37148-47-3Relevant articles and documents
Red-shifted tetra-ortho-halo-azobenzenes for photo-regulated transmembrane anion transport
Bo, Zonghua,Duarte, Fernanda,Kerckhoffs, Aidan,Langton, Matthew J.,Penty, Samuel E.
supporting information, p. 9058 - 9067 (2021/11/04)
Photo-responsive synthetic ion transporters are of interest as tools for studying transmembrane transport processes and have potential applications as targeted therapeutics, due to the possibility of spatiotemporal control and wavelength-dependent function. Here we report the synthesis of novel symmetric and non-symmetric red-shifted tetra-ortho-chloro- and tetra-ortho-fluoro azobenzenes, bearing pendant amine functionality. Functionalisation of the photo-switchable scaffolds with squaramide hydrogen bond donors enabled the preparation of a family of anion receptors, which act as photo-regulated transmembrane chloride transporters in response to green or red light. The subtle effects of chlorine/fluorine substitution,meta/parapositioning of the anion receptors, and the use of more flexible linkers are explored. NMR titration experiments on the structurally diverse photo-switchable receptors reveal cooperative binding of chloride in theZ, but notEisomer, by the two squaramide binding sites. These results are supported by molecular dynamics simulations in explicit solvent and model membranes. We show that this intramolecular anion recognition leads to effective switching of transport activity in lipid bilayer membranes, in which optimalZisomer activity is achieved using a combination of fluorine substitution andpara-methylene spacer units.
Preparation method of stable isotope labeled clenproperol
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Paragraph 0041-0045, (2021/07/09)
The invention relates to a preparation method of stable isotope labeled clenproperol, which comprises the following steps: by taking 4-amino-3,5-dichloroacetophenone (II) as a raw material, carrying out bromination reaction to prepare a compound (III), then carrying out improved Gabriel synthesis reaction, namely amination reaction with sodium diformamide to obtain a compound (IV), then carrying out hydrolysis and reduction to obtain a compound (VI), and carrying out reductive amination reaction to generate a target compound (I). The preparation method disclosed by the invention is reasonable in process design, low in raw material price, controllable in experimental process and simple and convenient to operate, various required labeled compounds such as D-labeled, 13C-labeled or D/13C double-labeled compounds can be conveniently synthesized, and the prepared target product is high in purity, can be used as an internal standard substance in the field of food safety detection, and has important practical application value.
Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer
Bantzi, Marina,Augsburger, Fiona,Loup, Jérémie,Berset, Yan,Vasilakaki, Sofia,Myrianthopoulos, Vassilios,Mikros, Emmanuel,Szabo, Csaba,Bochet, Christian G.
, p. 6221 - 6240 (2021/05/06)
The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is one of the more recently identified mammalian sources of H2S. A recent study identified several novel 3-MST inhibitors with micromolar potency. Among those, (2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one) or HMPSNE was found to be the most potent and selective. We now took the central core of this compound and modified the pyrimidone and the arylketone sides independently. A 63-compound library was synthesized; compounds were tested for H2S generation from recombinant 3-MST in vitro. Active compounds were subsequently tested to elucidate their potency and selectivity. Computer modeling studies have delineated some of the key structural features necessary for binding to the 3-MST's active site. Six novel 3-MST inhibitors were tested in cell-based assays: they exerted inhibitory effects in murine MC38 and CT26 colon cancer cell proliferation; the antiproliferative effect of the compound with the highest potency and best cell-based activity (1b) was also confirmed on the growth of MC38 tumors in mice.
Phenylethanolamine β receptor agonist synthetic method
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, (2019/07/04)
The invention discloses a phenylethanolamine β receptor agonist synthetic method, comprises the following steps: S1: the 4 - amino acetophenone dissolved in an organic solvent, with the electrophilic reagent occurs on the benzene ring substituted halogenated reaction, generating [...] intermediate; [...] intermediates in organic solvent or in water, under the catalysis of the metal catalyst with the cyanide reagent undergo nucleophilic substitution reaction, generating phenyl ketone intermediate; S2: phenyl ketone intermediates in organic solvent, with the copper bromide generating carbonyl α bromo reaction to produce α - bromoacetophenone intermediates; S3: α - bromoacetophenone intermediates in organic solvent with tert-butyl amine or isopropylamine reaction intermediates acetophenone amines; S4: acetophenone amine intermediates in organic solvent, with the reduction hydrogenation reagent react to generate the phenylethanolamine β receptor agonists; synthetic method of this invention a simple and highly efficient and cheap and easy to obtain, atom utilization is high, the synthetic product chemical purity is greater than 99%, to meet the detection requirements of the food safety.
