alpha-Methyl-4-(2-methylpropyl)-benzolessigsäure

buluofen · Advil · Buprofen · Nurofen · Ibuprofen DC90 · rufen · Dolgit · Motrin

Identifikatoren & physikalische Daten

CAS No.	15687-27-1
Summenformel	C13H18O2
Durchschnittliche Molmasse	206,28 g/mol
Monoisotopische Masse	206,13067982 g/mol
SMILES	CC(C)Cc1ccc(C(C)C(=O)O)cc1
InChIKey	HEFNNWSXXWATRW-UHFFFAOYSA-N
PubChem CID	3672
ChEMBL	CHEMBL521
ChEBI	CHEBI:5855
EC No.	239-784-6
DTXSID	DTXSID5020732
Lokaler Name	alpha-Methyl-4-(2-methylpropyl)-benzolessigsäure

Chemische & physikalische Eigenschaften

XLogP	3,5
Polarare Oberfläche (TPSA)	37,3
H-Brücken-Donoren	1
H-Brücken-Akzeptoren	2
Frei drehbare Bindungen	4
Schwere Atome	15
Formalladung	0
Komplexität	203
Arzneimittel	PharmaceuticalsPharmaceuticals -> Used in SwitzerlandPharmaceuticals -> NSAIDs
LogP (Verteilungskoeffizient)	log Kow= 3.97
Geruch	Characteristic odor
Color/Form	Colorless, crystalline stable solid
Löslichkeit	Readily sol in most org solventsVERY SOLUBLE IN ALCOHOLIn water, 21 mg/l @ 25 °C0.021 mg/mL at 25 °CPractically insoluble in water, freely soluble in acetone, in methanol and in methylene chloride. It dissolves in dilute solutions of alkali hydroxides and carbonates.
Human Drugs	FDA approved drugs -> Active ingredientEMA approved medicines: Human medicineMedicines administered to the neonate [c]
Endocrine Disruptors	Potential endocrine disrupting compound
Decomposition	When heated to decomposition it emits acrid smoke and fumes.
Schmelzpunkt	75-77.5 ºC75-77 °C76 °C77-78 °C
Dampfdruck	4.74X10-5 mm Hg @ 25 °C
Physical Description	Other Solid
Siedepunkt	157 °C (4 mmHg)
Dichte	1.0364 (rough estimate)
Brechungsindex	1.5500 (estimate)
Flammpunkt	9℃
Lagerbedingungen	2-8°C
pKa (Säurekonstante)	pKa 4.45± 0.04(H2O,t = 25±0.5,I=0.15(KCl))(Approximate)
Aggregatzustand	Crystalline Powder
Farbe	white to off-white
Biologische Quelle	synthetic (organic)
Merck	14,4881
Henry-Konstante	6.6×101 mol/(m3Pa) at 25℃, HSDB (2015)
BCS Class	2
Stabilität	Stable. Combustible. Incompatible with strong oxidizing agents.
Kosmetik-Inhaltsstoffe Funktionen	SKIN CONDITIONING
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
SMILES	CC(C)Cc1ccc(cc1)C(C)C(O)=O
LogP (Verteilungskoeffizient)	3.970
CAS Datenbank	15687-27-1(CAS DataBase Reference)
NIST chemische Informationen	Ibuprofen(15687-27-1)
EPA chemische Informationen	Benzeneacetic acid, .alpha.-methyl-4-(2-methylpropyl)- (15687-27-1)

