Flurbiprofen

Base Information

• Chemical Name: Flurbiprofen
• CAS No.: 5104-49-4
• Deprecated CAS: 51543-38-5
• Molecular Formula: C15H13FO2
• Molecular Weight: 244.265
• Hs Code.: 29163990
• European Community (EC) Number: 225-827-6,257-262-6
• NSC Number: 757037,685701
• UNII: 5GRO578KLP
• DSSTox Substance ID: DTXSID0037231
• Nikkaji Number: J73.105F,J33.114G
• Wikipedia: Flurbiprofen
• Wikidata: Q419890
• NCI Thesaurus Code: C508
• RXCUI: 4502
• Pharos Ligand ID: THH8FPRHHZR9
• Metabolomics Workbench ID: 145447
• ChEMBL ID: CHEMBL563
• Mol file: 5104-49-4.mol

Synonyms:2-Fluoro-alpha-methyl-(1,1'-biphenyl)-4-acetic Acid;Ansaid;Apo Flurbiprofen;Apo-Flurbiprofen;BTS 18322;BTS-18322;BTS18322;Cebutid;Dobrofen;E 7869;E-7869;E7869;Flubiprofen;Flugalin;Flurbiprofen;Flurbiprofen Sodium;Fluriproben;Froben;Froben SR;Neo Artrol;Novo Flurprofen;Novo-Flurprofen;Nu Flurbiprofen;Nu-Flurbiprofen;Ocufen;Ocuflur;ratio Flurbiprofen;ratio-Flurbiprofen;Strefen

Chemical Property of Flurbiprofen

Chemical Property:

• Appearance/Colour: white to off-white crystalline solid
• Vapor Pressure: 2.84mmHg at 25°C
• Melting Point: 110-112 °C(lit.)
• Refractive Index: 1.34
• Boiling Point: 376.2 °C at 760 mmHg
• PKA: pKa 3.80(H2O) (Uncertain)
• Flash Point: 181.3 °C
• PSA: 37.30000
• Density: 1.199 g/cm³
• LogP: 3.68080
• Storage Temp.: Store at RT
• Solubility.: methanol: soluble50mg/mL
• Water Solubility.: 8mg/L(room temperature)
• XLogP3: 4.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 244.08995782
• Heavy Atom Count: 18
• Complexity: 286

Purity/Quality:

98% ^*data from raw suppliers

Flurbiprofen ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,C
• Hazard Codes: T,C
• Statements: 25-23/24/25
• Safety Statements: 36/37/39-45

MSDS Files:

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Nonsteroidal Antiinflammatory Drugs
• Canonical SMILES: CC(C1=CC(=C(C=C1)C2=CC=CC=C2)F)C(=O)O
• Recent ClinicalTrials: A Study to Evaluate the Drug-drug Interaction Potential of BMS-986196 in Healthy Participants
• Recent EU Clinical Trials: Randomized, controlled, multi-center trial to evaluate the efficacy and safety of a Flurbiprofen 40 mg cutaneous hydrogel medicated plaster vs. placebo and vs. a marketed active comparator in the local symptomatic and short-term treatment of pain in acute strains, sprains or bruises of the soft tissues following blunt trauma, e.g. sports injuries
• Recent NIPH Clinical Trials: Multicentered Randomized study for knee osteoarthritis
• Uses: This product is anti-inflammatory drug for chronic arthritis and pain, inflammation of Deformation joint disease , and pain after surgery and tooth extraction. Mouse oral LD50 of 140mg/kg, rats 640-800mg/kg. A cyclooxygenase inhibitor An anti-inflammatory used as an analgesic. antiinflammatory, analgesic
• production method: It is obtained by 2-fluoro-linked acetophenone through oxidation, esterification, transesterification, hydrolysis, decarboxylation reaction.
• Description: Flurbiprofen synthesis was originally reported in 1974. During a study of the pharmacological properties of a large number of substituted phenylalkanoic acids, including ibuprofen and ibufenac, the most potent were found to be substituted 2-(4-biphenyl)propionic acids. Further toxicological and pharmacological studies indicated that flurbiprofen possessed the most favorable therapeutic profile, so it was selected for further clinical development. It was not marketed until 1987, when it was introduced as the sodium salt as Ocufen, the first topical NSAID indicated for ophthalmic use in the United States. The indication for Ocufen is the same as that for Profenal—that is, to inhibit intraoperative miosis induced by prostaglandins in cataract surgery.
• Indications: Flurbiprofen (Ansaid) is indicated for the treatment of rheumatoid arthritis and osteoarthritis. Its half-life, longer than that of many of the NSAIDs, allows for twice daily dosing.The most common adverse effects of flurbiprofen are similar to those of the other acidic NSAIDs. Flurbiprofen inhibits both COX isoforms about equally.
• Therapeutic Function: Antiinflammatory
• Clinical Use: Flurbiprofen is indicated as an oral formulation for the acute or long-term treatment of rheumatoid arthritis and osteoarthritis and as an ophthalmic solution for the inhibition of intraoperative miosis.
• Drug interactions: Potentially hazardous interactions with other drugs ACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect; increased risk of nephrotoxicity and hyperkalaemia. Analgesics: avoid concomitant use with other NSAIDs or aspirin; avoid concomitant use with ketorolac (increased side effects and haemorrhage). Antibacterials: possibly increased risk of convulsions with quinolones. Anticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparin, dabigatran and edoxaban - avoid long term use with edoxaban. Antidepressants: increased risk of bleeding with SSRIs or venlafaxine. Antidiabetics: effects of sulphonylureas enhanced. Antiepileptics: possibly enhanced effect of phenytoin. Antivirals: concentration possibly increased by ritonavir; increased risk of haematological toxicity with zidovudine. Ciclosporin: may potentiate nephrotoxicity. Cytotoxics: reduced excretion of methotrexate; increased risk of bleeding with erlotinib. Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect; hyperkalaemia with potassium-sparing diuretics. Lithium: excretion reduced (risk of lithium toxicity). Pentoxifylline: increased risk of bleeding. Tacrolimus: increased risk of nephrotoxicity

