329-01-1

Usage

Uses

Used in Pharmaceutical Industry:
3-(Trifluoromethyl)phenyl isocyanate is used as a reagent for the synthesis of heme-regulated inhibitor, which serves as selective activators of the eukaryotic initiation factor Alpha (eIF2α) phosphorylation arm of the endoplasmic reticulum stress response. 3-(Trifluoromethyl)phenyl isocyanate plays a crucial role in influencing cell proliferation, cell differentiation, and adaptation to stress, making it a valuable component in the development of pharmaceuticals targeting these processes.
Used in Chemical Synthesis:
3-(Trifluoromethyl)phenyl isocyanate is also utilized as a reagent in the preparation of sorafenib derivatives. Sorafenib is a multikinase inhibitor used in the treatment of various types of cancer, and the isocyanate compound contributes to the development of new and improved derivatives with enhanced efficacy and selectivity.

Synthesis

The preparation method is as follows: adding 3-trifluoromethylaniline and chlorobenzene to the reaction flask, stirring, mixing and dissolving it, cooling to 0-10° C., introducing dry hydrogen chloride to make it saturated, and then adding N,N-diisopropylamine. Butyl chloromethylamide, heated to 50°C and kept for 30min, and then introduced phosgene. After a certain amount of phosgene was introduced, the reaction was completed. Then the material is distilled and desolubilized to obtain the finished product.

Flammability and Explosibility

Notclassified

Safety Profile

Moderately toxic by ingestion, inhalation, and intraperitoneal routes. A lachrymator. Flammable liquid when exposed to heat, sparks, or flame. When heated to decomposition it emits very toxic fumes of NOx and F-. See also ISOCYANATES and FLUORIDES.

InChI:InChI=1/C8H4F3NO/c9-8(10,11)6-2-1-3-7(4-6)12-5-13/h1-4H

Upstream product

• 2164-17-2 fluometuron 
• 98-16-8 3-trifluoromethylaniline 
• 503-38-8 trichloromethyl chloroformate 
• 4461-33-0 benzoyl isocyanate 
• 75-44-5 phosgene 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 69563-05-9 (3-Trifluoromethyl-phenyl)-trimethylsilanyl-amine 
• 454-92-2 3-(trifluoromethyl)benzoic acid 

Downstream Products

• 13846-60-1 1-(4,5-dihydro-thiazol-2-yl)-1-phenyl-3-(3-trifluoromethyl-phenyl)-urea 
• 43066-08-6 6-methyl-3-(3-trifluoromethyl-phenyl)-[1,3]oxazine-2,4-dione 
• 25761-34-6 1-(2-Hydroxy-4-methyl-phenyl)-3-(3-trifluoromethyl-phenyl)-urea 
• 25761-35-7 1-[2-Hydroxy-5-(1,1,3,3-tetramethyl-butyl)-phenyl]-3-(3-trifluoromethyl-phenyl)-urea 
• 73161-42-9 4-hydroxy-1-methyl-2,2-dioxo-1,2-dihydro-2λ⁶-pyrido[2,3-c][1,2]thiazine-3-carboxylic acid 3-trifluoromethyl-anilide 
• 22546-21-0 C₁₀H₁₂F₃N₃O 
• 34174-29-3 N-(3-(trifluoromethyl)phenyl)-N'-(2-hydroxy-5-tert-butylphenyl)-urea 
• 25761-61-9 1-(2-Hydroxy-5-isopropyl-phenyl)-3-(3-trifluoromethyl-phenyl)-urea 
• 25847-86-3 1-(3-Hydroxy-biphenyl-4-yl)-3-(3-trifluoromethyl-phenyl)-urea 
• 22546-43-6 C₉H₁₀F₃N₃O 
• 32496-19-8 (3-Trifluoromethyl-phenyl)-carbamic acid 1,1-dimethyl-prop-2-ynyl ester 
• 29209-09-4 2-methyl-1,1,3-trioxo-1,2,3,4-tetrahydro-1λ⁶-benzo[e][1,2]thiazine-4-carboxylic acid 3-trifluoromethyl-anilide 
• 64393-14-2 1-cyclopropyl-3-(3-trifluoromethylphenyl)-urea 
• 25979-33-3 1-(2-Hydroxy-4,5-dimethyl-phenyl)-3-(3-trifluoromethyl-phenyl)-urea 

Relevant academic research and scientific papers

Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data using in silico model. Overall, we envision that these compounds can be further developed for the potential treatment of metastatic breast cancer.