Sicherheit & Vorschriften

GHS-Einstufung	WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P304+P340, P305+P351+P338, P318, P319, P330, P337+P317, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 511 reports by companies from 48 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.DangerH302: Harmful if swallowed [Warning Acute toxicity, oral]
Regulatorische Informationen	Chemical: Benzeneacetic acid, .alpha.-methyl-4-(2-methylpropyl)-Benzeneacetic acid, .alpha.-methyl-4-(2-methylpropyl)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzeneacetic acid, .alpha.-methyl-4-(2-methylpropyl)- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)Status: Active Update: 29-03-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/1270Ibuprofen: Does not have an individual approval but may be used under an appropriate group standard
Special Reports	Aycock DGIbuprofen: A MonographAm Pharm NS31 (1): 46-9 (1991). Nonprescription ibuprofen is useful for managing minor aches and pains, reducing fever, and relieving symptoms of dysmenorrhea. For these indications, ibuprofen's effectiveness has been judged to be equal or superior to other available nonprescription analgesics. Ibuprofen is not recommended for self treatment in children less than 12 years old.Smolinske SC et alToxic Effects of Nonsteroidal Anti-inflammatory Drugs in Overdose. An Overview of Recent Evidence on Clinical Effects and Dose-response RelationshipsDrug Saf 5 (4): 252-74 (1990).Maniglia R et alNon-steroidal Anti-inflammatory NephrotoxicityAnn Clin Lab Sci 18 (3): 240-52 (1988). Non-steroidal anti-inflammatory drugs have a wide range of use in clinical practice because of their analgesic and anti-inflammatory properties. However, their potential nephrotoxicity has been noted. The case histories were studied, retrospectively, in 13 patients who were taking non-steroidal anti-inflammatory drugs as follows: four on fenoprofen (Nalfon), three on naproxen (Naprosyn), two on ibuprofen (Motrin), two on sulindac (Clinoril), one on tolmetin (Tolectin), and one on indomethacin (Indocin) and who exhibited abnormal urinalysis or a deterioration in renal function. Nine of the patients underwent renal biopsies, and eight of these biopsies were positive for interstitial nephritis. In addition to the presentation of additional cases of non-steroidal anti-inflammatory drug nephrotoxicity, a brief review of the current theories of the nephrotoxic mechanism is presented.Linden CH, Townsend PLMetabolic Acidosis After Acute Ibuprofen OverdosageJ Pediatr 111 (6 Pt 1): 922-5 (1987). Despite the widespread use of non-steroidal anti-inflammatory drugs, the current number of reported cases of poisoning is small. However, with the introduction of 'over-the-counter' preparations of NSAIDs in some countries (e.g. ibuprofen in the UK and USA) an increased incidence of acute poisoning from this group of drugs can be expected.Busson MUpdate on Ibuprofen: Review ArticleJ Int Med Res 14 (2): 53-62 (1986). Non-steroidal anti-inflammatory drugs have become the principal mode of therapy for rheumatic diseases and their use has continued to increase despite concern expressed recently regarding potential hazards.
Hazard Classes and Categories	Acute Tox. 4 (100%)Acute toxicity (Oral) - Category 4
Lagerbedingungen	Preparations containing ibuprofen tablets should be stored in well closed, light resistant containers at 15-30 °C.
Entsorgungsverfahren	SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Wechselwirkungen	IN RABBITS AND IN HEALTHY HUMANS, IBUPROFEN ADMINISTERED BEFORE TOLBUTAMIDE ANTAGONIZED TOLBUTAMIDE HYPOGLYCEMIA.WHEN SULFAMETHIZOLE WAS COADMINISTERED TO DOGS WITH IBUPROFEN, BETA-ELIMINATION HALF-LIFE FOR SULFAMETHIZOLE WAS INCREASED APPROXIMATELY 10 TIMES COMPARED TO THE CONTROL VALUE. RESULTS SUGGEST THAT THE INCREASED TERMINAL HALF-LIFE OF SULFAMETHIZOLE CAUSED BY IBUPROFEN IS MAINLY A RESULT OF COMPETITIVE INTERACTIONS BETWEEN THEM AT THE RENAL SECRETORY LEVEL.In several short-term, controlled studies, ibuprofen did not have a substantial effect on the prothrombin time of patients receiving oral anticoagulantshowever, because ibuprofen may cause GI bleeding, inhibit platelet aggregation, and prolong bleeding time and because bleeding has occurred when ibuprofen and coumarin derivative anticoagulants were administered concomitantly, the drug should be used with caution and the patient carefully observed if the drug is used concomitantly with any anticoagulant /such as/ warfarin or /the thrombolytic agent streptokinase.To study a potential interaction between digoxin and two non-steroid anti-inflammatory drugs, indomethacin (50 mg three times daily) and ibuprofen (600 mg three times daily) were given for 10 days to 10 and 8 patients, respectively, on chronic digoxin treatment. Serum digoxin measured by fluorescence polarisation immunoassay increased significantly (p < 0.05) during treatment with indomethacin from pre-treatment values of 0.73 + or - 0.34 nmol/l (mean + or - standard deviation) to a mean value of 1.02 + or - 0.43 nmol/l, while administration of ibuprofen did not change the steady state serum concentration of digoxin. The result demonstrates that some non-steroidal anti-inflammatory drugs such as indomethacin increase serum digoxin to levels high in the therapeutic range. This should be taken into consideration when co-administering other drugs known to increase the serum concentration of digoxin such as several antiarrhythmics.For more Interactions (Complete) data for IBUPROFEN (17 total), please visit the HSDB record page.
Hepatotoxicity	Rates of serum aminotransferase elevations during low dose, chronic ibuprofen therapy are comparable to those that occur with placebo controls (0.4%). However, higher rates of ALT elevations occur with high, full doses of 2,400 to 3,200 mg daily (up to 16%). Generally, ALT elevations are mild and rarely above 100 U/L. Rare instances of drug fever arise within 1 to 4 weeks of starting ibuprofen which can be accompanied by serum aminotransferase elevations. If ibuprofen is continued in these situations, more severe liver injury and jaundice may arise. These outcomes may account for a rare case of hepatocellular injury attributed to conventional doses of ibuprofen.
