22510-33-4

Usage

Uses

Used in Pharmaceutical Development:
4'-Fluoro-4-hydroxy-biphenyl-3-carboxylic acid is used as a synthetic intermediate for the development of pharmaceuticals, given its capacity to be incorporated into the molecular structures of various biologically active compounds. Its presence in these molecules can influence their pharmacological properties, such as potency, selectivity, and metabolic stability.
Used in Research:
In the scientific community, 4'-Fluoro-4-hydroxy-biphenyl-3-carboxylic acid serves as a valuable research tool, enabling the investigation of structure-activity relationships and the exploration of novel chemical space. Its unique structural features make it an attractive candidate for probing the interactions between molecules and their biological targets.
Used in Materials Science:
4'-Fluoro-4-hydroxy-biphenyl-3-carboxylic acid is used as a component in the development of new materials, potentially contributing to the creation of advanced materials with tailored properties. Its reactivity and structural characteristics may be harnessed to produce materials with specific applications in areas such as electronics, coatings, or composites.
Used in Organic Chemistry:
As an organic compound, 4'-Fluoro-4-hydroxy-biphenyl-3-carboxylic acid is utilized in organic synthesis for the preparation of a range of chemical products. Its versatility in reactions allows for the synthesis of complex organic molecules, which can be applied in various industries, including pharmaceuticals, agrochemicals, and specialty chemicals.

Upstream product

• 89-55-4 5-bromosalicyclic acid 
• 352-13-6 4-flourophenylmagnesium bromide 
• 22510-35-6 methyl 4’-fluoro-4-hydroxy-[1,1’-biphenyl]-3-carboxylate 
• 22494-42-4 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid 
• 4068-75-1 methyl 5-iodosalicylate 
• 4068-76-2 5-bromo-2-hydroxy-benzoic acid methyl ester 
• 2263-65-2 3-carboxy-4-hydroxybenzenediazonium tetrafluoroborate 
• 64465-74-3 4'-fluoro-4-methoxy-biphenyl-3-carboxylic acid methyl ester 
• 40757-09-3 methyl 2-methoxy-5-iodobenzoate 
• 119-30-2 2-hydroxy-5-iodobenzoic acid 
• 1765-93-1 4-fluoroboronic acid 

Downstream Products

• 22494-35-5 4'-fluoro-3-methyl-[1,1'-biphenyl]-4-ol 
• 22494-27-5 FLUFENISAL 

Relevant academic research and scientific papers

Photochemical outcome modification of diflunisal by a novel cationic amphiphilic cyclodextrin

The effects of a novel cationic amphiphilic cyclodextrin (SC6CDNH2) on the photoprocesses of the phototoxic non-steroidal anti-inflammatory drug diflunisal (DF) have been investigated in aqueous medium. Association between DF and SC6CDNH2 was indicated by steady-state absorption, induced circular dichroism and fluorescence spectroscopy. Laser flash photolysis and steady-state photolysis experiments revealed a particular sensitivity of the DF photochemistry to the new microenvironment. Reduction of the triplet state generation efficiency, lengthening of its lifetime, changes in the photoionisation pathways, besides remarkable drug photostabilization and modification of the stable photoproducts distribution, were observed. A rationale for these modifications to the photochemistry of DF based on the multifaceted role of SC6CDNH2 in influencing the efficiency of the primary photochemical act and in interfering with secondary radical reactions is proposed. Relation of the overall results to the phototoxic effects displayed by the drug is also commented upon.

Diflunisal Derivatives as Modulators of ACMS Decarboxylase Targeting the Tryptophan-Kynurenine Pathway

In the kynurenine pathway for tryptophan degradation, an unstable metabolic intermediate, α-amino-β-carboxymuconate-?-semialdehyde (ACMS), can nonenzymatically cyclize to form quinolinic acid, the precursor for de novo biosynthesis of nicotinamide adenine dinucleotide (NAD+). In a competing reaction, ACMS is decarboxylated by ACMS decarboxylase (ACMSD) for further metabolism and energy production. Therefore, the inhibition of ACMSD increases NAD+ levels. In this study, an Food and Drug Administration (FDA)-approved drug, diflunisal, was found to competitively inhibit ACMSD. The complex structure of ACMSD with diflunisal revealed a previously unknown ligand-binding mode and was consistent with the results of inhibition assays, as well as a structure-activity relationship (SAR) study. Moreover, two synthesized diflunisal derivatives showed half-maximal inhibitory concentration (IC50) values 1 order of magnitude better than diflunisal at 1.32 ± 0.07 μM (22) and 3.10 ± 0.11 μM (20), respectively. The results suggest that diflunisal derivatives have the potential to modulate NAD+ levels. The ligand-binding mode revealed here provides a new direction for developing inhibitors of ACMSD.

