- Synthesis, antiproliferative and pro-apoptotic effects of nitrostyrenes and related compounds in Burkitt’s lymphoma
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Background: Cancers of the lymphatic cells (lymphomas) account for approximately 12% of malignant diseases worldwide. The nitrostyrene scaffold is identified as a lead target structure for the development of particularly effective compounds targeting Burkitt’s lymphoma (BL). Objectives: The aims of the curent study were to synthesise a panel of nitrostyrene compounds and to evaluate their activity in Burkitt’s lymphoma (BL). Methods: A panel of structurally varied compounds were designed and synthesised using Henry Knoevenagel condensation reactions. Single crystal X-Ray analysis confirmed the E configuration for six examples of these novel structures. A number of nitrostyrene-related compounds were also investigated including 1,3-bis(aryl)-2-nitropropenes together with heterocyclic scaffolds containing the nitrovinyl pharmacophore such as 3-nitro-2-phenyl-2H-chromenes. The antiproliferative activities of the compounds were evaluated using the BL cell lines EBV- MUTU-1 and EBV+ DG-75 (chemoresistant) to establish preliminary structure-activity relationships. Results: Lead compounds with optimized nitrostyrene scaffolds and 3-nitro-2-phenyl-2Hchromene structures were successfully established with typical IC50 values of 0.45 μM and 0.47 μM in MUTU-1 cells and 1.41 μM and 1.92 μM, respectively, in DG-75 cells. The mechanism of cell death was identified as apoptotic and the lead compound was found to elicit comparable apoptotic effects to Taxol in Burkitt’s lymphoma cell lines MUTU-1 and DG-75. Conclusion: This class of pharmaceutically active compounds with potential for the treatment of Burkitt’s lymphoma suggest a potential role for nitrostyrene based agents in chemotherapy.
- Byrne, Andrew J.,Bright, Sandra A.,Fayne, Darren,McKeown, James P.,McCabe, Thomas,Twamley, Brendan,Williams, Clive,Meegan, Mary J.
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p. 181 - 199
(2018/03/13)
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- PHTHALAZINE DERIVATIVES OF FORMULA (I) AS PCAF AND GCN5 INHIBITORS FOR USE IN THE TREATMENT OF CANCER
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The present invention relates to methods for treating PCAF and GCN5 mediated disorders using a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein ring A, R1, R3, R4, R5, and each Re have any of the values defined in the specification. Also included are novel compounds of Formula (I) and salts thereof, as well as pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.
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Page/Page column 103; 116
(2016/03/19)
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- Ethylenediamine: A highly effective catalyst for one-pot synthesis of aryl nitroalkenes via henry reaction and dehydration
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Ethylenediamine (H2NCH2CH2NH2) was found to be a highly effective catalyst for the condensation of aryl aldehydes with nitromethane (or nitroethane). When 1%-2% (mol%) of ethylenediamine was used as the catalyst, the one-pot reaction of aryl aldehydes with nitromethane (or nitroethane) by refluxing for 3-10 h efficiently afforded various arylnitroalkenes 1a-1y in 85%-97% yields. Ethylenediamine (H 2NCH2CH2NH2) was found to be a highly effective catalyst for the condensation of aryl aldehydes with nitromethane (or nitroethane). When 1-2 mol% of ethylenediamine was used as the catalyst, the one-pot reaction of aryl aldehydes with nitromethane (or nitroethane) by refluxing for 3-10 h efficiently afforded various aryl nitroalkenes 1a-1y in 85%-97% yields. Copyright
- Yang, Jianxin,Dong, Jing,Lue, Xia,Zhang, Qiang,Ding, Wei,Shi, Xiaoxin
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p. 2827 - 2833
(2013/08/23)
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- Ambiphilic dual activation role of a task-specific ionic liquid: 2-hydroxyethylammonium formate as a recyclable promoter and medium for the green synthesis of β-nitrostyrenes
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A cost-effective task-specific ionic liquid, 2-hydroxyethylammonium formate, efficiently promotes the condensation of nitroalkanes with various aldehydes to produce β-nitrostyrenes in high to excellent yields at room temperature. This reaction does not involve any hazardous organic solvent and toxic catalyst. The ionic liquid is recovered and recycled for subsequent reactions. In addition, a novel mechanism has been proposed invoking ambiphilic dual activation influence of the ionic liquid.
- Alizadeh, Abdolhamid,Khodaei, Mohammad M.,Eshghi, Ali
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scheme or table
p. 8295 - 8298
(2011/03/17)
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- Substituted 1,2,3,4-tetrahydroquinolin-6-yloxypropanes as β3-adrenergic receptor agonists: Design, synthesis, biological evaluation and pharmacophore modeling
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In search of potent β3-adrenergic receptor agonists, a series of novel substituted 1,2,3,4-tetrahydroquinolin-6-yloxypropanes has been synthesized and evaluated for their β3-adrenergic receptor agonistic activity (ranging from -17.73% to 90.64% inhibition at 10 μM) using well established Human SK-N-MC neuroblastoma cells model. Four molecules viz. 11, 15, 22 and 23 showed β3-AR agonistic IC50 value of 0.55, 0.59, 1.18 and 1.76 μM, respectively. These four candidates have been identified as possible leads for further development of β3-adrenergic receptor agonists for obesity and Type-II diabetes pharmacotherapy. The free OH and NH functions are found to be essential for β3-adrenergic receptor agonistic activity. Among the synthesized β3-adrenergic receptor agonists having 1,2,3,4-tetrahydroquinoline scaffold, the N-benzyl group is found to be superior over N-arylsulfonyl group. A putative pharmacophore model has been modeled considering the above four active molecules which distinguishes well between the active and inactive molecules.
