51543-39-6

Basic information

• Product Name: (S)-(+)-2-FLUORO-ALPHA-METHYL-4-BIPHENYLACETIC ACID
• Synonyms: (S)-(+)-FLURBIPROFEN;(S)-FLURBIPROFEN;(S)-(+)-2-FLUORO-ALPHA-METHYL-4-BIPHENYLACETIC ACID;Esflurbiprofen;(S)-2-fluoro-alpha-methyl[1,1'-biphenyl]-4-acetic acid;(S)-(+)-2-Fluoro-α-methyl-4-biphenylacetic acid;[1,1'-Biphenyl]-4-acetic acid, 2-fluoro-α-methyl-, (S)-;[1,1'-Biphenyl]-4-acetic acid, 2-fluoro-α-methyl-, (αS)-
• CAS NO: 51543-39-6
• Molecular Formula: C₁₅H₁₃FO₂
• Molecular Weight: 244.26
• EINECS: 257-263-1
• Mol File: 51543-39-6.mol
• Article Data: 72

Chemical Properties

• Melting Point: 109-110 °C(lit.)
• Boiling Point: 376.2 °C at 760 mmHg
• Flash Point: 181.3 °C
• Appearance: White to yellowish crystalline powder
• Density: 1.199 g/cm³
• Vapor Pressure: 2.5E-06mmHg at 25°C
• Refractive Index: 1.567
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: insoluble in H2O; ≥10.9 mg/mL in DMSO; ≥69.1 mg/mL in EtOH
• PKA: 4.14±0.10(Predicted)
• CAS DataBase Reference: (S)-(+)-2-FLUORO-ALPHA-METHYL-4-BIPHENYLACETIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(+)-2-FLUORO-ALPHA-METHYL-4-BIPHENYLACETIC ACID(51543-39-6)
• EPA Substance Registry System: (S)-(+)-2-FLUORO-ALPHA-METHYL-4-BIPHENYLACETIC ACID(51543-39-6)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 36/37/39-45
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• Hazardous Substances Data: 51543-39-6(Hazardous Substances Data)

Usage

Description

(S)-(+)-2-FLUORO-ALPHA-METHYL-4-BIPHENYLACETIC ACID, also known as (S)-Flurbiprofen, is a chiral molecule that is the S-enantiomer of Flurbiprofen. It is a nonsteroidal anti-inflammatory drug (NSAID) that selectively inhibits cyclooxygenase (COX) enzymes, which play a crucial role in the production of prostaglandins, leading to its anti-inflammatory and analgesic effects. (S)-(+)-2-FLUORO-ALPHA-METHYL-4-BIPHENYLACETIC ACID has been synthesized and studied for its potential therapeutic applications, particularly in the treatment of osteoarthritis.

Uses

Used in Pharmaceutical Industry:
(S)-(+)-2-FLUORO-ALPHA-METHYL-4-BIPHENYLACETIC ACID is used as an anti-inflammatory and analgesic agent for the treatment of osteoarthritis. It works by inhibiting the COX enzymes, which are responsible for the production of prostaglandins that cause inflammation and pain. (S)-(+)-2-FLUORO-ALPHA-METHYL-4-BIPHENYLACETIC ACID has been formulated with mentha oil and administered through a patch, providing a targeted and efficient method of delivery.
Used in Research and Development:
(S)-Flurbiprofen is used as a research compound for studying the effects of COX inhibition on various biological processes and diseases. Its selective inhibition of COX-1 and COX-2 enzymes makes it a valuable tool for understanding the role of these enzymes in inflammation, pain, and other conditions. Additionally, the compound's chiral nature allows for the investigation of the differences in biological activity between the Sand R-enantiomers, which can lead to the development of more effective and safer drugs.
Used in Drug Synthesis:
The synthetic approaches to (S)-Flurbiprofen have been reported in the chemical literature, and the compound has been approved as a drug by regulatory agencies such as the FDA and PMDA. This makes it an important compound in the field of drug synthesis, as it can be used as a starting material or a reference for the development of new NSAIDs with improved efficacy and reduced side effects.

Synthesis

The synthesis began with conversion of commercially available aniline 168 to racemic flurbiprofen (169) through a Sandmeyer reaction and subsequent phenyl group introduction through the use of sodium tetraphenylborate. A chiral resolution was then performed on the resulting stereogenic acid on multikilogram scale by treatment with (S)- 1-phenylethylamine in MeOH/toluene, which gave various yields of salt 170 as reported by the authors. Acidification with aqueous HCl delivered (S)-flurbiprofen (XXI). Importantly, with respect to green chemistry considerations, the (R)- enantiomer could be recycled by racemizing the undesired (R)- enantiomer 171 in refluxing methanolic sulfuric acid, improving the overall atom economy of the process and significantly reducing waste.

in vitro

it was found that the ic50 value of (s)-flurbiprofen was about 0.5 μm for both cox-1 and cox-2 in guinea pig whole blood [1].

in vivo

the efficacy of multiple applications of s(+)-flurbiprofen plaster (sfpp) was evaluated for the alleviation of inflammatory pain and edema in rat adjuvant-induced arthritis model. multiple applications of sfpp could exert a significant analgesic effect from the first day of application as compared to the other nsaid drugs. in terms of paw edema, sfpp could decrease edema from the second day after application. moreover, multiple applications of sfpp were found to be superior to those of other nsaid drugs in terms of the analgesic effect [2].

