T:Toxic;
79-04-9Relevant articles and documents
Design, synthesis, biological evaluation and molecular docking of new 1,3,4-oxadiazole homonucleosides and their double-headed analogs as antitumor agents
EL Mansouri, Az-eddine,Oubella, Ali,Mehdi, Ahmad,AitItto, Moulay Youssef,Zahouily, Mohamed,Morjani, Hamid,Lazrek, Hassan B.
, (2021)
A novel series of homonucleosides and their double-headed analogs containing theophylline, 1,3,4-oxadiazole, and variant nucleobases was designed and synthesized. The new derivatives were fully characterized by HRMS, FT-IR, 1H NMR, and 13C NMR. The cytotoxic activities of all prepared compounds were screened in vitro against four cell lines, including fibrosarcoma (HT-1080), breast (MCF-7 and MDA-MB-231), and lung carcinoma (A-549). The double-headed analogue 18 showed marked growth inhibition against all the cell lines tested, specifically in HT-1080, with an IC50 values of 17.08 ± 0.97 μM. The possible mechanism of apoptosis was investigated using Annexin V staining, caspase-3/7 activity, and analysis cell cycle progression. The compound 18 induced apoptosis through caspase-3/7 activation and cell-cycle arrest in HT-1080 and A-549 cells. The molecular docking confirms that the compound 18 activated caspase-3 via the formation of hydrogen bonds and hydrophobic interactions.
Green synthesis of 6-[2-aminothiazol-4-yl]-2-furylchromone
Sharma, Vinay Prabha,Kumar, Rakesh
, p. 3989 - 3991 (2014)
Synthesis of 2-aminothiazoles through Hantzsch method involves the use of bromine. An 2-aminothiazole system 6-[2-aminothiazol-4- yl]-2-furylchromone has been synthesized green chemically from 6-chloroacetyl-2-furylchromone and 6-acetyl-2-furylchromone during present study. The structures of new compounds were elucidated on the basis of IR and PMR-spectra.
Practical synthesis of quinoline-protected morpholino oligomers for light-triggered regulation of gene function
Deodato, Davide,Dore, Timothy M.
, (2020)
Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control. Nevertheless, some challenges associated with the preparation of these reagents have limited their broader use in biological settings. We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation. The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker. We used the alkynyl-functionalized linker for the preparation of two different ccMOs targeting the mRNA of the glutamic acid decarboxylase genes, gad1 and gad2. HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light. Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
Synthesis and Fungitoxic Evaluation of Acylamino-1,2,4-Triazoles
Kaur, Gurinderjit,Kaur, Harleen,Kaur, Pardeep,Sharma, Sunita,Singh, Ravneet
, p. 389 - 395 (2021/11/22)
Ten different acylamino-1,2,4-triazoles were prepared by the reaction of differently substituted benzoyl chlorides and acetyl chlorides with 4-amino-1,2,4-triazole using catalytic amount of triethylamine. The synthesized compounds were characterized using UV, 1H-nuclear magnetic resonance spectroscopy, and infrared spectroscopy. All the compounds were tested for their fungicidal potential against three fungal species, that is, Fusarium verticillioides, Macrophomina phaseolina, and Rhizoctonia solani using poisoned food technique. The synthesized compounds were tested at various concentrations along with standard carbendazim 50 WP. The amides synthesized by reaction of substituted benzoyl chlorides and 4-amino-1,2,4-triazole exhibited greater fungicidal activity against all the tested fungi as compared to the amides synthesized using substituted acetyl chlorides. Among all the tested compounds, 4-nitro-N-(4-H-1,2,4-triazol-4-yl)benzamide showed the maximum fungicidal activity with the least median effective dose (ED50) values of 100, 93, and 146 μg ml-1 against F verticillioides, M. phaseolina, and R. solani, respectively. All the compounds were found to be less effective than the standard used.
Alkylation of 5-Substituted Tetrazoles with Various Alcohols in 1,2-Dichloroethane in the Presence of BF3·Et2O
Egorov, S. A.,Ishchenko, M. A.,Ivanova, V. I.,Prokopovich, Ya. V.
, p. 1196 - 1203 (2020/10/02)
Abstract: The alkylation of 1H-tetrazole, 5-methyl-1H-tetrazole, and 5-phenyl-1H-tetrazole with primary, secondary, and tertiary alcohols, including benzylic and allylic ones, have been studied in 1,2-dichloroethane in the presence of boron trifluoride–diethyl ether complex. Neither primary nor secondary saturated alcohols alkylated tetrazoles in the given system. Tertiary alcohols such tert-butyl alcohol and adamantan-1-ol reacted with unsubstituted and 5-substituted tetrazoles to give 70–85% of the corresponding 2-alkyl-5-R-tetrazoles with high regioselectivity. The alkylation of 1H-tetrazole with benzyl alcohol afforded 55% of 2-benzyl-2H-tetrazole as the only product. The alkylation of 1H-tetrazole with various allylic alcohols led to the formation of mixtures of 2-alkyl-2H-tetrazoles with isomeric alkyl substituents.
3-Aminobenzenesulfonamides incorporating acylthiourea moieties selectively inhibit the tumor-associated carbonic anhydrase isoform IX over the off-target isoforms I, II and IV
Fattah, Tanzeela Abdul,Bua, Silvia,Saeed, Aamer,Shabir, Ghulam,Supuran, Claudiu T.
