ChemicalBook > Product Catalog > API > Antipyretic analgesics > Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) > Ketoprofen
Ketoprofen Chemical Properties
- Melting point:93-96°C
- Boiling point:357.5°C (rough estimate)
- Density 1.1565 (rough estimate)
- refractive index 1.5600 (estimate)
- storage temp. 0-6°C
- solubility Slightly soluble in chloroform and methanol.
- pkapKa 5.94(MeOH/H2O) (Uncertain)
- form solid
- Water Solubility 209mg/L(room temperature)
- Merck 14,5305
- CAS DataBase Reference22071-15-4(CAS DataBase Reference)
- NIST Chemistry ReferenceKetoprofen(22071-15-4)
- EPA Substance Registry SystemBenzeneacetic acid, 3-benzoyl-.alpha.-methyl- (22071-15-4)
- Language:EnglishProvider:2-(3-Benzoylphenyl)propionic acid
Ketoprofen Usage And Synthesis
- Used in Particular DiseasesAcute Gouty Arthritis:
Dosage and Frequency: 75 mg four times a day
- Chemical PropertiesWhite Crystalline Solid
- UsesAnti-inflammatory; analgesic
- UsesNatural Vitamin B12. analog
- UsesKetoprofen, a propionic acid derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties.
- DefinitionChEBI: An oxo monocarboxylic acid that consists of propionic acid substituted by a 3-benzoylphenyl group at position 2.
- IndicationsKetoprofen (Orudis) is indicated for use in rheumatoid and osteoarthritis, for mild to moderate pain, and in dysmenorrhea. The most frequently reported side effects are GI (dyspepsia, nausea, abdominal pain, diarrhea, constipation, and flatulence) and CNS related (headache, excitation). Edema and increased blood urea nitrogen have also been noted in more than 3% of patients. Ketoprofen can cause fluid retention and increases in plasma creatinine, particularly in the elderly and in patients taking diuretics.
- Manufacturing ProcessIn an initial step, the sodium derivative of ethyl (3-benzoylphenyl)
cyanoacetate is prepared as follows: (3-benzoylphenyl)acetonitrile (170 9) is
dissolved in ethyl carbonate (900 g). There is added, over a period of 2 hours,
a sodium ethoxide solution [prepared from sodium (17.7 g) and anhydrous
ethanol (400 cc)], the reaction mixture being heated at about 105° to 115°C
and ethanol being continuously distilled. A product precipitates. Toluene (500
cc) is added, and then, after distillation of 50 cc of toluene, the product is
allowed to cool. Diethyl ether (600 cc) is added and the mixture is stirred for
1 hour. The crystals which form are filtered off and washed with diethyl ether
(600 cc) to give the sodium derivative of ethyl (3-benzoylphenyl)cyanoacetate
Then, ethyl methyl(3-benzoylphenyl)cyanoacetate employed as an intermediate material is prepared as follows: The sodium derivative of ethyl (3-benzoylphenyl)cyanoacetate (131 g) is dissolved in anhydrous ethanol (2 liters). Methyl iodide (236 g) is added and the mixture is heated under reflux for 22 hours, and then concentrated to dryness under reduced pressure (10 mm Hg). The residue is taken up in methylene chloride (900 cc) and water (500 cc) and acidified with 4N hydrochloric acid (10 cc). The methylene chloride solution is decanted, washed with water (400 cc) and dried over anhydrous sodium sulfate. The methylene chloride solution is filtered through a column containing alumina (1,500 g). Elution is effected with methylene chloride (6 liters), and the solvent is evaporated under reduced pressure (10 mm Hg) to give ethyl methyl(3-benzoylphenyl)cyanoacetate (48 g) in the form of an oil.
In the final production preparation, a mixture of ethyl methyl(3- benzoylphenyl)cyanoacetate (48 g), concentrated sulfuric acid (125 cc) and water (125 cc) is heated under reflux under nitrogen for 4 hours, and water (180 cc) is then added. The reaction mixture is extracted with diethyl ether (300 cc) and the ethereal solution is extracted with N sodium hydroxide (300 cc). The alkaline solution is treated with decolorizing charcoal (2 g) and then acidified with concentrated hydrochloric acid (40 cc). An oil separates out, which is extracted with methylene chloride (450 cc), washed with water (100 cc) and dried over anhydrous sodium sulfate. The product is concentrated to dryness under reduced pressure (20 mm Hg) to give a brown oil (33.8 g).
