Diflunisal

Base Information

• Chemical Name: Diflunisal
• CAS No.: 22494-42-4
• Molecular Formula: C13H8F2O3
• Molecular Weight: 250.202
• Hs Code.: 2918290000
• European Community (EC) Number: 245-034-9
• NSC Number: 756728
• UNII: 7C546U4DEN
• DSSTox Substance ID: DTXSID5022932
• Nikkaji Number: J3.155K
• Wikipedia: Diflunisal
• Wikidata: Q2602750
• NCI Thesaurus Code: C47489
• RXCUI: 3393
• Pharos Ligand ID: BXS2UURH6WPK
• Metabolomics Workbench ID: 43139
• ChEMBL ID: CHEMBL898
• Mol file: 22494-42-4.mol

Synonyms:Apo Diflunisal;Apo-Diflunisal;ApoDiflunisal;Diflunisal;Dolobid;Dolobis;Dolocid;MK 647;MK-647;MK647;Novo Diflunisal;Novo-Diflunisal;NovoDiflunisal;Nu Diflunisal;Nu-Diflunisal;NuDiflunisal

Chemical Property of Diflunisal

Chemical Property:

• Appearance/Colour: White solid
• Vapor Pressure: 2.75E-07mmHg at 25°C
• Melting Point: 207-209 °C
• Refractive Index: 1.601
• Boiling Point: 386.9 °C at 760 mmHg
• PKA: pKa 3.3 (H2O I=0.1) (Uncertain)
• Flash Point: 187.8 °C
• PSA: 57.53000
• Density: 1.437 g/cm³
• LogP: 3.03560
• Storage Temp.: Refrigerator
• Solubility.: Practically insoluble in water, soluble in ethanol (96 per cent). It dissolves in dilute solutions of alkali hydroxides.
• Water Solubility.: 6.186mg/L(24.99 oC)
• XLogP3: 4.4
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 2
• Exact Mass: 250.04415044
• Heavy Atom Count: 18
• Complexity: 311

Purity/Quality:

99%, ^*data from raw suppliers

Diflunisal ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn, Xi
• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38-63
• Safety Statements: 22-26-36

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antiinflammatory Agents
• Canonical SMILES: C1=CC(=C(C=C1C2=C(C=C(C=C2)F)F)C(=O)O)O
• Recent ClinicalTrials: The Effects Diflunisal on the Levels of BMS-986165 in Healthy Participants
• Recent EU Clinical Trials: Unicentre, open, uncontrolled clinical trial to assess the morphological, biochemical and functional effects of Diflunisal treatment in patients with transthyretin cardiac amyloidosis
• Recent NIPH Clinical Trials: Treatment of transthyretin amyloidosis using diflunisal
• Description: Diflunisal is more potent than aspirin but produces fewer side effects and has a biological half-life three to four times greater than that of aspirin. It is rapidly and completely absorbed on oral administration, with peak plasma levels being achieved within 2 to 3 hours of administration. It is highly bound (99%) to plasma proteins after absorption. Its elimination half-life is 8 to 12 hours, and it is excreted into urine primarily as glucuronide conjugates. The most frequently reported side effects include disturbances of the GI system (e.g., nausea, dyspepsia, and diarrhea), dermatological reactions, and CNS effects (e.g., dizziness and headache). Diflunisal is a non-steroidal anti-inflammatory drug (NSAID) that inhibits both COX-1 (IC50 = 113 μM) and COX-2 (IC50s = 8.2 and 134 μM for human whole blood assay and human-modified whole blood assays, respectively). Peak plasma levels are achieved within two hours, with little metabolism before excretion in the urine. The terminal plasma half-life is approximately eight hours.
• Uses: As a prostaglandin synthetase inhibitor, diflunisal exhibits analgesic, fever-reducing, and anti-inflammatory action. It is used for long- and short-lasting symptomatic relief of low to moderate pain in osteoarthritis and rheumatoid arthritis. Salicylate; non-selective cyclo-oxygenase inhibitor; antipyretic; analgesic; anti- inflammatory. Diflunisal acts as an analgesic agent, used in Alzheimer’s studies (1,2,3) as an anti-inflammatory. As well as in autolytic regulation of human kallikrein -related peptidase 6 (4).
• Therapeutic Function: Analgesic, Antiinflammatory
• Clinical Use: Diflunisal (pKa 3.3) was introduced in the United States in 1982 and has gained considerable acceptance as an analgetic and as a treatment of rheumatoid arthritis and osteoarthritis. Diflunisal is metabolized primarily to ether and ester glucuronide conjugates.

