16642-92-5

Usage

Uses

Used in Pharmaceutical Industry:
4-(Trifluoromethyl)cinnamic acid is used as an internal standard for the determination of A77 1726 (2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide) in plasma by high-performance liquid chromatography (HPLC). Its chemical stability and compatibility with the HPLC method make it an ideal choice for accurate and reliable quantification of the target compound in biological samples.
Used in Chemical Synthesis:
Due to its unique chemical structure, 4-(Trifluoromethyl)cinnamic acid can be employed as a building block or intermediate in the synthesis of various organic compounds, particularly those with trifluoromethylated aromatic moieties. Its reactivity and stability can be exploited in the development of new pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Analytical Chemistry:
The distinct chemical properties of 4-(Trifluoromethyl)cinnamic acid, such as its white crystalline nature and compatibility with HPLC, make it suitable for use in analytical chemistry as a reference material or standard for the calibration of analytical instruments and methods.

InChI:InChI=1/Cr.3FH.3H2O/h;3*1H;3*1H2/q+3;;;;;;/p-3

Upstream product

• 455-19-6 4-Trifluoromethylbenzaldehyde 
• 141-82-2 malonic acid 
• 124-38-9 carbon dioxide 
• 1034330-32-9 5,5-dimethyl-2-[2-(4-trifluoromethylphenyl)ethen-1-yl]-1,3,2-dioxaborinane 
• 455-13-0 4-Iodobenzotrifluoride 
• 79-10-7 acrylic acid 
• 101466-85-7 ethyl 4-trifluoromethylcinnamate 
• 95123-61-8 4-(trifluoromethyl)cinnamaldehyde 
• 402-43-7 p-trifluoromethylphenyl bromide 
• 292638-85-8 acrylic acid methyl ester 
• 705-31-7 4-trifluoromethylphenylacetylene 
• 15164-44-0 p-(iodophenyl)carboxaldehyde 
• 144-62-7 oxalic acid 
• 95123-61-8 (2E)-3-(4-trifluoromethylphenyl)prop-2-enal 

Downstream Products

• 101466-85-7 ethyl 4-trifluoromethylcinnamate 
• 66432-14-2 N-[(E)-2-(4-Trifluoromethyl-phenyl)-vinyl]-formamide 
• 120681-07-4 3-(4-trifluoromethyl-phenyl)-acryloyl chloride 
• 53473-36-2 3-(4-trifluoromethylphenyl)propionic acid 
• 1350518-46-5 C₁₇H₁₄F₃NO₂ 
• 1574277-10-3 (E)-1-(2-cyclohexylvinyl)-4-(trifluoromethyl)-benzene 
• 95123-61-8 4-(trifluoromethyl)cinnamaldehyde 

Relevant academic research and scientific papers

Discovery of Novel Benzothiazepinones as Irreversible Covalent Glycogen Synthase Kinase 3β Inhibitors for the Treatment of Acute Promyelocytic Leukemia

Recently, irreversible inhibitors have attracted great interest in antitumors due to their advantages of forming covalent bonds to target proteins. Herein, some benzothiazepinone compounds (BTZs) have been designed and synthesized as novel covalent GSK-3β inhibitors with high selectivity for the kinase panel. The irreversible covalent binding mode was identified by kinetics and mass spectrometry, and the main labeled residue was confirmed to be the unique Cys14 that exists only in GSK-3β. The candidate 4-3 (IC50 = 6.6 μM) showed good proliferation inhibition and apoptosis-inducing ability to leukemia cell lines, low cytotoxicity on normal cell lines, and no hERG inhibition, which hinted the potential efficacy and safety. Furthermore, 4-3 exhibited decent pharmacokinetic properties in vivo and remarkably inhibited tumor growth in the acute promyelocytic leukemia (APL) mouse model. All the results suggest that these newly irreversible BTZ compounds might be useful in the treatment of cancer such as APL.

Photo-Promoted Decarboxylative Alkylation of α, β-Unsaturated Carboxylic Acids with ICH2CN for the Synthesis of β, γ-Unsaturated Nitriles

An efficient, catalyst/photocatalyst-free, and cost-effective methodology for the decarboxylative alkylation of α,β-unsaturated carboxylic acids to synthesize β,γ-unsaturated nitriles has been developed. The reaction proceeded in an environmentally benign atmosphere of blue light-emitting diode irradiation with K2CO3 and water at room temperature. The methodology worked for a wide range of substrates (22 examples) with up to 83% yield. The protocol is also compatible for gram-scale synthesis.

