- Hydrogen-bonded molecular ladders in S-(4-nitrophenyl)thioglycolic acid
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Hydrogen-bonded molecular ladders in S-(4-nitrophenyl)thioglycolic acid was studied. The supramolecular structure of S-(4-nitrophynl)thioglycolic acid, O2NC6H4S-CH2COOH where both C-H···O hydrogen bonds and arom
- Glidewell, Christopher,Low, John N.,Skakle, Janet M. S.,Wardell, James L.
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- Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells
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A family of carbonyl-substituted diphenylpyrimidine derivatives (Car-DPPYs) with strong activity against focal adhesion kinase (FAK), were described in this manuscript. Among them, compounds 7a (IC50 = 5.17 nM) and 7f (IC50 = 2.58 nM) displayed equal anti-FAK enzymatic activity to the lead compound TAE226 (6.79 nM). In particular, compound 7a also exhibited strong antiproliferative activity against several stubborn cancer cells, including AsPC-1 cells (IC50 = 0.105 μM), BxPC-3 cells (IC50 = 0.090 μM), and MCF-7/ADR cells (IC50 = 0.59 μM). Additionally, compound 7a also showed great antitumor efficacy in vivo via aAsPC-1 cancer Xenograft mouse model. The preliminary mechanism study by Western blot analysis revealed that 7a repressed FAK phosphorylation in AsPC cancer cells. Taken together, the results indicate that compound 7a may serve as a promising preclinical candidate for treatment of stubborn cancers.
- Wang, Luhong,Ai, Min,Yu, Jiawen,Jin, Lingling,Wang, Changyuan,Liu, Zhihao,Shu, Xiaohong,Tang, Zeyao,Liu, Kexin,Luo, Hui,Guan, Wenshun,Sun, Xiuli,Ma, Xiaodong
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p. 154 - 162
(2019/04/13)
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- Thiopyrimidine heterocycle anti-tumor compounds as well as preparation method and application thereof
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The invention relates to thiopyrimidine heterocycle anti-tumor compounds as well as a preparation method and an application thereof. The anti-tumor compounds specifically have the structure shown in aformula (I). The invention also relates to the compounds shown in the formula (I), pharmaceutically acceptable salts of the compounds or pharmaceutical composition containing the compounds. The pharmaceutical composition can treat tumor diseases by inhibiting wild type EGFR (epidermal growth factor receptor) and mutant type EGFR-T790M PTK (protein tyrosine kinase) and is particularly applied to treatment of small cell lung cancer, non-small cell lung cancer and EGFR-T790M mutant type non-small cell lung cancer.
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Paragraph 0038; 0046; 0047
(2018/11/03)
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- Structural optimization of diphenylpyrimidine scaffold as potent and selective epidermal growth factor receptor inhibitors against L858R/T790M resistance mutation in nonsmall cell lung cancer
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A new class of thiodiphenylpyrimidine analogs (Thio-DPPY) were synthesized as potent and selective EGFR T790M inhibitors to overcome gefitinib resistance in nonsmall cell lung cancer (NSCLC). This structural optimization led to the identification of two p
- Yi, Yuanyuan,Wang, Luhong,Zhao, Dan,Huang, Shanshan,Wang, Changyuan,Liu, Zhihao,Sun, Huijun,Liu, Kexin,Ma, Xiaodong,Li, Yanxia
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p. 1988 - 1997
(2018/09/06)
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- Synthesis of thioether andrographolide derivatives and their inhibitory effect against cancer cells
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A series of novel thioether andrographolide derivatives were synthesized by incorporating various aromatic (or heteroaromatic) substituents into C-12 or 14-OH. A total of 38 andrographolide derivatives were prepared and evaluated for their in vitro inhibi
- Liu, Yi,Liang, Ren-Ming,Ma, Qing-Ping,Xu, Kai,Liang, Xin-Yong,Huang, Wei,Sutton, Robert,Ding, Jie,O'Neil, Paul M.,Cheng, Chun-Ru
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p. 1268 - 1274
(2017/07/07)
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- Electrophilic and nucleophilic pathways in ligand oxide mediated reactions of phenylsulfinylacetic acids with oxo(salen)chromium(V) complexes
