked poses showed important binding features mostly based on interactions due to aromatic moieties and oxygen atoms of the compound. Cation-pi/pi-pi interactions together with hydrogen bond forces were the key players responsible for ligand anchoring in the active sites. The striking results accomplished both in docking computations and experimental findings ascertained that the compound 6g can serve as a scaffold for both AChE and BChE inhibition.
- Larik, Fayaz Ali,Saeed, Aamer,Faisal, Muhammad,Hamdani, Salma,Jabeen, Farukh,Channar, Pervaiz Ali,Mumtaz, Amara,Khan, Imtiaz,Kazi, Mahar Ali,Abbas, Qamar,Hassan, Mubashir,Korabecny, Jan,Seo, Sung-Yum
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- Wavelength-Orthogonal Photocleavable Monochromophoric Linker for Sequential Release of Two Different Substrates
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A wavelength-orthogonal photocleavable monochromophoric linker was developed that is based on a 3-acetyl-9-ethyl-6-methylcarbazole (AEMC) moiety substituted at both the phenacyl and benzylic positions with different carboxylic acids. The different carboxylic acids were released sequentially upon irradiation with light of λ ≥ 365 nm and λ ≥ 290 nm, respectively.
- Venkatesh, Yarra,Chaudhuri, Amrita,Mondal, Saugat,Shah, Sk. Sheriff,Singh, N. D. Pradeep
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p. 295 - 299
(2020/01/02)
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- Palladium-Catalyzed 2-(Neopentylsulfinyl)aniline Directed C–H Acetoxylation and Alkenylation of Arylacetamides
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The 2-(neopentylsulfinyl)aniline directing group that promotes rapid palladium-catalyzed C–H acetoxylation and alkenylation of arylacetamides has been developed. The acetoxylation reaches completion within only 40 min at 100 °C and leads to the bis-functionalized products. Alternatively, the reaction can be carried out at room temperature, which is beneficial for sensitive substrates. For the alkenylation, we have developed a protocol in which easily available 1-substituted cyclopropanols were employed as equivalents of vinyl ketones.
- Barysevich, Maryia V.,Laktsevich-Iskryk, Marharyta V.,Krech, Anastasiya V.,Zhabinskii, Vladimir N.,Khripach, Vladimir A.,Hurski, Alaksiej L.
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supporting information
p. 937 - 943
(2020/02/25)
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- Nickel-Catalyzed Cross-Coupling of Alkyl Carboxylic Acid Derivatives with Pyridinium Salts via C-N Bond Cleavage
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The electrophile-electrophile cross-coupling of carboxylic acid derivatives and alkylpyridinium salts via C-N bond cleavage is developed. The method is distinguished by its simplicity and steers us through a variety of functionalized ketones in good to excellent yields. Besides acid chlorides, carboxylic acids were also employed as acylating agents, which enabled us to incorporate acid-sensitive functional groups such as MOM, BOC, and acetal. Control experiments with TEMPO revealed a radical pathway.
- Pulikottil, Feba Thomas,Pilli, Ramadevi,Suku, Rohith Valavil,Rasappan, Ramesh
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supporting information
p. 2902 - 2907
(2020/04/09)
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- Base-promoted Lewis acid catalyzed synthesis of quinazoline derivatives
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A one-pot protocol has been developed for the synthesis of quinazolinones from amide-oxazolines with TsCl via a cyclic 1,3-azaoxonium intermediate and 6π electron cyclization in the presence of a Lewis acid and base. The process is operationally simple and has a broad substrate scope. This method provides a unique strategy for the construction of quinazolinones.
- Cui, Xin-Feng,Hu, Fang-Peng,Huang, Guo-Sheng,Lu, Guo-Qiang
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supporting information
p. 4376 - 4380
(2020/10/20)
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- Regioselective Intramolecular Allene Amidation Enabled by an EDA Complex**
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The addition of radicals to unsaturated precursors is a powerful tool for the synthesis of both carbo- and heterocyclic organic building blocks. The recent advent of mild ways to generate N-centered radicals has reignited interest in exploiting highly regio-, chemo-, and stereoselective transformations that employ these reactive intermediates. While the additions of aminyl, iminyl, and amidyl radicals to alkenes and alkynes have been well-studied, analogous additions to allenes are scarce. Allenes offer several attractive features, including potential for selective amidation at three distinct sites via judicious choice of precursor or radical source, the opportunity for axial-to-point chirality transfer, and productive trapping of vinyl or allyl radical intermediates to diversify functionality in the products. In this article, we report a regioselective addition of amidyl radicals to allenes to furnish an array of valuable N-heterocycle scaffolds.
- Liu, Lu,Ward, Robert M.,Schomaker, Jennifer M.