IC 50

0.5 μm for both cox-1 and cox-2 in guinea pig whole blood

references

[1] barnett, j. ,chow, j.,ives, d., et al. purification, characterization and selective inhibition of human prostaglandin g/h synthase 1 and 2 expressed in the baculovirus system. biochimica et biophysica acta 1209, 130-139 (1994).[2] sugimoto m et al. topical anti-inflammatory and analgesic effects of multiple applications of s(+)-flurbiprofen plaster (sfpp) in a rat adjuvant-induced arthritis model. drug dev res. 2016 jun;77(4):206-11. [3] yataba i, otsuka n, matsushita i, matsumoto h, hoshino y. the efficacy and safety of s-flurbiprofen plaster in the treatment of knee osteoarthritis: a phase ii, randomized, double-blind, placebo-controlled, dose-finding study. j pain res. 2017 apr 11;10:867-880.

InChI:InChI=1/C15H13FO2/c1-10(15(17)18)12-7-8-13(14(16)9-12)11-5-3-2-4-6-11/h2-10H,1H3,(H,17,18)/t10-/m0/s1

Upstream product

• 189130-24-3 (2S)-2-(2-fluoro-biphenyl-4-yl)-propan-1-ol 
• 111-87-5 octanol 
• 5104-49-4 fluorobiprofen 
• 64-17-5 ethanol 
• 189076-03-7 (S)-2-(2-Fluoro-biphenyl-4-yl)-2-methyl-oxirane 
• 137361-33-2 α-Methyl-3-fluoro-4-phenylbenzeneacetyl chloride 
• 133628-14-5 (S)-2-(3-fluoro-4-phenyl)phenylpropionaldehyde 
• 90500-55-3 (±)-methyl 2-(4-amino-3-fluorophenyl)propanoate 
• 749917-25-7 2-(3-fluoro-4-iodophenyl)propionic acid 
• 113544-32-4 (R)-3-O-(2-(2-fluoro-4-biphenyl)propionyl)-1,2-O-isopropylidene-α-D-glucofuranose 
• 113544-38-0 methyl 2-(2-fluoro-4-biphenylyl)propionate 
• 67-56-1 methanol 
• 621-76-1 tripropyl orthoformate 
• 113544-32-4 (S)-3-O-(2-(2-fluoro-4-biphenyl)propionyl)-1,2-O-isopropylidene-α-D-glucofuranose 

Downstream Products

• 5104-49-4 fluorobiprofen 
• 5104-49-4 (R)-flurbiprofen 
• 5104-49-4 (S)-(+)-flurbiprofen 
• 1130608-93-3 (R)-2-(2-fluoro-biphenyl-4-yl)-N-(3-{3-[4-(3-{3-[2-(2-fluoro-biphenyl-4-yl)-(R)-propionylamino]-propylamino}-propylamino)-3,6-dioxo-cyclohexa-1,4-dienylamino]-propylamino}-propyl)-propionamide 

Relevant articles and documents

An efficient method for the synthesis of (S)-flurbiprofen by 1,2-rearrangement of the aryl group

(S)-Flurbiprofen (1) is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve pain and inflammation associated with osteoarthritis. Herein a new and practical method for the preparation of 1 from 4-bromo-2-fluorobiphenyl (2) is reported, which achieves a good overall yield (20%) and high enantioselectivity (96%). This method avoids the use of expensive catalysts and affords the possibility of large-scale manufacturing with simple operations.

Enantioselective Synthesis of Chiral Carboxylic Acids from Alkynes and Formic Acid by Nickel-Catalyzed Cascade Reactions: Facile Synthesis of Profens

We report a stereoselective conversion of terminal alkynes to α-chiral carboxylic acids using a nickel-catalyzed domino hydrocarboxylation-transfer hydrogenation reaction. A simple nickel/BenzP* catalyst displayed high activity in both steps of regioselective hydrocarboxylation of alkynes and subsequent asymmetric transfer hydrogenation. The reaction was successfully applied in enantioselective preparation of three nonsteroidal anti-inflammatory profens (>90 % ees) and the chiral fragment of AZD2716.

Synthesis of a TNF inhibitor, flurbiprofen and an: I -Pr analogue in enantioenriched forms by copper-catalyzed propargylic substitution with Grignard reagents

The copper-catalyzed substitution reaction of diethyl phosphate derived from TMSCCCH(OH)CH2CH2OTBDPS with 3-c-C5H9-4-MeOC6H3MgBr, followed by several transformations, afforded a tumor necrosis factor inhibitor possessing a Ph-acetylene moiety. The inhibitor was also synthesized from phenylacetylene phosphate PhCCCH(OP(O)(OEt)2)CH2CH2OTBDPS. Furthermore, the substitution of phosphates derived from TMSCCCH(OH)CH3 and TMSCCCH(OH)-i-Pr with 3-F-4-PhC6H3MgBr gave the corresponding substitution products, which were transformed to flurbiprofen and its i-Pr analogue, respectively. The copper-catalyzed substitutions in these syntheses proceeded in a regio- and stereoselective manner. This journal is