Basic information Used in Particular Diseases Safety Supplier Related
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Ketoprofen

Basic information Used in Particular Diseases Safety Supplier Related

Ketoprofen Basic information

Product Name:
Ketoprofen
Synonyms:
  • ORUDIS
  • ORUVAIL
  • RARECHEM AL BO 1306
  • M-BENZOYLHYDRATROPIC ACID
  • 2-(meta-benzoylphenyl) propionic acid
  • 19583 RP
  • 19583rp
  • 2-(3-benzoylphenyl)-propionicaci
CAS:
22071-15-4
MF:
C16H14O3
MW:
254.28
EINECS:
244-759-8
Product Categories:
  • ACTRON
  • Other APIs
  • Pharmaceutical raw material
  • API
  • Analgesics
  • Lipid signaling
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Pharmaceutical
  • Active Pharmaceutical Ingredients
  • APIs
  • Pharmaceutical ingredients
Mol File:
22071-15-4.mol
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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.
pka
pKa 5.94(MeOH/H2O) (Uncertain)
form 
solid
Water Solubility 
209mg/L(room temperature)
Merck 
14,5305
InChIKey
DKYWVDODHFEZIM-UHFFFAOYSA-N
CAS DataBase Reference
22071-15-4(CAS DataBase Reference)
NIST Chemistry Reference
Ketoprofen(22071-15-4)
EPA Substance Registry System
Benzeneacetic acid, 3-benzoyl-.alpha.-methyl- (22071-15-4)
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Safety Information

Hazard Codes 
T
Risk Statements 
25-36/37/38-23/24/25
Safety Statements 
26-45-36/37/39
RIDADR 
2811
WGK Germany 
3
RTECS 
UE7570000
TSCA 
Yes
HazardClass 
6.1(b)
PackingGroup 
III
HS Code 
29183000
Toxicity
LD50 orally in rats: 101 mg/kg (Ueno)

MSDS

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Ketoprofen Usage And Synthesis

Used in Particular Diseases

Acute Gouty Arthritis:
Dosage and Frequency: 75 mg four times a day

Chemical Properties

White Crystalline Solid

Originator

Profenid,Specia,France,1973

Uses

Anti-inflammatory; analgesic

Uses

Natural Vitamin B12. analog

Uses

Ketoprofen, a propionic acid derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties.

Definition

ChEBI: An oxo monocarboxylic acid that consists of propionic acid substituted by a 3-benzoylphenyl group at position 2.

Indications

Ketoprofen (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 Process

In 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 (131 g).
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 name

Actron (Bayer); Orudis (Wyeth); Oruvail (Wyeth).

Therapeutic Function

Antiinflammatory

General Description

Ketoprofen (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 allergens

Ketoprofen 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.

Pharmacokinetics

Ketoprofen 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 Use

Ketoprofen, 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 Profile

Poison 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.

Veterinary Drugs and Treatments

Ketoprofen 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.

KetoprofenSupplier

Ereal Chemical Co., Ltd. Gold
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Shanghai Boyle Chemical Co., Ltd.
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Mr Qiu:021-50182298(Demestic market) Miss Xu:021-50180596(Abroad market)
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J & K SCIENTIFIC LTD.
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21-61259100-
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sh@meryer.com