Synthesis and biological evaluation of novel 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives as potential antitumor agents

A novel series of 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives were synthesized and evaluated against different tumor cell lines. Experiments in vitro showed that these derivatives could inhibit the proliferation of two kinds of human cancer cell lines (HepG2, HCT116) at low micromolar concentrations and the most potent analog 5q possessed broad-spectrum antiproliferative activity. Experiments in vivo demonstrated that 5q could effectively prolong the longevity of colon carcinoma-burdened mice and slow down the progression of cancer cells by suppression of angiogenesis and the induction of apoptosis and necrosis.

Design, synthesis and anticancer activity of a new series of n-aryl-n′-[4-(Pyridin-2-ylmethoxy)benzyl]urea derivatives

The development of cancer treatments requires continuous exploration and improvement, in which the discovery of new drugs for the treatment of cancer is still an important pathway. In this study, based on the molecular hybridization strategy, a new structural framework with an N-aryl-N’-arylmethylurea scaffold was designed, and 16 new target compounds were synthesized and evaluated for their antiproliferative activities against four different cancer cell lines A549, MCF7, HCT116, PC3, and human liver normal cell line HL7702. The results have shown seven compounds with 1-methylpiperidin-4-yl groups having excellent activities against all four cancer cell lines, and they exhibited scarcely any activities against HL7702. Among them, compound 9b and 9d showed greatly excellent activity against the four kinds of cells, and the IC50 for MCF7 and PC3 cell lines were even less than 3μM.

Urea compound with gibberellin function inhibition activity as well as preparation method and application thereof

The invention belongs to the technical field of plant growth regulators, and particularly discloses a urea compound and a preparation method and application thereof. The structure of the urea compoundis shown as a formula I in the specification. The preparation method of the urea compound provided by the invention has the advantages of cheap raw materials, simple process, mild reaction conditionsand high yield. Related activity studies find that the compound shown in the formula I has good regulation activity on plant growth, can effectively reduce the plant height and promote generation ofside roots, can be used for weed control at high concentration, and is a potential plant growth regulator.

Synthesis and biological evaluation of a new series of 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as new anticancer agents

The diaryl ureas are very important fragments in medicinal chemistry. By means of computer-aided design, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives were designed and synthesized, and evaluated for their antiproliferative activity against A549, HCT-116, PC-3 cancer cell lines, and HL7702 human normal liver cell lines in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Most of the target compounds demonstrate significant antiproliferative effects on all the selective cancer cell lines. The calculated IC50 values were reported. The target compound 1-(4-chlorophenyl)-3-{4-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methoxy}phenyl}urea (7u) demonstrated the most potent inhibitory activity (IC50 = 2.39 ± 0.10 μM for A549 and IC50 = 3.90 ± 0.33 μM for HCT-116), comparable to the positive-control sorafenib (IC50 = 2.12 ± 0.18 μM for A549 and IC50 = 2.25 ± 0.71 μM for HCT-116). Conclusively, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as the new anticancer agents were discovered, and could be used as the potential BRAF inhibitors for further research.

Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression

Aurora Kinase B is a serine-threonine kinase known to be overexpressed in several cancers, with no inhibitors approved for clinical use. Herein, we present the discovery and optimization of a series of novel quinazoline-based Aurora Kinase B inhibitors. The lead inhibitor SP-96 shows sub-nanomolar potency in Aurora B enzymatic assays (IC50 = 0.316 ± 0.031 nM). We identified the important pharmacophore features resulting in selectivity against receptor tyrosine kinases. Particularly, SP-96 shows >2000 fold selectivity against FLT3 and KIT which is important for normal hematopoiesis. This could diminish the adverse effect of neutropenia reported in the clinical trials of the Aurora B inhibitor Barasertib, which inhibits FLT3 and KIT in addition to Aurora B. Enzyme kinetics of SP-96 shows non-ATP-competitive inhibition which makes it a first-in-class inhibitor. Further, SP-96 shows selective growth inhibition in NCI60 screening, including inhibition of MDA-MD-468, a Triple Negative Breast Cancer cell line.

