405-78-7

Usage

Uses

Used in Pharmaceutical Industry:
(4-FLUOROPHENOXY)ACETYL CHLORIDE is used as a synthetic intermediate for the development of new pharmaceutical compounds. Its reactivity allows for the creation of esters and amides, which are essential in the synthesis of various drugs.
Used in Anti-inflammatory Applications:
(4-FLUOROPHENOXY)ACETYL CHLORIDE is used as a key component in the study and synthesis of anti-inflammatory oxa lipoxin A4 analogs. These analogs are designed to have enhanced chemical and metabolic stability, which can potentially improve their effectiveness in treating inflammation-related conditions.

Upstream product

• 79-37-8 oxalyl dichloride 
• 405-79-8 2-(4-fluorophenoxy)ethanoic acid 
• 371-41-5 4-Fluorophenol 
• 79-11-8 chloroacetic acid 
• 777-87-7 ethyl 2-(4-fuorophenoxy)acetate 

Downstream Products

• 2249-32-3 (4-fluoro-phenoxy)-acetic acid-(2-dimethylamino-ethyl ester); hydrochloride 
• 15088-65-0 N-<2-Diazo-3-oxo-4-(4-fluor-phenoxy)-butyryl>-glycin-aethylester 
• 70932-05-7 3-fluoro-10-[4-(4-fluorophenoxyacetyl)piperazino]-8-isopropyl-10,11-dihydrodibenzo(b,f)thiepin 
• 54504-79-9 (4-fluoro-phenoxy)-acetic acid 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-ethyl ester 
• 826990-54-9 [(4-fluorophenoxyacetyl)(ethoxycarbonyl)methylene]triphenylphosphorane 
• 1031434-76-0 C₂₃H₁₉FN₂O₃ 
• 1207983-09-2 N-(4-(3-bromoanilino)quinazolin-6-yl)-2-(4-fluorophenoxy)-acetamide 
• 1217309-95-9 1-(4-(2-amino-6-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-2-(4-fluorophenoxy)ethanone 
• 1395103-30-6 2-(4-fluorophenoxyacetoxy)(phenyl)methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one 
• 1395103-36-2 2-(4-fluorophenoxyacetoxy)(methyl)methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one 
• 1395103-25-9 2-[(4-fluorophenoxy)acetoxy](furan-2-yl)methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one 
• 1374761-63-3 N-ethyl-2-(4-fluorophenoxy)-N-(thiophen-2-ylmethyl)acetamide 
• 85630-52-0 5-Chloro-N-(2-diethylamino-ethyl)-4-[2-(4-fluoro-phenoxy)-acetylamino]-2-methoxy-benzamide 
• 1426-78-4 4-Fluor-phenoxyessigsaeure-<2-dimethylamino-aethylester> 

Relevant academic research and scientific papers

Herbicidal activity and application cyclic of phosphonates

Among alkylphosphonates Io,O,O-dimethyl 1-(2,4-dichlorophenoxyacetoxy) ethylphosphonate (clacyfos) was found to be an effective inhibitor against dicotyledons PHDc and exhibited excellent herbicidal activity in our previous work. According to our study on the alkylphosphonates Io, both R1 and R2 groups in the structural unit of phosphorus-containing played a very important role in herbicidal activity. Therefore, a series of 2-[1-(substituted phenoxycarboxy)alkyl]-5,5-dimethyl-1,3,2-dioxaphosphinane-2-one containing fluorine II was obtained by the modification of alkylphosphonates Io. The bioassay results showed that cyclic phosphonate II-6 with CH3 as R, 2-Cl,4-F as Yn exhibited promising herbicidal activity. Its herbicidal activity, weed-controlling spectrum, selectivity between crops and weeds were further evaluated in greenhouse and field.

Structure-based design, synthesis and evaluation of 2,4-diaminopyrimidine derivatives as novel caspase-1 inhibitors

Interleukin-1β converting enzyme contributes in various inflammatory and autoimmune diseases by maturing pro-inflammatory cytokines IL-1β, IL-18 and IL-33. Therefore, inhibition caspase-1 may provide a potential therapeutic strategy for the treatment of chronic inflammatory diseases. Here we have reported structure-based design, synthesis and biological evaluation of 2,4-diaminopyrimidine derivatives (6a-6w) as potential caspase-1 inhibitors. Six compounds 6m, 6n, 6o, 6p, 6q and 6r showed significant enzymatic inhibition with IC5 0 ranging from 0.022 to 0.078 μM. These compounds also displayed excellent cellular potency at sub-micromolar concentration. Moreover, molecular docking studies provided the useful binding insights specific for caspase-1 inhibition. All these results indicated that compounds 6m, 6n and 6o could be potential leads for the development of newer caspase-1 inhibitors as anti-inflammatory agents.

