Ibuprofen

Base Information

• Chemical Name: Ibuprofen
• CAS No.: 15687-27-1
• Deprecated CAS: 58560-75-1,139466-08-3
• Molecular Formula: C13H18O2
• Molecular Weight: 206.285
• Hs Code.: 2916.39
• European Community (EC) Number: 239-784-6
• NSC Number: 757073,256857
• UNII: WK2XYI10QM
• DSSTox Substance ID: DTXSID5020732
• Nikkaji Number: J3.134H
• Wikipedia: Ibuprofen
• Wikidata: Q186969
• NCI Thesaurus Code: C561
• RXCUI: 5640
• Pharos Ligand ID: JSNCQPWTHATF
• Metabolomics Workbench ID: 141986
• ChEMBL ID: CHEMBL521
• Mol file: 15687-27-1.mol

Synonyms:Advil;alpha-Methyl-4-(2-methylpropyl)benzeneacetic Acid;Benzeneacetic Acid, alpha-methyl-4-(2-methylpropyl)- trimethylsilyl ester;Brufen;Ibumetin;Ibuprofen;Ibuprofen Zinc;Ibuprofen, (+-)-Isomer;Ibuprofen, (R)-Isomer;Ibuprofen, (S)-Isomer;Ibuprofen, Aluminum Salt;Ibuprofen, Calcium Salt;Ibuprofen, Copper (2+) Salt;Ibuprofen, Magnesium Salt;Ibuprofen, Potassium Salt;Ibuprofen, Sodium Salt;Ibuprofen, Zinc Salt;Ibuprofen-Zinc;Motrin;Nuprin;Rufen;Salprofen;Trauma Dolgit Gel;Trauma-Dolgit Gel

Chemical Property of Ibuprofen

Chemical Property:

• Appearance/Colour: Colourless, crystalline solid
• Vapor Pressure: 0.000139mmHg at 25°C
• Melting Point: 77-78 °C(lit.)
• Refractive Index: 1.5500 (estimate)
• Boiling Point: 319.6 °C at 760 mmHg
• PKA: pKa 4.45± 0.04(H2O,t = 25±0.5,I=0.15(KCl))(Approximate)
• Flash Point: 216.7 °C
• PSA: 37.30000
• Density: 1.029 g/cm³
• LogP: 3.07320
• Storage Temp.: -20?C Freezer
• Solubility.: Practically insoluble in water, freely soluble in acetone, in methanol and in methylene chloride. It dissolves in dilute solutions of alkali hydroxides and carbonates.
• Water Solubility.: insoluble
• XLogP3: 3.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 4
• Exact Mass: 206.130679813
• Heavy Atom Count: 15
• Complexity: 203

Purity/Quality:

99.8% ^*data from raw suppliers

racIbuprofen ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,N
• Hazard Codes: Xn,N,T,F
• Statements: 22-63-51/53-39/23/24/25-23/24/25-11
• Safety Statements: 36-61-36/37-45-16-7

