37536-92-8Relevant academic research and scientific papers
Chemoproteomic Profiling Reveals Ethacrynic Acid Targets Adenine Nucleotide Translocases to Impair Mitochondrial Function
Ye, Zi,Zhang, Xiaoyun,Zhu, Yuangang,Song, Tong,Chen, Xiaowei,Lei, Xiaoguang,Wang, Chu
, p. 2413 - 2422 (2018)
Ethacrynic acid (EA) is a diuretic drug that is widely used to treat high-blood pressure and swelling caused by congestive heart failure or kidney failure. It acts through noncovalent inhibition of the Na+-K+-2Cl- cotransporter in the thick ascending limb of Henle's loop. Chemically, EA contains a Michael acceptor group that can react covalently with nucleophilic residues in proteins; however, the proteome reactivity of EA remains unexplored. Herein, we took a quantitative chemoproteomic approach to globally profile EA's targets in cancer cells. We discovered that EA induces impaired mitochondrial function accompanied by increased ROS production. Our profiling revealed that EA targets functional proteins on mitochondrial membranes, including adenine nucleotide translocases (ANTs). Site-specific mapping identified that EA covalently modifies a functional cysteine in ANTs, a mutation of which resulted in the rescuing effect on EA-induced mitochondrial dysfunction. The newly discovered modes of action offer valuable information to repurpose EA for cancer treatment.
Discovery, synthesis and biological characterization of a series of: N -(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1 H -pyrazol-5-yl)acetamide ethers as novel GIRK1/2 potassium channel activators
Alnouti, Yazen,Aretz, Christopher D.,Chhonker, Yashpal S.,Dhuria, Nikilesh V.,Du, Yu,Gautam, Nagsen,Hopkins, Corey R.,Kumar, Sushil,Lesiak, Lauren,Sharma, Swagat,Weaver, C. David
supporting information, p. 1366 - 1373 (2021/09/28)
The present study describes the discovery and characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as G protein-gated inwardly-rectifying potassium (GIRK) channel activators. From our previous lead optimization efforts, we have identified a new ether-based scaffold and paired this with a novel sulfone-based head group to identify a potent and selective GIRK1/2 activator. In addition, we evaluated the compounds in tier 1 DMPK assays and have identified compounds that display nanomolar potency as GIRK1/2 activators with improved metabolic stability over the prototypical urea-based compounds. This journal is
The synthesis and evaluation of phenoxyacylhydroxamic acids as potential agents for Helicobacter pylori infections
Ni, Wei-Wei,Liu, Qi,Ren, Shen-Zhen,Li, Wei-Yi,Yi, Li-Li,Jing, Heng,Sheng, Li-Xin,Wan, Qin,Zhong, Ping-Fu,Fang, Hai-Lian,Ouyang, Hui,Xiao, Zhu-Ping,Zhu, Hai-Liang
supporting information, p. 4145 - 4152 (2018/07/13)
Two series of ω-phenoxy contained acylhydroxamic acids as novel urease inhibitors were designed and synthesized. Biological activity evaluations revealed that ω-phenoxypropinoylhydroxamic acids were more active than phenoxyacetohydroxamic acids. Out of these compounds, 3-(3,4-dichlorophenoxy)propionylhydroxamic acid c24 showed significant potency against urease in both cell free extract (IC50 = 0.061 ± 0.003 μM) and intact cell (IC50 = 0.89 ± 0.05 μM), being over 450- and 120-fold more potent than the clinically prescribed urease inhibitor AHA, repectively. Non-linear fitting of experimental data (V-[S]) suggested a mixed-type inhibition mechanism and a dual site binding mode of these compounds.
Preparation method of chlorophenoxyacetic ester
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Paragraph 0064; 0066, (2019/01/08)
The invention provides a preparation method of chlorophenoxyacetic ester, wherein the preparation method comprises the following steps: A) carrying out reaction of glycolic acid and alcohol in tolueneto obtain glycolic ester; B) carrying out reaction of glycolic ester and metal alkoxide to obtain a metal salt of glycolic ester; and C) carrying out reaction of the metal salt of glycolic ester andchlorobenzene to obtain the chlorophenoxyacetic ester. The chlorophenoxyacetic ester is synthesized by condensation of chlorobenzene with the metal salt of glycolic ester, the use of chlorophenol withunpleasant odor is effectively avoided, the production of highly toxic dioxins is eliminated, and the product quality and the operating environment of the production site are greatly improved. Motherliquor containing effective ingredients cannot be produced, so the loss of effective ingredients is effectively avoided and the yield of the product is improved.
Synthesis and biological activity of 1-(Substituted phenoxyacetoxy)- 1-(pyridin-2-yl or thien-2-yl)methylphosphonates
Wang, Tao,Wang, Wei,Peng, Hao,He, Hongwu
, p. 173 - 179 (2015/01/30)
A series of novel O,O-dimethyl 1-(substituted phenoxyacetoxy)-1-(pyridin-2-yl or thien-2-yl)methylphosphonates 6a-n and 7a-d were synthesized. Their structures were confirmed by IR, 1H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays show that some of the title compounds exhibit moderate to good herbicidal and fungicidal activities. For example, the title compounds 6a, 6c, 6l, 6m, and 7d possess 90-100% inhibition against most of the tested plants at the dosage of 1500 g ai/ha, whereas the title compounds 6b, 6g-h and 6n possess 92-100% inhibition against Fusarium oxysporum, Phyricularia grisea, Botrytis cinereapers, Gibberella zeae, Sclerotinia sclerotiorum, and Cercospora beticola at the concentration of 50mg/L.
Synthesis and biological activity of α-oxo-2-pyridyl methyl phosphinates
Wang, Tao,He, Hong Wu
scheme or table, p. 1884 - 1891 (2009/09/06)
In an attempt to discover novel compounds with high activity and low toxicity, a series of new O,O-dimethyl-α-(substituted phenoxyacetoxy)-2- pyridyl methyl phosphinates, 5a-5h, have been designed and synthesized by the reaction of substituted phenoxyacetic chloride with 1-hydroxy-2-pyridyl methyl phosphinate, The structures of all new compounds were characterized by elementary analysis, IR, 1H NMR, and MS spectroscopies. The results of preliminary bioassay indicate that most of the target compounds have excellent inhibitory activities on barnyard grass and rape. Copyright Taylor & Francis Group, LLC.
Synthesis of ethyl phenoxyacetate derivatives under conditions of phase-transfer catalysis and ultrasonic irradiation
Kukovinets,Yamansarova,Kukovinets,Zainullin,Galin,Shakhova,Zorin,Kunakova,Tolstikov
, p. 1331 - 1333 (2007/10/03)
An effective procedure has been proposed for preparation of ethyl phenoxyacetate derivatives from ethyl bromoacetate and substituted phenols in the presence of K2CO3 and phase-transfer catalyst under ultrasonic irradiation.
Synthesis, diuretic activity and conformation of a new thiopyranylidene ketone derived from aryloxyacetic acid
Nurich,Beranger,Devaux,et al.
, p. 49 - 54 (2007/10/02)
The synthesis of a new thiopyranylidene ketone derived from 2,3-dichlorophenoxyacetic acid is described. Diuretic screening after oral administration in mice indicates weak activity compared to that observed for tienilic acid. The conformation shown by X-