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The mechanism of oxidative decarboxylation of phenylsulfinylacetic acids (PSAA) by oxo(salen)Cr(V)+ ion in the presence of ligand oxides has been studied spectrophotometrically in acetonitrile medium. Addition of ligand oxides (LO) causes a red shift in the λmax values of oxo(salen) complexes and an increase in absorbance with the concentration of LO along with a clear isobestic point. The reaction shows first-order dependence on oxo(salen)-chromium(V)+ ion and fractional-order dependence on PSAA and ligand oxide. Michaelis-Menten kinetics without kinetic saturation was observed for the reaction. The order of reactivity among the ligand oxides is picoline N-oxide > pyridine N-oxide > triphenylphosphine oxide. The low catalytic activity of TPPO was rationalized. Both electron-withdrawing and electron-donating substituents in the phenyl ring of PSAA facilitate the reaction rate. The Hammett plots are non-linear upward type with negative ρ value for electron-donating substituents, (ρ- = -0.740 to -4.10) and positive ρ value for electron-withdrawing substituents (ρ+ = +0.057 to +0.886). Non-linear Hammett plot is explained by two possible mechanistic scenarios, electrophilic and nucleophilic attack of oxo(salen)chromium(V)+-LO adduct on PSAA as the substituent in PSAA is changed from electron-donating to electron-withdrawing. The linearity in the log k vs. Eox plot confirms single-electron transfer (SET) mechanism for PSAAs with electron-donating substituents.
- Subramaniam,Sugirtha Devi,Anbarasan
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p. 164 - 173
(2016/06/06)
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- Highly specific N-monomethylation of primary aromatic amines
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A synthetic methodology for the specific conversion of primary aromatic amines into their N-monomethyl derivatives under very mild conditions is presented. Anilines are treated with 4-nitrobenzenesulfonyl (nosyl) chloride to generate the corresponding sulfonamides 2 in high yields. The subsequent N-methylation reaction of the sulfonamides 2 with a solution of diazomethane is rapid and quantitative. Removal of the nosyl protecting group is readily carried out using the reagent system mercaptoacetic acid/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) affording the N-monomethylated aromatic amines 4. The procedure is convenient, efficient, and gives rise to the N-monomethyl-anilines exclusively.
- Le Pera, Adolfo,Leggio, Antonella,Liguori, Angelo
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p. 6100 - 6106
(2007/10/03)
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- Highly stereoselective asymmetric pummerer reactions that incorporate intermolecular and intramolecular nonbonded S...O interactions
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New chiral sulfoxides (RS,S)-3, (SS,S)-3, (R S,S)-4, and (SS,S)-4 and known chiral sulfoxides (R S)-5, (RS)-6, and (RS)-7 were synthesized, and the stereochemistry of the new sulfoxides (RS,S)-3 and (R S,S)-4 was determined by X-ray crystallographic analysis. In their crystallographic structures, the intramolecular nonbonded S...O close contacts were recognized. Analyses of several sulfoxide complexes including rac-11 with N,N-dimethylacetamide (DMAC) or N-methyl-2-pyrrolidone (NMP) in a MeOH solution utilizing cold-spray ionization mass spectrometry provided, for the first time, direct information for intermolecular nonbonded S...O interactions between sulfoxides and amide (or lactam) in a solution. Highly diastereoselective and enantioselective Pummerer reactions based on the concept of intermolecular and intramolecular nonbonded S...O interactions were performed by treatment of several chiral sulfoxides (RS, S)-3, (SS, S)-3, (RS, S)-4, (SS, S)-4, (R S)-5, (RS)-6, and (RS)-7 with acetic anhydride and trimethylsilyl triflate (TMSOTf) in DMAC, NMP, N,N-dimethylformamide, and N-formylpiperidine. Mechanistic studies on these facile stereoselective Pummerer reactions revealed the necessity for the amide/TMSOTf complex, such as 26 or 27, to be an efficient activation reagent for Ac2O and a trapping reagent for the released acetate ion, and that DMAC and NMP had a positive effect on this highly stereoselective chiral transfer reaction.
