Carprofen Chemical Properties

Melting point:

186-1880C

Boiling point:

509.1±35.0 °C(Predicted)

Density 

1.2011 (rough estimate)

refractive index 

1.5200 (estimate)

storage temp. 

Sealed in dry,2-8°C

solubility 

DMSO: soluble20mg/mL, clear

form 

powder

pka

4.84±0.30(Predicted)

color 

white to beige

Merck 

14,1862

InChI

InChI=1S/C15H12ClNO2/c1-8(15(18)19)9-2-4-11-12-7-10(16)3-5-13(12)17-14(11)6-9/h2-8,17H,1H3,(H,18,19)

InChIKey

PUXBGTOOZJQSKH-UHFFFAOYSA-N

SMILES

N1C2=C(C=C(Cl)C=C2)C2=C1C=C(C(C)C(O)=O)C=C2

CAS DataBase Reference

53716-49-7(CAS DataBase Reference)

EPA Substance Registry System

9H-Carbazole-2-acetic acid, 6-chloro-.alpha.-methyl- (53716-49-7)

Safety Information

Hazard Codes 

T,Xn

Risk Statements 

25-36/37/38-20/21/22

Safety Statements 

45-36-26

RIDADR 

UN 2811

WGK Germany 

3

RTECS 

FE3180000

HazardClass 

6.1

PackingGroup 

III

HS Code 

29339900

Toxicity

LD50 orally in mice: 400 mg/kg (Berger, Corraz)

Carprofen Usage And Synthesis

Description

Carprofen is a non-steroidal anti-inflammatory drug (NSAID) commonly used in animals to combat pain and inflammation, particularly as associated with osteoarthritis. Like many NSAIDs, carprofen inhibits both cyclooxygenases COX-1 and COX-2 (IC₅₀s = 22.3 and 3.9 μM, respectively). It also inhibits fatty acid amide hydrolase (IC₅₀ = 74 μM), blocking the metabolism of the cannabinoid receptor ligand, arachidonoyl ethanolamide .

Chemical Properties

Off-White Crystalline Solid

Originator

Imadyl,Roche,Switz.,1981

History

Carprofen has strong anti-inflammatory and analgesic activity. It has been used in human medicine for more than 10 years at doses of 150 to 600 mg per day. In human clinical trials, Carprofen was generally well tolerated. Most adverse reactions were transient and mild, such as gastrointestinal discomfort or pain and nausea. The incidence of side effects in humans is similar to that of aspirin and other NSAIDs. However, for commercial reasons, carprofen has been withdrawn from the market and is no longer available for human use.

Uses

Carprofen is a non-steroidal anti-inflammatory drug (NSAID) commonly used in animals to combat pain and inflammation, particularly as associated with osteoarthritis. Like many NSAIDs, carprofen inhibits both cyclooxygenases COX-1 and COX-2 (IC50s = 22.3 and 3.9 μM, respectively). It also inhibits fatty acid amide hydrolase (IC50 = 74 μM), blocking the metabolism of the cannabinoid receptor ligand, arachidonoyl ethanolamide .

Uses

antiinflammatory, analgesic

Uses

Carprofen is a non steroidal anti-inflammatory that is used by veterinarians for the relief of arthritic systems in dogs. It can be used for joint pain or post operative inflammation. Carprofen, is al so used for the relief from pain and inflammation associated with osteoarthritis, hip dysplasia and other joint issues.

Definition

ChEBI: Propanoic acid in which one of the methylene hydrogens is substituted by a 6-chloro-9H-carbazol-2-yl group. A non-steroidal anti-inflammatory drug, it is no longer used in human medicine but is still used for treatment of arthritis in elderly dogs.

Manufacturing Process

A mixture of 34.9 g of 6-chloro-α-methyl-1,2,3,4-tetrahydrocarbazole-2-acetic acid ethyl ester (mixture of diastereomers), 350 ml CP xylene and 56.0 g of p-chloranil was stirred and heated under an atmosphere of dry nitrogen. The reaction flask was wrapped in aluminum foil in order to keep out any extraneous light. After the reaction mixture had stirred at reflux temperature for 6 hours, heating and stirring were stopped and the reaction mixture was left overnight at room temperature. The supernatant liquid was decanted through a filter. The residue was triturated with 100 ml of warm benzene and the supernatant liquid was decanted through a filter. This process was repeated three more times. Ether (300 ml) was added to the combined filtrates. The solution was extracted with cold 2 N sodium hydroxide (3 x 100 ml), washed by extraction with water until neutral and dried over anhydrous magnesium sulfate. Following filtration of the desiccant and evaporation of the solvent, a residue of 35.5 g remained. Crystallization from 50 ml of methanol gave 14.8 g of 6-chloro-α-methylcarbazole-2-acetic acid ethyl ester, MP 106°- 107.5°C (43.2%).
A stirred mixture of 11 g of 6-chloro-α-methylcarbazole-2-acetic acid ethyl ester, 100 ml ethanol and 100 ml of 3 N sodium hydroxide was heated (N2 atmosphere). After 2 hours at reflux, the reaction mixture was concentrated to dryness under reduced pressure. Water (300 ml) and ice (200 g) were added to the residue and concentrated hydrochloric acid was added until the mixture was strongly acid. The acidic mixture was extracted with ether (3 x 200 ml). The ether extracts were combined, washed by extraction with water (3 x 100 ml) and dried over anhydrous magnesium sulfate. Following filtration of the desiccant and evaporation of the solvent, a yield of 9.89 (98.2%) was obtained. Crystallization from CHCl3 yielded 6.2 g (62.0%) of 6-chloro-α- methylcarbazole-2-acetic acid, MP 197°-198°C. A second crop of 1.6 g, MP 195°-199°C was obtained from the mother liquors.

Therapeutic Function

Antiinflammatory

Mechanism of action

Carprofeng is a non-narcotic NSAID with analgesic and antipyretic properties. It acts in the same way as most NSAIDs in that Carprofeng acts by inhibiting cyclooxygenase (COX), which selectively inhibits COX-2, thereby inhibiting the release of several prostaglandins involved in the chronic inflammatory response that is thought to be present in canine OA.

Side effects

Common side effects of Carprofeng in dogs include vomiting, diarrhoea, loss of appetite, constipation, behavioural changes; and in severe cases, black stools, gastrointestinal ulcers and gastrointestinal haemorrhage, jaundice, skin changes, involuntary muscle movements, and kidney damage (increased thirst, increased urination, and refusal to eat).

Veterinary Drugs and Treatments

Carprofen is labeled (in the USA) for the relief of pain and inflammation in dogs. It may also prove to be of benefit in other species as well, but data is scant to support its safety beyond very short-term use at this time. In Europe, carprofen is reportedly registered for single dose use in cats, but there have been reported problems (e.g., vomiting) with cats receiving more than a single dose.
Carprofen is being investigated for antineoplastic effects in dogs and may be a useful adjunctive treatment for some types of tumors with COX-2 overexpression.

Carprofen(53716-49-7)Related Product Information

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• Ethyl chloroacetate
• Methyl chloroacetate
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• Ethyl 2-(Chlorosulfonyl)acetate
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• Acetic anhydride
• Difluorochloromethane
• 5-Chloroindole
• 6-Methylindole
• Carprofen, Vetranal
• Phenylacetic acid
• Carprofen Related Compound A
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• 6-ISOPROPYLINDOLE 97
• 1-(6-Chloro-9H-carbazol-2-yl)ethanone (Carprofen Impurity)
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