7761-30-0

Usage

Uses

Used in Pharmaceutical Industry:
2-(4-FLUOROBENZOYL)ACETIC ACID is used as a chemical intermediate for the synthesis of serine/threonine kinase inhibitors. These inhibitors play a crucial role in treating various diseases by targeting and modulating the activity of specific kinases, which are often dysregulated in pathological conditions.
As a Serine/Threonine Kinase Inhibitor:
2-(4-FLUOROBENZOYL)ACETIC ACID is used as a serine/threonine kinase inhibitor for the development of therapeutic agents to treat diseases associated with the dysregulation of these kinases. By inhibiting the activity of these enzymes, the compound can potentially help in the management and treatment of conditions such as cancer, autoimmune disorders, and neurological diseases.
In Drug Development:
2-(4-FLUOROBENZOYL)ACETIC ACID serves as a key building block in the design and synthesis of novel drug candidates targeting serine/threonine kinases. Its unique chemical structure allows for the development of highly specific and potent inhibitors, which can be further optimized for improved efficacy, selectivity, and pharmacokinetic properties.
In Research and Development:
2-(4-FLUOROBENZOYL)ACETIC ACID is also used in academic and industrial research settings to study the structure-activity relationships of serine/threonine kinase inhibitors. By understanding the interactions between 2-(4-FLUOROBENZOYL)ACETIC ACID and its target kinases, researchers can gain valuable insights into the design of more effective and safer therapeutic agents.

Upstream product

• 111649-72-0 α-acetylamino-4-fluoro-cinnamic acid 
• 459-57-4 4-fluorobenzaldehyde 
• 125772-83-0 (Z)-4-(4-fluorobenzylidene)-2-methyloxazol-5(4H)-one 
• 459-32-5 4-fluorocinnamic acid 
• 18125-46-7 (R)-4-fluorophenylalanine 
• 461-72-3 2,4-imidazolidinedione 
• 586-08-3 4-(4-fluorophenyl)methylene-2-methyl-5(4H)-oxazolone 
• 56-40-6 glycine 
• 166116-63-8 4-(4-fluoro-benzylidene)-2-methyl-4H-oxazol-5-one 
• 1132-68-9 L-4-fluorophenylalanine 

Downstream Products

• 124980-94-5 (2R)-3-(4-fluorophenyl)-2-hydroxypropanoic acid 
• 1567951-49-8 C₁₈H₁₄FNO₃ 
• 1260656-25-4 C₁₇H₁₁F₂NO₂ 
• 53484-49-4 3-(4-fluorophenyl)-2-hydroxypropionic acid 
• 1132-68-9 L-4-fluorophenylalanine 
• 18125-46-7 (R)-4-fluorophenylalanine 
• 119-61-9 benzophenone 
• 1356930-04-5 C₁₁H₁₃FN₂O₂S 

Relevant academic research and scientific papers

Bio-inspired enantioselective full transamination using readily available cyclodextrin

The mimics of vitamin B6-dependent enzymes that catalyzed an enantioselective full transamination in the pure aqueous phase have been realized for the first time through the establishment of a new “pyridoxal 5′-phosphate (PLP) catalyzed non-covalent cyclodextrin (CD)-keto acid inclusion complexes” system, and various optically active amino acids have been obtained.

SERINE/THREONINE KINASE INHIBITORS

Compounds of Formula I or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such diseases, or associated pathological conditions are disclosed.

Synthesis of D- and L-Phenylalanine Derivatives by Phenylalanine Ammonia Lyases: A Multienzymatic Cascade Process

The synthesis of substituted D-phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one-pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple high-throughput solid-phase screening method has also been developed to identify PALs with higher rates of formation of non-natural D-phenylalanines. The best variants were exploited in the chemoenzymatic cascade, thus increasing the yield and ee value of the D-configured product. Furthermore, the system was extended to the preparation of those L-phenylalanines which are obtained with a low ee value using PAL amination.