Green synthesis of biphenyl carboxylic acids via Suzuki–Miyaura cross-coupling catalyzed by a water-soluble fullerene-supported PdCl2 nanocatalyst

A green synthesis of variously substituted biphenyl carboxylic acids was achieved through Suzuki–Miyaura cross-coupling of a bromobenzoic acid with an aryl boronic acid using a water-soluble fullerene-supported PdCl2 nanocatalyst (C60-TEGs/ PdCl2). Yields of more than 90% were obtained at room temperature in 4 h using 0.05 mol% catalyst and 2 equiv. K2CO3.

Tuning transthyretin amyloidosis inhibition properties of iododiflunisal by combinatorial engineering of the nonsalicylic ring substitutions

Two series of iododiflunisal and diflunisal analogues have been obtained by using a two step sequential reaction solution-phase parallel synthesis. The synthesis combined an aqueous Suzuki-Miyaura cross-coupling and a mild electrophilic aromatic iodination step using a new polymer-supported iodonium version of Barluengas reagent. From a selected set of 77 noniodinated and 77 iodinated diflunisal analogues, a subset of good transthyretin amyloid inhibitors has been obtained with improved turbidimetry inhibition constants, high binding affinity to transthyretin, and good selectivity for TTR compared to other thyroxine binding proteins.

A highly efficient catalyst of a nitrogen-based ligand for the Suzuki coupling reaction at room temperature under air in neat water

Glycine, as a kind of commercially available and inexpensive ligand, is used to prepare an air-stable and water-soluble catalyst for the Suzuki-Miyaura reaction in our study. In the presence of 0.1% [PdCl2(NH 2CH2COOH)2] as the catalyst, extremely excellent catalytic activity towards the Suzuki-Miyaura coupling of aryl halides containing the carboxyl group with various aryl boronic acids is observed at room temperature under air in neat water. the Partner Organisations 2014.

Suzuki-Miyaura cross coupling reactions with Phenoldiazonium salts

The Suzuki-Miyaura coupling of phenol diazonium salts and aryl trifluoroborates yields 4-hydroxybiaryls in a protecting group-free synthesis. The Royal Society of Chemistry 2011.

Diflunisal Analogues Stabilize the Native State of Transthyretin. Potent Inhibition of Amyloidogenesis

Analogues of diflunisal, an FDA-approved nonsteroidal antiinflammatory drug (NSAID), were synthesized and evaluated as inhibitors of transthyretin (TTR) aggregation, including amyloid fibril formation. High inhibitory activity was observed for 26 of the compounds. Of those, eight exhibited excellent binding selectivity for TTR in human plasma (binding stoichiometry > 0.50, with a theoretical maximum of 2.0 inhibitors bound per TTR tetramer). Biophysical studies reveal that these eight inhibitors dramatically slow tetramer dissociation (the rate-determining step of amyloidogenesis) over a duration of 168 h. This appears to be achieved through ground-state stabilization, which raises the kinetic barrier for tetramer dissociation. Kinetic stabilization of WT TTR by these eight inhibitors is further substantiated by the decreasing rate of amyloid fibril formation as a function of increasing inhibitor concentration (pH 4.4). X-ray cocrystal structures of the TTR·182 and TTR·202 complexes reveal that 18 and 20 bind in opposite orientations in the TTR binding site. Moving the fluorines from the meta positions in 18 to the ortho positions in 20 reverses the binding orientation, allowing the hydrophilic aromatic ring of 20 to orient in the outer binding pocket where the carboxylate engages in favorable electrostatic interactions with the ε-ammonium groups of Lys 15 and 15′. The hydrophilic aryl ring of 18 occupies the inner binding pocket, with the carboxylate positioned to hydrogen bond to the serine 117 and 117′ residues. Diflunisal itself appears to occupy both orientations based on the electron density in the TTR·12 structure. Structure-activity relationships reveal that para-carboxylate substitution on the hydrophilic ring and dihalogen substitution on the hydrophobic ring afford the most active TTR amyloid inhibitors.

Palladium catalyzed cross-coupling reaction of Grignard reagents with halobenzoic acids, halophenols and haloanilines

Convenient syntheses of substituted benzoic acids, phenols and anilines have been achieved by using palladium catalyzed cross-coupling reactions between Grignard reagents and aryl halides containing carboxy, hydroxy and amino groups without a protection-deprotection sequence.

Ligandless palladium catalyzed reactions of arylboronic acids and sodium tetraphenylborate with aryl halides in aqueous media

Polyfunctional biaryls are prepared by a modified Suzuki cross-coupling reaction between arylboronic acids or sodium tetraphenylborate and aryl halides ArX. X = 1. Br. Cl in aqueous solvents or neat water using a phosphine-free palladium catalyst, and in the presence of bases (Na2CO3 or NaOH). All four phenyl groups of Ph4BNa participate ill the reaction. The reaction of Ph4BNa with aryl halides proceeds in water with high catalytic efficiency (250,000 catalytic cycles).

Reaction of Organoboron Compounds with Organic Halides in Aqueous Media, Catalyzed by "Ligand-Free" Palladium

The results of investigations of the reactions between aryllboric acids or sodium tetraphenylborate and organic halides in water and DMF- and acetone-water mixtures, catalyzed by palladium salts containing no phosphine ligands [Pd(OAc)2, PdCl2], are considered.