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supporting information
p. 13783 - 13787
(2020/10/06)
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- Synthesis, in silico study and antimicrobial activity of new piperine derivatives containing substituted δ-esters
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A series of fifteen new piperine-derived diesters was synthesized through the substitution reaction between the salt of piperic acid, obtained through piperine basic hydrolysis, with the δ-chloro-esters, obtained through the cleavage of tetrahydrofuran (THF) with acyl chlorides in the presence of ZnCl2. The final compounds were obtained with yields ranging from 50 to 84% and were characterized by infrared (IR) and 1H and 13C nuclear magnetic resonance spectroscopy (NMR). The new compounds were evaluated in silico in regard to their ADME (absorption, distribution, metabolism, and excretion) properties, and in vitro for their antimicrobial activity against bacteria strains (Staphylococcus aureus and Pseudomonas aeruginosas), yeast fungi (Candida albicans and C. tropicalis) and filamentous fungi (Aspergillus fumigatus, A. flavus and A. niger). The results from the in silico studies of Lipinski's rule of five showed that most compounds present good pharmacological possibilities, and the results from in vitro antimicrobial activity showed that 8 of the 15 synthesized compounds displayed antimicrobial activity, inhibiting the growth of 40-80% of tested strains, with a minimum inhibitory concentration (MIC) interval ranging from 1024 to 256 μg mL-1
- Barbosa-Filho, José M.,Brandao, Maria C. R.,De Athayde-Filho, Petr?nio F.,Dutra, Thalisson F.,Lima, Edeltrudes O.,Lira, Bruno F.,Neto, Hermes Diniz,Trindade, Emmely O.
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p. 2590 - 2602
(2020/11/18)
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- 3-Aminobenzenesulfonamides incorporating acylthiourea moieties selectively inhibit the tumor-associated carbonic anhydrase isoform IX over the off-target isoforms I, II and IV
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We describe the synthesis of a series of novel 1-aroyl/acyl-3-(3-aminosulfonylphenyl) thioureas (4a–k) acting as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. Reaction of alkyl/aryl isothiocyanates with 3-aminobenzenesulfonamide afforded a series of the title compounds incorporating a variety of short as well as highly lipophilic long tails. The newly synthesized sulfonamides were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IV, and IX). Several compounds showed interesting inhibitory activity. The tumor-associated hCA IX was the most sensitive isoform to inhibition with these compounds, with KIs in the range of 21.5–44.0 nM and selectivity ratios over the major cytosolic isoform hCA II in the range of 3.35–37.3. The sulfonamides incorporating the phenylacetylthioureido and pentadecanoylthioureido moieties were the most hCA IX-selective inhibitors detected in this work, making them of interest for further investigations.
- Fattah, Tanzeela Abdul,Bua, Silvia,Saeed, Aamer,Shabir, Ghulam,Supuran, Claudiu T.
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p. 123 - 128
(2018/10/20)
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- Isoalantolactone derivative, pharmaceutical composition and application thereof
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The invention relates to an isoalantolactone derivative, a pharmaceutical composition and application thereof, especially use of the isoalantolactone derivative shown as formula (I) or a salt pharmaceutical compound thereof in preparation of adjuvant drugs treating cancer, a pharmaceutical composition containing a therapeutically effective amount of isoalantolactone derivative (I) or its salt anda pharmaceutically acceptable carrier or a composition with other anticancer drugs.
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Paragraph 0014
(2019/02/02)
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- Set-up and validation of a high throughput screening method for human monoacylglycerol lipase (MAGL) based on a new red fluorescent probe
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Monoacylglycerol lipase (MAGL) is a serine hydrolase that has a key regulatory role in controlling the levels of 2-arachidonoylglycerol (2-AG), the main signaling molecule in the endocannabinoid system. Identification of selective modulators of MAGL enables both to provide new tools for investigating pathophysiological roles of 2-AG, and to discover new lead compounds for drug design. The development of sensitive and reliable methods is crucial to evaluate this modulatory activity. In the current study, we report readily synthesized long-wavelength putative fluorogenic substrates with different acylic side chains to find a new probe for MAGL activity. 7-Hydroxyresorufinyl octanoate proved to be the best substrate thanks to the highest rate of hydrolysis and the best Km and Vmax values. In addition, in silico evaluation of substrates interaction with the active site of MAGL confirms octanoate resorufine derivative as the molecule of choice. The well-known MAGL inhibitors URB602 and methyl arachidonylfluorophosphonate (MAFP) were used for the assay validation. The assay was highly reproducible with an overall average Z0 value of 0.86. The fast, sensitive and accurate method described in this study is suitable for low-cost high-throughput screening (HTS) of MAGL modulators and is a powerful new tool for studying MAGL activity.
- Miceli, Matteo,Casati, Silvana,Ottria, Roberta,Di Leo, Simone,Eberini, Ivano,Palazzolo, Luca,Parravicini, Chiara,Ciuffreda, Pierangela
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- Formamide catalyzed activation of carboxylic acids-versatile and cost-efficient amidation and esterification
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A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (E-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
- Huy, Peter H.,Mbouhom, Christelle
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p. 7399 - 7406
(2019/08/20)
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- Preparation method of [3-14C] marked 17alpha-estradiol
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The invention belongs to the technical field of synthesis of compounds marked by radioisotope 14C, and provides a preparation method of [3-14C] marked 17alpha-estradiol. The preparation method includes the following steps that 17beta-acylated elollactone and 14C marked acetylchloride serve as starting materials, and a condensation reaction, a primary hydrolysis reaction, a Mitsunobu reaction, an aromatization reaction and a secondary hydrolysis reaction are carried out to obtain [3-14C] marked 17alpha-estradiol. The method has the advantages that the synthesis cost is low, the line is short and the product yield is high. Besides, the preparation method is easy to operate and suitable for large-scale production.
