- Metal–Organic Framework-Encapsulated CoCu Nanoparticles for the Selective Transfer Hydrogenation of Nitrobenzaldehydes: Engineering Active Armor by the Half-Way Injection Method
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A novel armor-type composite of metal–organic framework (MOF)-encapsulated CoCu nanoparticles with a Fe3O4 core (Fe3O4@SiO2-NH2-CoCu@UiO-66) has been designed and synthesized by the half-way injection method, which successfully serves as an efficient and recyclable catalyst for the selective transfer hydrogenation. In this half-way injection approach, the pre-synthetic Fe3O4@SiO2-NH2-CoCu was injected into the UiO-66 precursor solution halfway through the MOF budding period. The formed MOF armor could play a role of providing significant additional catalytic sites besides CoCu nanoparticles, protecting CoCu nanoparticles, and improving the catalyst stability, thus facilitating the selective transfer hydrogenation of nitrobenzaldehydes into corresponding nitrobenzyl alcohols in high selectivity (99 %) and conversion (99 %) rather than nitro group reduction products. Notably, this method achieves the precise assembly of a MOF-encapsulated composite, and the ingenious combination of MOF and nanoparticles exhibits excellent catalytic performance in the selective hydrogen transfer reaction, implementing a “1+1>2” strategy in catalysis.
- Li, Yang,Li, Yu-Nong,Zheng, Jian-wei,Dong, Xiao-yun,Guo, Rong-xiu,Wang, Yi-ming,Hu, Ze-nan,Ai, Yongjian,Liang, Qionglin,Sun, Hong-bin
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supporting information
p. 1080 - 1087
(2020/12/18)
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- AHR INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
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Paragraph 0298; 0299; 0300
(2019/03/02)
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- Combined production method for substituted benzaldehyde, substituted benzyl alcohol and substituted benzoic acid
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The invention discloses a combined production method for substituted benzaldehyde, substituted benzyl alcohol and substituted benzoic acid. The method comprises the following steps: (1) oxidation: a step of continuously introducing substituted toluene, a catalyst and oxygen-contained gas into an oxidation reactor and carrying out reaction so as to obtain oxidation reaction liquid; (2) hydrolyzation: a step of allowing the oxidation reaction liquid to continuously enter a hydrolysis reactor, and continuously adding water into the hydrolysis reactor and carrying out reaction so as to obtain a hydrolysis reaction mixture; (3) liquid-liquid layering: a step of layering the hydrolysis reaction mixture so as to obtain an oil phase and an aqueous phase; and (4) separation of products: a step of subjecting the oil phase to distillation so as to respectively obtain incompletely-reacted substituted toluene, substituted benzyl alcohol and substituted benzaldehyde, and subjecting the aqueous phase to cooling, crystallizing and filtering so as to obtain filtrate and substituted benzoic acid. The combined production method provided by the invention has the advantages of high raw material conversion rate, few by-products, good selectivity of target products, greenness and environmental protection.
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Paragraph 0079; 0080
(2017/01/31)
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- SUBSTITUTED 1H-INDAZOL-1-OL ANALOGS AS INHIBITORS OF BETA CATENIN/TCF PROTEIN-PROTEIN INTERACTIONS
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In one aspect, the invention relates to substituted lH-benzo[d][l,2,3]triazol-l-ol analgoues, derivatives thereof, and related compound; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders, e.g. various tumors and cancers, associated with β-catenin/Tcf protein- protein interaction dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Paragraph 300
(2013/08/28)
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- KINASE INHIBITORS
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The present invention relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein variables R, Ar, X, and Ar1 and n are as defined herein. The compounds are capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
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Paragraph 0151-0152
(2013/12/03)
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- Synthesis and structure-activity relationships of nitrobenzyl phosphoramide mustards as nitroreductase-activated prodrugs
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A series of nitrobenzyl phosphoramide mustards and their analogs was designed and synthesized to explore their structure-activity relationships as substrates of nitroreductases from Escherichia coli and trypanosomes and as potential antiproliferative and antiparasitic agents. The position of the nitro group on the phenyl ring was important with the 4-nitrobenzyl phosphoramide mustard (1) offering the best combination of enzyme activity and antiproliferative effect against both mammalian and trypanosomatid cells. A preference was observed for halogen substitutions ortho to benzyl phosphoramide mustard but distinct differences were found in their SAR of substituted 4-nitrobenzyl phosphoramide mustards in E. coli nitroreductase-expressing cells and in trypanosomatids expressing endogenous nitroreductases.
- Hu, Longqin,Wu, Xinghua,Han, Jiye,Chen, Lin,Vass, Simon O.,Browne, Patrick,Hall, Belinda S.,Bot, Christopher,Gobalakrishnapillai, Vithurshaa,Searle, Peter F.,Knox, Richard J.,Wilkinson, Shane R.