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Nonsteroidal Antiinflammatory Drugs
• Canonical SMILES: CC(C)CC1=CC=C(C=C1)C(C)C(=O)O
• Recent ClinicalTrials: Pain Management Following Sinus Surgery
• Recent EU Clinical Trials: A Phase III Prospective, Randomized, Multicenter, Double-Blind, Placebo-controlled clinical study to evaluate the efficacy and safety of fixed dose combination (FDC) product Ibuprofen/Paracetamol/Phenylephrine Hydrochloride 200 mg/500 mg/10 mg film-coated tablets (containing Ibuprofen 200 mg, Paracetamol 500 mg and Phenylephrine Hydrochloride 10 mg) compared to Doregrippin? 500 mg/10 mg film-coated tablets (containing Paracetamol 500 mg and Phenylephrine Hydrochloride 10 mg) and Nurofen? 200 mg Tablets (containing Ibuprofen 200 mg) for the temporary relief of cold and flu symptoms, i.e. mild to moderate pain, sore throat, fever and nasal congestion.
• Recent NIPH Clinical Trials: The effect of intravenous ibuprofen on postoperative pain and opioid consumption after pediatric cardiac surgery
• description: Ibuprofen belongs to a non-steroidal anti-inflammatory analgesic. It has excellent anti-inflammatory, analgesic and antipyretic effect with less adverse reactions. It has been widely used in the world, as the world's best-selling non-prescription drugs. It, together with aspirin and paracetamol are listed as the three key antipyretic analgesics products. In our country, it is mainly used in pain alleviation and anti-rheumatism, etc. It has much less applications in the treatment of cold and fever compared with paracetamol and aspirin. There are a dozens of pharmaceutical companies qualified for production of ibuprofen in China. But the bulk of the domestic market sales of ibuprofen have been occupied by Tianjin Sino-US Company. The Ibuprofen was co-discovered by Dr. Stewart Adams (later he becomes a professor and won the Medal of the British Empire) and his team including CoLinBurrows and Dr. John Nicholson. The aim of the initial study was to develop a "super aspirin" to obtain an alternative for the treatment of rheumatoid arthritis that is comparable to that of aspirin but with less serious adverse reactions. For other drugs such as phenylbutazone, it has a high risk of causing adrenal suppression and other adverse events such as gastrointestinal ulcers. Adams decided to look for a drug with good gastrointestinal resistance, which is particularly important for all non-steroidal anti-inflammatory drugs. Phenyl acetate drugs have aroused people's interest. Although some of these drugs have been found to be at risk of causing ulcers based on the dog's test, Adams is aware of that this phenomenon may be due to a relatively long half-life of the drug clearance. In this class of drugs there is a compound – ibuprofen, which has a relatively short half-life, sustaining only 2 hours. Among the screened alternative drugs, although it is not the most effective, it is the most secure. In 1964, ibuprofen had become the most promising alternative to aspirin.
• Indications: Alleviate the acute phase of various kinds of chronic arthritis such as rheumatoid arthritis, osteoarthritis, spondyloarthropathies, gouty arthritis and rheumatoid arthritis as well as persistent symptoms of joint swelling and pain. It can be used for the non-cause treatment and control of disease. For the treatment of various kinds of non-joint soft tissue rheumatic pain, such as shoulder pain, tenosynovitis, bursitis, myalgia and post-exercise pain. For the treatment of acute mild to moderate pain such as: post-surgery, post-trauma, post-strain, primary dysmenorrhea, toothache, headache and so on. It has an antipyretic effect against the fever of adults and children. Ibuprofen (Advil, Motrin) is used as an analgesic and antipyretic as well as a treatment for rheumatoid arthritis and degenerative joint disease. The most frequently observed side effects are nausea, heartburn, epigastric pain, rash, and dizziness. Incidence of GI side effects is lower than with indomethacin.Visual changes and cross-sensitivity to aspirin have been reported. Ibuprofen inhibits COX-1 and COX-2 about equally. It decreases platelet aggregation, but the duration is shorter and the effect quantitatively lower than with aspirin. Ibuprofen prolongs bleeding times toward high normal value and should be used with caution in patients who have coagulation deficits or are receiving anticoagulant therapy.
• Drug Interactions: Drinking or combination with other non-steroidal anti-inflammatory drugs can increase the gastrointestinal side effects, and have the risk of ulcers. Long-term combination with acetaminophen can increase the toxic side effects on the kidney. Combination with aspirin or other salicylic acid drugs causes no increase in the efficacy, but cam cause gastrointestinal adverse reactions and increase of the bleeding tendency. Combination with heparin, dicoumarol and other anticoagulants as well as platelet aggregation inhibitors has the risk for increasing bleeding. Combination with furosemide can weaken the sodium excretion effect and antihypertensive effect. Combination with verapamil and nifedipine can increase the plasma concentration of the product. Ibuprofen can increase the plasma concentration of digoxin; pay attention to adjusting the dose of digoxin upon co-administration. Ibuprofen can enhance the role of anti-diabetic drugs (including oral hypoglycemic agents). The goods, when used in combination with antihypertensive drugs can affect the antihypertensive effect of the latter one. Probenecid can reduce the excretion of the goods, increase the concentration of blood, thereby increasing the toxicity, so it is proper to reduce the dosage upon co-administration. The goods can reduce the excretion of methotrexate, increase the blood concentration which can reach up to the level of poisoning, so the goods should not be used with medium or large doses of methotrexate.
• Description: Ibuprofen is a white, crystalline anti-infl ammatory drug used in numerous medications. It is the active ingredient marketed under various trade names including Advil, Motrin, and Nurofen. Ibuprofen is a nonsteroidal anti-infl ammatory drug (NSAID) used as a pain reliever (analgesic), fever reducer (antipyretic), and inflammation reducer. Infl ammation is a general physiological response to tissue damage characterized by swelling, pain, and heat.Ibuprofen works by inhibiting the enzyme cyclooxygenase (COX), which in turn interferes with the synthesis of prostaglandins. COX exists as several coenzyme forms that are similar in structure: COX-1, COX-2, COX-3; ibuprofen is a nonselective inhibitor of both COX-1 and COX-2. COX-1 is continually produced in mammalian cells throughout the body in response to physiological stimuli. It is responsible for the production of prostaglandins, which get their name because it was originally believed they were synthesized in the prostate gland. In fact, prostaglandins are synthesized throughout the body and act like hormones by stimulating action in target cells. Prostaglandins, which are fatty acid compounds consisting of a 20-carbon chain including a 5 carbon ring, are involved in numerous physiological processes including renal function, blood clotting, and stomach mucus production. COX-2 is synthesized only in specifi c parts of the body (kidneys, brain, trachea) as needed and is therefore called an induced enzyme. COX-2 produces prostaglandins in response to tissue damage and infl ammation. Infl ammatory prostaglandins produce swelling, pain, and fever.
• Uses: 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. A selective cyclooxygenase inhibitor (IC50=14.9uM). Inhibits PGH synthase-1 and PGH synthase-2 with comparable potency Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory. Antibiotic
• Therapeutic Function: Antiinflammatory
• Clinical Use: Ibuprofen is indicated for the relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis, the relief of mild to moderate pain, the reduction of fever, and the treatment of dysmenorrhea.
• 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 of 2 or more NSAIDs, including aspirin (increased side effects); avoid with ketorolac (increased risk of side effects and haemorrhage); possibly reduced antiplatelet effect with aspirin. 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 ritonavir. 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 decreased. Pentoxifylline: increased risk of bleeding. Tacrolimus: increased risk of nephrotoxicity.