, p. 123 - 128 (2018/10/20)
We describe the synthesis of a series of novel 1-aroyl/acyl-3-(3-aminosulfonylphenyl) thioureas (4a–k) acting as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. Reaction of alkyl/aryl isothiocyanates with 3-aminobenzenesulfonamide afforded a series of the title compounds incorporating a variety of short as well as highly lipophilic long tails. The newly synthesized sulfonamides were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IV, and IX). Several compounds showed interesting inhibitory activity. The tumor-associated hCA IX was the most sensitive isoform to inhibition with these compounds, with KIs in the range of 21.5–44.0 nM and selectivity ratios over the major cytosolic isoform hCA II in the range of 3.35–37.3. The sulfonamides incorporating the phenylacetylthioureido and pentadecanoylthioureido moieties were the most hCA IX-selective inhibitors detected in this work, making them of interest for further investigations.
A high-purity 3, 5, 6 - trichloro-pyridine -2 - sodium alcoholate production process (by machine translation)
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Paragraph 0045; 0064, (2019/04/04)
The present invention relates to the technical field of chemical material production, and in particular relates to a high-purity 3, 5, 6 - trichloro-pyridine - 2 - sodium alcoholate production process, comprises the following steps: chlorine acetyl chloride; preparing trichlor; addition cyclization: the protection of inert gas atmosphere by adding solvent, the pure product of the chloroacetyl chloride, acrylonitrile and catalyst, the temperature of the stirred to back flow, so that the reflux to return to below the liquid level, reduced pressure distillation, heat filter, the catalyst can be recycled for use, get filtrate for use; preparing 3, 5, 6 - trichloro-pyridine - 2 - sodium alcoholate crude; for preparing high-purity 3, 5, 6 - trichloro-pyridine - 2 - sodium alcoholate. The invention solves the problems in the prior art 3, 5, 6 - trichloro-pyridine - 2 - sodium alcoholate preparation technical difficulty is high, the yield is low and low purity of, the prepared 3, 5, 6 - trichloro-pyridine - 2 - sodium alcoholate has high purity, high yield and relatively shallow the advantages of luster, reasonable production process and is favorable for industrial production. (by machine translation)
Design, synthesis and biological study of potent and covalent HER-2 tyrosine kinase inhibitors with low cytotoxicity in vitro
Jin, Shuyu,Sun, Xiuyun,Liu, Dan,Xie, Hua,Rao, Yu
, p. 1333 - 1345 (2019/05/06)
The discovery and development of a novel HER-2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer are presented in this article. EGFR family has been recognized as a crucial meditator in the cancer progression; HER-2 tyrosine kinase was one of the members among them. In the effort to explore potent HER-2 inhibitors, a novel series of 4-anilino-3-cyanoquinoline derivatives have been designed, synthesized and evaluated. Most compounds possessed modest proliferation inhibition on SK-BR-3 cell line and HER-2 kinase. Compound 16 appeared to be the most potent compound (HER-2 kinase IC50: 19.4?nM, SK-BR-3 IC50: 94?nM). In the experiment of cellular cytotoxicity assay, compound 16 shows a much lower cytotoxicity than neratinib on Beas-2b cell line (Human bronchial epithelial cells). In conclusion, compound 16 would be a promising lead compound for further anti-breast cancer drug discovery.
Synthesis and bioactivities of diamide derivatives containing a phenazine-1-carboxamide scaffold
Zhu, Xiang,Zhang, Min,Yu, Linhua,Xu, Zhihong,Yang, Dan,Du, Xiaoying,Wu, Qinglai,Li, Junkai
supporting information, p. 2453 - 2460 (2018/03/29)
Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series of novel phenazine-1-carboxylic acid diamide derivatives were designed and synthesised. Their structures were confirmed by 1H-NMR and HRMS. The bioassays showed that some of the target compounds exhibited promising in vitro fungicidal activities, and exhibited excellent and selective herbicidal activities. Particularly, compounds c, h, o and s displayed root length inhibition activities against barnyard grass with the rate of more than 80%. Compound c exhibited the best activity among all the target compounds against barnyard grass stalk length with the IC50 value of 0.158?mmol/L, and compound o exhibited the best and wide spectrum inhibition against barnyard grass root length and rape in both root length and stalk length herbicidal activities with its IC50 values of 0.067, 0.048 and 0.059?mmol/L respectively. The analysis of preliminary Structure-Activity Relationships provides the theoretical basis for further design of phenazine-1-carboxylic acid.
Synthesis method of chloroacetyl chloride
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Paragraph 0020-0022, (2019/03/28)
The invention discloses a synthesis method of chloroacetyl chloride (ClCH2COCl). To be specific, the synthesis method is characterized in that an activated carbon loaded lewis acid catalyst is used for catalyzing gaseous acetyl chloride and chlorine to perform an alpha-halogenation reaction in a contact reactor to generate the chloroacetyl chloride. Lewis acid is specifically ferric chloride or aluminium chloride, and the consumption of the lewis acid is 1-7% of the total material input of acetyl chloride. The synthesis method disclosed by the invention is high in catalyst utilizing rate, highin selectivity, and less in byproducts, and the purity of a product is higher than or equal to 99.5%; the reaction is performed at low temperature; the energy consumption is low; the environmental pollution is small; and the reaction equipment structure is simple, and the operation is easy.