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Paragraph 0089; 0091-0093
(2019/06/07)
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- Detailed investigation of anticancer activity of sulfamoyl benz(sulfon)amides and 1H–pyrazol–4–yl benzamides: An experimental and computational study
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Cancer is the second leading cause of mortality worldwide. Therapeutic approach to cancer is a multi-faceted one, whereby many cellular/enzymatic pathways have been discovered as important drug targets for the treatment of cancer. A major disadvantage of most of the currently available anticancer drugs is their non-selective cytotoxicity towards cancerous as well as healthy cells. Another major hurdle in cancer therapy is the development of resistance to anticancer drugs. This necessitates the discovery of new molecules with potent and selective cytotoxic activity towards only cancerous cells, with minimum or no damage to the normal/healthy cells. Herein we report detailed investigation into the anticancer activity of sulfamoyl benz(sulfon)amides (1a-1g, 2a-2k) and 1H–pyrazol–4–yl benzamides (3a-3j) against three cancer cell lines, breast cancer cells (MCF–7), bone-marrow cancer cells (K–562) and cervical cancer cells (HeLa). For comparison, screening against healthy baby hamster kidney cells (BHK-21) was carried out. All compounds exhibited selective cytotoxicity towards cancerous cells. Cell cycle analysis was carried out using flow cytometry, followed by fluorescence microscopic analysis. DNA interaction and docking studies were also carried out.
- Iqbal, Jamshed,Ejaz, Syeda Abida,Saeed, Aamer,al-Rashida, Mariya
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- Visible Light-Mediated Decarboxylative Alkylation of Pharmaceutically Relevant Heterocycles
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A net redox-neutral method for the decarboxylative alkylation of heteroarenes using photoredox catalysis is reported. Additionally, this method features the use of simple, commercially available carboxylic acid derivatives as alkylating agents, enabling the facile alkylation of a variety of biologically relevant heterocyclic scaffolds under mild conditions.
- Sun, Alexandra C.,McClain, Edward J.,Beatty, Joel W.,Stephenson, Corey R. J.
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supporting information
p. 3487 - 3490
(2018/06/26)
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- Synthesis of Piperidine Derivatives by Rhodium- Catalyzed Tandem Reaction of N-Sulfonyl-1,2,3-Triazole and Vinyl Ether
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A chemoselective tandem reaction of 4-acyloxymethylene-1-sulfonyl-1,2,3-triazole and vinyl ether was reported, producing polysubstituted piperidine derivatives in up to 96% yield. The key intermediate N-sulfonyl 1-azadiene generated by migration of the OAc group to the α-imino rhodium carbene was isolated and a plausible mechanism was proposed. Several related ring systems were constructed from the highly functionalized products. (Figure presented.).
- Yu, Sisi,An, Yuehui,Wang, Wenlin,Xu, Ze-Feng,Li, Chuan-Ying
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supporting information
p. 2125 - 2130
(2018/04/17)
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- Eugenol ester analogue and preparation method thereof as well as insecticide
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The invention relates to a eugenol ester analogue and application thereof and in particular relates to the eugenol ester analogue and a preparation method thereof as well as insecticide. The preparation method of the eugenol ester analogue comprises the following steps: (1) carrying out acylating chlorination on substituted carboxylic acid to obtain an intermediate product; (2) enabling the intermediate product and eugenol to react under the condition that an acid binding agent and an organic solvent exist, so as to obtain the eugenol ester analogue, wherein a substituent group in the substituted carboxylic acid is selected from one of C1 to C10 alkyl, C1 to C10 alkenyl, aryl, furyl and imidazolyl. The eugenol ester analogue prepared by the method provided by the invention has a remarkablelethal effect on agricultural insect pests and the insect pests also can have an octopamine agonist poisoning symptom; the eugenol ester analogue can be used as the insecticide and is widely appliedto agriculture.
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Paragraph 0053-0055
(2018/07/30)
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- Design and Synthesis of Natural Product Inspired Libraries Based on the Three-Dimensional (3D) Cedrane Scaffold: Toward the Exploration of 3D Biological Space
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A chemoinformatic method was developed to extract nonflat scaffolds embedded in natural products within the Dictionary of Natural Products (DNP). The cedrane scaffold was then chosen as an example of a nonflat scaffold that directs substituents in three-dimensional (3D) space. A cedrane scaffold that has three orthogonal handles to allow generation of 1D, 2D, and 3D libraries was synthesized on a large scale. These libraries would cover more than 50% of the natural diversity of natural products with an embedded cedrane scaffold. Synthesis of three focused natural product-like libraries based on the 3D cedrane scaffold was achieved. A phenotypic assay was used to test the biological profile of synthesized compounds against normal and Parkinson's patient-derived cells. The cytological profiles of the synthesized analogues based on the cedrane scaffold revealed that this 3D scaffold, prevalidated by nature, can interact with biological systems as it displayed various effects against normal and Parkinson's patient-derived cell lines.
- Tajabadi, Fatemeh Mazraati,Pouwer, Rebecca H.,Liu, Miaomiao,Dashti, Yousef,Campitelli, Marc R.,Murtaza, Mariyam,Mellick, George D.,Wood, Stephen A.,Jenkins, Ian D.,Quinn, Ronald J.
