51146-56-6

Basic information

• Product Name: (S)-(+)-Ibuprofen
• Synonyms: (2s)-2-[4-(2-methylpropyl)phenyl]propionic acid;DEXIBUPROFEN;(S)-(+)-2-(4-ISOBUTYLPHENYL)PROPIONIC ACID;(S)-(+)-4-ISOBUTYL-ALPHA-METHYLPHENYLACETIC ACID;(S)-(+)-IBUPROFEN;(S)-IBUPROFEN;s(+)-2-(4-isobutylphenyl)propionic;S(+)-IBUPROFEN ACTIVE ISOMER OF IBUP
• CAS NO: 51146-56-6
• Molecular Formula: C₁₃H₁₈O₂
• Molecular Weight: 206.28
• EINECS: 1308068-626-2
• Product Categories: Chiral Reagents;Chiral Compound;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;AMIDATE
• Mol File: 51146-56-6.mol
• Article Data: 157

Chemical Properties

• Melting Point: 49-53 °C(lit.)
• Boiling Point: 285.14°C (rough estimate)
• Flash Point: >230 °F
• Appearance: white/solid
• Density: 1.0364 (rough estimate)
• Vapor Pressure: 0.000139mmHg at 25°C
• Refractive Index: 59 ° (C=2, EtOH)
• Storage Temp.: Store at RT
• Solubility: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: 1.5 mg/mL
• PKA: 4.41±0.10(Predicted)
• Water Solubility: insoluble
• Stability: Stable. Incompatible with strong oxidizing agents.
• BRN: 3590022
• CAS DataBase Reference: (S)-(+)-Ibuprofen(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(+)-Ibuprofen(51146-56-6)
• EPA Substance Registry System: (S)-(+)-Ibuprofen(51146-56-6)

Safety Data

• Hazard Codes: Xn
• Statements: 63-22
• Safety Statements: 45-36/37
• WGK Germany: 3
• Hazardous Substances Data: 51146-56-6(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 51146-56-6 differently. You can refer to the following data:
1. Dexibuprofen, the S-(+)-isomer of the widely used NSAID agent ibuprofen, was launched in Austria for the treatment of rheumatoid arthritis. While the racemic compound is commonly used clinically, the antiinflammatory activity is mediated via the S-isomer by inhibition of prostaglandin synthesis. It has also been demonstrated that the R-isomer is converted to the Santipode in vivo via a CoA thioester intermediate. Since CoA plays a pivotal role in intermediary metabolism and maintenance of the [acyl-CoA], generation of R-ibuprofen-CoA competitively inhibits many CoA-dependent reactions, which consequently produces perturbations of hepatocyte Intermediary metabolism and mitocondrial function. Pure S-ibuprofen usage, therefore, is preferred allowing a reduction in dosage level and an improved side effect profile.
2. Ibuprofen is a non-steroidal anti-inflammatory drug with diverse biochemical actions, most notably inhibiting COX-1 and COX-2 (IC50s = 2.6 and 1.53, μM, respectively). It is commonly synthesized as a racemic mixture of (S)- and (R)-isomers. (S)-Ibuprofen is an enantiomer that more potently inhibits COX activity, thromboxane formation, and platelet aggregation than the (R)-form. (S)-Ibuprofen also inhibits activation of NF-κB more effectively than (R)-ibuprofen (IC50s = 62 and 122 μM, respectively). However, the enantiomers are equipotent in blocking superoxide formation, β-glucuronidase release, and LTB4 generation by stimulated neutrophils (IC50 values range from 0.14 to 0.58 μM). A majority of (R)-ibuprofen can be inverted to (S)-ibuprofen in humans after oral administration.

Originator

Gebro Broschek (Austria)

Uses

Different sources of media describe the Uses of 51146-56-6 differently. You can refer to the following data:
1. A nonsteroidal anti-inflammatory drug (NSAID); activity resides primarily in the (S)-isomer
2. Ibuprofen is a non-steroidal anti-inflammatory drug with diverse biochemical actions, most notably inhibiting COX-1 and COX-2 (IC50s = 2.6 and 1.53, μM, respectively). It is commonly synthesized as a racemic mixture of (S)- and (R)-isomers. (S)-Ibuprofen is an enantiomer that more potently inhibits COX activity, thromboxane formation, and platelet aggregation than the (R)-form. (S)-Ibuprofen also inhibits activation of NF-κB more effectively than (R)-ibuprofen (IC50s = 62 and 122 μM, respectively). However, the enantiomers are equipotent in blocking superoxide formation, β-glucuronidase release, and LTB4 generation by stimulated neutrophils (IC50 values range from 0.14 to 0.58 μM). A majority of (R)-ibuprofen can be inverted to (S)-ibuprofen in humans after oral administration.

Brand name

Seractil

General Description

(S)-(+)-Ibuprofen is the enantiomer associated with the anti-inflammatory action of ibuprofen, which is widely used as a nonsteroidal anti-inflammatory drug in racemic form.

Biological Activity

Non-steroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase 1 and cyclooxygenase 2 (IC 50 values are 12 and 80 μ M respectively). Active isomer of ibuprofen.

Clinical Use

NSAID and analgesic

Drug interactions

Potentially hazardous interactions with other drugsACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect, increased risk of nephrotoxicity and hyperkalaemia.Analgesics: avoid concomitant use of 2 or more NSAIDs, including aspirin (increased side effects); avoid with ketorolac (increased risk of 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 heparins, dabigatran and edoxaban - avoid long term use with edoxaban.Antidepressants: increased risk of bleeding with SSRIs and venlaflaxine.Antidiabetic agents: effects of sulphonylureas enhanced.Antiepileptics: possibly increased phenytoin concentration.Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavirCiclosporin: may potentiate nephrotoxicityCytotoxics: reduced excretion of methotrexate; increased risk of bleeding with erlotinibDiuretics: increased risk of nephrotoxicity; antagonism of diuretic effect; hyperkalaemia with potassium-sparing diuretics.Lithium: excretion decreased.Pentoxifylline: increased risk of bleeding.Tacrolimus: increased risk of nephrotoxicity

Metabolism

Dexibuprofen is the S(+)-enantiomer of ibuprofen. After metabolic transformation in the liver (hydroxylation and carboxylation), the pharmacologically inactive metabolites are completely excreted, mainly by the kidneys (90%), but also in the bile.

Purification Methods

Crystallise the (+) and (-) acids from EtOH or aqueous EtOH. The racemate which crystallises from pet ether with m 75-77o is sparingly soluble in H2O and has IR (film) 1705 (C=O), 2300—3700 (OH broad)cm-1. It is used as a non-steroidal anti-inflammatory. [Shiori et al. J Org Chem 43 2936 1978, Kaiser et al. J Pharm Sci 65 269 1976, J Pharm Sci 81 221 1992, Freer Acta Cryst (C) 49 1378 1993 for the (S+)-enantiomer.]

InChI:InChI=1/C13H18O2/c1-9(2)8-11-4-6-12(7-5-11)10(3)13(14)15/h4-7,9-10H,8H2,1-3H3,(H,14,15)/t10-/m0/s1

Upstream product

• 593-60-2 Vinyl bromide 
• 125231-12-1 1-(4-isobutylphenyl)ethylzinc bromide 
• 201230-82-2 carbon monoxide 
• 63444-56-4 p-isobutylstyrene 
• 41283-72-1 ibuprofen ethyl ester 
• 15687-27-1 ibuprofen 
• 61566-34-5 (+/-)-ibuprofen methyl ester 
• 58609-73-7 2-(4-isobutylphenyl)propanenitrile 
• 85711-18-8 1-isobutyl-4-[(R)-1-methylallyl]benzene 
• 85711-17-7 1-isobutyl-4-[(S)-1-methylallyl]benzene 
• 113544-36-8 (S)-2-(4-Isobutyl-phenyl)-propionic acid (3aR,5R,6S,6aR)-5-(1,2-dihydroxy-ethyl)-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-6-yl ester 
• 123054-56-8 2-(4-Isobutyl-phenyl)-propionic acid (S)-1,2-dimethyl-propyl ester 
• 123054-49-9 2-(4-Isobutyl-phenyl)-propionic acid (R)-methoxycarbonyl-phenyl-methyl ester 
• 123054-48-8 2-(4-Isobutyl-phenyl)-propionic acid (R)-cyclohexyl-methoxycarbonyl-methyl ester 

Downstream Products

• 121734-80-3 (S)-2-(4-Isobutyl-phenyl)-N-((S)-1-phenyl-ethyl)-propionamide 
• 81576-55-8 (S)-(+)-methyl 2-(4-isobutylphenyl)propionate 
• 15687-27-1 ibuprofen 
• 114937-30-3 (2S)-2-<4-(2-Methylpropyl)phenyl>propan-1-ol 
• 278184-66-0 2,5-dioxopyrrolidin-1-yl (S)-2-(4-isobutylphenyl)propanoate 
• 115588-20-0 (2S)-2-(4-isobutylphenyl)-propionyl chloride 
• 266359-83-5 reparixin 
• 824432-34-0 (S)-8-bromo-n-octyl α-methyl-2-(4-[2-methylpropyl]benzene)acetate 
• 925681-77-2 (S)-4-isobutyl-α-methylphenylacetic acid 2-oxo-1,2,2-triphenylethyl ester 

Relevant articles and documents

High pressure CO2-controlled reactors: Enzymatic chiral resolution in emulsions

In this work we have reported the formulation of a CO2-based micelle stabilized by nontoxic TMN series surfactants. Enantioselection of racemic ibuprofen catalyzed by Candida antarctica lipase B (CALB) was used as a model reaction. The effect of reactive parameters, such as temperature, pH, pressure, and water content on reactive environment and conversion has been discussed. For the resolution of racemic ibuprofen in CO2-based micelles, the enzymatic activity reached a high level at 45 °C, with pressure 250 bar, pH 7.4, and water to surfactant ratio W0 25. In addition, the relatively long-chain length in TMN-10 could help the esterification and trans-esterification processes, which resulted in an efficient reaction rate in a CO2-based micelle system. Enzymatic catalysis has been conducted in a CO2-based system rather than in the conventional media to make the enzyme reaction greener. The better resolution efficiency in high pressure CO2-based micelles could be achieved within a relatively short period of time compared with other traditional reactive systems. The Royal Society of Chemistry 2014.

Enantioselective analysis of ibuprofen enantiomers in mice plasma and tissues by high-performance liquid chromatography with fluorescence detection: Application to a pharmacokinetic study

A direct fluorometric high-performance liquid chromatography (HPLC) method was developed and validated for the analysis of ibuprofen enantiomers in mouse plasma (100?μl) and tissues (brain, liver, kidneys) using liquid–liquid extraction and 4-tertbutylphenoxyacetic acid as an internal standard. Separation of enantiomers was accomplished in a Chiracel OJ-H chiral column based on cellulose tris(4-methylbenzoate) coated on 5?μm silica-gel, 250 x 4.6?mm at 22?°C with a mobile phase composed of n-hexane, 2-propanol, and trifluoroacetic acid that were delivered in gradient elution at a flow rate of 1?ml min?1. A fluorometric detector was set at: λexcit. = 220?nm and λemis. = 290?nm. Method validation included the evaluation of the selectivity, linearity, lower limit of quantification (LLOQ), within-run and between-run precision and accuracy. The LLOQ for the two enantiomers was 0.125 μg ml?1 in plasma, 0.09?μg g?1 in brain, and 0.25?μg g?1 in for liver and kidney homogenates. The calibration curves showed good linearity in the ranges of each enantiomers: from 0.125 to 35?μg ml?1 for plasma, 0.09–1.44?μg g?1 for brain, and 0.25–20?μg g?1 for liver and kidney homogenates. The method was successfully applied to a pharmacokinetic study of ibuprofen enantiomers in mice treated i.v. with 10?mg kg?1 of racemate.

Enzymatic hydrolytic resolution of racemic ibuprofen ethyl ester using an ionic liquid as cosolvent

The aim of this study was to develop an ionic liquid (IL) system for the enzymatic resolution of racemic ibuprofen ethyl ester to produce (S)-ibuprofen. Nineteen ILs were selected for use in buffer systems to investigate the effects of ILs as cosolvents for the production of (S)-ibuprofen using thermostable esterase (EST10) from Thermotoga maritima. Analysis of the catalytic efficiency and conformation of EST10 showed that [OmPy][BF4] was the best medium for the EST10-catalyzed production of (S)-ibuprofen. The maximum degree of conversion degree (47.4%), enantiomeric excess of (S)-ibuprofen (96.6%) and enantiomeric ratio of EST10 (177.0) were achieved with an EST10 concentration of 15 mg/mL, racemic ibuprofen ethyl ester concentration of 150 mM, at 75°C, with a reaction time of 10 h. The reaction time needed to achieve the highest yield of (S)-ibuprofen was decreased from 24 h to 10 h. These results are relevant to the proposed application of ILs as solvents for the EST10-catalyzed production of (S)-ibuprofen.

Resolution of (R,S)-ibuprofen catalyzed by immobilized Novozym40086 in organic phase

The enantioselective esterification of ibuprofen catalyzed by Novozym40086 was successfully conducted in organic solvent. Removing-water reagent was added into the reaction mixture to remove water produced in the esterification. The effects of temperature, n-hexanol concentration, ibuprofen concentration, and loading of enzymes were investigated. Under the condition of equilibrium, the thermodynamic equilibrium constant (K) of 7.697 and enantioselectivity (E) of 8.512 were obtained. The esterification reaction achieved its equilibrium in approximately 30?hours with conversion of 56% and eeS of 93.78%. The predicted values of X and eeS were 67.90% and 95.60%, respectively. The experimental value is approximately equal to the theoretical value, which indicates the feasibility of ideal models.

Facile conversion of racemic ibuprofen to (S)-ibuprofen

The methyl ester of ibuprofen was quantitatively formed by Fischer esterification and converted into (S)-ibuprofen in 94% yield with an ee of 94% under dynamic kinetic resolution conditions at pH 9.8, using Candida rugosa lipase, and 20% DMSO. The (R)-methyl ibuprofen ester was observed to racemize by chiral HPLC without the Candida rugosa lipase present. The rates of in situ racemization and enzymatic hydrolysis for the dynamic kinetic resolution were determined to be 0.026 ± 0.004 and 0.053 ± 0.004 h-1, respectively. The rate of enzymatic hydrolysis when no DMSO was present was twice as fast but no racemization occurred. A facile purification of enriched (S)-ibuprofen was developed. Overall, 88% of racemic ibuprofen by weight was converted into (S)-ibuprofen with an ee of 99.7%.

A novel system consisting of easily recyclable dendritic Ru-BINAP catalyst for asymmetric hydrogenation

Dendritic Ru-BINAP catalysts functionalized with alkyl chain at the periphery together with organic binary solvent system that exhibited phase separation induced by addition of a little water have been employed for asymmetric hydrogenation, leading to high catalytic activity and en-antioselectivity as well as facile catalyst recycling.

Reshaping the active pocket of esterase Est816 for resolution of economically important racemates

Bacterial esterases are potential biocatalysts for the production of optically pure compounds. However, the substrate promiscuity and chiral selectivity of esterases usually have a negative correlation, which limits their commercial value. Herein, an efficient and versatile esterase (Est816) was identified as a promising catalyst for the hydrolysis of a wide range of economically important substrates with low enantioselectivity. We rationally designed several variants with up to 11-fold increased catalytic efficiency towards ethyl 2-arylpropionates, mostly retaining the initial substrate scope and enantioselectivity. These variants provided a dramatic increase in efficiency for biocatalytic applications. Based on the best variant Est816-M1, several variants with higher or inverted enantioselectivity were designed through careful analysis of the structural information and molecular docking. Two stereoselectively complementary mutants, Est816-M3 and Est816-M4, successfully overcame and even reversed the low enantioselectivity, and several 2-arylpropionic acid derivatives with highEvalues were obtained. Our results offer potential industrial biocatalysts for the preparation of structurally diverse chiral carboxylic acids and further lay the foundation for improving the catalytic efficiency and enantioselectivity of esterases.

2,2′-Bipyridine-α,α′-trifluoromethyl-diol ligand: Synthesis and application in the asymmetric Et2Zn alkylation of aldehydes

A chiral 2,2′-bipyridine ligand (1) bearing α,α′-trifluoromethyl-alcohols at 6,6′-positions was designed in five steps affording either the R,R or S,S enantiomer with excellent stereoselectivities, i.e. 97% de, >99% ee and >99.5% de, >99.5% ee, respectively. The key step for reaching high levels of stereoselectivity was demonstrated to be the resolution of the α-CF3-alcohol using (S)-ibuprofen as the resolving agent. An initial application for the 2,2′-bipyridine-α,α′-CF3-diol ligand was highlighted in the ZnII-catalyzed asymmetric ethylation reaction of aromatic, heteroaromatic, and aliphatic aldehydes. Synergistic electron deficiency and steric hindrance properties of the newly developed ligand afforded the corresponding alcohols in good to excellent yields (up to 99%) and enantioselectivities (up to 95% ee). As observed from single crystal diffraction analysis, the complexation of the 2,2′-bipyridine-α,α′-CF3-diol ligand generates an unusual hexacoordinated ZnII.