- Synthesis and anticonvulsant activity of phenoxyacetyl derivatives of amines, including aminoalkanols and amino acids
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A series of 17 new phenoxyacetamides has been prepared via multistep chemical synthesis as a continuation of the research carried out by our group on di- and tri-substituted phenoxyalkyl and phenoxyacetyl derivatives of amines. The obtained compounds vary in an amide component, for example aminoalkanol or (un)modified amino acid moieties were introduced. The structures of selected products were confirmed by means of crystallographic methods. All 17 compounds were the subject of preliminary screening for potential anticonvulsant activity (MES, 6 Hz and/or scMET tests) and neurotoxicity (rotarod) in mice after intraperitoneal administration, while several active compounds were subsequently examined in additional models (e.g. MES and rotarod-rats, p.o. or i.p., hippocampal kindling-rats, i.p.). Finally, safety studies (cytotoxicity and cell proliferation assays on astrocytes, metabolic stability assessment, mutagenicity evaluation) were performed for several active compounds, including the most promising one (R-(?)-2-(2,6-dimethylphenoxy)-N-(1-hydroxypropan-2-yl)acetamide, MES ED50 = 12.00 mg per kg b.w., rats, p.o.).
- Pańczyk, Katarzyna,Zelaszczyk, Dorota,Koczurkiewicz, Paulina,S?oczyńska, Karolina,P?kala, El?bieta,Zes?awska, Ewa,Nitek, Wojciech,Zmudzki, Pawe?,Marona, Henryk,Waszkielewicz, Anna
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p. 1933 - 1948
(2018/11/24)
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- Double - (to - alkoxybenzyl propenone) glutathione - S - transfers the sulfur of the enzyme dives inhibitors
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The invention discloses a bis-(p-alkoxy benzene acrylketone) like glutathione-S-transferase potential inhibitor. Structure and living features of the potential inhibitor are as follows: two p-alkoxy benzene acrylketone units are linked to two amino groups, alcoholic hydroxyl groups and carboxyl groups or one amino group and one alcoholic hydroxyl group which are spaced by less than 8 single bonds through amide and/or ester bond, wherein compounds obtained are substrate and inhibitor of glutathione-S-transferase, namely GST; the GST catalyzes carbon-carbon bond and reduced glutathione, namely GSH, of alpha, beta-unsaturated ketone of each p-alkoxy benzene acrylketone unit in the compounds and generates a compound, namely product, through Michael addition. The product shows a stronger inhibiting efficacy on the GST, so that the compound is a GST potential inhibitor; the product has a stronger inhibiting efficacy on human GST isozyme mu in comparison with human GST isozyme alpha and pi; and the compounds can enter into cells, and can enhance inhibiting effect of cis-platinum on drug-resistant carcinoma cell growth.
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Paragraph 0072; 0076; 0078
(2020/05/08)
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- Synthesis and Biological Activity of Ethyl 4-Alkyl-2-(2-(substituted phenoxy)acetamido)thiazole-5-carboxylate
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(Chemical Equation Presented) A series of novel ethyl 4-(methyl or trifluoromethyl)-2-(2-(substituted phenoxy)acetamido)thiazole-5-carboxylates 7a, 7b, 7c, 7d, 7e and 8f, 8g, 8h, 8i, 8j, 8k, 8l, 8m, 8n, 8o, 8p, 8q, 8r were synthesized, and their structures were confirmed by IR, 1H-NMR, MS spectra and elemental analysis. The results of preliminary bioassays show that some of the title compounds exhibit moderate to good herbicidal activities. Compared with the fluorine free compounds 7a, 7b, and 7e, the compounds bearing fluorine 8g, 8j, and 8q showed higher herbicidal activities with 70-100% inhibition against Capsella bursa-pastoris, Amaranthus restroflexus, and Eclipta prostrata at the dosage of 150 g/ha, which indicated that the trifluoromethyl on the thiazole ring was beneficial for the herbicidal activity. Furthermore, compounds 8f, 8g, 8h, 8i, 8j, 8k, 8l, 8m, 8n, 8o, 8p, 8q, 8r were tested for fungicidal activity against Pseudoperonospora cubensis at 500 μg/mL. Compounds 8f and 8q showed the best fungicidal activity with more than 80% inhibition.
