112897-97-9

Usage

Chemical Properties

white to light yellow crystal powder

Uses

trans-3,4-Difluorocinnamic Acid is a starting material in the preparation of Ticagrelor (T437700), which is the first reversible oral P2Y12 receptor antagonist, provides faster, greater, and more consistent ADP-receptor inhibition than Clopidogrel.

InChI:InChI=1/C9H6F2O2/c10-7-3-1-6(5-8(7)11)2-4-9(12)13/h1-5H,(H,12,13)/p-1/b4-2+

Upstream product

• 348-61-8 1-bromo-3,4-difluorobenzene 
• 79-10-7 acrylic acid 
• 110-89-4 piperidine 
• 34036-07-2 3,4 difluorobenzaldehyde 
• 141-82-2 malonic acid 

Downstream Products

• 605658-32-0 3-chloro-5,6-difluorobenzo[b]thiophene-2-carbonyl chloride 
• 211568-07-9 (E)-3-(3,4-difluorophenyl)acryloyl azide 
• 1012319-52-6 C₁₉H₁₁BrF₂O₂ 
• 218430-47-8 (E)-methyl 3-(3,4-difluorophenyl)acrylate 
• 1262885-03-9 3-(3,4-difluoropheny)acrylic acid 4-iodophenyl ester 
• 1262884-62-7 C₂₉H₂₆F₂O₃ 
• 1262884-63-8 C₃₀H₂₈F₂O₃ 
• 1262884-65-0 C₃₁H₃₀F₂O₃ 
• 1262884-67-2 C₃₂H₃₂F₂O₃ 
• 1262884-69-4 3-(3,4-difluorophenyl)acrylic acid 4-(4-decyloxyphenylethynyl)phenyl ester 
• 1262884-71-8 C₃₅H₃₈F₂O₃ 
• 1262884-73-0 C₃₀H₂₄F₆O₃ 
• 31105-90-5 (L)-2-amino-3-(3,4-difluorophenyl)propanoic acid 
• 376608-68-3 (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl trans-(1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxylate 

Relevant academic research and scientific papers

Environment-friendly preparation method of ticagrelor intermediate

The invention discloses an environment-friendly preparation method of a ticagrelor intermediate. According to the method, (E)-3-(3,4-difluorophenyl)menthyl acrylate with chiral menthol groups is obtained by subjecting 3,4-difluorobenzaldehyde used as a ra

NOVEL SMALL MOLECULES THAT BIND AND/OR MODULATE DIFFERENTFORMS OF TAU OLIGOMERS

The present invention relates to novel small molecules of Formulas I, II, III, Ilia, Illb, and IV and pharmaceutically acceptable salts thereof, as well as the preparation and the use thereof.

Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design

A series of 3,4-disubstituted piperidine derivatives were obtained based on a conformational restriction strategy and a lead compound, A12, that exhibited potent in vitro and in vivo antitumor efficacies; however, obvious safety issues limited its further development. Thus, systematic exploration of the structure-activity relationship of compound A12, involving the phenyl group, hinge-linkage, and piperidine moiety, led to the discovery of the superior 3,4,6-trisubstituted piperidine derivative E22. E22 showed increased potency in Akt1 and cancer cell inhibition, remarkably reduced human ether-a-go-go-related gene blockage, and significantly improved safety profiles. Compound E22 also exhibited good kinase selectivity, had a good pharmacokinetic profile, and displayed very potent in vivo antitumor efficacy, with over 90% tumor growth inhibition in the SKOV3 xenograft model. Further mechanistic studies were conducted to demonstrate that compound E22 could significantly inhibit the phosphorylation of proteins downstream of Akt kinase in cells and tumor tissue from the xenograft model.

Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms I, II, IX and XII inhibitors

A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (KIs in the range of 0.50–50.5 nM), hCA IX (KIs of 1.8–228.5 nM), and hCA XII (KIs of 3.5–96.2 nM) being less effective as inhibitors of the off target isoform hCA I. A detailed structure–activity relationship study demonstrates that the nature and position of substituents present on the aromatic part of the scaffold strongly influence the inhibition of CA isoforms. As hCA II, IX and XII are involved in pathologies such as glaucoma and hypoxic, and metastatic tumors, compounds of the type reported in this work may be useful preclinical candidates.

Telescopic one-pot condensation-hydroamination strategy for the synthesis of optically pure L-phenylalanines from benzaldehydes

A chemo-enzymatic telescopic approach was designed for the synthesis of L-arylalanines in high yield and optical purity, starting from commercially available and inexpensive substituted benzaldehydes. The method exploits a chemical Knoevenagel–Doebner condensation (optimised to give complete conversions in a short reaction time, employing microwave irradiation) and a biocatalytic phenylalanine ammonia lyase mediated hydroamination (for the stereoselective addition of ammonia). The two reactions can be run sequentially in one pot, bringing together the advantages of chemical and biological catalysis. The preparative applicability was demonstrated with the synthesis of five L-dihalophenylalanines (71–84% yield, 98–99% ee) of relevance as molecular probes, for medicinal chemistry and for the synthesis of pharmaceutical ingredients.

Design, synthesis and biological evaluation of cinnamic acyl shikonin derivatives

Inducing apoptosis is an important and promising therapeutic approach to overcome cancer. Here, we described a series of novel synthesized compounds, cinnamic acyl shikonin derivatives (1b-19b), which were synthesized starting from shikonin and cinnamic acids, which exhibit anticancer activity via inducing apoptosis in vitro. Our flow cytometry results showed that compound 8b((E)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent -3-enyl-3-(3-(trifluoromethyl) phenyl)acrylate) (IC50=0.69, 0.65, 1.62 μm for human SW872-s, A875 and A549 cell lines, respectively) exhibited conspicuous anticancer activities and has low cell toxicity in vitro. Therefore, we considered that compound 8b is potentially to be a candidate of anticancer agent. The proliferation inhibitory effect of compound 8b was associated with its apoptosis-inducing effect by activating caspase-3, caspase-7, caspase-9, and PARP. When the level of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, and cleaved PARP are rise, apoptosis of cancer cells will be induced.

Synthesis and mesomorphic properties of tolane-based fluorinated liquid crystals with an acrylate linkage

Six series of tolane-based fluorinated liquid crystals containing an acrylate linker were synthesized and their mesomorphic properties were characterized. The compounds generally exhibit SmA and N phases in wide temperature ranges. The introduction of acrylate linkers increases the clearing points by 20°C-30°C and suppresses the formation of higher ordered monotropic SmB phases. para-Fluorination is favorable for the mesophase stability, whereas meta-fluorination is not. The introduction of a 2,3,5,6-tetrafluorophenylene group decreases the clearing points and also suppresses the formation of the monotropic SmB phase. Copyright Taylor & Francis Group, LLC.

Novel triazolo pyrimidine compounds

The present invention relates to a pyrimidine compound (I) useful as a pharmaceutical intermediate, to a process for preparing said pyrimidine compound, to intermediates used in said process, and to the use of said pyrimidine compound in the preparation of pharmaceuticals.

Process for the preparation of cyclopropyl carboxylic acid esters and derivatives

The invention relates to a novel process for the preparation of certain cyclopropyl carboxylic acid esters and other cyclopropyl carboxylic acid derivatives; a novel process for the preparation of dimethylsulfoxonium methylide and dimethylsulfonium methylide; to the use of certain cyclopropyl carboxylic acid esters in a process for the preparation of intermediates that can be used in the synthesis of pharmaceutically active entities; and to certain intermediates provided by these processes.

Medicaments for the selective treatment of tumor tissues

Medicinal products for the selective control of tumor tissue and a method for control of such tumor tissue by administration of such product to a host. The products comprise: (a) two different compounds having a pH below 7 when the compounds are present i