- Oxidative Cyclization-Induced Activation of a Phosphoinositide 3-Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics
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In this work, we designed a prodrug that reacts with cellular oxidative equivalents leading to ether cleavage and cyclization to release an active phosphatidylinositol 3-kinase (PI3K) inhibitor. We show that the compound reduces affinity for PI3KA relative to the PI3K inhibitor, is slow to intercellularly oxidize, and is resistant to liver microsomes. We observed modest activity in untreated acute myeloid leukemia cells and 14-fold selectivity relative to non-cancerous cells. The cellular activity of the compound can be modulated by the addition of antioxidants or oxidants, indicating the compound activity is sensitive to cellular reactive oxygen species (ROS) state. Co-treatment with cytosine arabinoside or doxorubicin was used to activate the compound inside cells. We observed strong synergistic activity specifically in acute myeloid leukemia (AML) cancer cells with an increase in selective anticancer activity of up to 90-fold. Thus, these new self-cyclizing compounds can be used to increase the selectivity of anticancer agents.
- Zhu, Haizhou,Mishra, Rosalin,Yuan, Long,Abdul Salam, Safnas F.,Liu, Jing,Gray, George,Sterling, Alyssa D.,Wunderlich, Mark,Landero-Figueroa, Julio,Garrett, Joan T.,Merino, Edward J.
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supporting information
p. 1933 - 1939
(2019/11/19)
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- Method for synthesizing benzothiazolone-based and 1,3-disubstituted urea-based derivatives through activation of CO2
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The present invention relates to a method for synthesizing benzothiazolone-based and 1,3-disubstituted urea-based derivatives through activation of CO2. According to the present invention, an inexpensive and easily-available sulfur-containing metal salt compound is first used as an activation catalyst for CO2, and a reaction raw material and CO2 are converted into a corresponding target compound at a low reaction temperature under a low CO2 pressure; and the method has high atomic economy, can reduce the generation of by-products, meets the standards of environmental friendliness and environmentally friendly chemistry, and is the effective way capable of completely utilizing CO2 as the renewable resource, developing new energy and achieving the beneficial cycle of carbon in nature.
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Paragraph 0054; 0055; 0056; 0059; 0060
(2018/09/12)
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- Sulfated polyborate-catalyzed efficient and expeditious synthesis of (un)symmetrical ureas and benzimidazolones
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The excellent catalytic potential of sulfated polyborate is utilized in the synthesis of (un)symmetrical ureas and benzimidazolones by heating amines or substituted OPDA and urea or N-phenylureas under a solvent-free condition at 120 °C is described. The key advantages of the present protocol are phosgene-free, and other hazardous reagents or organic solvent free, high reaction rates and yields, simple workup procedure, and recyclability of the catalyst.
- Rekunge, Deelip S.,Khatri, Chetan K.,Chaturbhuj, Ganesh U.
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supporting information
p. 4304 - 4307
(2017/10/12)
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- BROMODOMAIN INHIBITORS FOR TREATING DISEASE
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Disclosed herein are compounds and compositions useful in the treatment of bromodomain-containing protein-mediated diseases, such as cancer, having the structure of Formula I: Methods of inhibiting activity of a bromodomain-containing protein in a human or animal subject are also provided.
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Paragraph 0180-0181
(2016/03/19)
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- Facile Synthesis of Benzo[ d ]azol-2(3 H)-ones Using 2-Phenoxycarbonyl-4,5-dichloropyridazin-3(2 H)-one as Green CO Source
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Developing eco-friendly, stable, and easy-to-handle acyl sources is of great importance in synthetic and green chemistry. This study describes the synthesis of benzo[d]azol-2(3H)-ones such as benzo[d]thiazol-2(3H)-ones, benzo[d]oxazol-2(3H)-ones, and benzo[d]imidazol-2(3H)-ones using 2-phenoxycarbonyl-4,5-dichloropyridazin-3(2H)-one in one pot. The reaction reported is carried out under neutral or acidic conditions in the presence of zinc or sodium bicarbonate to give the corresponding heterocycles in good to excellent yields. The reaction uses a solid stable carbonyl source that is a recyclable functional-group carrier, pyridazin-3(2H)-one.