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p. 6609 - 6628
(2018/07/25)
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- Synthesis and spectroscopic/DFT structural characterization of coordination compounds of Nb(V) and Ti(IV) with bioactive carboxylic acids
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The reactions are reported of NbX5 (X = Cl, Br), TiCl4 and Ti(OiPr)4 with a selection of carboxylic acids exhibiting a known biological role, in a chlorinated solvent. The reactions of NbX5 with acetylsalicylic acid (aspirin) proceeded with selective deacetylation of the organic reactant and formation of the salicylate complexes NbX4(C7H5O3) (1a, X = Cl; 1b, X = Br) in 60–65% yields. NbCl5 reacted with diclofenac and ethacrynic acid (EA-CO2H) to give NbCl3[κ3O,O,N-O2CCH2(C6H4)NC6H3Cl2], 2 (80% yield), and NbCl4(O2C-EA), 3 (72% yield), respectively. Ti(OiPr)4 reacted with ethacrynic acid giving Ti(OiPr)2(O2C-EA)2, 4, in 74% yield, as a mixture of two isomers. All the products were characterized by means of analytical and spectroscopic methods, moreover DFT studies were carried out to give insight into structural features.
- De Palo, Alice,Biancalana, Lorenzo,Bortoluzzi, Marco,Alessandra Martini, Maria,Marchetti, Fabio,Pampaloni, Guido
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p. 208 - 214
(2017/12/26)
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- Synthesis method for organic synthesis of intermediate acetylchloride
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The invention relates to a synthesis method for organic synthesis of an intermediate acetylchloride. The method mainly includes the steps of: adding a 5mol 2-methyl-phenylacetic acid solution and 6-6.5mol selenium chloride into a reaction container with stirring and reflux equipment, then carrying out reaction at 30-35DEG C for 80-110min, performing reflux for 50-70min, conducting reduced pressuredistillation, collecting 40-45DEG C fraction, conducting washing with a dimethylamine solution and a dichloromethane solution respectively, and performing dehydration with a dehydrating agent, thus obtaining the finished product acetylchloride.
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Paragraph 0011; 0013; 0014; 0015
(2018/07/30)
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- Arylamine nitrogen mustard derivative N,N-bis(2-chloroethyl)-N'-acetyl-1,4-phenylenediamine and preparation method thereof
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The invention specifically discloses a structural formula of an arylamine nitrogen mustard derivative N,N-bis(2-chloroethyl)-N'-acetyl-1,4-phenylenediamine and a preparation method of the derivative. The method comprises the following steps: preparing N,N-bis(2-chloroethyl)-1,4-phenylenediamine; filling a reactor with N,N-bis(2-chloroethyl)-1,4-phenylenediamine, dichloromethane and triethylamine, cooling in an ice-water bath, stirring, dropwise adding a mixed solution of acetyl chloride and dichloromethane into the reactor, removing the ice-water bath after dropwise adding, reacting at the room temperature for 2-14 hours, washing, drying and distilling after the reaction is completed, purifying the distilled filter cake, thereby obtaining the product. The arylamine nitrogen mustard derivative disclosed by the invention can effectively reduce the toxic or side effects of nitrogen mustard on the premise of enhancing the therapeutic index of the nitrogen mustard and has the curative effects of sterilizing and diminishing inflammation so as to reduce the risk of causing complications due to decrease in immunity after chemotherapy of a patient.
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Paragraph 0055-0057
(2017/08/29)
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- Novel inhibitors of tyrosinase produced by the 4-substitution of TCT (П)
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Novel Tyrosinase Inhibitors of 4-functionalized Thiophene-2-carbaldehyde thiosemicarbazone (TCT) derivatives (1–8) had been synthesized and Spectrofluorimetry, 1H and 13C NMR titration and Molecular docking had been used to investigate their inhibitory activities and mechanisms on tyrosinase. The results showed that the inter-molecular interactions or hydrogen bond formation by increasing length of carbon chain or introducing benzene ring to the 4-functionalized ester group promoted or stabilized formation of complexes between modifier and tyrosinase, and enhanced the inhibitory activity of modifiers. The inhibitory activity of 4-benzoy methoxy-TCT was much stronger than that of any other synthesized tested modifiers, which was well explained by molecular docking and further verified by spectrofluorimetry and NMR titration by assuming that there existed an inter-molecular interaction besides formation of hydrogen bonds between the amino acid residues ASN260, GLU256, HIS85 of enzyme and the modifier.We concluded that 4-benzoy methoxy substitution of TCT was a good route obtaining novel tyrosinase inhibitors and deserved further studies.
- Liu, Jing,Li, Mengrong,Yu, Yanying,Cao, Shuwen
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p. 1096 - 1106
(2017/06/07)
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- Synthesis of gibberellic acid derivatives and their effects on plant growth
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A series of novel C-3-OH substituted gibberellin derivatives bearing an amide group were designed and synthesized from the natural product gibberellic acid (GA3). Their activities on the plant growth regulation of rice and Arabidopsis were evaluated in vivo. Among these compounds, 10d and 10f exhibited appreciable inhibitory activities on rice (48.6% at 100 μmol/L) and Arabidopsis (41.4% at 100mol/L), respectively. These results provide new insights into the design and synthesis of potential plant growth regulators.
