582-65-0

Usage

Uses

Used in Veterinary Medicine:
4,4,4-Trifluoro-1-(4-fluorophenyl)butane-1,3-dione is used as an intermediate in the synthesis of Mavacoxib (M197900) for the development of veterinary drugs. The application reason is that Mavacoxib is a long-acting COX-2 inhibitor, which helps in treating pain and inflammation in dogs suffering from degenerative joint disease.

InChI:InChI=1/C10H6F4O2/c11-7-3-1-6(2-4-7)8(15)5-9(16)10(12,13)14/h1-4H,5H2

Upstream product

• 383-63-1 ethyl trifluoroacetate, 
• 403-42-9 1-(4-fluorophenyl)ethanone 
• 450-95-3 2-fluoroacetophenone 

Downstream Products

• 77086-78-3 2,2,2-Trifluoro-1-[3-(4-fluoro-phenyl)-4H-benzo[1,4]thiazin-2-yl]-ethanone 
• 188817-22-3 1-(4-Bromo-phenyl)-5-(4-fluoro-phenyl)-3-trifluoromethyl-1H-pyrazole 
• 170569-88-7 mavacoxib 
• 188817-07-4 5-(4-fluorophenyl)-1-(4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole 
• 515845-17-7 5-(4-fluorophenyl)-1-phenyl-3-trifluoromethyl-1H-pyrazole 

Relevant academic research and scientific papers

Biocatalytic Strategy for the Highly Stereoselective Synthesis of CHF2-Containing Trisubstituted Cyclopropanes

The difluoromethyl (CHF2) group has attracted significant attention in drug discovery and development efforts, owing to its ability to serve as fluorinated bioisostere of methyl, hydroxyl, and thiol groups. Herein, we report an efficient biocat

Tetrahydropyrimidinones/thiones stabilized by trifluoromethyl-containing β-diketones

A library of new hydropyrimidinone/thione compounds was synthesized via the classical Biginelli reaction using hydrated cerium(III) chloride as the catalyst. The presence of a trifluoromethyl or methyl group in the diketone starting material has been established to selectively control the outcome of the Biginelli reaction where one of the two possible pyrimidinone/thione compounds is formed. The results showed that the electronic effects of substituents of the diketone directly affect the product formation. The synthesized compounds were fully characterized using 1H, 13C, and two dimensional NMR (2D NMR) spectroscopy, single crystal X-ray diffractometry, FT-IR, and ESI-HDMS techniques. We also report on the uncommon one-bond correlations which were observed in the HMBC spectra and the interesting long-range heteronuclear coupling of fluorine to hydrogen and carbon.

Development of celecoxib-derived antifungals for crop protection

Selective COX-2 inhibitor celecoxib was found directly inhibiting the growth of tested phytopathogenic fungi with the inhibitory rate ranging from 30 to 40% at 100 μg/ml. Lead optimization of celecoxib led to the identification of compound 12 among its derivatives as the most active antifungal candidate. The antifungal effect of compound 12 was supposed to be independent of COX-2 inhibition. Transcriptome profiling analysis of Fusarium graminearium (PH-1) treated with compound 12 brought about 406 up-regulated and 572 down-regulated differentially express genes (DEGs) respectively.

An Integrated Continuous Flow Micro-Total Ultrafast Process System (μ-TUFPS) for the Synthesis of Celecoxib and Other Cyclooxygenase Inhibitors

Integrated continuous manufacturing has emerged as a promising device for the rapid manufacturing of active pharmaceutical ingredients (APIs). We herein report a newly designed continuous flow micro-total process system platform for the rapid manufacturing of celecoxib, a selective nonsteroidal anti-inflammatory drug. This approach has been proven generally for the synthesis of several alkyl and aryl substituted pyrazoles. In order to minimize the tedious work-up process of potential reaction intermediates/products, we have developed a continuous flow extraction and separation platform to carry out the entire reaction sequence resulting in a short residence time with good yield. The present process was further extended to gram-scale synthesis of the COX-2-related API, viz. celecoxib, in the continuous flow process.

N-(3-((4-trifluoromethyl)-2-pyrimidinyl)aminophenyl)-2,6-difluorobenzene sulfamide derivative

The invention discloses N-(3-((4-trifluoromethyl)-2-pyrimidinyl)aminophenyl)-2,6-difluorobenzene sulfamide having an anti-tumor activity and a derivative thereof, and synthesis methods thereof. The N-(3-((4-trifluoromethyl)-2-pyrimidinyl)aminophenyl)-2,6-difluorobenzene sulfamide has a structural formula as shown in Formula I. The synthesis method disclosed by the invention comprises the followingsteps: performing nucleophilic substitution on 2,6-difluorobenzenesulfonyl chloride and m-phenylenediamine to obtain sulfonamide; enabling an amino group of N-(3-aminophenyl)-2,6-difluorobenzene sulfamide to react with cyanamide to obtain guanidine salt; then preparing a series of different substituted 1,3-diketone compounds; finally, enabling the guanidine salt to react with 1,3-diketone to forma pyrimidine ring, and ingeniously introducing the anactive group of the pyrimidine ring into a molecular structure. According to the N-(3-((4-trifluoromethyl)-2-pyrimidinyl)aminophenyl)-2,6-difluorobenzene sulfamide and the synthesis method, the antitumor multiplication inhibition activity, the solubility and the like of a compound is adjusted by changing a substituent of the pyrimidine ring, and the compound has the advantage of simple and convenient adjustment.