Technology Process of Ibuprofen

There total 213 articles about Ibuprofen 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: 90%

ibuproxam (53648-05-8) → 1-(4-isobutyl-phenyl)-ethanone (38861-78-8) + ibuprofen (15687-27-1,58560-75-1) + 4'-(2-methylpropyl)acetophenone oxime (74305-51-4) + 4-(2-methylpropyl)phenylethylamine (164579-51-5)

Guidance literature:

at 110 ℃; for 24h; under 760 Torr; Product distribution; other temperature, reaction time;

DOI:10.1002/jps.2600690511

Reference yield: 87%

→ ibuprofen (15687-27-1,58560-75-1) + (+/-)-ibuprofen methyl ester (61566-34-5)

Guidance literature:

Reference yield: 83%

→ ibuprofen (15687-27-1,58560-75-1) + (S)-ibuprofen (51146-56-6,58560-75-1)

Guidance literature:

upstream raw materials:

4-Butyl-α-methyl-β-dichlorostyren

1-Isobutyl-4-(1-methyl-2,2-bis-methylsulfanyl-vinyl)-benzene

trichlorofluoromethane

1-(4-isobutyl-phenyl)-ethanone

Downstream raw materials:

2-(4-isobutylphenyl)propionic acid N-oxysuccinimide ester

4-Nitrophenyl 2-(4-isobutylphenyl)propanoate

11,17-di-hydroxy-3,20-diketo-pregn-1,4-diene-21-yl-2-(4-isobutylphenyl)propanoate

2-(4-Isobutylphenyl)-propionsaeure-(11β,17-dihydroxy-3,20-dioxo-4-pregnen-21-yl)-ester

Refernces

• 1、 Khan,Akhter, Mymoona. "Synthesis, pharmacological activity and hydrolytic behavior of glyceride prodrugs of ibuprofen". . p. 371 - 376. Retrieved 2005.
• 2、 Nugent, William A.,McKinney, Ronald J.. "Nickel-Catalyzed Markovnikov Addition of Hydrogen Cyanide to Olefins. Application to Nonsteroidal Antiinflammatories". . p. 5370 - 5372. Retrieved 1985.
• 3、 Walker,Pillai. "-". . p. 3707. Retrieved 1977.
• 4、 Jayasree,Seayad,Chaudhari. "Highly active supported palladium catalyst for the regioselective synthesis of 2-arylpropionic acids by carbonylation". . p. 1067 - 1068. Retrieved 1999.
• 5、 Tamura, Yasumitsu,Shirouchi, Yoshiaki,Haruta, Jun-ichi. "Synthesis of Methyl 2-Arylpropanoates by 1,2-Aryl Migration of Aryl Ethyl Ketones using Diacetoxyphenyliodine". . p. 231 - 232. Retrieved 1984.
• 6、 Seayad,Jayasree,Chaudhari. "Carbonylation of vinyl aromatics: Convenient regioselective synthesis of 2-arylpropanoic acids". . p. 459 - 461. Retrieved 1999.
• 7、 Chimichi,Innocenti,Orzalesi. "Thermal decomposition of ibuproxam". . p. 521 - 523. Retrieved 1980.
• 8、 Shiori,Kawai. "-". . p. 2936. Retrieved 1978.
• 9、 Reetz, Manfred T.,Carballeira, Jose Daniel,Peyralans, Jerome,Hoebenreich, Horst,Maichele, Andrea,Vogel, Andreas. "Expanding the substrate scope of enzymes: Combining mutations obtained by CASTing". . p. 6031 - 6038. Retrieved 2006.
• 10、 An, Yi,Chen, Fener,Li, Weijian,Li, Yaling,Tang, Pei,Wang, Zhenzhen,Wu, Mengjuan,Xue, Yansong. "The total synthesis of (-) -strempeliopine: Via palladium-catalyzed decarboxylative asymmetric allylic alkylation". . p. 1402 - 1405. Retrieved 2022/02/09.