- Synthesis and structure-activity relationships of small-molecular di-basic esters, amides and carbamates as flaviviral protease inhibitors
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Inhibitors of the flaviviral serine proteases, which are crucial for the replication of dengue and West-Nile virus, have attracted much attention over the last years. A dibasic 4-guanidinobenzoate was previously reported as inhibitor of the dengue protease with potency in the low-micromolar range. In the present study, this lead structure was modified with the intent to explore structure-activity relationships and obtain compounds with increased drug-likeness. Substitutions of the guanidine moieties, the aromatic rings, and the ester with other functionalities were evaluated. All changes were accompanied by a loss of inhibition, indicating that the 4-guanidinobenzoate scaffold is an essential element of this compound class. Further experiments indicate that the target recognition of the compounds involves the reversible formation of a covalent adduct.
- Sundermann, Tom R.,Benzin, Clarissa V.,Dra?i?, Tonko,Klein, Christian D.
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p. 187 - 194
(2019/05/21)
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- Preparation method of electronic-grade 4,4'-diaminobenzanilide
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The invention discloses a preparation method of electronic-grade 4,4'-diaminobenzanilide. The preparation method comprises the following steps: 1, 4,4'-dinitrobenzanilide is prepared from 4-nitroaniline and 4-nitrobenzoyl chloride through a reaction; 2, crude 4,4'-diaminobenzanilide is obtained from 4,4'-dinitrobenzanilide through catalytic hydrogenation; 3, crude 4,4'-diaminobenzanilide obtainedin step 2, a recrystallization solvent and activated carbon are added to an autoclave simultaneously, recrystallization and activated carbon decoloration are performed simultaneously at 100-150 DEG Cunder nitrogen protection, and electronic-grade 4,4'-diaminobenzanilide is obtained. The appropriate recrystallization solvent is selected and recrystallization and activated carbon decoloration are performed simultaneously, so that electronic-grade 4,4'-diaminobenzanilide with high purity and low ion content is obtained finally, and special requirements of high-performance electronics industry are met.
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Paragraph 0013; 0015-0017; 0026; 0028-0030
(2018/08/28)
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- Chemo- and Site-Selective Alkyl and Aryl Azide Reductions with Heterogeneous Nanoparticle Catalysts
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Site-selective modification of bioactive natural products is an effective approach to generating new leads for drug discovery. Herein, we show that heterogeneous nanoparticle catalysts enable site-selective monoreduction of polyazide substrates for the generation of aminoglycoside antibiotic derivatives. The nanoparticle catalysts are highly chemoselective for reduction of alkyl and aryl azides under mild conditions and in the presence of a variety of easily reduced functional groups. High regioselectivity for monoazide reduction is shown to favor reduction of the least sterically hindered azide. We hypothesize that the observed selectivity is derived from the greater ability of less-hindered azide groups to interact with the surface of the nanoparticle catalyst. These results are complementary to previous Staudinger reduction methods that report a preference for selective reduction of electronically activated azides.
- Udumula, Venkatareddy,Nazari, S. Hadi,Burt, Scott R.,Alfindee, Madher N.,Michaelis, David J.
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p. 4423 - 4427
(2016/07/12)
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- Design, synthesis and biological evaluation of 4-Amino-N-(4-aminophenyl) benzamide analogues of quinoline-based SGI-1027 as inhibitors of DNA methylation
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Quinoline derivative SGI-1027 (N-(4-(2-amino-6-methylpyrimidin-4-ylamino) phenyl)-4-(quinolin-4-ylamino)benzamide) was first described in 2009 as a potent inhibitor of DNA methyltransferase (DNMT) 1, 3A and 3B. Based on molecular modeling studies, performed using the crystal structure of Haemophilus haemolyticus cytosine-5 DNA methyltransferase (MHhaI C5 DNMT), which suggested that the quinoline and the aminopyridimine moieties of SGI-1027 are important for interaction with the substrates and protein, we designed and synthesized 25 derivatives. Among them, four compounds - namely the derivatives 12, 16, 31 and 32 - exhibited activities comparable to that of the parent compound. Further evaluation revealed that these compounds were more potent against human DNMT3A than against human DNMT1 and induced the re-expression of a reporter gene, controlled by a methylated cytomegalovirus (CMV) promoter, in leukemia KG-1 cells. These compounds possessed cytotoxicity against leukemia KG-1 cells in the micromolar range, comparable with the cytotoxicity of the reference compound, SGI-1027. Structure-activity relationships were elucidated from the results. First, the presence of a methylene or carbonyl group to conjugate the quinoline moiety decreased the activity. Second, the size and nature of the aromatic or heterocycle subsitutents effects inhibition activity: tricyclic moieties, such as acridine, were found to decrease activity, while bicyclic substituents, such as quinoline, were well tolerated. The best combination was found to be a bicyclic substituent on one side of the compound, and a one-ring moiety on the other side. Finally, the orientation of the central amide bond was found to have little effect on the biological activity. This study provides new insights in to the structure-activity relationships of SGI-1027 and its derivative. Ep-(igenet)-ic! Guided by modeling studies, derivatives of the known DNA methyltransferase (DNMT) inhibitor SGI-1027 were designed, synthesized and evaluated. Structure-activity relationships were derived from the results, leading to the identification of derivatives with improved potency and potential for further development.
- Rilova, Elodie,Erdmann, Alexandre,Gros, Christina,Masson, Veronique,Aussagues, Yannick,Poughon-Cassabois, Valerie,Rajavelu, Arumugam,Jeltsch, Albert,Menon, Yoann,Novosad, Natacha,Gregoire, Jean-Marc,Vispe, Stephane,Schambel, Philippe,Ausseil, Frederic,Sautel, Francois,Arimondo, Paola B.,Cantagrel, Frederic
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p. 590 - 601
(2014/03/21)
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- Novel 2-phenyl-3-{4'-[N-(4"-aminophenyl)carbamoyl]-phenyl}- quinazoline-4(3H)one-6-sulphonic acid based mono azo reactive dyes
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A series of new heterocyclic mono azo reactive dyes 7a-m were prepared by diazotization of 2-phenyl-3-{4'-[N-(4"-aminophenyl)carbamoyl]-phenyl}- quinazoline-4(3H)-one-6-sulphonic acid (3) and coupling with various cyanurated coupling components 6a-m and their dyeing performance on silk, wool and cotton fibres was assessed. These dyes were found to give a variety of colour shades with very good depth and levelness on the fibres. All the compounds were identified by conventional method (IR and 1H-NMR) and elemental analyses. The percentage dye bath exhaustion on different fibres was reasonably good and acceptable. The dyed fibre showed moderate to very good fastness to light, washing and rubbing.
- Patel, Divyesh R.,Patel, Keshav C.
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scheme or table
p. 177 - 188
(2012/01/02)
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- Basic azo dyestuffs of the 3-cyano-2,4,6-triamino pyridine series
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The new basic azo dyestuffs of the formula STR1 wherein the symbols have the meaning given in the description, are suitable for dyeing synthetic and naturally occurring substrates which can be dyed with basic dyestuffs.
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