- Shakya, Neeraj,Roy, Kuldeep K.,Saxena, Anil K.
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experimental part
p. 830 - 847
(2009/07/25)
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- DERIVATIVES OF 4-(2-AMINO-1-HYDROXYETHYL)PHENOL AS AGONISTS OF THE BETA2 ADRENERGIC RECEPTOR
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The present invention provides a compound of formula (I): wherein: ? R1 is a group selected from -CH2OH,-NH(CO)H and ? R2 is a hydrogen atom; or ? R1together with R2 form the group -NH-C(O)-CH=CH-, wherein the nitrogen atom is bound to the carbon atom in the phenyl ring holding R1and the carbon atom is bound to the carbon atom in the phenyl ring holding R2 ? R3a and R3bare independently selected from the group consisting of hydrogen atoms and C1-4alkyl groups, ? n represents an integer from 1 to 3; ? Ad represents 1-adamantyl or 2-adamantyl group, or a pharmaceutically-acceptable salt or solvate or stereoisomer thereof.
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Page/Page column 20
(2009/07/03)
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- An efficient synthesis of (E)-nitroalkenes catalyzed by recoverable diamino-functionalized mesostructured polymers
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A clean, efficient, and simple method has been developed for synthesis of (E)-nitroalkenes using FDU-ED as an efficient catalyst. The reactions proceeded with moderate to high yields (60-96%) under mild conditions. The catalyst FDU-ED is recyclable and can be reused more than seven times without significant loss of activity and selectivity.
- Yan, Shaoyu,Gao, Yuan,Xing, Rong,Shen, Yali,Liu, Yueming,Wu, Peng,Wu, Haihong
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p. 6294 - 6299
(2008/09/21)
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- Solvent-free nucleophilic addition of N-alkylhydroxylamines to substituted nitroolefins: Formation of nitrones by a tandem process
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Nucleophilic addition of 1-methyl-2-arylethylhydroxylamine to substituted β-nitrostyrene under solvent-free conditions has led to unexpected nitrones via a tandem process involving 1,4-addition and elimination. Copyright Taylor & Francis Group, LLC.
- Amutha, Chinnadurai,Muthusubramanian, Shanmugam
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p. 328 - 337
(2008/04/01)
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- Catalytic activity of aminopropyl xerogels in the selective synthesis of (E)-nitrostyrenes from nitroalkanes and aromatic aldehydes
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Various aminopropyl-functionalized silicas (APS) were prepared by the sol-gel technique using different tetraethyl orthosilicate/ aminopropyltriethoxysilane (TEOS/ATS) ratios and tested as base catalysts for the nitroaldol reaction. The solids were fully characterized. It was proved that the amount of organic component strongly influences the composition and textural properties of the hybrid organic-inorganic materials. In particular, when ATS was increased to more than 40%, pore volume collapse was observed and a significant decrease in interaction with benzaldehyde reagent was revealed by FT-IR. Catalytic activity in the nitroaldol reaction was correlated with chemical composition and textural properties, suggesting that the catalyst efficiency depends on accessibility to the catalytic sites. In all cases, (E)-nitrostyrene was selectively obtained.
- Sartori,Bigi,Maggi,Sartorio,Macquarrie,Lenarda,Storaro,Coluccia,Martra
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p. 410 - 418
(2007/10/03)
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- Microwave-induced solvent-free, rapid and efficient synthesis of conjugated nitroalkenes using sulfated zirconia
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Sulfated Zirconia catalyzed synthesis of conjugated nitroalkenes has been carrried out under solvent-free condition using sulfated zirconia. Recyclability of catalyst, isolation of pure products by simple filtration and evaporation are important features of this method.
- Bandgar,Kasture
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p. 1239 - 1241
(2007/10/03)
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- Microwave-Assisted Henry Reaction: Solventless Synthesis of Conjugated Nitroalkenes
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In a solventless system and under microwave irradiation, nitroalkanes react with arylaldehydes in the presence of a catalytic amount of ammonium acetate to afford, in one step, conjugated nitroalkenes without the isolation of intermediary β-nitro alcohols. - Key Words: Arylaldehydes; Nitroalkanes; Ammonium acetate; Conjugated nitroalkenes; Henry reaction; Microwave irradiation
- Varma, Rajender S.,Dahiya, Rajender,Kumar, Sudhir
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p. 5131 - 5134
(2007/10/03)
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- Ethanamine derivatives their preparation and use in pharmaceutical compositions
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The compounds of formula (II): STR1 in which R1 is a hydrogen, fluorine, chlorine or bromine atom or a hydroxyl, hydroxymethyl, methyl, methoxyl, amino, formamido, acetamido, methylsulphonylamido, nitro, benzyloxy, methylsulphonylmethyl, ureido, trifluoromethyl or p-methoxybenzylamino group; R2 is a hydrogen, fluorine, chlorine or bromine atom or a hydroxyl group; R3 is a hydrogen, chlorine or bromine atom or a hydroxyl group, R4 is a hydrogen atom or a methyl group; R5 is a hydrogen atom or a methyl group; R6 is a hydrogen, fluorine or chlorine atom or a methyl, methoxyl or hydroxy group; X is an oxygen atom or a bond; Y is an alkylene group of up to 6 carbon atoms or a bond; and Z is an alkylene, alkenylene or alkynylene group of up to 10 carbon atoms, have been found to possess anti-obesity and/or anti-hyperglycaemic activity.
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