BETA-HYDROXYETHYLAMINES FOR USE IN THE TREATMENT OR PREVENTION OF NON-ALCOHOLIC FATTY LIVER DISEASES
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Page/Page column 63; 64, (2019/04/11)
There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of a non-alcoholic fatty liver disease (NAFLD), such as non-alcoholic steatohepatitis (NASH), wherein X, R1, R2, R3 and n have meanings as provided in the description.
Β - secretase enzyme has the function of inhibiting compound, the preparation of the compounds and use thereof
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Paragraph 0089; 0090, (2018/03/26)
The invention discloses a compound capable of inhibiting beta-secretase, and a preparation method and application thereof. The structure of the compound is shown in a formula I, formula II or formula III as described in the specification. In the formula I, X is S or NH; R1 is selected from hydrogen and nitro group; R2 and R4 are same or different and independently selected from the group consisting of hydrogen, halogen, nitro group and substituted aryl group; R3 is selected from the group consisting of hydrogen, nitro group, straight-chain and branched-chain alkyl and substituted alkyl groups with a carbon number of 1 to 4, alkylamino or alkyloxy group with a carbon number of 1 to 4 and alkylamido group with a carbon number of 1 to 4; R is located at position 2, 3 or 4 of a benzene ring and selected from the group consisting of hydrogen, straight-chain and branched-chain alkyl and substituted alkyl groups with a carbon number of 1 to 4, alkylamino or alkyloxy group with a carbon number of 1 to 4 and alkylamido group with a carbon number of 1 to 4. In the formula II, R is selected from different substituted aryl groups. In the formula III, R is selected from hydrogen or cyano group. Experiments prove that the compound provided by the invention has good beta-secretase inhibitory activity and has wide application values as a beta-secretase inhibitor.
Synthetic method of deuterium-labeled D9-clenbuterol hydrochloride
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Paragraph 0011; 0042-0044, (2019/01/14)
The invention belongs to the field of food safety and standard substance synthesis, and discloses a synthetic method of deuterium-labeled D9-clenbuterol hydrochloride. According to the method, 4-amino-3,5-dichloroacetophenone is taken as a raw material and subjected to three-step reaction including bromination, D9 tert-butyl amination and reduction, and deuterium-labeled D9-clenbuterol hydrochloride is generated. The method is simple to operate, reaction conditions are mild (most reactions are performed at room temperature), reaction routes are reasonable, the process is advanced, the processing method is simple, and a product is easy to purify. Meanwhile, the total conversion rate of D9-tert-butylamine as the core raw material in the synthesis process of D9-clenbuterol hydrochloride is increased to 40% from 4.2%, yield is increased to 64%, and the method has good economic value and social value.
COMPOUNDS FOR THE TREATMENT OF HYPERGLYCAEMIA
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Page/Page column 66; 67, (2017/09/28)
There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of hyperglycaemia or a disorder characterized by hyperglycaemia, such as type 2 diabetes, wherein X, R1, R2, R3 and n have meanings as provided in the description.
Deuterium marked D9 Synthesis method of clenbuterol hydrochloride and synthesis method of synthetic intermediate thereof
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Paragraph 0046; 0047; 0048, (2017/08/25)
The invention relates to a synthesis method of D9-clenbuterol hydrochloride labeled by deuterium as a stable isotope, in particular relates to a synthesis method of a synthesis intermediate of the D9-clenbuterol hydrochloride labeled by deuterium and belongs to the field of standard product synthesis and commodity inspection. According to the synthesis methods disclosed by the invention, 4-amino-alpha-bromine-3, 5-dichloroacetophenone reacts with D9-tert-butylamine, a feed ratio is changed, and other organic bases are selected to replace the D9-tert-butylamine to provide an alkali environment, so that the D9-tert-butylamine is only used for participating in reaction, and thus the conversion rate of the D9-tert-butylamine is remarkably increased. Compared with the prior art, the synthesis methods has the advantage that the use of expensive raw materials is reduced, the utilization ratio of D9-tert-butylamine is increased, a reduction method is optimized, the reduction yield is increased and reaches up to 94 percent, the chemical purity of products reaches 99 percent, and the products have good economical value.
2-Substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamides as BACE1 inhibitors: Synthesis, biological evaluation and?docking studies
Yan, Gang,Hao, Lina,Niu, Yan,Huang, Wenjie,Wang, Wei,Xu, Fengrong,Liang, Lei,Wang, Chao,Jin, Hongwei,Xu, Ping
, p. 462 - 475 (2017/06/19)
In this work, a series of 2-substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamide derivatives were developed as β-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. In addition, the selected compounds were tested with affinity (KD) towards BACE-1, blood brain barrier (BBB) permeability and cytotoxicity. The studies revealed that the most potent analog 41 (IC50 = 4.6 μM) with high predicted BBB permeability and low cellular cytotoxicity, could serve as a good lead structure for further optimization.