- Tian, Hao,Xu, Yiren,Liu, Shaojin,Jin, Dingsha,Zhang, Jianjun,Duan, Liusheng,Tan, Weiming
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- Design, synthesis and biological evaluation of Lenalidomide derivatives as tumor angiogenesis inhibitor
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Lenalidomide is a type of immunomodulatory agent with anti-tumor activity by mainly expressed in the anti-angiogenesis. In order to enhance the pharmacological activity of Lenalidomide, a series of Lenalidomide derivatives were designed as tumor angiogenesis inhibitors. The potential anti-angiogenesis targets of Lenalidomide derivatives were virtual screened on Auto-Dock 4.0 by using reverse docking method. The six target proteins, such as vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, BCR-ABL tyrosine kinase, p38 mitogen activated protein kinase and metal protein kinase, were chosen as the targets. The Lenalidomide derivatives were synthesized by alkylated, acylated or sulfonylated Lenalidomide and verified by the 1H NMR, 13C NMR and LC–MS. Their anti-cancer activities were detected by using CCK-8 in the esophageal carcinoma cell line EC9706. The results indicate that the inhibitory activities of Lenalidomide derivatives were higher than that of Lenalidomide.
- Hu, Shengquan,Yuan, Libin,Yan, Hong,Li, Zhigang
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supporting information
p. 4075 - 4081
(2017/08/23)
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- Alpha-amino acrylate microbicide and preparation method and application thereof
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The invention provides an alpha-amino acrylate microbicide and a preparation method and application thereof. The alpha-amino acrylate microbicide has a specific chemical structure formula shown as a formula I, and the formula I is shown in the description. The alpha-amino acrylate microbicide has the advantages that by utilizing the design principle of pesticide molecules, a medical leading compound with anti-coronavirus activity is performed with structure modification of agricultural plant virus-resisting activity, a series of alpha-amino acrylate derivatives is designed and synthesized, and particularly, the alpha-amino acrylate derivative containing piperidine ring is synthesized; the known compound is used as a positive reference compound to systematically screen the biology activity; a plurality of high-efficiency anti-virus leading molecules are provided for the developing of new pesticides, and the positive meaning is realized for the reduction application of the pesticide and the protection of environment ecology.
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Paragraph 0069
(2017/10/13)
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- Brain-targeting eslicarbazepine ester prodrug and application thereof
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The invention relates to an eslicarbazepine ester prodrug and an application thereof, wherein the prodrug is a compound represented by the formula (I) or optical isomers or physiologically acceptable salts of the compound represented by the formula (I), wherein R represents a lipophilic substituent. The compound represented by the formula (I) is the eslicarbazepine ester prodrug containing the lipophilic substituent, is converted into eslicarbazepine through metabolism in vivo to play pharmacological effects, and can be applied in preparation of drugs for treatment, prevention or adjuvant treatment of central nervous system diseases, such as epilepsy and the like.
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Paragraph 0097
(2017/08/28)
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- Byproduct hydrogen chloride reusing method
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The invention discloses a byproduct hydrogen chloride reusing method. The byproduct hydrogen chloride reusing method comprises the following steps: firstly, inflating mixed gas of acetylene and oxygen into the bottom of a ketene producing tower, and under the action of vacuum, completing synthesis of ketene CH2=C=O within one second by using a Zn0\CaO\AgO catalyst bed with silica gel as a carrier; secondly, under the action of vacuum, enabling gaseous ketene to enter an acetyl chloride producing tower, inflating dried and purified byproduct hydrogen chloride HCL gas into the bottom of the tower, and performing addition reaction on the two gases to generate acetyl chloride; thirdly, under the action of vacuum, enabling the acetyl chloride gas to enter a condensing tower, cooling and condensing into liquid acetyl chloride, and recycling into an acetyl chloride dropwise adding or collecting tank so as to recycle the byproduct hydrogen chloride as a chemical intermediate acetyl chloride product. The byproduct hydrogen chloride reusing method has the beneficial effects of a reasonable structural design and a wide application range.
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Paragraph 0024; 0025
(2017/08/27)
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- Anhydrides from aldehydes or alcohols via oxidative cross-coupling
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A novel type of metal-free oxidative cross-coupling for the synthesis of symmetrical and mixed anhydrides from aldehydes or benzylic alcohols has been developed. The aldehydes or alcohols were converted in situ into their corresponding acyl chlorides, which were then reacted with an array of carboxylic acids. The methodology has a general applicability, and was successfully employed to prepare either aromatic or aliphatic symmetrical anhydrides and mixed anhydrides, which are very unstable compounds.
- Gaspa, Silvia,Amura, Ida,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 931 - 939
(2017/02/10)
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- Transition-Metal-Free Synthesis of N-Aryl Hydroxamic Acids via Insertion of Arynes
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An efficient and transition-metal-free N-arylation of amides via the insertion of arynes into the N-H bonds in the N-alkoxy amides is described. A variety of the reactive functional groups including the reactive aldehyde carbonyl group, furan ring, carbon-carbon double bonds, and free N-H bond of indole are found to be compatible with this process. In particular, the protocol is applicable in the synthesis of structurally diverse N-aryl hydroxamates and hydroxamic acids derived from N-protecting amino acids and peptides. In the presence of multiple amide N-H bonds, the N-arylation reaction can proceed selectively in the N-H bonds of terminal N-OBn amides giving rise to the desired N-aryl hydroxamates.