Technology Process of Flurbiprofen

There total 273 articles about Flurbiprofen 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%

α-methyl-(2-fluoro-4-biphenylyl)acetonitrile (74648-00-3) → fluorobiprofen (5104-49-4)

Guidance literature:

With sodium hydroxide; In ethanol; water; at 110 ℃; for 5h;

DOI:10.1002/anie.201804794

Reference yield: 99.0%

methyl 2-(2-fluoro-4-biphenylyl)propionate (113544-38-0,113544-39-1,114376-61-3,66202-86-6) → fluorobiprofen (5104-49-4)

Guidance literature:

With sulfuric acid; water; In 1,4-dioxane; at 120 ℃; for 4h; Inert atmosphere;

DOI:10.1016/j.chempr.2019.07.023

Reference yield: 99.0%

C12H16FNO5S (1201594-47-9) + phenylboronic acid (98-80-6) → fluorobiprofen (5104-49-4)

Guidance literature:

C₁₂H₁₆FNO₅S; phenylboronic acid; With potassium phosphate; bis(tricyclohexylphosphine)nickel(II) dichloride; In toluene; at 130 ℃; for 24h; Inert atmosphere;

With sulfuric acid; In 1,4-dioxane; water; at 100 ℃; for 6h;

DOI:10.1021/ja906477r

upstream raw materials:

diphenyl N-<2-(2-fluoro-4-biphenylyl)-1-pyrrolidinopropylidene>phosphoramidate

3-(2-fluorobiphenyl-4-yl)butan-2-one

2-(2-Fluoro-biphenyl-4-yl)-N,N-dimethyl-propionamide

methyl 2-(2-fluoro-4-biphenylyl)propionate

Downstream raw materials:

(S)-(+)-flurbiprofen

(R)-flurbiprofen

methyl 2-(2-fluoro-biphenyl-4-yl)propionate

methyl 2-(2-fluoro-biphenyl-4-yl)propionate

Refernces

• 1、 Uekama,Imai,Maeda,Irie,Hirayama,Otagiri. "Improvement of dissolution and suppository release characteristics of flurbiprofen by inclusion complexation with heptakis(2,6-di-O-methyl)-β-cyclodextrin". . p. 841 - 845. Retrieved 1985.
• 2、 Tamborini, Lucia,Romano, Diego,Pinto, Andrea,Bertolani, Arianna,Molinari, Francesco,Conti, Paola. "An efficient method for the lipase-catalysed resolution and in-line purification of racemic flurbiprofen in a continuous-flow reactor". . p. 78 - 82. Retrieved 2012.
• 3、 Spizzo, Patrizia,Basso, Alessandra,Ebert, Cynthia,Gardossi, Lucia,Ferrario, Valerio,Romano, Diego,Molinari, Francesco. "Resolution of (R,S)-flurbiprofen catalysed by dry mycelia in organic solvent". . p. 11005 - 11010. Retrieved 2007.
• 4、 Chen, Zhi,Zhang, Wei,Wang, Liping,Fan, Huajun,Wan, Qiang,Wu, Xuehao,Tang, Xunyou,Tang, James Z.. "Enantioseparation of Racemic Flurbiprofen by Aqueous Two-Phase Extraction With Binary Chiral Selectors of L-dioctyl Tartrate and L-tryptophan". . p. 650 - 657. Retrieved 2015.
• 5、 Cai, Liangzhao,Guo, Xingjie,Liu, Beibei,Sun, Jiayi,Yu, Jia. "Chiral liquid chromatography-mass spectrometry (LC-MS/MS) method development with β-cyclodextrin (β-CD) derivatized chiral stationary phase for the enhanced separation and determination of flurbiprofen enantiomers: Application to a stereoselective pharmacokinetic study". . p. 10334 - 10342. Retrieved 2020.
• 6、 Chen, Hua,Dai, Yuhao,Liu, Yu,Luo, Kaihong,Zhang, Yi. "An efficient method for the synthesis of (S)-flurbiprofen by 1,2-rearrangement of the aryl group". . . Retrieved 2022/03/15.
• 7、 Chen, Shuming,Gao, Anthony Z.,Ivlev, Sergei I.,Meggers, Eric,Nie, Xin,Ye, Chen-Xi,Zhang, Chenhao. "Catalytic α-Deracemization of Ketones Enabled by Photoredox Deprotonation and Enantioselective Protonation". supporting information. p. 13393 - 13400. Retrieved 2021/09/03.