Defining the mechanism of action and enzymatic selectivity of psammaplin A against its epigenetic targets

Psammaplin A (11c) is a marine metabolite previously reported to be a potent inhibitor of two classes of epigenetic enzymes: histone deacetylases and DNA methyltransferases. The design and synthesis of a focused library based on the psammaplin A core has been carried out to probe the molecular features of this molecule responsible for its activity. By direct in vitro assay of the free thiol generated upon reduction of the dimeric psammaplin scaffold, we have unambiguously demonstrated that 11c functions as a natural prodrug, with the reduced form being highly potent against HDAC1 in vitro (IC50 0.9 nM). Furthermore, we have shown it to have high isoform selectivity, being 360-fold selective for HDAC1 over HDAC6 and more than 1000-fold less potent against HDAC7 and HDAC8. SAR around our focused library revealed a number of features, most notably the oxime functionality to be important to this selectivity. Many of the compounds show significant cytotoxicity in A549, MCF7, and W138 cells, with the SAR of cytotoxicity correlating to HDAC inhibition. Furthermore, compound treatment causes upregulation of histone acetylation but little effect on tubulin acetylation. Finally, we have found no evidence for 11c functioning as a DNMT inhibitor.

D-amino acid dehydrogenase and method of making D-amino acids

Polypeptides capable of catalyzing the reductive amination of a 2-ketoacid to its corresponding D-amino acid are provided. The polypeptides can be prepared by mutagenesis of, e.g., a diaminopimelate dehydrogenase. Also provided is a method of making a D-amino acid using a catalytically active polypeptide, wherein a 2-ketoacid is allowed to contact the polypeptide in the presence of a nicotinamide cofactor and ammonia or an ammonia source.

Development of a continuous enzymatic process for the preparation of (R)-3-(4-fluorophenyl)-2-hydroxy propionic acid

While many methods have been reported for the synthesis of chiral 2-hydroxy acids, few of them have proven to be reliable toward the synthesis of the title compound in terms of overall yield and enantioselectivity. Herein we describe a continuous enzymatic process for an efficient synthesis of (R)-3-(4-fluorophenyl)-2-hydroxy propionic acid at multikilogram scale with a high space-time yield (560 g/(L·d)) using a membrane reactor. The product was generated in excellent enantiomeric excess (ee > 99.9%) and good overall yield (68-72%).

Combinatorial synthesis through disulfide exchange: Discovery of potent psammaplin A type antibacterial agents active against methicillin-resistant Staphylococcus aureus (MRSA)

Psammaplin A is a symmetrical bromotyrosine-derived disulfide natural product isolated from the Psammaplysilla sponge, which exhibits in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Inspired by the structure of this marine natural product, a combinatorial scrambling strategy for the construction of heterodimeric disulfide analogues was developed and applied to the construction of a 3828-membered library starting from 88 homodimeric disulfides. These psammaplin A analogues were screened directly against various gram positive bacterial strains leading to the discovery of a series of potent antibacterial agents active against methicillin-resistant Staphylococcus aureus (MRSA). Among the most active leads derived from these studies are compounds 104, 105, 113, 115, 123, and 128. The present, catalytically-induced, disulfide exchange strategy may be extendable to other types of building blocks bearing thiol groups facilitating the construction of diverse discovery-oriented combinatorial libraries.

Palladium-Catalyzed Double and Single Carbonylations of β-Amino Alcohols. Selective Synthesis of Morpholine-2,3-diones and Oxazolidin-2-ones and Applications for Synthesis of α-Oxo Carboxylic Acids

Catalytic cross double carbonylation of secondary amines and alcohols proceeds in the presence of [PdCl2(MeCN)2] and CuI under carbon monoxide (80 atm) and oxygen (5 atm). Catalytic intramolecular double carbonylation of β-amino alcohols gives morpholine-2,3-diones, which are excellent protecting compounds of amino alcohols and important precursors for biologically active nitrogen compounds. In contrast, catalytic single carbonylation of β-amino alcohols under a mixture (1 : 1) of carbon monoxide and oxygen (1.0 atm) proceeds to give oxazolidin-2-ones selectively. The reaction can be explained by assuming a mechanism which includes intramolecular nucleophilic attack of the hydroxy group of (hydroxyethyl)aminocarbonyl ligands on the CO ligand of the carbamoylpalladium(II) complexes, followed by reductive elimination to give morpholine-2,3-diones. In contrast, direct nucleophilic attack of the hydroxy group to the carbamoyl group affords oxazolidin-2-ones. As a common intermediate for the double and single carbonylations, carbamoylpalladium(II) complex has been isolated by the reaction of [PdCl2(PMe3)2] with β-amino alcohol under CO. The present double carbonylation of amino alcohols provides a novel and convenient method for synthesis of α-oxo carboxylic acids. Thus, the morpholine-2,3-diones obtained undergo reaction with Grignard reagents chemoselectively at the ester positions to give 2-substituted 2-hydroxymorpholin-3-ones, which undergo acid hydrolysis to give α-oxo carboxylic acids.