Umweltverhalten	TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,400(SRC), determined from a log Kow of 3.97(2) and a regression-derived equation(3), indicates that ibuprofen is expected to have slight mobility in soil(SRC). Volatilization of ibuprofen from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.5X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 4.7X10-5 mm Hg(4), and water solubility, 21 mg/l(5). Ibuprofen is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). A half-life of 20 days using water samples from Lake Greifensee, Switzerland incubated at room temperature for 37 days with 200 ng/l racemic ibuprofen(6) indicates that biodegradation in soil may be an important environmental fate process(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,400(SRC), determined from a log Kow of 3.97(2) and a regression-derived equation(3), indicates that ibuprofen is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.5X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 4.7X10-5 mm Hg(4), and water solubility, 21 mg/l(5). The pKa of ibuprofen is 4.9(6), indicating that this compound will primarily exist in the dissociated form in the environment and anions generally do not adsorb to organic carbon and clay more strongly than their neutral counterparts(7). Hydrolysis is not expected be an important environmental fate process as carboxylic acids are generally resistant to hydrolysis(3). According to a classification scheme(8), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(9), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A half-life of 20 days using water samples from lake Greifensee, Switzerland incubated at room temperature for 37 days with 200 ng/l racemic ibuprofen(10) indicates that biodegradation in water may be an important environmental fate process(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ibuprofen, which has a vapor pressure of 4.7X10-5 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase ibuprofen is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 32 hrs(SRC), calculated from its rate constant of 1.16X10-11 cu cm/molecule-sec at 25 °C(3). Particulate-phase ibuprofen may be removed from the air by wet and dry deposition(SRC).
Unerwünschte Wirkungen	Gastrointestinal bleeding is a well-known adverse effect of ibuprofen usage and can lead to gastritis, ulceration, hemorrhage, or perforation. Inhibition of COX isoform production reduces prostaglandin levels, which are involved in gastroprotective mucus secretion. This effect is more pronounced with non-selective NSAIDsselective COX-2 inhibitors are associated with a lower incidence of gastrointestinal complications, which is of particular concern in children. Ibuprofen is more commonly used than other NSAIDs due to its favorable safety profile. Using ibuprofen over-the-counter without medical consultation increases the risk of high dosage levels and short-term interval dosing that may precipitate gastrointestinal complications.
Milk Concentrations	Not excreted in breast milk. /from Table II/
Toxizitätsübersicht	Signs and Symptoms of Overdose
Effluent Concentrations	Ibuprofen was qualitatively identified in municipal wastewater at the Iona Island (British Columbia, Canada) treatment plant(1). The compound has been measured in an effluent sedimentation tank, River Rhine water, and unspecified river water samples at up to 12 ug/l, <5 to 41 ng/l, and 17 to 139 ng/l, respectively(2). Ibuprofen was present in the effluent of wastewater treatment plants in Switzerland at concentrations of up to 3 ug/l(3). The compound, which was detected in effluent from a municipal sewage treatment plant near Frankfurt/Main, Germany, decreased by 90% from a daily influent load of 250 g/day(4). Ibuprofen was not detected in 16 effluent samples from treatment plants in Germany, detection limit of 0.010 ug/l(4).
Soil Adsorption/Mobility	The Koc of ibuprofen is estimated as 3,400(SRC), using a log Kow of 3.97(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that ibuprofen is expected to have slight mobility in soil. The pKa of ibuprofen is 4.91(4), indicating that this compound will primarily exist in the dissociated form in the environment and anions generally do not adsorb to organic carbon and clay more strongly than their neutral counterparts(5).
Human Toxicity Excerpts	Gastrointestinal side effects are experienced by 5-15% of patients taking ibuprofenepigastric pain, nausea, heartburn, & sensations of "fullness" in the GI tract are the usual difficulties. However, the incidence of theses side effects is less with ibuprofen than with aspirin or indomethacin. Other side effects of ibuprofen have been reported less frequently. They include thrombocytopenia, skin rashes, headache, dizziness & blurred vision, & in a few cases, toxic amblyopia, fluid retention, & edema.3 YOUNG WOMEN TAKING IBUPROFEN FOR SYSTEMIC LUPUS ERYTHEMATOSUS DISCONTINUED THERAPY: ON REINSTITUTION OF THERAPY, PROFOUND HYPOTENSION & HEADACHES DEVELOPED WITHIN HR.FATAL AUTOIMMUNE HEMOLYTIC ANEMIA OCCURRED COINCIDENT WITH ORAL ADMIN OF IBUPROFEN 400 MG 3 TIMES/DAY IN 49-YR OLD MALE.15/21 BLACK PATIENTS SHOWED THINNING OR LOSS OF HAIR WHILE TAKING IBUPROFEN. NORMAL GROWTH RETURNED UPON DISCONTINUATION MEDICATION. POSSIBLE THAT IBUPROFEN ACTS ON PROTEIN TO CAUSE BRITTLENESS, FRAGILITY WHEN HAIR IS EXPOSED TO STRAIGHTENERS, PROCESSES, PERMANENT WAVE PROCEDURES.For more Human Toxicity Excerpts (Complete) data for IBUPROFEN (18 total), please visit the HSDB record page.
Artificial Pollution Sources	Ibuprofen's production and use as an anti-inflammatory, analgesic, and antipyretic(1) may result in its release to the environment through various waste streams(SRC).
Environmental Biodegradation	AEROBIC: Ibuprofen has shown to be inherently biodegradable by sewage treatment(1). However, analysis of activated sludge from the wastewater treatment plant at Gossau, Switzerland indicates that a residence time in excess of 6 hours is required for complete removal of ibuprofen(2). A half-life of 20 days was determined from a study using water samples from lake Greifensee, Switzerland that were incubated at room temperature for 37 days with 200 ng/l racemic ibuprofen(2). Influent concentration of 0.3 ug/l in Brazilian treatment plants showed a removal efficiency of ranging from 22-75%(3).
Drug Induced Liver Injury	Drug Induced Liver Injury Rank (DILIrank 2.0)IbuprofenvLess-DILI-concern3Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015
Wassergefährdungsklasse (WGK)	WGK 1
TSCA-Inventar-Status	TSCA listed
Zollcode	29163920
R-Sätze (R)	22-63-51/53-39/23/24/25-23/24/25-11
Toxizität	LD50 in male mice, rats (mg/kg): 495, 626 i.p.1255, 1050 orally (Orzalesi)
Gefahrensymbole	Xn
Sicherheitshinweise (S)	36-61-36/37-45-16-7
Lagerklasse	11 - Combustible Solids
Gefahrstoffdaten	15687-27-1(Hazardous Substances Data)
Gefahrenklasse	Acute Tox. 4 OralEye Irrit. 2STOT SE 3