- Ryu, Ki Eun,Kim, Bo Ram,Sung, Gi Hyeon,Yoon, Hyo Jae,Yoon, Yong-Jin
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supporting information
p. 1985 - 1990
(2015/09/01)
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- COMPOUNDS USEFUL AS ANTIBIOTIC TOLERANCE INHIBITORS
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The disclosure provides compounds and pharmaceutical compositions of the compounds useful for treating chronic and acute bacterial infections. Certain of the compounds are compounds and salts of general Formula VIII Certain compounds of this disclosure are MvfR inhibitors. MvfR inhibitors reduce the formation of antibiotic tolerant bacterial strains and are useful for treating Gram-negative bacterial infections and reducing the virulence of Pseudomonas aeruginosa. Methods of treating bacterial infections in a patient, including Pseudomonas aeruginosa infections, are also provided by the disclosure.
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Page/Page column 54
(2014/11/13)
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- Preparation of 2(3H)-benzimidazolone and its derivative under aqueous condition as a potential agent for antidiabetic compounds
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A focused library of 2(3H)-benzimidazolone and its derivatives has been synthesized in an attempt to identify their antidiabetic potential. All the products have been synthesized under aqueous conditions in lesser time with better yield and purity. A new effective and convenient method for in situ synthesis of five member heterocyclic ring by reaction of phenylene diamine with urea in solvent phase. All the synthesized compounds were characterized by modern spectroscopic techniques.
- Abbas, Muhammad Azhar,Hameed, Shahid,Kressler, Joerg
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p. 509 - 511
(2013/02/22)
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- DBU-based ionic-liquid-catalyzed carbonylation of o-phenylenediamines with CO2 to 2-benzimidazolones under solvent-free conditions
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Herein, a new route was presented to synthesize 2-benzimidazolones via the carbonylation of o-phenylenediamines with CO2 catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-based ionic liquids under solvent-free conditions. DBU acetate ([DBUH][OAc]) displayed high efficiency for catalyzing the reactions of CO2 with o-phenylenediamines, and a series of benzimidazolones were obtained in high yields. It was demonstrated that [DBUH][OAc] could serve as a bifunctional catalyst for these reactions with the cation activating CO2 and the anion activating o-phenylenediamines. This protocol provides an effective and environmentally friendly alternative route for production of benzimidazolones, and extends the chemical utilization of CO2 in organic synthesis as well.
- Yu, Bo,Zhang, Hongye,Zhao, Yanfei,Chen, Sha,Xu, Jilei,Hao, Leiduan,Liu, Zhimin
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p. 2076 - 2082
(2013/09/24)
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- A bifunctional tungstate catalyst for chemical fixation of CO2 at atmospheric pressure
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No pressure: A simple monomeric tungstate, [WO4]2-, serves as a highly efficient homogeneous catalyst for various transformations of CO2 at atmospheric pressure. The tungsten-oxo moiety activates CO2 and the substrate simultaneously. The catalyst system is high yielding and applicable to a wide range of substrates such as amines (see scheme), 2-aminobenzonitriles, and propargylic alcohols. Copyright
- Kimura, Toshihiro,Kamata, Keigo,Mizuno, Noritaka
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supporting information; experimental part
p. 6700 - 6703
(2012/08/28)
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- 2, 4 -DIAMINOPYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
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The present invention relates to novel pyrimide derivatives of formula (I): that are useful as kinase inhibitors. More particularly, the present invention relates to novel pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders.
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Page/Page column 161
(2012/05/20)
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- Assembly of substituted 1H-benzimidazoles and 1,3-dihydrobenzimidazol-2- ones via CuI/L-proline catalyzed coupling of aqueous ammonia with 2-iodoacetanilides and 2-iodophenylcarbamates
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(Chemical Equation Presented) CuI/L-proline catalyzed coupling of aqueous ammonia with 2-iodoacetanilides and 2-iodophenylcarbamates affords the aryl amination products at room temperature, which undergo in situ additive cyclization under acidic conditions or heating to give substituted 1H-benzimidazoles and 1,3-dihydrobenzimidazol-2-ones, respectively. A wide range of functional groups including ketone, nitro, iodo, bromo, and ester are tolerated under these reaction conditions, providing these heterocycles with great diversity.