This oil is dissolved in benzene (100 cc) and chromatographed through silica (430 g). After elution with ethyl acetate, there is collected a fraction of 21 liters, which is concentrated to dryness under reduced pressure (20 mm Hg). The crystalline residue (32.5 g) is recrystallized from acetonitrile (100 cc) and a product (16.4 g), MP 94°C, is obtained. On recrystallization from a mixture of benzene (60 cc) and petroleum ether (200 cc), there is finally obtained 2- (3-benzoylphenyl)propionic acid (13.5 g), MP 94°C.
- brand nameActron (Bayer); Orudis (Wyeth); Oruvail (Wyeth).
- Therapeutic FunctionAntiinflammatory
- General DescriptionKetoprofen (Orudis, Rhodis) and suprofen (Profenal) areclosely related to fenoprofen in their structures, properties,and indications. Even though ketoprofen has been approvedfor OTC use (Orudis KT, Actron), its GI side effects aresimilar to indomethacin, and therefore its useshould be closely monitored, especially in patients with GIor renal problems.
- Contact allergensKetoprofen is an anti-inflammatory drug, used both topically and systemically. It is above all a photoaller- gen, responsible for photoallergic or photo-worsened contact dermatitis, with sun-induced, progressive, severe, and durable reactions. Recurrent photosensitiv- ity is possible for many years. Photosensitivities are expected to thiophene-phenylketone derivatives such as tiaprofenic acid and suprofen, to ketoprofen esters such as piketoprofen, and to benzophenone derivatives (see above) such as fenofibrate and benzophenone-3. Concomitant photosensitivities without clinical rel- evance have been observed to fenticlor, tetrachloro- salicylanilide, triclosan, tribromsalan, and bithionol.
- PharmacokineticsKetoprofen is rapidly and nearly completely absorbed on oral administration, reaching peak plasma levels within 0.5 to 2 hours. It is highly plasma protein bound (99%) despite a lower acidity (pKa = 5.9) than some other NSAIDs. Wide variation in plasma half-lives has been reported. It is metabolized by glucuronidation of the carboxylic acid, CYP3A4 and CYP2C9 hydroxylation of the benzoyl ring, and reduction of the keto function.
- Clinical UseKetoprofen, unlike many NSAIDs, inhibits the synthesis of leukotrienes and leukocyte migration into inflamed joints in addition to inhibiting the biosynthesis of prostaglandins. It stabilizes the lysosomal membrane during inflammation, resulting in decreased tissue destruction. Antibradykinin activity also has been observed. Bradykinin is released during inflammation and can activate peripheral pain receptors. In addition to anti-inflammatory activity, ketoprofen also possesses antipyretic and analgetic properties. Although it is less potent than indomethacin as an anti-inflammatory agent and an analgetic, its ability to produce gastric lesions is about the same.
- Safety ProfilePoison by ingestion,subcutaneous, intravenous, rectal, and intraperitoneal routes. Human systemic effects by an unspecified route:headache, nausea or vomiting, and degenerative changesin the brain, changes in kidney tubules. An experimentalteratogen.
- Chemical SynthesisKetoprofen, 2-(3-benzoyl)propionic acid (3.2.37), is synthesized from
3-methylbenzophenone, which undergoes bromination and forms 3-bromo-methylbenzophenone (3.2.33). The reduction of the resulting product by sodium cyanide gives
3-cyanomethylbenzophenone (3.2.34), which is reacted with the diethyl ester of carbonic
acid in the presence of sodium ethoxide. The resulting cyanoacetic ester derivative (3.2.25)
is alkylated by methyl iodide and the resulting product (3.2.36) undergoes acidic hydrolysis, forming ketoprofen (3.2.37) [104–106].
- Veterinary Drugs and TreatmentsKetoprofen is labeled for use in horses for the alleviation of inflammation and pain associated with musculoskeletal disorders. Like flunixin (and other NSAIDs), ketoprofen potentially has many other uses in a variety of species and conditions. There are approved dosage forms for dogs and cats in Europe and Canada. Some consider ketoprofen to be the NSAID of choice for use short-term for analgesia in cats.
- KETOPROFEN USP(CRM STANDARD) dl-Ketoprofen-13CD3 Glucuronid,Ketoprofen-13CD3 Glucuronide,rac Ketoprofen-13CD3 Acyl-b-D-glucuronide,rac Ketoprofen-13CD3 Acyl--D-glucuronide,dl-Ketoprofen-13CD3 Glucuronide Desmethyl Ketoprofen Folic acid Phenylacetic acid 4-Methoxyphenylacetic acid Propionic anhydride 4-Hydroxyphenylacetic acid L-Ketoprofen trometamol Testosterone phenylacetate Ketoprofen Ibuprofen Ascoric Acid Ethyl 2-(Chlorosulfonyl)acetate 4-Methylphenylacetic acid m-Toluic acid 2-Hydroxyphenylacetic acid Propionic acid
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