Metal-Free Hydropyridylation of Thioester-Activated Alkenes via Electroreductive Radical Coupling

An electrochemical hydropyridylation of thioester-activated alkenes with 4-cyanopyridines has been developed. The reactions experience a tandem electroreduction of both substrates on the cathode surface, protonation, and radical cross-coupling process, resulting in a variety of valuable pyridine variants, which contain a tertiary and even a quaternary carbon at the α-position of pyridines, in high yields. The employment of thioesters to the conjugated alkenes enables no requirement of catalyst and high temperature, representing a highly sustainable synthetic method.

Meta-substituted piperlongumine derivatives attenuate inflammation in both RAW264.7 macrophages and a mouse model of colitis

Piperlongumine (PL) has been showed to have multiple pharmacological activities. In this study, we reported the synthesis of three series of PL derivatives, and evaluation of their anti-inflammatory effects in both lipopolysaccharide (LPS)-induced Raw264.7 macrophages and a dextran sulfate sodium (DSS)-induced mouse model of colitis. Our results presented that two meta-substituent containing derivatives 1–3 and 1–6, in which γ-butyrolactam replaced α,β-unsaturated δ-valerolactam ring of PL, displayed low cytotoxicity and effective anti-inflammatory activity. Molecular docking also showed that the meta-substituted derivative, compared with the corresponding ortho- or para-substituted derivative, had significant interactions with the amino acid residues of CD14, which was the core receptors recognizing LPS. In vitro and in vivo studies, 1–3 and 1–6 could inhibit the expression of pro-inflammatory cytokines, and the excessive production of reactive nitrogen species and reactive oxygen species. Oral administration of 100 mg/kg/day of 1–3 or 1–6 alleviated the severity of clinical symptoms of colitis in mice, and significantly reduced the colonic tissue damage to protect the colonic tissue from the DSS-induced colitis. These results suggested that meta-substituted derivatives 1–3 and 1–6 were potential anti-inflammatory agents, which may lead to future pharmaceutical development.

(E)-4-methyl-2-(4-(trifluoromethyl) styryl) oxazole compound as well as preparation method and application thereof

The invention belongs to the technical field of medicines, relates to a compound with anti-tumor activity and a specific chemical structure, and in particular relates to an (E)-4-methyl-2-(4-(trifluoromethyl) styryl) oxazole compound as well as a preparation method and an application thereof. The structural general formula of the compound is shown in the specification, wherein an R1 group is substituted by a 2-position, 3-position or 4-position mono-substituted fluorine atom, methyl, chlorine atom, methoxy group, bromine atom or an unsubstituted group; and the R2 group is substituted by a 2-position, 3-position or 4-position mono-substituted methoxy group, a chlorine atom or an unsubstituted group. Pharmacological studies show that the compound has certain inhibitory activity on human non-small cell lung cancer A549 cells, can be used for preparing anti-tumor drugs, and opens up a new way for deep research and development of tumor drugs in the future. The preparation method provided by the invention is simple and feasible, relatively high in yield and easy for large-scale production.

Photocatalytic Oxidative [2+2] Cycloelimination Reactions with Flavinium Salts: Mechanistic Study and Influence of the Catalyst Structure

Flavinium salts are frequently used in organocatalysis but their application in photoredox catalysis has not been systematically investigated to date. We synthesized a series of 5-ethyl-1,3-dimethylalloxazinium salts with different substituents in the positions 7 and 8 and investigated their application in light-dependent oxidative cycloelimination of cyclobutanes. Detailed mechanistic investigations with a coumarin dimer as a model substrate reveal that the reaction preferentially occurs via the triplet-born radical pair after electron transfer from the substrate to the triplet state of an alloxazinium salt. The very photostable 7,8-dimethoxy derivative is a superior catalyst with a sufficiently high oxidation power (E=2.26 V) allowing the conversion of various cyclobutanes (with Eox up to 2.05 V) in high yields. Even compounds such as all-trans dimethyl 3,4-bis(4-methoxyphenyl)cyclobutane-1,2-dicarboxylate can be converted, whose opening requires a high activation energy due to a missing pre-activation caused by bulky adjacent substituents in cis-position.

Iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabled aldehyde C-H methylation

A practical and general iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabling aldehyde C-H methylation for the synthesis of methyl ketones has been developed. This mild, operationally simple method uses ambient air as the sole oxidant and tolerates sensitive functional groups for the late-stage functionalization of complex natural-product-derived and polyfunctionalized molecules.

Piperlongumine analogs promote A549 cell apoptosis through enhancing ROS generation

Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electronwithdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2–C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity. Moreover, the protein containing sulfydryl or seleno, such as TrxR, could be irreversibly inhibited by the C2–C3 double bond of PL analogs, and boost intracellular ROS generation. Then, the ROS accumulation could disrupt the redox balance, induce lipid peroxidation, lead to the loss of MMP (Mitochondrial Membrane Potential), and ultimately result in cell cycle arrest and A549 cell line death. In conclusion, PL analogs could induce in vitro cancer apoptosis through the inhibition of TrxR and ROS accumulation.

Discovery of 3-cinnamamido-n-substituted benzamides as potential antimalarial agents

Background: Malaria is one of the most devastating parasitic diseases, yet the discovery of antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed in the past 50 years, while the emergence of drug-resistance continues to appear. Objective: This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3- cinnamamido-N-substituted benzamides. Methods: In this study, a screening of our compound library was carried out against the multidrugsensitive Plasmodium falciparum 3D7 strain. Derivatives of the hit were designed, synthesized and tested against P. falciparum 3D7 and the in vivo antimalarial activity of the most active compounds was evaluated using the method of Peters’ 4-day suppressive test. Results: The retrieved hit compound 1 containing a 3-cinnamamido-N-substituted benzamide skeleton showed moderate antimalarial activity (IC50 = 1.20 μM) for the first time. A series of derivatives were then synthesized through a simple four-step workflow, and half of them exhibited slightly better antimalarial effect than the precursor 1 during the subsequent in vitro assays. Additionally, compounds 11, 23, 30 and 31 displayed potent activity with IC50 values of approximately 0.1 μM, and weak cytotoxicity against mammalian cells. However, in vivo antimalarial activity is not effective, which might be ascribed to the poor solubility of these compounds. Conclusion: In this study, the phenotypic screen of our compound library resulted in the first report of a 3-cinnamamide framework with antimalarial activity and 40 derivatives were then designed and synthesized. Subsequent structure-activity studies showed that compounds 11, 23, 30 and 31 exhibited the most potent and selective activity against the P. falciparum 3D7 strain with IC50 values around 0.1 μM. Our work herein sets another example of phenotypic screen-based drug discovery, leading to potentially promising candidates of novel antimalarial agents once given further optimization.

Synthesis, crystal structure, and catalytic activity of bridged-bis(N-heterocyclic carbene) palladium(II) complexes in selective Mizoroki-Heck cross-coupling reactions

A series of three 1,3-propanediyl bridged bis(N-heterocyclic carbene)palladium(II) complexes (Pd-BNH1, Pd-BNH2, and Pd-BNH3), with + I effect order of the N-substituents of the ligand (isopropyl > benzyl > methoxyphenyl), was the subject of a spectroscopic, structural, computational and catalytic investigation. The bis(NHC)PdBr2 complexes were evaluated in Mizoroki-Heck coupling reactions of aryl bromides with styrene or acrylate derivatives and showed high catalytic efficiency to produce diarylethenes and cinnamic acid derivatives. The X-ray structure of the most active palladium complex Pd-BNH3 shows that the Pd(II) center is bonded to the two carbon atoms of the bis(N-heterocyclic carbene) and two bromide ligands in cis position, resulting in a distorted square planar geometry. The NMR data of Pd-BNH3 are consistent with a single chair-boat rigid conformer in solution with no dynamic behavior of the 8-membered ring palladacycle in the temperature range 25–120 °C. The catalytic activities of three Pd-bridged bis(NHC) complexes in the Mizoroki-Heck cross-coupling reactions were not found to have a direct correlation with +I effect order of the N-substituents of the ligand. However, a direct correlation was found between the DFT calculated absolute softness of the three complexes with their respective catalytic activity. The highest calculated softness, in the case of Pd-BNH3, is expected to favor the coordination steps of both the soft aryl bromides and alkenes in the Heck catalytic cycle.