Application of 1,5-diaryl-3-pyrazole compound in prevention and control of agricultural fungal diseases

The invention belongs to the technical field of pesticides, and particularly relates to application of 1,5-diaryl-3-pyrazole compound in prevention and control of agricultural fungal diseases. The general structural formula of the 1,5-diaryl-3-pyrazole compound is as shown in the description, wherein R1 is selected from fluorine, methoxyl or methyl; and R2 is selected from -CHOOH, -SO2NH2, -NO2, -F,-C1 or -Br. Compared with a traditional agricultural fungicide, the 1,5-diaryl-3-pyrazole compound provided by the invention is unique in structure, adopts an action mechanism different from that ofa traditional fungicide, and has no cross resistance risks on resistance strains generated by an existing fungicide.

Design and synthesis of novel benzenesulfonamide containing 1,2,3-triazoles as potent human carbonic anhydrase isoforms I, II, IV and IX inhibitors

In a quest to discover new biologically active compounds, a series of twenty novel heterocyclic derivatives substituted at position 5 with -H (7a-7j) or -CF3 (8a-8j), bearing benzenesulfonamide at N-1 position and various aroyl groups at position 4 of the 1,2,3-triazole ring was synthesized and screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibition potential against four human (h) isoforms hCA I, II, IV and IX. All the compounds (7a-7j and 8a-8j) were synthesized via [3+2] cycloaddition reaction from 4-azidobenzenesulfonamide. Interestingly, compounds 7a-7j were prepared in one pot manner via enaminone intermediate using novel methodology. All the newly synthesized compounds (7a-7j & 8a-8j) were found to be excellent inhibitors of edema related isoform hCA I with their inhibition constant (Ki) ranging from 30.1 to 86.8 nM as compared to standard drug acetazolamide (AAZ) with Ki = 250 nM. Further it was found that most of tested compounds were weaker inhibitors of isoform, hCA II although compounds 7b, 7d-7e, 8a, 8d-8f, 8i (mostly with electron withdrawing substituents) have shown better inhibition potential (Ki i = 52.4 nM) than AAZ (Ki = 74 nM) while against tumor associated hCA IX, all the compounds have shown moderate inhibition potential. Present study have added one more step in exploring the 1,2,3-triazlole moiety in the medicinal field.

An SAR study of hydroxy-trifluoromethylpyrazolines as inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader assay

The proteins Orai1 and STIM1 control store-operated Ca2+ entry (SOCE) into cells. SOCE is important for migration, invasion and metastasis of MDA-MB-231 human triple negative breast cancer (TNBC) cells and has been proposed as a target for cancer drug discovery. Two hit compounds from a medium throughput screen, displayed encouraging inhibition of SOCE in MDA-MB-231 cells, as measured by a Fluorescence Imaging Plate Reader (FLIPR) Ca2+ assay. Following NMR spectroscopic analysis of these hits and reassignment of their structures as 5-hydroxy-5-trifluoromethylpyrazolines, a series of analogues was prepared via thermal condensation reactions between substituted acylhydrazones and trifluoromethyl 1,3-dicarbonyl arenes. Structure-activity relationship (SAR) studies showed that small lipophilic substituents at the 2- and 3-positions of the RHS and 2-, 3- and 4-postions of the LHS terminal benzene rings improved activity, resulting in a novel class of potent and selective inhibitors of SOCE.

NOVEL COMPOUNDS AS ROR GAMMA MODULATORS

The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein ring A, ring B, L, R1, R2, R3, R4, R5, Ra, Rb, n, m, p and q are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORγt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer.

Synthesis method of 5-(4-fluorophenyl)-N, N-dimethyl-7-trifluoromethylpyrazol[1, 5-a] pyrimidine-3-amide

The invention discloses a synthesis method of 5-(4-fluorophenyl)-N, N-dimethyl-7-trifluoromethylpyrazol[1, 5-a] pyrimidine-3-amide. The synthesis method includes: using arone which is low in cost and easy to obtain as a starting raw material; synthesizing arone and para-trifluoromethyl ethyl acetate into an intermediate-aryl butanedione, adding glacial acetic acid and aminopyrazol, and heating for backflow to generate a target intermediate; hydrolyzing to obtain 5-aryl-7-substitutent pyrazol[1, 5-a] pyrimidine acid, and obtaining a target product through condensation reaction. Through continuous reaction of condensation and cyclization, 5-(4-fluorophenyl)-N, N-dimethyl-7-trifluoromethylpyrazol[1, 5-a] pyrimidine-3-amide is synthesized with high yield. The synthesis method is simple and convenient to operate and high in yield, and the product is easy to purify.