326-91-0

Usage

Uses

Used in Solvent Extraction Analysis:
Thenoyltrifluoroacetone is used as an extracting agent for the separation and selective enrichment of metal ions in solvent extraction analysis.
Used in Respiratory Chain Inhibition:
TTFA is used as an inhibitor of the respiratory chain complex II, causing inhibition of mitochondrial respiration by binding to two ubiquinone binding sites, Qp and Qd. This inhibition has been shown to cause a delay in overall cell cycle progression, leading to oxidative stress.
Used in Antimicrobial Applications:
Thenoyltrifluoroacetone is used as an inhibitor of respiration in animals and bacteria, specifically by binding at the quinone reduction site of succinate ubiquinone oxidoreductase.
Used in Environmental Applications:
TTFA is used as a reagent for the determination of actinides and lanthanides, as well as for the extractive spectrophotometric determination of ruthenium at pH 4.0 (acetate buffer).
Used in Assay Development:
Thenoyltrifluoroacetone has been used as an alternative β-diketone for in-house assay development since NTA was not commercially available until recently.
Used in Enzyme Inhibition:
TTFA is used to inhibit porcine liver carboxylesterase, with an IC50 of 0.54 μM.

Purification Methods

Crystallise the dione from hexane or *benzene. (Anaqueous solutions slowly decompose it). It has 1638(C=O), 1657(C=C)cm-1 . The oxime crystallises from H2O or aqueous EtOH. It is used for the determination of Actinides and Lanthanides. [Chaston et al. Aust J Chem 18 673 1956, Jeffrey et al. In Vogel’s Textbook of Qunatitative Chemical Analysis 5thedn J Wiley & Sons, p170 1989, Beilstein 17 III/IV 5989, 17/11 V 128.]

References

1) Sun?et al.?(2005),?Crystal Structure of Mitochondrial Respiratory Membrane Protein Complex II; Cell?121?1043 2) Byon?et al.?(2008),?Mitochondrial dysfunction by complex II inhibition delays overall cell cycle progression via reactive oxygen species production; J. Cell Biochem.?104?1747 3) Siebels and Dr?se (2013),?Q-site inhibitor induced ROS production of mitochondrial complex II is attenuated by TCA cycle dicarboxylates; Biochim. Biophys. Acta?1827?1156 4) Zhang and Fariss (2002),?Thenoyltrifluoroacetone, a potent inhibitor of carboxylesterase activity; Biochem. Pharmacol.?63?751

InChI:InChI=1/C4H3F3O2/c5-4(6,7)3(9)1-2-8/h2H,1H2

Upstream product

• 88-15-3 2-Acetylthiophene 
• 383-63-1 ethyl trifluoroacetate, 
• 59354-21-1 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione enol 
• 407-25-0 trifluoroacetic anhydride 
• 15788-02-0 1,1,1-trifluoro-4-hydroxy-4-(2-thienyl)-3-buten-2-one 
• 148-24-3 8-quinolinol 
• 615-07-6 sodium 2-thenoyltrifluoroacetylacetonate 
• 407-38-5 2,2,2-trifluoroethyl trifluoroacetate 

Downstream Products

• 396-63-4 4-thiophen-2-yl-6-trifluoromethyl-pyrimidin-2-ylamine 
• 22123-04-2 2-phenyl-6-(5-thiophen-2-yl-3-trifluoromethyl-pyrazol-1-yl)-4-trifluoromethyl-pyridine 
• 67804-95-9 6-(2'-Thienyl)-4-trifluoromethylpyrimidin-2(1H)-on 
• 3335-45-3 2-oxo-6-(thiophen-2-yl)-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile 
• 26974-16-3 5-(thiophen-2-yl)-3-(trifluoromethyl)-1H-pyrazole 
• 128228-97-7 2-<3-trifluoromethyl-5-(2-thienyl)pyrazol-1-yl>-4-p-chlorophenylthiazole 
• 104960-50-1 4-(trifluoromethyl)-1,2-dihydro-6-(thiophen-2-yl)-2-thioxopyridine-3-carbonitrile 
• 82137-58-4 2-[1-(2-Chloro-phenyl)-3-oxo-3-thiophen-2-yl-propyl]-malononitrile 
• 82127-03-5 3-(4-fluorophenyl-3-oxo-1-(2-thienyl)propyl)propanedinitrile 
• 81829-55-2 2-(3-(2-thienyl)-3-oxo-1-phenylpropyl)malononitrile 
• 82137-59-5 3-(4-chlorophenyl-1-(2-thienyl)-3-oxopropyl)propanedinitrile 
• 82127-06-8 2-[1-(4-Bromo-phenyl)-3-oxo-3-thiophen-2-yl-propyl]-malononitrile 
• 82127-05-7 2-(3-Oxo-3-thiophen-2-yl-1-o-tolyl-propyl)-malononitrile 
• 128228-85-3 4-(4-Nitro-phenyl)-2-(5-thiophen-2-yl-3-trifluoromethyl-pyrazol-1-yl)-thiazole 

