86-90-8Relevant articles and documents
An Isosteric and Fluorescent DNA Base Pair Consisting of 4-aminophthalimide and 2,4-diaminopyrimidine as C-Nucleosides
Merkel, Marcus,Dehmel, Lars,Ernsting, Nikolaus P.,Wagenknecht, Hans-Achim
, p. 384 - 388 (2017)
A 13mer DNA duplex containing the artificial 4-aminophthalimide:2,4-diaminopyrimidine (4AP:DAP) base pair in the central position was characterized by optical and NMR spectroscopy. The fluorescence of 4AP in the duplex has a large Stokes shift of Δλ=124 nm and a quantum yield of ΦF=24 %. The NMR structure shows that two interstrand hydrogen bonds are formed and confirms the artificial base pairing. In contrast, the 4-N,N-dimethylaminophthalimide moiety prefers the syn conformation in DNA. The fluorescence intensity of this chromophore in DNA is very low and the NMR structure shows no significant interaction with DAP. Primer-extension experiments with DNA polymerases showed that not only is the 4AP C nucleotide incorporated at the desired position opposite DAP in the template, but also that the polymerase is able to progress past this position to give the full-length product. The observed selectivity supports the NMR results.
COMPOUNDS AND USES THEREOF
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Page/Page column 316, (2021/08/06)
The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.
In pursuit of a selective hepatocellular carcinoma therapeutic agent: Novel thalidomide derivatives with antiproliferative, antimigratory and STAT3 inhibitory properties
Nutt, Michael J.,Yee, Yeung Sing,Buyan, Amanda,Andrewartha, Neil,Corry, Ben,Yeoh, George C.T.,Stewart, Scott G.
, (2021/03/30)
Advanced stage liver cancer is predominantly treated with the multi-kinase inhibitor sorafenib; however, this therapeutic agent lacks selectivity in its cytotoxic actions and is associated with poor survival outcomes. Herein we report the design and preparation of several thalidomide derivatives, including a variety of novel thioether-containing forms that are especially rare in the literature. Importantly, two of the derivatives described are potent antiproliferative agents with dose-dependent selectivity for tumorigenic liver progenitor cells (LPC) growth inhibition (up to 36% increase in doubling time at 10 μM) over non-tumorigenic cells (no effect at 10 μM). Furthermore, these putative anti-liver cancer agents were also found to be potent inhibitors of tumorigenic LPC migration. This report also describes these derivatives’ effects on several key signalling pathways in our novel liver cell lines by immunofluorescence and AlphaLISA assays. Aryl thioether derivative 7f significantly reduced STAT3 phosphorylation (23%) and its nuclear localisation (16%) at 10 μM in tumorigenic LPCs, implicating the IL-6/JAK/STAT3 axis is central in the mode of action of our derivatives.
Synthesis method of 4-halogenated phthalic anhydride and derivative thereof
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Paragraph 0024-0027; 0029-0032; 0034-0037; 0039-0042; 0044-0, (2020/12/30)
The invention relates to a synthetic method of 4-halogenated phthalic anhydride and a derivative of the 4-halogenated phthalic anhydride, and solves the technical problems of low product purity, poorproduct performance, complex synthetic process and low utilization ratio of monohalide isomers and polyhalides in the existing production process. The method specifically comprises the following steps: dissolving phthalic anhydride in an organic solvent, and introducing a halogenating reagent under the action of iron powder and a Lewis acid catalyst to prepare a halogenated phthalic anhydride mixture; rectifying and purifying the polyhalogenated phthalic anhydride mixture to obtain a 4-halogenated phthalic anhydride pure product; and continuing subjecting residual halogenated phthalic anhydride mixture to halogenation reaction under the action of fuming sulfuric acid and the catalyst to prepare tetrahalogenated phthalic anhydride, and to realize comprehensive utilization of the raw materials. The method is widely applied to the technical field of flame retardant synthesis.
Dihydroxyphenyl Sulfonylisoindoline Derivatives
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Paragraph 058; 060; 0116, (2018/06/12)
Provided are compounds that are inhibitors of pyruvate dehydrogenase kinase (PDK), and pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition.
PROCESS FOR THE PREPARATION OF ORGANIC BROMIDES
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Paragraph 00139; 00141; 00162, (2017/07/28)
The present invention provides a process for the preparation of organic bromides, by a radical bromodecarboxylation of carboxylic acids with a bromoisocyanurate.