Synthesis and Biological Activity of 4-[(Substituted Phenoxyacetoxy)methyl]-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane-1-one

A series of novel 4-[(substituted phenoxyacetoxy)methyl]-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane-1-one 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m, 4n, 4o 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 4b, 4c, 4f, 4h, 4i, and 4j possess 90–100% inhibition against the growth of roots of both rape and barnyard grass at 10 mg/L. Moreover, the title compounds 4f, 4g, and 4h possess 75–89% inhibition against Botrytis cinerea at the concentration of 50 mg/L.

Synthesis and Antimicrobial Activity of Novel 2-Substituted Phenoxy-N-(4-substituted Phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)acetamide Derivatives

A series of 2-substituted phenoxy-N-(4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazole-2-yl)acetamide derivatives 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h, 8i, 8j, 8k, 8l, 8m, 8n, 8o, 8p, 8q, 8r, 8s, 8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine 5. Their structures were confirmed by 1H NMR, 13C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their antimicrobial activity against three types of plant fungi (Gibberella zeae, Phytophthora infestans, and Paralepetopsis sasakii) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac)] showing promising results. In particular, 8b, 8f, 8g, and 8h exhibited excellent antibacterial activity against Xoo, with 50% effective concentration (EC50) values of 35.2, 80.1, 62.5, and 82.1 μg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 μg/mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.

Discovery and development of a novel class of phenoxyacetyl amides as highly potent TRPM8 agonists for use as cooling agents

The paper presents the activity trends for a novel series of phenoxyacetyl amides as human TRPM8 receptor agonists. This series encompasses in vitro activity values ranging from the micromolar to the picomolar levels. Sensory evaluation of these molecules highlights their relevance as cooling agents for oral applications. The positive outcome of the complete evaluation of N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide resulted in its approval for Generally Recognized As Safe (GRAS) status by the Flavor & Extract Manufacturer Association (FEMA) as FEMA 4809.

Privileged 1,2,4-oxadiazoles in anticancer drug design: Novel 5-aryloxymethyl-1,2,4-oxadiazole leads for prostate cancer therapy

Based on the structure of the previously identified leads, new series of compounds containing 1,2,4-oxadiazole core was designed. A small, diverse library of 51 compounds including both 2-(acylamino)ethyl and 2-ureidoethyl side chains was synthesized using parallel chemistry and tested for antiproliferative activity against prostate cancer DU-145 cell line. Four hit compounds - all belonging to 2-ureidoethyl series - were identified and three compounds were confirmed as 10-20 μM inhibitors. The similarity in compounds' periphery and the data obtained previously suggest a similar mode of action for these compounds which was postulated as tubulin inhibition and was confirmed by in silico docking. These data provide further evidence for the privileged character of 1,2,4-oxadiazoles in antiproliferative compound design.

Synthesis and Biological Activity of Ethyl 4-Alkyl-2-(2-(substituted phenoxy)acetamido)thiazole-5-carboxylate

(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.

Synthesis and biological activity of 1-(Substituted phenoxyacetoxy)- 1-(pyridin-2-yl or thien-2-yl)methylphosphonates

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 herbicidal activity of [(Substituted Phenoxyacetoxy) (Substituted Phenyl)Methyl](Methyl) phosphinates containing fluorine

A series of [(substituted phenoxyacetoxy)(substituted phenyl)methyl] (methyl)phos- phinates containing fluorine were designed and synthesized. All the synthesized compounds were identified by elemental analysis, IR, 1H NMR, mass spectrometry. O-methyl [(2-fluorophenoxyacetoxy)(2,4- dichlorophenyl)methyl](methyl)phosphinate was further analyzed by X-ray single-crystal diffraction. Their herbicidal activity against a set of weed species was examined. Some of the compounds showed potential herbicidal activity, which provided some indications for further studies on structure modification. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors

Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.