- Zhang, Lanlan,Geng, Yu,Jin, Zhong
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p. 3542 - 3552
(2016/05/24)
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- Design synthesis and biological evaluation of novel N-nitro acid amide derivatives as lead compounds of herbicide
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A series of N-nitro acid amide derivatives compounds were synthesized based on the active site of target acetohydroxyacid synthase (AHAS, EC: 2.2.1.6) enzyme. All the structures of newly prepared compounds were thoroughly characterized by satisfied IR and 1H NMR spectra. The IC50 values against AHAS enzyme and EC50 values for herbicidal activity against Amaranthus mangostanus L. and Sorghum sudanense of all synthesized target compounds were determined. The compounds II-10, II-21, and II-22 with IC50 values of 7.09 mg/L, 9.07 mg/L, and 9.11 mg/L and the compounds II-8 and II-22 with EC50 values of 9.87 mg/L and 19.88 mg/L against root of Amaranthus mangostanus L. and Sorghum sudanense were illustrated, respectively. Meanwhile, the possible reasons for the lower activity of compounds were analyzed by molecular docking prediction.
- Qi, Xiaojuan,Tang, Wenjie,Gao, Shan,Gao, Min,Chen, Changshui,Zhang, Qingye
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- New orally active diphenylmethyl-based ester analogues of dihydroartemisinin: Synthesis and antimalarial assessment against multidrug-resistant Plasmodium yoelii nigeriensis in mice
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A new series of ester analogues of artemisinin 8a–f, incorporating diphenylmethyl as pharmacologically privileged substructure, and 8g–j have been prepared and evaluated for their antimalarial activity against multidrug-resistant (MDR) Plasmodium yoelii nigeriensis in Swiss mice via oral route. These diphenylmethyl-based ester analogues 8a–f were found to be 2–4 folds more active than the antimalarial drugs β-arteether 4 and artesunic acid 5. Ester 8a, the most active compound of the series, provided complete protection to the infected mice at 24?mg/kg?×?4?days as well as 12?mg/kg?×?4?days, respectively. In this model β-arteether provided 100% and 20% protection at 48?mg/kg?×?4?days and 24?mg/kg?×?4?days, respectively.
- Chaudhary, Sandeep,Naikade, Niraj K.,Tiwari, Mohit K.,Yadav, Lalit,Shyamlal, Bharti Rajesh K.,Puri, Sunil K.
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p. 1536 - 1541
(2016/07/27)
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- Synthesis and Anti-Staphylococcal Activity of 2,4-Disubstituted Diphenylamines
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Infections caused by Staphylococcus aureus are ubiquitous and life threatening. Evolution of resistant strains has necessitated the need to continuously discover new drugs to combat such organisms. Diphenyl ethers, such as triclosan, have recently shown potential as antibacterial agents. In this study, a series of diphenyl amines were synthesized and evaluated for in vitro antibacterial activity against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Pseudomonas putida) bacteria. Preliminary results showed that six of the twelve synthesized molecules were active against Staphylococcus aureus. Most notable amongst them were compounds 2(2,4-dinitrophenylamino) phenol and 2(2-dinitrophenylamino)phenol having minimum inhibitory concentration (MIC) in the range of 7.8-15.6 μg mL-1 and 7.8-62.5 μg mL-1 respectively for all the eight selected organisms. Five active compounds from the preliminary results were further screened against resistant S. aureus cultures where compounds 2(2,4-dinitrophenylamino)phenol, 2(2-dinitrophenylamino)phenol and 2-chloro-N-(2-(2,4-dichlorophenylamino)phenyl)acetamide gave encouraging results having MIC in the range 3.9-7.8 μg mL-1 for most of the organisms. Results obtained above for the selected organisms and the resistant S. aureus strains conclude that hydroxyl group at 2-position of ring B potentiates the antibacterial activity and overcomes the antibiotic resistance.
- Mehton, Ramandeep K.,Meshram, Vineet,Saxena, Sanjai,Chhibber, Manmohan
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p. 1236 - 1244
(2016/08/16)
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- Α-terpineol fatty acid ester derivatives and use
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The invention belongs to the technical field of medicine and discloses alpha-terpineol aliphatic ester and a preparation with the compound. The alpha-terpineol aliphatic ester is formed by alpha-terpineol and fatty acid after esterification reaction. According to a method, first, fatty acid and thionyl chloride react to prepare acyl chloride, and then acyl chloride and alpha-terpineol react to prepare the alpha-terpineol aliphatic ester. The alpha-terpineol ester can be used as penetration enhancers to be used for external preparations of patching agents, Cataplasm, ointment agents, gel agents and the like, accordingly, the percutaneous absorptive amount of medicine is improved, and the alpha-terpineol aliphatic ester is good percutaneous absorptive penetration enhancers and has wide application prospect.
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Paragraph 0041; 0042
(2017/03/18)
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- A mild method for the replacement of a hydroxyl group by halogen. 1. Scope and chemoselectivity
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α-Chloro-, bromo- and iodoenamines, which are readily prepared from the corresponding isobutyramides have been found to be excellent reagents for the transformation of a wide variety of alcohols or carboxylic acids into the corresponding halides. Yields are high and conditions are very mild thus allowing for the presence of sensitive functional groups. The reagents can be easily tuned allowing therefore the selective monohalogenation of polyhydroxylated molecules. The scope and chemoselectivity of the reactions have been studied and reaction mechanisms have been proposed.