Relevant academic research and scientific papers

Studies on the adsorption and photocatalytic degradation of an EuIII(TTFA)3(MePhTerpy) complex on the TiO2 surface

The luminescent dye EuropiumIII(thenoyltrifluoroacetone)(4′-(4-methylphenyl)-2,2′:6′,2′′-terpyridine) (EuIII(TTFA)3(MePhTerpy)) has been proposed as a probe molecule for a fast photocatalytic test of TiO2-materials. For an industrial application of this test method the underlying photocatalytic reaction mechanism and the degradation products of the dye need to be known. Hence, in this study the adsorption and the photocatalytic degradation of the luminescent dye on the TiO2 surface were investigated by means of ATR-FTIR spectroscopy and GC/MS analysis. The dye is adsorbed by the thenoyltrifluoroacetone (TTFA) ligand on the TiO2 surface as evinced by the respective ATR-FTIR spectra. It is assumed that TTFA and TiO2 form hydrogen bonds. Upon UV illumination the ATR-FTIR spectra reveal a degradation of the TTFA ligand forming trifluoroacetic acid (TFAA) and 2-thiophenecarboxylic acid (TCA). GC/MS analysis confirms the ATR-FTIR results because TCA and TFAA are also detected here. Additionally, 2-thiophenecarboxaldehyde is observed, which is proposed to be an intermediate that is further oxidized to TCA.

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.

Discovery and structure-resistance relationship study of new thieno[2,3-b] pyridine HCV NS4B inhibitors

The non-structural protein 4B (NS4B) of hepatitis C virus (HCV) has emerged as a promising target for chronic hepatitis C treatment. The thieno[2,3-b]pyridine HCV inhibitor 2 has demonstrated properties as a NS4B inhibitor. Subsequent hybridization of 2 with our recently published imidazo[2,1-b]thiazole NS4B inhibitor 3 resulted in the discovery of several more potent compounds with sub-micromolar EC50 against HCV genotype 1b replicon. More importantly, the resistant profile study of the new synthesized HCV inhibitors illustrated that the bicyclic scaffold would mediate the resistance of H3R and Q26R mutations, while the piperazinone motif would mediate the resistance of H94R, F98C and V105M mutations, and the C3- amino group would disrupt the interaction between piperazinone motif and NS4B. This structure-resistance relationship detail could help us to develop new NS4B inhibitors with higher resistant barrier in the future.

APOPTOSIS INHIBITORS

The invention provides compounds that are inhibitors or covalent modifiers of succinate dehydrogenase subunit B (SDHB) and/or inhibitors of apoptosis, and pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition.

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.

Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors

Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC50 = 33.8 μM) characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC50 = 16.8 μM) and 9d (IC50 = 12.3 μM) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents.

Discovery of Highly Potent 2-Sulfonyl-Pyrimidinyl Derivatives for Apoptosis Inhibition and Ischemia Treatment

A series of 2-sulfonyl-pyrimidinyl derivatives was developed as apoptosis inhibitors. These represent the first class of apoptosis inhibitors that function through stabilizing mitochondrial respiratory complex II. Starting from a phenotypic screen hit with micromolar activity, we optimized the cellular apoptosis inhibition activity of 2-sulfonyl-pyrimidinyl derivatives to picomolar level (compound 42, also named as TC9-305). The therapeutic potential of these new apoptosis inhibitors was further demonstrated by their neuroprotective effect on an ischemic animal model.

A Sequential Route to Cyclopentenes from 1,6-Enynes and Diazo Ketones through Gold and Rhodium Catalysis

This work reports the construction of cyclopentene cores from 1,6-enynes and aryl diazo ketones through two new reaction sequences involving initial gold-catalyzed cyclization of 1,6-enynes with diazo species, followed by rhodium-catalyzed skeletal rearrangement of the resulting 3-cyclopropyl-2-en-1-ones. In most instances the rhodium-catalyzed reactions afforded cyclopentene derivatives whereas several n-alkyl- or ortho-substituted phenyl ketones delivered seven-membered oxacycles. A plausible mechanism provides rationales for these two distinct products. (Figure presented.).

1,5-Diketones Synthesis via Three-Component Cascade Reaction

A mild and efficient cascade synthesis of 1,5-diketones from readily available N,N-dicyclohexylmethylamine, 1,3-dicarbonyl compounds, and trifluoromethyl β-diketones has been developed. This cascade reaction occurs via an oxidation/Mannich reaction/Cope elimination/Michael addition/retro-Claisen reaction sequence, and provides multiple C-C bond formations in one pot. In addition, exquisite chemoselectivity is achieved in the reaction between 1,3-dicarbonyl compounds and trifluoromethyl β-diketones.

Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors

Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50 = 3.3 μM, SI >30.3, 12b, EC50 = 3.5 μM, SI >28.6, 10l, EC50 = 3.9 μM, SI >25.6, 12o, EC 50 = 4.5 μM, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents.