2-[4-(2-methylpropyl)phenyl]propanoic acid

• ChemBase ID: 922
• Molecular Formular: C13H18O2
• Molecular Mass: 206.28082
• Monoisotopic Mass: 206.13067982
• SMILES: OC(=O)C(c1ccc(CC(C)C)cc1)C
• Canonical SMILES: CC(Cc1ccc(cc1)C(C(=O)O)C)C
• InChI: InChI=1S/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)
• InChIKey: HEFNNWSXXWATRW-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[4-(2-methylpropyl)phenyl]propanoic acid
• IUPAC Traditional name: ibuprofen; 2-[4-(2-methylpropyl)phenyl]propanoic acid; ibuprofen, (+-)-
• Brand Name: Actiprofen; Adran; Advil; Advil Liqui-Gels; Amersol; Amibufen; Anco; Andran; Anflagen; Apo-Ibuprofen; Apsifen; Apsifen-F; Artril 300; Bluton; Brufanic; Brufen; Brufort; Buburone; Butylenin; Cap-Profen; Children's Advil; Children's Elixsure; Children's Ibuprofen; Children's Motrin; Codral; Dolgin; Dolgirid; Dolgit; Dolo-Dolgit; Dolocyl; Ebufac; Epobron; Femadon; Fenbid Spansule; Haltran; Ibu; Ibu-Attritin; Ibu-Slo; Ibu-Tab; Ibu-Tab 200; Ibufen; Ibumetin; Ibuprin; Ibuprocin; Ibuprohm; Ibutid; Ifen; Inabrin; Inoven; Junior Strength Advil; Junior Strength Ibuprofen; Junior Strength Motrin; Lamidon; Lebrufen; Lidifen; Liptan; Medipren; Midol; Midol 200; Motrin; Mynosedin; Napacetin; Nobfelon; Nobfen; Nobgen; Novogent N; Novoprofen; Nuprin; Nurofen; Pantrop; Paxofen; Pedia-Profen; Pediaprofen; Pediatric Advil; Profen; Rafen; Rebugen; Roidenin; Rufen; Seclodin; Suspren; Tab-Profen; Tabalon; Trendar; Urem; NeoProfen
• Synonyms: P-Isobutylhydratropic Acid; Para-Isobutylhydratropic Acid; Ibuprophen; Ibuprofen; α-Methyl-4-(isobutyl)phenylacetic acid; (±)-2-(4-Isobutylphenyl)propanoic acid; Ibuprofen; 2-[4-(2-methylpropyl)phenyl]propanoic acid; 2-(4-Isobutylphenyl)propanoic acid; Genpril; Brufen; Nurofen; Motrin; Ibren; Ibup; α-Methyl-4-[2-methylpropyl] benzeneacetic Acid; IBUPROFEN USP GRADE; Apsifen; Codafen; Ebufac; Femafen; Proflex; Lidifen; Lobufen; Paxofen; 2-(4-Isobutylphenyl)propionic Acid; rac Ibuprofen; Ibuprofen; 4-Isobutyl-alpha-methylphenylacetic acid; α-甲基-4-(异丁基)苯乙酸; (±)-2-(4-异丁基苯基)丙酸; 布洛芬; 4-异丁基-α-甲基苯基乙酸

Database IDs

• CAS Number: 58560-75-1; 15687-27-1
• EC Number: 239-784-6
• MDL Number: MFCD00010393
• Merck Index: 144881
• PubChem SID: 46507255; 24277715; 160964385; 24896130
• PubChem CID: 3672

CALCULATED PROPERTIES

JChem

• Acid pKa: 4.851939
• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 3.1079764
• LogD (pH = 7.4): 1.3373861
• Log P: 3.8435583
• Molar Refractivity: 60.7319 cm^3
• Polarizability: 23.648134 Å^3
• Polar Surface Area: 37.3 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.5
• LOG S: -3.48
• Solubility (Water): 6.84e-02 g/l

PROPERTIES

Physical Property

• Solubility: 0.049 mg/ml; Dichloromethane; Ether; Ethyl Acetate; Methanol
• Apperance: White Solid; white to off-white
• Melting Point: 75 - 77.5 °C; 75-77°C; 75-78°C; 77 - 78°C
• Boiling Point: 157°C/4mm
• Density: .2 - .6 g/cm^3 (bulk density)
• Vapor Pressure: .000012 hPa at 25 °C
• Hydrophobicity(logP): 3.6; 3.679

Safety Information

• Storage Condition: -20°C; -20°C Freezer; Room Temperature (15-30°C)
• Storage Warning: IRRITANT
• RTECS: MU6640000
• European Hazard Symbols: Nature polluting (N); X; Harmful (Xn)
• UN Number: UN3077
• German water hazard class: 3
• Hazard Class: 9
• Packing Group: III
• Risk Statements: 22; 22-51/53-63; R:22
• Safety Statements: 36; 36/37-61; S:36/37/39
• TSCA Listed: false; 是
• GHS Pictograms: GHS06; GHS07; GHS08; GHS09
• GHS Signal Word: Warning
• GHS Hazard statements: H301-H361-H411-H401; H302
• GHS Precautionary statements: P281-P273-P301+P310-P321-P405-P501A
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves

Pharmacology Properties

• Gene Information: human ... ALB(213), ALOX5(240), CYP1A2(1544), CYP2C9(1559), IL8RA(3577), PTGS1(5742), PTGS2(5743)mouse ... Alox5(11689)rat ... Alox5(25290), Ptgs1(24693)
• Mechanism of Action: Cyclooxygenase (COX) inhibitor; Prostaglandin antagonist

Product Information

• Purity: ≥98% (GC); ≥98% (HPLC); 95%; 98%; 99%
• Grade: USP; VETRANAL™, analytical standard
• Salt Data: Free Base
• Suitability: meets USP testing specifications; suitable for 1694 per US EPA
• Application(s): Analgesic; Antipyretic; Non-steroidal antiinflammatory agent
• Pharmacopeia Traceability: traceable to BP 539; traceable to PhEur I0020000; traceable to USP 1335508
• Empirical Formula (Hill Notation): C13H18O2

DETAILS

MP Biomedicals - 02190216

Crystalline
An anti-inflammatory and analgesic. Also inhibits cyclooxygenase, PGH synthase-1 and PGH synthase -2.

DrugBank - DB01050

• Drug Groups: approved
• Description: Ibuprofen, a propionic acid derivative, is a prototypical nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties.
• Indication: For symptomatic treatment of rheumatoid arthritis, juvenile rheumatoid arthritis and osteoarthritis. May be used to treat mild to moderate pain and for the management of dysmenorrhea. May be used to reduce fever. Has been used with some success for treating ankylosing spondylitis, gout and psoriatic arthritis. May reduce pain, fever and inflammation of pericarditis. May be used IV with opiates to relieve moderate to severe pain. Ibuprofen lysine may be used IV to treat patent ductus arteriosus (PDA) in premature neonates.
• Pharmacology: Ibuprofen is a nonsteroidal anti-inflammatory agent (NSAIA) or nonsteroidal anti-inflammatory drug (NSAID), with analgesic and antipyretic properties. Ibuprofen has pharmacologic actions similar to those of other prototypical NSAIAs, which are thought to act through inhibition of prostaglandin synthesis.
• Toxicity:

  Side effects: May cause peripheral edema and fluid retention. Use caution in patients with congestive heart failure or severe uncontrolled hypertension. May cause dyspepsia, heartburn, nausea, vomiting, anorexia, diarrhea, constipation, stomatitis, flatulence, bloating, epigastric pain, and abdominal pain. Peptic ulcer and GI bleeding have been reported. May also cause dizziness, headache and nervousness. Acute renal failure accompanied by acute tubular necrosis has been reported. ;

  Most common symptoms of overdose are abdominal pain, nausea, vomiting, lethargy, vertigo, drowsiness (somnolence), dizziness and insomnia. Other symptoms of overdose include headache, loss of consciousness, tinnitus, CNS depression, convulsions and seizures. May rarely cause metabolic acidosis, abnormal hepatic function, hyperkalemia, renal failure, dyspnea, respiratory depression, coma, acute renal failure, and apnea (primarily in very young pediatric patients).

  ;

  LD₅₀=1255mg/kg(orally in mice)

• Affected Organisms: Humans and other mammals
• Biotransformation: R-enanatiomer undergoes extensive enantiomeric conversion (53-65%) to the more active S-enantiomer in vivo. Metablized by oxidation to 2 inactive metabolites: (+)-2[4′-(2-hydroxy-2-methylpropyl)phenyl]propionic acid and (+)-2-[4′-(2-carboxypropyl)phenyl]propionic acid. Very small amounts of 1-hydroxyibuprofen and 3-hydroxyibuprofen have been recovered from urine. Cytochrome P450 2C9 is the major catalyst in the formation of oxidative metabolites. Oxidative metabolites may be conjugated to glucuronide prior to excretion.
• Absorption: ~ 80% absorbed from GI tract;

  Time to reach peak plasma concentration = 47 minutes (suspension), 62 minutes (chewable tablets), 120 minutes (conventional tablets)

• Half Life: 2-4 hours
• Protein Binding: 90-99% to whole human plasma and site II of purified albumin, binding appears to be saturable and becomes non-linear at concentrations exceeding 20 mcg/ml.
• Elimination: Ibuprofen is rapidly metabolized and eliminated in the urine.
• References: Zawada ET Jr: Renal consequences of nonsteroidal antiinflammatory drugs. Postgrad Med. 1982 May;71(5):223-30. [Pubmed] ; Townsend KP, Pratico D: Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J. 2005 Oct;19(12):1592-601. [Pubmed] ; Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A: Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann Neurol. 2005 Dec;58(6):963-7. [Pubmed] ; Geisslinger G, Dietzel K, Bezler H, Nuernberg B, Brune K: Therapeutically relevant differences in the pharmacokinetical and pharmaceutical behavior of ibuprofen lysinate as compared to ibuprofen acid. Int J Clin Pharmacol Ther Toxicol. 1989 Jul;27(7):324-8. [Pubmed] ; Bergner T, Przybilla B: Photosensitization caused by ibuprofen. J Am Acad Dermatol. 1992 Jan;26(1):114-6. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1638

Research Area

• Description: Inflammation

Biological Activity

• Description: Ibuprofen (Advil, Dolgesic) is an anti-inflammatory inhibitor targeting COX-1 and COX-2 with IC50 of 13 μM and 370 μM, respectively.
• Targets: COX-1; COX-2
• IC50: 13 μM; 370 μM ^[1]
• In Vitro: Ibuprofen works by inhibiting the enzyme cyclooxygenase COX-1 and COX-2, which convert arachidonic acid to prostaglandin H2 (PGH2). Its action is similar to aspirin, indomethacin and all other NSAIDs in intact cells, broken cells, and purified enzyme preparations. ^[1] Ibuprofen inhibits the constitutive activation of NF-κB and IKKα in the androgen-independent prostate tumor cells PC-3 and DU-145. It sensitizes prostate cells to ionizing radiation and blocks stimulated activation of NF-κB following exposure to TNFα or ionizing radiation in the androgen-sensitive prostate tumor cell line LNCaP. Both of these cannot be attributed directly to inhibition of IκB-α kinase but to inhibition of an upstream regulator of IKKα. ^[2] Ibuprofen exerts an anticancer effect by reducing survival of cancer cells. Ibuprofen is more efficacious than aspirin and acetaminophen, and comparable with (R)-flurbiprofen and indomethacin in induction of p75^NTR protein (a tumor and metastasis suppressor) expression in cell lines from bladder and other organs. ^[3]
• In Vivo: Ibuprofen reacts with the heme group of cyclooxygenase to prevent arachidonic acid conversion. Prior exposure to Ibuprofen in vivo protects cyclooxygenase completely from the irreversible effects of aspirin in platelets. ^[4] Ibuprofen treatment is effective in attenuating joint inflammation and early articular cartilage degeneration in the adult female Sprague-Dawley rat model induced by high-repetition and high-force (HRHF) task. It dose this by blocking the increases in serum C1 and 2C (a biomarker of collagen I and II degradation) as well as the ratio of collagen degradation to synthesis (C1, 2C/CPII, the latter a biomarker of collage type II synthesis) induced by HRHF. ^[5]
• Clinical Trials: Phase IV completed in evaluating the analgesic effect of Ibuprofen 400, 600 and 800 mg, Paracetamol 500 and 1000 mg, and Paracetamol 1000 mg plus 60 mg Codeine on acute pain after third molar surgery.
• Features: Ibuprofen is a core medicine in the World Health Organization's "WHO Model List of Essential Medicines", which is a list of the minimum medical requirements for a basic healthcare system.

Protocol

• Protocol: Kinase Assay ^[1]
• Radiochemical enzyme assays for COX-1 and COX-2: 10 μL of purified COX-1 (0.7-0.8 μg) or COX-2 (3.0 units, 0.3μg) is activated with 50 μL of cofactor solution [l-epinephrine (1.3 mg/mL), reduced glutathione (0.3 mg/mL), and hematin (1.3 mg/mL) in oxygen-free Tris-HCl buffer (pH 8.0)]. The enzyme solution (60 μL) is added to Ibuprofen solutions or DMSO (20 μL) after [^14C]arachidonic acid is added in 0.2 mL eight-strip test tubes and preincubated 10 minutes on ice. Samples are incubated for 15 minutes at 37 °C, after which the reaction is terminated by addition of 10 μL of 2 M HCl and 5 μL of carrier solution (PGE2 and PGF2α, 0.2 μg/mL of each in EtOH). The unmetabolized arachidonic acid is separated from the prostaglandin products by column chromatography and eluted with n-hexane-dioxane-glacial acetic acid (70:30:1). The prostaglandin products are then eluted with EtOAc-MeOH (85:15), and the samples are counted in a Packard scintillation spectrometer. IC50 values are obtained by linear regression analysis.
• Protocol: Cell Assay ^[3]
• Cell Lines: Bladder epithelial cell line T24, RT-4 transitional cell papilloma bladder cell line, 5637 primary carcinoma bladder cell line, HCT-116, MDAMB231, MCF7, HEK293, A549, SKOV3 and DU145
• Concentrations: Dissolved in DMSO at a concentration of 200 mM for making the stock solution, final concentration ~2 mM
• Incubation Time: 48 hours
• Methods: Each cell line is incubated with Ibuprofen of various concentrations for 48 hours. Cell survival is estimated by the MTT assay, and cell death is determined by Hoechst staining used to distinguish between intact cell nuclei and fragmented nuclei undergoing cell death. Cells are lysed and analyzed by western blotting for detection of the p75^NTR protein.
• Protocol: Animal Study ^[5]
• Animal Models: Female Sprague-Dawley rats with joint inflammation induced by high-repetition and high-force (HRHF) tasks
• Formulation: Dissolved in DMSO and diluted in saline
• Doses: 45 mg/kg
• Administration: Taken orally every day

References

• References: [1] Noreen Y, et al. J Nat Prod, 1998, 61(1), 2-7.
• References: [2] Palayoor ST, et al. Oncogene, 1999, 18(51), 7389-7394.
• References: [3] Khwaja F, et al. Cancer Res, 2004, 64(17), 6207-6213.
• References: [4] Rao GH, et al. Arteriosclerosis, 1983, 3(4), 383-388.
• References: [5] Driban JB, et al. J Biomed Biotechnol, 2011, 2011, 691412-691428.

Sigma Aldrich - I4883

Biochem/physiol Actions
Cyclooxygenase (COX) inhibitor that has greater activity against COX-1 than against COX-2.
Packaging
1, 5, 10 g in poly bottle

Sigma Aldrich - I110

Biochem/physiol Actions
Cyclooxygenase (COX) inhibitor that has greater activity against COX-1 than against COX-2.

Sigma Aldrich - 77519

Biochem/physiol Actions
Cyclooxygenase (COX) inhibitor that has greater activity against COX-1 than against COX-2.

Sigma Aldrich - 32424

Biochem/physiol Actions
Cyclooxygenase (COX) inhibitor that has greater activity against COX-1 than against COX-2.
Legal Information
VETRANAL is a trademark of Sigma-Aldrich Co. LLC

Sigma Aldrich - I7905

Biochem/physiol Actions
Cyclooxygenase (COX) inhibitor that has greater activity against COX-1 than against COX-2.

Toronto Research Chemicals - I140000

A selective cyclooxygenase inhibitor (IC50=14.9uM). Inhibits PGH synthase-1 and PGH synthase-2 with comparable potency.

REFERENCES

• Zawada ET Jr: Renal consequences of nonsteroidal antiinflammatory drugs. Postgrad Med. 1982 May;71(5):223-30. Pubmed
• Townsend KP, Pratico D: Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J. 2005 Oct;19(12):1592-601. Pubmed
• Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A: Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann Neurol. 2005 Dec;58(6):963-7. Pubmed
• Geisslinger G, Dietzel K, Bezler H, Nuernberg B, Brune K: Therapeutically relevant differences in the pharmacokinetical and pharmaceutical behavior of ibuprofen lysinate as compared to ibuprofen acid. Int J Clin Pharmacol Ther Toxicol. 1989 Jul;27(7):324-8. Pubmed
• Bergner T, Przybilla B: Photosensitization caused by ibuprofen. J Am Acad Dermatol. 1992 Jan;26(1):114-6. Pubmed
• Driban JB, et al. J Biomed Biotechnol, 2011, 2011, 691412-691428.
• Noreen Y, et al. J Nat Prod, 1998, 61(1), 2-7.
• Palayoor ST, et al. Oncogene, 1999, 18(51), 7389-7394.
• Khwaja F, et al. Cancer Res, 2004, 64(17), 6207-6213.
• Rao GH, et al. Arteriosclerosis, 1983, 3(4), 383-388.
• Busson, M., et al.: J. Int. Med Res., 14, 53 (1986)
• Meade, E.A., et al.: J. Biol. Chem., 268, 6610 (1986)
• Davies, N.M., et al.: Clin. Pharmacokinet., 34, 101 (1986)
• Davies, N.M. et al., Clin. Pharmacokinet., 1998, 34, 101-154, (rev)
• Higgins, J.D. et al., Anal. Profiles Drug Subst., 2001, 27, 265-300, (rev)
• Aldrich Library of 13C and 1H FT NMR Spectra, 1992, 2, 1011B, (nmr)
• U.K. Pat., 1964, 971 700; CA, 61, 14591, (synth, pharmacol)
• Adams, S.S. et al., Arch. Int. Pharmacodyn. Ther., 1969, 178, 115
• Adams, S.S. et al., Toxicol. Appl. Pharmacol., 1969, 15, 310, (metab, tox)
• McConnell, J.F., Cryst. Struct. Commun., 1974, 3, 73, (cryst struct)
• Ger. Pat., 1975, 2 508 895; CA, 84, 5394, (lysine, salt)
• Kaiser, D.G. et al., J. Pharm. Sci., 1976, 65, 269, (resoln, glc, bibl)
• Shiori, T. et al., J.O.C., 1978, 43, 2936, (synth)
• Nicholson, J.S., Chron. Drug Discovery, 1982, 1, 149, (rev)
• Ghislandi, V. et al., Farmaco, Ed. Sci., 1982, 37, 81, (abs config)
• Gruber, K. et al., Arzneim.-Forsch., 1983, 33, 1176, (pharmacol, tox)
• Hiyama, T. et al., Synthesis, 1986, 645, (synth)
• Yamauchi, T. et al., Synthesis, 1986, 1044, (synth)
• Nicoll-Griffith, D.A., J. Chromatogr., 1987, 402, 179, (resoln)
• Negwer, M., Organic-Chemical Drugs and their Synonyms, 6th edn., Akademie-Verlag, 1987, 2867, (synonyms)
• Eur. Pat., 1988, Gist-Brocades; Shell Int. Res., 274 146; CA, 110, 113203, (dexibuprofen lysine)
• Wolber, E.K.A. et al., Chem. Ber., 1991, 124, 1667, (synth, pmr)
• Gonzalez, A., Synth. Commun., 1991, 21, 1353, (synth)
• Freer, A.A., Acta Cryst. C, 1993, 49, 1378, (cryst struct)
• Sonawane, H.R. et al., Tetrahedron, 1994, 50, 1243, (synth)
• Lalonde, J.J. et al., J.A.C.S., 1995, 117, 6845, (resoln)
• Martindale, The Extra Pharmacopoeia, 31st edn., Pharmaceutical Press, 1996, 50
• Shankland, N. et al., Acta Cryst. C, 1997, 53, 951-954, (cryst struct)