Anwendungen & Verwendung

History

Ibuprofen was developed while searching for an alternative pain reliever to aspirin in the 1950s. It and related compounds were synthesized in 1961 by Stewart Adams, John Nicholson, and Colin Burrows who were working for the Boots Pure Drug Company in Great Britain. Adams and Nicholson filed for a British patent on ibuprofen in 1962 and obtained the patent in 1964; subsequent patents were obtained in the United States. The first clinical trials for ibuprofen were started in 1966. Ibuprofen was introduced under the trade name Brufen in 1969 in Great Britain. It was introduced in the United States in 1974. Ibuprofen was initially off ered by prescription, but it became available in over-the-counter medications in the 1980s.

Verwenden

A common goal in the development of pain and inflammation medicines has been the creation of compounds that have the ability to treat inflammation, fever, and pain without disrupting other physiological functions. General pain relievers, such as aspirin and ibuprofen, inhibit both COX-1 and COX-2. A medication's specificaction toward COX-1 versus COX-2 determines the potential for adverse side effects. Medications with greater specificity toward COX-1 will have greater potential for producing adverse side effects. By deactivating COX-1, nonselective pain relievers increase the chance of undesirable side effects, especially digestive problems such as stomach ulcers and gastrointestinal bleeding. COX-2 inhibitors, such as Vioxx and Celebrex, selectively deactivate COX-2 and do not aff ect COX-1 at prescribed dosages. COX-2 inhibitors are widely prescribed for arthritis and pain relief. In 2004, the Food and Drug Administration (FDA) announced that an increased risk of heart attack and stroke was associated with certain COX-2 inhibitors. This led to warning labels and voluntary removal of products from the market by drug producers; for example, Merck took Vioxx off the market in 2004. Although ibuprofen inhibits both COX-1 and COX-2, it has several times the specificity toward COX-2 compared to aspirin, producing fewer gastrointestinal side effects.