- Mo, Wenyan,Shi, Yanxia,He, Junbo,Li, Baoju,Peng, Hao,He, Hongwu
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p. 183 - 187
(2016/02/10)
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- The synthesis of ethacrynic acid thiazole derivatives as glutathione S-transferase pi inhibitors
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Glutathione S-transferase pi (GSTpi) is a phase II enzyme which protects cells from death and detoxifies chemotherapeutic agents in cancer cells. Ethacrynic acid (EA) is a weak GSTpi inhibitor. Structure modifications were done to improve the ability of EA to inhibit GSTpi activity. Eighteen EA thiazole derivatives were designed and synthesized. Compounds 9a, 9b and 9c with a replacement of carboxyl group of EA by a heterocyclic thiazole exhibited improvement over EA to inhibit GSTpi activity.
- Li, Ting,Liu, Guyue,Li, Hongcai,Yang, Xinmei,Jing, Yongkui,Zhao, Guisen
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scheme or table
p. 2316 - 2322
(2012/05/07)
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- Studies of O,O-Dimethyl α-(2,4-Dichlorophenoxyacetoxy) ethylphosphonate (HW02) as a new herbicide. 1. Synthesis and herbicidal activity of HW02 and analogues as novel inhibitors of pyruvate dehydrogenase complex
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On the basis of the previous work for optimization of O,O-diethyl α-(substituted phenoxyacetoxy)alkylphosphonates, further extensive syntheticmodifications were made to the substituents in alkylphosphonate and phenoxymoieties of the title compounds. New O,O-dimethyl α-(substituted phenoxyacetoxy)alkylphosphonates were synthesized as potential inhibitors of pyruvate dehydorogenase complex (PDHc). Their herbicidal activity and efficacy in vitro against PDHc were examined. Some of these compounds exhibited significant herbicidal activity and were demonstrated to be effective inhibitors of PDHc from three different plants. The structure-activity relationships of these compounds including previously reported analogous compoundswere studied by examining their herbicidal activities. Both inhibitory potency against PDHc and herbicidal activity of title compounds could be increased greatly by optimizing substituent groups of the title compounds. O,O-Dimethyl α-(2,4- dichlorophenoxyacetoxy)ethylphosphonate (I-5), which acted as a competitive inhibitor of PDHc with much higher inhibitory potency against PDHc from Pisum sativum and Phaseolus radiatus than from Oryza sativa, was found to be themost effective compound against broadleaf weeds and showed potential utility as herbicide.
- He, Hong-Wu,Yuan, Jun-Lin,Peng, Hao,Chen, Ting,Shen, Ping,Wan, Shu-Qing,Lee, Yanjun,Tan, Hong-Liang,He, Ya-Hui,He, Jun-Bo,Li, Yan
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scheme or table
p. 4801 - 4813
(2011/12/04)
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- The synthesis of α,β-unsaturated carbonyl derivatives with the ability to inhibit both glutathione S-transferase P1-1 activity and the proliferation of leukemia cells
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Ethacrynic acid (EA), an α,β-unsaturated carbonyl compound, is a glutathione S-transferase P1-1 (GSTP1-1) inhibitor. Twenty-one novel EA derivatives have been synthesized. The effects of these compounds on GSTP1-1 activity and on the proliferation of human leukemia HL-60 cells have been determined. Compounds with a halogen substitution at the 3′-position of the aromatic ring have greater inhibitory effects on GSTP1-1 activity than those of compounds with a methyl substitution there. Compounds with substitutions at both the 2′- and 3′-positions of the aromatic ring have more antiproliferative ability than those with one substitution at 3′-position. Esterification of the carboxyl group appears to increase the antiproliferative ability.
- Zhao, Guisen,Liu, Chuan,Wang, Rui,Song, Dandan,Wang, Xiaobing,Lou, Hongxiang,Jing, Yongkui
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p. 2701 - 2707
(2008/02/07)
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- Synthesis of analogs of juvenile hormons proceeding from phenol derivatives
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New potential juvenoids, esters of alkenoic and alkadienoic acids with phenoxy-and phenoxy-phenoxyethanol were synthesized, and also esters of phenoxyacetic acid with alkenols amd alkadienols.
- Yamansarova,Kukovinets,Kukovinets,Zainullin,Galin,Kunakova,Zorin,Tolstikov
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p. 246 - 255
(2007/10/03)
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- Solvent-free synthesis of substituted phenoxyacetic acids under microwave irradiation
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A comparison of microwave-activated vs. classical organic synthesis is presented for a variety of growth-regulator compounds with a phenoxyacetic acid structure. Microwave-assisted nucleophilic substitutions are safely and conveniently carried out in an open vessel, without any solvent. Yields are very good, and reaction times are extremely short.
- Nagy, Gabriela,Filip, Sorin V.,Surducan, Emanoil,Surducan, Vasile
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p. 3729 - 3736
(2007/10/03)
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