Design, synthesis and antitumor assessment of phenylureas bearing 5-fluoroindolin-2-one moiety

Background: The development of novel antineoplastic agents remains highly desirable. Objective: This study focuses on the design, synthesis, and antitumor evaluation of phenyl ureas bearing 5-fluoroindolin-2-one moiety. Methods: Three sets of phenylureas were designed and synthesized and their antiproliferative abil-ity was measured against four human carcinoma cell lines (Hela, Eca-109, A549, and MCF-7) via MTT assay. In vivo anticancer activity was further evaluated in xenograft models of human breast cancer (MCF-7). Results: A total of twenty-one new compounds were synthesized and characterized by means of1 H and13 C NMR as well as HR-MS. Three sets of compounds (1a?1c, 2a?2c, and 3a?3c) were ini-tially constructed, and preliminary antiproliferative activities of these molecules were evaluated against Hela, Eca-109, A549 and MCF-7, highlighting the meta-substituted phenylureas (1a?1c) as the most cytotoxic set. A series of meta-substituted phenylureas derivatives (1d?1o) were then designed and synthesized for structure-activity relationship study. Most of the new compounds showed desirable cytotoxicity, among which compound 1g exhibited the most remarkable cyto-toxic effects against the tested human cancer cells with IC50 values ranging from 1.47 to 6.79 μM. Further studies showed that compound 1g suppressed tumor growth in human breast cancer (MCF-7) xenograft models without affecting the body weight of its recipients. Conclusion: In this study, twenty-one new compounds, containing the privileged structures of phenylurea and 5-fluoroindolin-2-one, were designed and synthesized. Subsequent structure-activity studies showed that 1g was the most bioactive antitumor agent among all tested com-pounds, hence a potentially promising lead compound once given further optimization.

Thiazolinone heterocyclic compound, preparation method, medicinal composition and application thereof

The invention provides a thiazolinone heterocyclic compound, a preparation method, a medicinal composition and an application thereof. The invention provides an application of the thiazolinone heterocyclic compound in preparation of an NLRP3 inflammasome inhibitor. The thiazolinone heterocyclic compound has a structure as a formula I or an isomer, a prodrug, or a pharmaceutically acceptable solvate or salt thereof.

Design, Synthesis and Biological Evaluation of a New Series of 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea Derivatives as Antiproliferative Agents

To discover new antiproliferative agents with high efficacy and selectivity, a new series of 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea derivatives (7a–7t) were designed, synthesized and evaluated for their antiproliferative activity against A549, HCT-116 and PC-3 cancer cell lines in vitro. Most of the target compounds demonstrated significant antiproliferative effects on all the selective cancer cell lines. Among them, the target compound, 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-{4-{{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}thio}phenyl}urea (7i) was identified to be the most active one against three cell lines, which was more potent than the positive control with an IC50 value of 1.53 ± 0.46, 1.11 ± 0.34 and 1.98 ± 1.27 μM, respectively. Further cellular mechanism studies confirmed that compound 7i could induce the apoptosis of A549 cells in a concentration-dependent manner and elucidated compound 7i arrests cell cycle at G1 phase by flow cytometry analysis. Herein, the studies suggested that the 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea skeleton might be regarded as new chemotypes for designing effective antiproliferative agents.

Synthetic method of medical intermediate semi-carboamidrazone

The invention discloses a synthesis method of medical intermediate semicarbazone. According to a method, the semicarbazone is synthesized by taking dichloroethane, triphosgene, m-trifluoromethyl aniline, phenyl isonitrile, hydrazine hydrate, N-(3-trifluoromethyl phenyl)-semicarbazide and thiophene-2-formaldehyde as main raw materials and using the N-(3-trifluoromethyl phenyl)-semicarbazide. Aftersulfo group modified-SZ@SBA-15-SO3H catalyst is added, thiophene-2-formaldehyde is added, so that sediments are produced immediately; a thiophene ring is a five-atom and six-electron conjugate structure; after thiophene-2-formaldehyde-N(4)-m-trifluoromethyl phenyl semicarbazone is generated under the catalytic action, as -CN and the thiophene ring form conjugation, electrons are more dispersive and more stable; the semicarbazone preparation method has the characteristics of simplicity, feasibility, short preparation period and the like; the raw materials and the catalyst which are used in a technological process are high in efficiency, simple, convenient, easy to recycle, regenerable, extremely environmentally friendly and wide in application range, and has an excellent catalysis effect onsemicarbazone synthesis reaction.