- Nagao, Yoshimitsu,Miyamoto, Satoshi,Miyamoto, Motoyuki,Takeshige, Hiroe,Hayashi, Kazuhiko,Sano, Shigeki,Shiro, Motoo,Yamaguchi, Kentaro,Sei, Yoshihisa
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p. 9722 - 9729
(2007/10/03)
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- (4-Nitrophenylsulfinyl)acetic acid, a three-dimensional hydrogen-bonded framework built from a combination of two-centre O-H...O and C-H...O hydrogen bonds and a three-centre C-H...(O)2 hydrogen bond
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Molecules of the title compound, C8H7NO5S, are linked into sheets by a combination of two-centre hydrogen bonds, one of type O-H...O [H...O = 1.81 A, O...O = 2.648 (2) A and O-H...O = 173°] and three of type C-H...O [H...O
- Glidewell, Christopher,Low, John N.,Skakle, Janet M.S.,Wardell, James L.
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p. o124-o126
(2007/10/03)
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- KINETICS AND MECHANISM OF OXIDATION OF (ARYLTHIO)ACETIC ACIDS BY PYRIDINIUM HYDROBROMIDE PERBROMIDE
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Oxidation of several monosubstituted (phenylthio)acetic acids (PTAA) by pyridinium hydrobromide perbromide (PHPB) was studied in aqueous acetic acid.The reaction is first order with respect to PHPB.Michaelis-Menten type kinetics are observed with respect to (arylthio)acetic acid.The effect of solvent composition indicates that the transition state is more polar than the reactants.The formation constants of the intermediate substrate-PHPB complexes and the rates of their decomposition were determined at different temperatures.The rates of oxidation of para and meta-substituted (phenylthio)acetic acids were correlated with Hammett's substituent constants.The ρ value is -1.60 at 35 deg c.The rates of oxidation of ortho substituted compounds are correlated with Charton's triparametric equation.A mechanism involving the decomposition of the intermediate complex in the slow rate-determining step affording a sulphonium ion which hydrolyses in a subsequent fast step to the sulphoxide is proposed.
- Karunakaran, K.,Elango, K. P.
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p. 429 - 434
(2007/10/02)
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- 2- and 4-Nitrobenzenesulfonamides: Exceptionally versatile means for preparation of secondary amines and protection of amines
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2- and 4-nitrobenzenesulfonamides, readily prepared from primary amines, undergo smooth alkylation by Mitsunobu reaction or by conventional methods to give N-alkylated sulfonamides in near quantitative yields. These sulfonamides could be deprotected readily via Meisenheimer complexes upon treatment with thiolates in DMF at room temperature, giving secondary amines in high yields.
- Fukuyama, Tohru,Jow, Chung-Kuang,Cheung, Mui
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p. 6373 - 6374
(2007/10/02)
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- Reaction of 3-Phenylglycidic Esters. Part 2. Stereo- and Regio-selectivity in the Oxirane Ring Opening of Methyl trans-3-(4-Methoxyphenyl)glycidate with Various Thiophenols and the Effects of Solvent and Temperature
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The effects of the solvent and temperature on the reaction of the trans-glycidate (1) with various substituted thiophenols (2) in the presence or absence of a catalyst have been investigated.The temperature had a surprisingly large effect on the stereochemistry of the oxirane ring-opening of (1).At room temperature, the erythro-isomer (4) (trans-opening product) was obtained as a major product in the absence of catalyst, while the cis-opening product (3) (threo-isomer) was produced predominantly at higher temperature.On the other hand, in a dipolar aprotic solvent, the regioisomer (5) was formed, the yield increasing with the electron-donating ability of the substituents on (2).The formation of compound (5) may involve single-electron transfer as a key step.
- Hashiyama, Tomiki,Inoue, Hirozumi,Takeda, Mikio,Aoe, Keiichi,Kotera, Keishi
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p. 421 - 428
(2007/10/02)
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- Determination of potentially mutagenic and carcinogenic electrophiles in environmental samples
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Direct acting mutagens are common in many types of environmental samples. Most direct acting mutagens are electrophiles. The nucleophile 4-nitrothiophenol reacts readily with electrophilic alkyl halides and epoxides to form thioethers which have absorptio
- Cheh,Carlson
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p. 1001 - 1006
(2007/10/02)
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