- Munyemana, Fran?ois,George, Isabelle,Devos, Alain,Colens, Alain,Badarau, Eduard,Frisque-Hesbain, Anne-Marie,Loudet, Aurore,Differding, Edmond,Damien, Jean-Marie,Rémion, Jeanine,Van Uytbergen, Jacqueline,Ghosez, Léon
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p. 420 - 430
(2015/12/31)
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- Preparation and properties of a novel form-stable phase change material based on a gelator
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A series of gelators (Gm, m is the length of the alkyl tails, m = 2, 4, 6, 8, 10, 12, 14, 16 and 18) containing 4,4′-diaminodiphenylmethane moieties were synthesized. The chemical structures of Gm were confirmed by 1H NMR and MS. The form-stable phase change materials (FSPCMs) were prepared by introducing Gm into paraffin. The minimum gelation concentration (MGC) and gel-to-sol transition temperature (TGS) properties were tested by the "tube-testing method". It found that Gm (m = 2, 4, 6) was insoluble in paraffin, while the MGC and TGS of Gm (m = 8, 10, 12, 14, 16, 18) increased with the increase of alkyl chain. The structure and morphology of the PCMs were systematically investigated by FT-IR, POM, 1D WXAD and SEM. Experimental results revealed that paraffin was restricted because the gelators could self-assemble into three-dimensional netted structures, leading to form the shape-stable PCMs without leakage even above their melting point. The thermal properties were studied by DSC. The research showed that the G18/paraffin FSPCMs exhibited excellent thermal stability and high heat storage density. The shape stability of G18/paraffin was investigated by rheological measurements, indicating that solid hard gel soft gel liquid was observed with the increase of temperature. This work is useful in the comprehensive academic research and industrial application of PCMs.
- Wu, Dang,Wen, Wen,Chen, Sheng,Zhang, Hailiang
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supporting information
p. 2589 - 2600
(2015/02/19)
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- Aromatic cation activation: Nucleophilic substitution of alcohols and carboxylic acids
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A new method for the nucleophilic substitution of alcohols and carboxylic acids using aromatic tropylium cation activation has been developed. This article reports the use of chloro tropylium chloride for the rapid generation of alkyl halides and acyl chlorides under very mild reaction conditions. It demonstrates, for the first time, the synthetic potential of tropylium cations in promoting chemical transformations.
- Nguyen, Thanh V.,Bekensir, Alp
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supporting information
p. 1720 - 1723
(2014/04/17)
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- Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): Pharmacological characterization and assessment in a rat model of cocaine dependence
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As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu 3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
- Dhanya, Raveendra-Panickar,Sheffler, Douglas J.,Dahl, Russell,Davis, Melinda,Lee, Pooi San,Yang, Li,Nickols, Hilary Highfield,Cho, Hyekyung P.,Smith, Layton H.,D'Souza, Manoranjan S.,Conn, P. Jeffrey,Der-Avakian, Andre,Markou, Athina,Cosford, Nicholas D.P.
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p. 4154 - 4172
(2014/06/09)
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- Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D2-like receptors
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Homodimers of dopamine D2-like receptors are suggested to be of particular importance in the pathophysiology of schizophrenia and, thus, serve as promising targets for the discovery of atypical antipsychotics. This study describes the development of a series of novel bivalent molecules with a pharmacophore derived from the dopamine receptor antagonist haloperidol. These dimers were investigated in comparison to their monomeric analogues for their D2long, D2short, D3, and D4 receptor binding and the ability to bridge two neighboring receptor protomers. Radioligand binding studies provided diagnostic insights when Hill slopes close to two for the bivalent ligand 13 incorporating 22 spacer atoms and a comparative analysis with monovalent control ligands indicated a bivalent binding mode with a simultaneous occupancy of two neighboring binding sites.
- Salama, Ismail,L?ber, Stefan,Hübner, Harald,Gmeiner, Peter
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supporting information
p. 3753 - 3756
(2014/09/16)
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- CDC42 INHIBITOR AND USES THEREOF
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A compound having the structure of formula I and its use as a Cdc42 inhibitor. Morphological analyses of filopodia, western blots of Ccd42 phosphorylation, and the experiments on cellular wound healing and on growth cone formation all demonstrate that the compound provided in the present invention is able to inhibit all tested Cdc42-mediated processes. The compounds effectively inhibited the effects of Cdc42 and effectively inhibit Cdc42-related cellular functions involving actin, such as Golgi organization and cell movement.
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Page/Page column
(2014/05/06)
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- Halogen exchange by reaction of CpRu(Cl)(PPh3)2 with MeC(O)X (X = Br, I) and its mechanistic study
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The treatment of CpRu(Cl)(PPh3)2 with MeC(O)X offers a very convenient procedure for the synthesis of CpRu(X)(PPh3) 2. The proposed mechanism involves an intermediate produced by the concerted liberation of PPh3 by the incoming MeC(O)X and the subsequent subtraction of the X atom by the Ru atom to form a radical pair.
