22071-15-4 Usage
Description
Ketoprofen is a potent non-steroidal anti-inflammatory drug (NSAID) belonging to the propionic acid class. It is a white crystalline powder that is odorless or nearly odorless, with a melting point of about 93-96 °C. Ketoprofen is known for its analgesic, anti-inflammatory, and antipyretic effects, and is particularly effective in treating various types of pain, inflammatory symptoms, colds, and post-operative conditions.
Uses
Used in Pharmaceutical Industry:
Ketoprofen is used as an anti-inflammatory and analgesic agent for the treatment of conditions such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and gout. It is known for its stronger anti-inflammatory effect compared to ibuprofen and its lower toxicity, making it a preferred choice for patients with gastrointestinal or renal problems.
Used in Pain Management:
Ketoprofen is used as a pain reliever for various types of pain, including musculoskeletal pain, post-operative pain, and dental pain. Its high efficacy and short half-life contribute to its widespread use in pain management.
Used in Cold and Flu Treatment:
Ketoprofen is used as an antipyretic agent to reduce fever and alleviate symptoms associated with colds and flu.
Used as a Natural Vitamin B12 Analog:
Ketoprofen is also used as a natural analog of Vitamin B12, providing potential health benefits and supporting various bodily functions.
Used in Veterinary Medicine:
Ketoprofen is used as an anti-inflammatory and analgesic agent in veterinary medicine, helping to manage pain and inflammation in animals.
Brand Names:
Some of the brand names under which Ketoprofen is marketed include Actron (Bayer), Orudis (Wyeth), and Oruvail (Wyeth).
Used in Particular Diseases
Acute Gouty Arthritis:
Dosage and Frequency:?75 mg four times a day
Originator
Profenid,Specia,France,1973
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.
Therapeutic Function
Antiinflammatory
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.
Biochem/physiol Actions
It serves as an efficient drug to treat ankylosing spondylitis, rheumatoid arthritis and osteoarthritis. It also has antipyretic and analgesic effects. Ketoprofen prevents the action of prostaglandin synthetase.
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.
Synthesis
Ketoprofen, 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 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.
Drug interactions
Concomitant use of alcohol or other NSAIDs after taking ketoprofen can increase gastrointestinal side effects and may cause ulcers. When ketoprofen is used together with aspirin or other salicylic acid drugs, the efficacy cannot be increased, but the incidence of gastrointestinal side effects and bleeding tendency increases. Concomitant use of ketoprofen with anticoagulants increases the risk of bleeding. Ketoprofen can enhance the effect of antidiabetic drugs and reduce the antihypertensive effect of antihypertensive drugs; ketoprofen and corticosteroids can be used together, which can significantly reduce the symptoms of inflammation. Ketoprofen should not be used with methotrexate to prevent poisoning. When ketoprofen is used with probenecid, verapamil, and nifedipine, the dose should be reduced; when ketoprofen is used with digoxin, the dose of digoxin should be adjusted.
Metabolism
Two processes are involved in the biotransformation of
ketoprofen: one very minor (hydroxylation), and the other
largely predominant (conjugation with glucuronic acid).
Less than 1% of the dose of ketoprofen administered is
recovered in unchanged form in the urine, whereas the
glucuronide metabolite accounts for about 65-75%. The
drug is excreted as metabolites essentially by the urinary
route. The rate of excretion is rapid, since 50% of the dose
administered is eliminated in the first 6 hours.
Check Digit Verification of cas no
The CAS Registry Mumber 22071-15-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,2,0,7 and 1 respectively; the second part has 2 digits, 1 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 22071-15:
(7*2)+(6*2)+(5*0)+(4*7)+(3*1)+(2*1)+(1*5)=64
64 % 10 = 4
So 22071-15-4 is a valid CAS Registry Number.
InChI:InChI=1/C16H14O3/c1-11(16(18)19)13-8-5-9-14(10-13)15(17)12-6-3-2-4-7-12/h2-11H,1H3,(H,18,19)/t11-/m0/s1
22071-15-4Relevant articles and documents
Ester Prodrugs of Ketoprofen: Synthesis, Hydrolysis Kinetics and Pharmacological Evaluation
Dhokchawle,Tauro,Bhandari
, p. 46 - 50 (2015)
The ester prodrugs of ketoprofen with various naturally available antioxidants; menthol, thymol, eugenol, guiacol, vanillin and sesamol have been synthesized by the dicyclohexyl carbodiimide (DCC) coupling method, purified and characterized by spectral data. Further, their, partition coefficients have been determined as well as, hydrolytic studies performed. The synthesized compounds are more lipophilic compared to the parent moieties and are stable in acidic environment, which is a prerequisite for their oral absorption. Under gastric as well as intestinal pH conditions these prodrugs showed variable susceptibility towards hydrolysis. The title compounds when evaluated for anti-inflammatory, analgesic activities and ulcerogenicity, showed improvement over the parent drug.
Ketoprofen intermediate as well as preparation method and application thereof
-
, (2020/03/12)
The invention relates to the field, of medicine synthesis, in particular to a ketoprofen intermediate and a preparation method and application. thereof to prepare the ketoprofen, reaction formula by sequentially performing an oxidation reaction, substitution reaction, deamination, deamination and an acidic hydrolysis reaction after formation of the isoxazole compound, by a Diels,Alder reaction with a phenylacetic acid by. a Diels :Alder reaction of a phenylacetic acid. In-flight, X2 or. Ortho or para, R to nitro or amino group1 - COCONR4 R5 , COX1 , COOR2 Or - CNCNCNR2 , R3 , R4 , R5 , R6 The same or different is H or C. 1 - C6 Alkyl, X1 , X2 The same or different is F, Cl, Br or I.
Palladium-Catalyzed α-Arylation of Carboxylic Acids and Secondary Amides via a Traceless Protecting Strategy
He, Zhi-Tao,Hartwig, John F.
supporting information, p. 11749 - 11753 (2019/08/26)
A novel traceless protecting strategy is presented for the long-standing challenge of conducting the palladium-catalyzed α-arylation of carboxylic aids and secondary amides with aryl halides. Both of the presented coupling processes occur with a variety of carboxylic acids and amides and with a variety of aryl bromides containing a broad range of functional groups, including base-sensitive functionality like acyl, alkoxycarbonyl, nitro, cyano, and even hydroxyl groups. Five commercial drugs were prepared through this method in one step in 81-96% yield. Gram-scale synthesis of medication Naproxen and Flurbiprofen with low palladium loading further highlights the practical value of this method.