Development of Dihydroxyphenyl Sulfonylisoindoline Derivatives as Liver-Targeting Pyruvate Dehydrogenase Kinase Inhibitors
Tso, Shih-Chia,Lou, Mingliang,Wu, Cheng-Yang,Gui, Wen-Jun,Chuang, Jacinta L.,Morlock, Lorraine K.,Williams, Noelle S.,Wynn, R. Max,Qi, Xiangbing,Chuang, David T.
supporting information, p. 1142 - 1150 (2017/02/19)
Pyruvate dehydrogenase kinases 1-4 (PDK1-4) negatively control activity of the pyruvate dehydrogenase complex (PDC) and are up-regulated in obesity, diabetes, heart failure, and cancer. We reported earlier two novel pan-PDK inhibitors PS8 [4-((5-hydroxyisoindolin-2-yl)sulfonyl)benzene-1,3-diol] (1) and PS10 [2-((2,4-dihydroxyphenyl)sulfonyl)isoindoline-4,6-diol] (2) that targeted the ATP-binding pocket in PDKs. Here, we developed a new generation of PDK inhibitors by extending the dihydroxyphenyl sulfonylisoindoline scaffold in 1 and 2 to the entrance region of the ATP-binding pocket in PDK2. The lead inhibitor (S)-3-amino-4-(4-((2-((2,4-dihydroxyphenyl)sulfonyl)isoindolin-5-yl)amino)piperidin-1-yl)-4-oxobutanamide (17) shows a ～8-fold lower IC50 (58 nM) than 2 (456 nM). In the crystal structure, the asparagine moiety in 17 provides additional interactions with Glu-262 from PDK2. Treatment of diet-induced obese mice with 17 resulted in significant liver-specific augmentation of PDC activity, accompanied by improved glucose tolerance and drastically reduced hepatic steatosis. These findings support 17 as a potential glucose-lowering therapeutic targeting liver for obesity and type 2 diabetes.
Industrial preparation method of 5-bromophthalide
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, (2017/09/01)
The invention relates to a preparation method of 5-bromophthalide and mainly solves such production technical problems of an existing preparation method as expensive raw material, dangerous and complex operation, relatively low yield, high quantity of generated three wastes and etc. The technical scheme of the invention is as follows: an industrial preparation method of 5-bromophthalide is characterized in that 5-bromophthalide is obtained through three step reactions of bromination, ammoniation and reduction by taking a conventional and easily available ammoniation as a raw material. The chemical reaction formula is as shown in the description. The method provided by the invention is mainly used for industrial preparation of 5-bromophthalide.
Preparation method of 4-bromo phthalic anhydride
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Paragraph 0025, (2016/12/01)
The invention belongs to the field of chemical engineering, and relates to a preparation method of 4-bromo phthalic anhydride. The preparation method includes the following steps that sodium hydroxide is dissolved in water, phthalic anhydride and a phase transfer catalyst are added and evenly mixed, a reaction is performed in the mode that programmed temperature control is performed in three stages and reactants are added in three times, 20% fuming sulphuric acid is added for acidification, a sodium bisulfite aqueous solution is added after cooling for removing excessive bromine, an organic solvent is added for extraction, the organic solvent is removed through distillation, then temperature is increased to obtain a crude 4-bromo phthalic anhydride product, rectification dehydration is performed under the vacuum condition, fraction is collected, and the finished 4-bromo phthalic anhydride product is obtained. Compared with a multi-step reaction in the prior art, the process steps are simplified, the product yield is high, the production energy consumption is reduced, the three-waste emission is greatly reduced, the energy consumption and wastewater treatment cost for extraction of 4-bromophthalic acid crystals are reduced, production cost is reduced, and environmental protection pressure is relieved.
Synthesis and biological evaluation of novel aromatic imide-polyamine conjugates
Li, Ming,Wang, Yuxia,Zhang, Jianying,Xie, Songqiang,Wang, Chaojie,Wu, Yingliang
, (2016/12/16)
Three types of conjugates in which aromatic imide scaffolds were coupled to diverse amine/polyamine motifs were synthesized, and their antitumor activities were evaluated in vitro and in vivo. Results showed that the conjugate 11e of 1,8-naphthilimide with spermine had pronounced effects on inhibiting tumor cell proliferation and inducing tumor cell apoptosis via ROS-mediated mitochondrial pathway. The in vivo assays on three H22 tumor transplant models revealed that compound 11e exerted potent ability in preventing lung cancer metastasis and extending lifespan. Furthermore, the efficacy of 11e in inhibiting tumor growth and improving body weight index were better than that of positive control, amonafide. Our study demonstrates that compound 11e is a valuable lead compound for further investigation.