- Diao, Xiaoqiong,Wang, Yuji,Jiang, Yongwen,Ma, Dawei
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experimental part
p. 7974 - 7977
(2010/02/28)
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- Quinazoline and benzimidazole MCH-1R antagonists
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We have modified the previously reported 2-aminoquinoline 1 to provide two novel series of MCH-1R antagonists. Representative compounds from the quinazoline and benzimidazole series have been shown to be potent and selective, with promising in vitro eADME profiles.
- Arienzo, Rosa,Cramp, Sue,Dyke, Hazel J.,Lockey, Peter M.,Norman, Dennis,Roach, Alan G.,Smith, Phil,Wong, Melanie,Wren, Stephen P.
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p. 1403 - 1407
(2007/10/03)
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- BICYCLIC COMPOUNDS AND THEIR THERAPEUTIC USE
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Compounds of the formula (1) are useful as MCH mediator, and in the therapy of obesity.
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Page/Page column 52
(2010/02/11)
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- A Novel Method for the Synthesis of 2(3H)-Benzimidazolones, 2(3H)-Benzoxazolone, and 2(3H)-Benzothiazolone via in Situ Generated Ortho Substituted Benzoic Acid Azides: Application of Ammonium Azide and Vilsmeier Complex for Acid Azide Generation
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An easy and generalized route to 2(3H)-benzimidazolones, 2(3H)-benzoxazolone and 2(3H)-benzothiazolone is attempted. A novel one-pot method for the in situ generation and cyclisation of ortho substituted benzoic acid azides is reported via the application of ammonium azide and Vilsmeier complex.
- Sridhar, Radhakrishnan,Perumal, Paramasivan T.
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p. 735 - 742
(2007/10/03)
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- Synthese de Nouvelles 4-Acetonylidene-1,5-benzodiazepin-2-ones III: Etude de la Reaction de Condensation des o-Phenylenediamines monosubstituees avec la γ-pyrone
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Condensation of unsymmetrical aromatic diamines (4-methyl-, 4-chloro-, and 4-nitrophenylenediamines) 2-4 with 2-hydroxy-6-methyl-4-pyrone 1 have been examinated. The structure of isomerie 4-acetonylidene-1,5-benzodiazepin-2-ones 5-10 and benzimidazoles 11-16 obtained from competitive reactions have been established by the spectrale data (1H NMR, IR and mass spectrum). The position of the substituents in 6/9 and 7/10 was proved by comparison with samples with authentic structures.
- Abbassi, M. El,Essassi, E. M.,Fifani, J.
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p. 205 - 210
(2007/10/03)
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- Substituted arylsulfonamides and benzamides
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This invention relates to substituted arylsulfonamides and benzamides possessing aniarrhythmic activity, to pharmaceutical compositions and to methods for production thereof.
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- REACTIONS OF METHYL ESTERS OF N-(2,4-DINITROPHENYL)GLYCINE AND N-METHYL-N-(2,4-DINITROPHENYL)GLYCINE WITH SODIUM METHOXIDE
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The reaction of methyl ester of N-(2,4-dinitrophenyl)glycine (I) with sodium methoxide produces 5-nitro-2(3H)benzimidazolone (III).The product identity has been proved by its isolation from the reaction mixture under conditions similar to those of kinetic experiments and by independent synthesis.The reaction of methyl ester of N-methyl-N-(2,4-dinitrophenyl)glycine with methoxide proceeds in two steps, the second one being substantially slower.The first step produces N-methyl-2-nitroso-4-nitroaniline (IV), which can be prepared by this reaction in good yield andpurity.N-Methyl-2-nitroso-4-nitroaniline undergoes subsequent reactions in the methoxide solutions.Products of the subsequent reactions have not been identified at the starting ester II concentrations of about 10-4 mol l-1, whereas at higher concentrations of the starting substance the reaction produces 2-amino-2'-methylamino-5,5'-dinitro-ONN-azoxybenzene (V) and 2,2'-bis(methylamino)-5,5'-dinitroazoxybenzene (VI).
- Machacek, Vladimir,Sterba, Vojeslav,Kolb, Ivan,Lycka, Antonin
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p. 1044 - 1052
(2007/10/02)
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