Technology Process of Diflunisal

There total 41 articles about Diflunisal which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.0%

5-bromosalicyclic acid (89-55-4) + 2,4-difluorophenylboronic acid (144025-03-6) → 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid (22494-42-4)

Guidance literature:

With 2-[5-(4-methylphenyl)isoxazol-3-yl]-5-(5-phenylisoxazol-3-yl)-1,3,4-oxadiazole·2PdCl₂; potassium carbonate; In water; N,N-dimethyl-formamide; at 100 ℃; for 0.0166667h;

DOI:10.1007/s10593-018-2216-z

Reference yield: 99.0%

methyl 2',4'-difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylate (55544-00-8) → 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid (22494-42-4)

Guidance literature:

With potassium hydroxide; In water; at 80 ℃; for 3h; Green chemistry;

DOI:10.1002/adsc.201800462

Reference yield: 99.0%

methyl 5-(2',4'-difluorophenyl)-2-methoxybenzoate → 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid (22494-42-4)

Guidance literature:

methyl 5-(2',4'-difluorophenyl)-2-methoxybenzoate; With boron tribromide; In dichloromethane; at -78 ℃; for 1h; Inert atmosphere;

With sodium hydroxide; In methanol; for 4h; Reflux;

DOI:10.1002/adsc.201600205

upstream raw materials:

carbon dioxide

2,4-difluorophenylamine

methoxybenzene

benzene

Downstream raw materials:

Diflunisal acyl glucuronide

2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid hydrazide

2',4'-Difluoro-4-hydroxy-biphenyl-3-carboxylic acid [1-phenyl-meth-(E)-ylidene]-hydrazide

2',4'-Difluoro-4-hydroxy-biphenyl-3-carboxylic acid [1-(4-fluoro-phenyl)-meth-(E)-ylidene]-hydrazide

Refernces

• 1、 Chen, Wen-Bo,Xing, Chun-Hui,Dong, Jie,Hu, Qiao-Sheng. "Electron-Poor, Fluoro-Containing Arylboronic Acids as Efficient Coupling Partners for Bis(1,5-cyclooctadiene)nickel(0)/Tricyclohexylphosphine-Catalyzed Cross-Coupling Reactions of Aryl Arenesulfonates". . p. 2072 - 2076. Retrieved 2016.
• 2、 Ghaderi, Arash,Kambe, Nobuaki,Le, Liyuan,Lu, Hao,Qiu, Renhua,Tang, Ting,Tong, Zhou,Wong, Wai-Yeung,Xu, Zhi,Yin, Shuang-Feng,Zeng, Dishu,Zhang, Dejiang,Zhang, Zhao. "Nickel- and Palladium-Catalyzed Cross-Coupling of Stibines with Organic Halides: Site-Selective Sequential Reactions with Polyhalogenated Arenes". . p. 854 - 867. Retrieved 2022/01/19.
• 3、 Liu, Wanyun,Zhou, Xiuming,Huo, Ping,Li, Jingbo,Mei, Guangquan. "Green synthesis of biphenyl carboxylic acids via Suzuki–Miyaura cross-coupling catalyzed by a water-soluble fullerene-supported PdCl2 nanocatalyst". . p. 50 - 52. Retrieved 2019/06/21.