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p. 3986 - 3991
(2011/08/06)
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- Substituent effects on the kinetics of reductively-initiated fragmentation of nitrobenzyl carbamates designed as triggers for bioreductive prodrugs
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4-Nitrobenzyl carbamates are of interest as triggers for bioreductive drugs, particularly in conjunction with the E. coli B nitroreductase, which efficiently reduces them to the corresponding hydroxylamines. These then fragment to release highly toxic amine-based toxins. While many 4-nitrobenzyl carbamate derivatives have been evaluated as bioreductive drugs, there has been no systematic study of substituent effects on the rate of this fragmentation (which should be as fast as possible following reduction). We therefore prepared a series of 2-, 3- and α-substituted 4-[N-methyl-N-(4-nitrobenzyloxycarbonyl)amino]phenylacetamides as model compounds to study these effects. The majority of the carbamates were prepared by in situ formation of the chloroformate of the appropriate 4-nitrobenzyl alcohol and reaction with methyl 4-(methylamino)phenylacetate, followed by ester hydrolysis and 1,1′-carbonyl-diimidazole (CDI) mediated coupling with N,N-dimethylaminoethylamine. The hydroxylamines were generated by 60Co γ-ray irradiation of the nitro compounds in aqueous phosphate-buffered-propan-2-ol. The reactions were analysed by reverse-phase HPLC to determine the maximum half-life (Mt1/2) of the hydroxylamines generated, and the extent of release of amine from these after 10 half-lives (t∞). The parent (unsubstituted) hydroxylaminobenzyl carbamate had a Mt1/2 of 16 min under these conditions, while that of the corresponding α-methyl analogue was 9.5 min. Electron-donating substituents on the benzyl ring also accelerated fragmentation, with the data being fitted to the equation log(Mt1/2) = 0.57σ + 1.30, where σ represents σp for 2-substituents and σm for 3-substituents. The acceleration of fragmentation of the hydroxylamines with increasing substituent electron-donation is consistent with the proposed mechanism, and is presumably due to stabilisation of the developing positive charge on the benzylic carbon. The extent of release of amine (t∞) also increased with increasing substituent electron-donation. These data suggest that the standard 4-nitrobenzyl carbamate trigger for nitroreductase enzyme (NTR) prodrugs can likely be improved on, by increasing the rate of fragmentation by the use of α-methyl and/or electron-donating benzyl substituents. The Royal Society of Chemistry 1999.
- Hay, Michael P.,Sykes, Bridget M.,Denny, William A.,O'Connor, Charmian J.
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p. 2759 - 2770
(2007/10/03)
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- Non-Peptide Angiotensin II Receptor Antagonists. 2. Design, Synthesis, and Biological Activity of N-Substituted (Phenylamino)phenylacetic Acids and Acyl Sulfonamides
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The design, synthesis, and biological activity of a new class of highly potent non-peptide AII receptor antagonists derived from N-substituted (phenylamino)phenylacetic acids and acyl sulfonamides which exhibit a high selectivity for the AT1 receptor are described.A series of N-substituted (phenylamino)phenylacetic acids (9) and acyl sulfonamides (16) and a tetrazole derivative (19) were synthesized and evaluated in the in vitro AT1 (rabbit aorta) and AT2 (rat midbrain) binding assay.The (phenylamino)phenylacetic acids 9c (AT1 IC50=4 nM, AT2 IC50=0.74 μM), 9d (AT1 IC50=5.3 nM, AT2 IC50=0.49 μM), and 9e (AT1 IC50=5.3 nM, AT2 IC50=0.56 μM) were found to be the most potent AT1-selective AII antagonists in the acid series.Incorporation of various substituents in the central and bottom phenyl rings led to a decrease in the AT1 and AT2 binding affinity of the resulting compounds.Replacement of the carboxylic acid (CO2H) in 9c, 9d, and 9e with the bioisostere acyl sulfonamide (CONHSO2Ph) resulted in a (5-7)-fold increase in the AT1 potency of 16a (AT1 IC50=0.9 nM, AT2 IC50=0.2 μM), 16b (AT1 IC50=1 nM, AT2 IC50=2.9 μM), and 16c (AT1 IC50=0.8 nM, AT2 IC50=0.42 μM) and yielded acyl sulfonamides with subnanomolar AT1 activity.Incorporation of the acyl sulfonamide (CONHSO2Ph) for the CO2H of 9c not only enhanced the AT1 potency but also effected a marked increase in the AT2 potency of 16a (AT2 IC50=0.74 μM of 9c vs 0.2 μM of 16a) and made it the most potent AT2 antagonist in this study.Replacement of the CO2H of 9b with the bioisostere tetrazole resulted in 19 (AT1 IC50=15 nM) with a 2-fold loss in the AT1 and a complete loss in the AT2 binding affinity. (Phenylamino)phenylacetic acid 9c demonstrated good oral activity in AII-infused conscious normotensive rats at an oral dose of 1.0 mg/kg by inhibiting the pressor response for >6 h.Acyl sulfonamides 16a-c displayed excellent in vivo activity by blocking the AII-induced pressor response for >6 h after oral administration in conscious rats at a 3.0 mg/kg dose level.Both acyl sulfonamides 16a and 16c exhibited superior in vivo activity in rats compared to that of (phenylamino)phenylacetic acid 9c.
- Dhanoa, Daljit S.,Bagley, Scott W.,Chang, Raymond S. L.,Lotti, Victor J.,Chen, Tsing-Bau,et al.
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p. 4239 - 4249
(2007/10/02)
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