- Kuniyasu, Hitoshi,Sanagawa, Atsushi,Nakajima, Takuya,Iwasaki, Takanori,Kambe, Nobuaki,Bobuatong, Karan,Ehara, Masahiro
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supporting information
p. 34 - 37
(2014/08/18)
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- CAJANINE STRUCTURE ANALOGOUS COMPOUND, PREPARATION METHOD AND USE
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Provided are cajanine structure analogous compounds, synthesis method and pharmacological effects thereof, the compounds of the present invention having the structure as represented by general formulas I, II, III, IV and V. Also provided are pharmaceutical compositions containing the compounds as active ingredient, and uses thereof; the compounds of the present invention having the pharmacological activities such as anti-virus, anti-virus-infection, nerve protection, anti-metabolic-diseases and the like. Also provided is a chemical total synthesis preparation method of the natural products cajanine, cajanine A and cajanine C. The present invention lays a foundation for the in-depth study and development of the compounds as clinical drugs in the future.
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Paragraph 0260
(2015/01/06)
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- Design, synthesis and insecticidal activity of novel anthranilic diamides with benzyl sulfide scaffold
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A series of novel anthranilic diamides with benzyl sulfide scaffold were synthesized, in which N-pyridylpyrazole moiety generally regarded as key pharmacophore was abandoned. The target compounds were characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The preliminary bioassays indicated that half of the title compounds were endowed with good insecticidal activities against armyworm (Mythimna sepatara) at the concentration of 500 mg/L. Exhilaratingly, the synthesized compound 3a was also active against Tetranychus cinnabarinus at 100 mg/L. The difference in activities between the target compounds was influenced by the substituents, which provided some hints for further investigation on structure modifications.
- Chen, Yin-Bo,Li, Ji-Ling,Shao, Xu-Sheng,Xu, Xiao-Yong,Li, Zhong
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p. 673 - 676
(2013/07/26)
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- Effect of ester on rhodium-catalyzed intermolecular [5+2] cycloaddition of 3-acyloxy-1,4-enynes and alkynes
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We systematically examined the effect of different esters on the rhodium-catalyzed intermolecular [5+2] cycloaddition of 3-acyloxy-1,4-enynes and alkynes with a concomitant 1,2-acyloxy migration. Significant rate acceleration was observed for benzoate substrates bearing an electron-donating substituent. The cycloaddition can now be conducted under much more practical conditions for most terminal alkynes. The Royal Society of Chemistry 2013.
- Schienebeck, Casi M.,Robichaux, Patrick J.,Li, Xiaoxun,Chen, Lianqing,Tang, Weiping
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supporting information
p. 2616 - 2618
(2013/04/23)
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- Discovery of N-(4-sulfamoylphenyl)thioureas as Trypanosoma brucei leucyl-tRNA synthetase inhibitors
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Human African trypanosomiasis (HAT) is one of the most neglected diseases in the tropic regions, which is fatal if not treated in time. There is an urgent need for new therapeutics, especially those in new chemical classes. Leucyl-tRNA synthetase (LeuRS) has been paid much attention as a recently clinically validated antimicrobial target. Our group has previously reported T. brucei LeuRS (TbLeuRS) inhibitors, including benzoxaboroles targeting the editing site and pyrrolinones targeting the synthetic site. Here we report the discovery of N-(4-sulfamoylphenyl)thioureas as a new class of TbLeuRS inhibitors. The R1 and R2 groups, reminiscent of the leucyl and adenyl regions of aa-AMP and aa-AMS, were optimized to result in a significant 13-fold increase of inhibitory activity (compound 19, IC 50 = 13.7 μM). Aided by ligand-protein docking, the 1,3-substitution at the central phenyl ring was predicted and proved to give significantly improved activity (59, IC50 = 1.1 μM). This work provided a new scaffold for the exploration of novel inhibitors against TbLeuRS, which may become potential therapeutics for the treatment of HAT.
- Zhang, Fenglong,Du, Jin,Wang, Qing,Hu, Qinghua,Zhang, Jiong,Ding, Dazhong,Zhao, Yaxue,Yang, Fei,Wang, Enduo,Zhou, Huchen
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p. 5310 - 5324
(2013/08/23)
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- Bromination of enamines from tertiary amides using the petasis reagent: A convenient one-pot regioselective route to bromomethyl ketones
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An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.
- Kobeissi, Marwan,Cherry, Khalil,Jomaa, Wissam
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supporting information
p. 2955 - 2965
(2013/09/02)
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- Anti-HIV and NO production inhibition activities of epi-aleuritolic acid derivatives
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Fifteen epi-aleuritolic acid derivatives were synthesized and evaluated for anti-HIV activity in 293 T cells and NO production inhibition activity. Of the derivatives, 1, 2, 3, 4, 11, and 13 showed relatively potent anti-HIV activity with EC50 values ranging from 5.80 to 13.30 μM. The most potent compound, 3α-2′,2′-dimethylsuccinic acyl epialeuritolic acid (11), displayed significant anti-HIV activity with an EC50 value of 5.80 μM. Compounds 1, 3, 4, and 11 showed NO inhibition activity, with IC50 values ranging from 3.40 to 7.10 μM and compound 1 inhibited NO production with an IC50 value of 3.40 μM.
- Liu, Jia-Bao,Zhang, Ying,Cui, Bao-Song,Cao, Ying-Li,Yuan, Shao-Peng,Guo, Ying,Hou, Qi,Li, Shuai
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p. 515 - 524
(2013/09/02)
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