Carprofen

Carprofen is a nonsteroid anti-inflammatory agent, acts as a multi-target FAAH/COX inhibitor, with IC50s of 3.9 μM, 22.3 μM and 78.6 μM for COX-2, COX-1 and FAAH, respectively.

Solid

Carprofen is 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. It has a role as a non-steroidal anti-inflammatory drug, an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor and a photosensitizing agent. It is a member of carbazoles and an organochlorine compound.|Carprofen is a non-steroidal anti-inflammatory drug (NSAID) that is used by veterinarians as a supportive treatment for the relief of arthritic symptoms in geriatric dogs. Carprofen was previously used in human medicine for over 10 years (1985-1995). It was generally well tolerated, with the majority of adverse effects being mild, such as gastro-intestinal pain and nausea, similar to those recorded with aspirin and other non-steroidal anti-inflammatory drugs. It is no longer marketed for human usage, after being withdrawn on commercial grounds.

The solid formed is removed by filtration, washed with acetic acid/water (1:1) and water and then dried. The 192 g. of crude 6-chloro-alpha-methyl-carbazole-2-acetic acid obtained are dissolved in 1.2 liters of 1 N potassium hydroxide, the solution is extracted with four 300 ml. portions of diethyl ether and acidified by the addition of 100 ml. of concentrated hydrochloric acid while cooling in an ice-bath under nitrogen.The mixture is stirred for 15 minutes, the precipitated solid is removed by filtration, washed with water and dried. 167.7 G. of product are obtained. The last purification is carried out by crystallization from 4.7 liters of boiling 1, 2-dichloroethane with 8.0 g. of active carbon. The solution is cooled overnight, the crystals are removed by filtration, washed with dichloroethane and dried. There are obtained 103.8 g. (57.3% of theory) of almost white 6-chloro-alpha-methyl-carbazole-2-acetic acid having a melting point of 198.5-201 C.Thus, specific examples of antiphlogistic carboxylic acids whose acyl residues are represented by B are the following: ... 6, 11-dihydro-11-oxo-dibenz[b, e]oxepine-3-acetic acid, 6, 11-dihydro-11-oxo-dibenz[b, e]oxepine-2-acetic acid, alpha-methyl-5-oxo-5H-dibenzo[a, d] cycloheptene-2-acetic acid, 2-(4-chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid, 6-chloro-alpha-methyl-9H-carbazole-2-acetic acid, alpha-ethyl-4-(2-methylpropyl)-phenyl-acetic acid, alpha-methyl-3-phenoxy-phenyl-acetic acid, 2-(2, 4-dichlorophenoxy)-phenyl-acetic acid, ......ach is hydrogen or jointly represent oxygen, sulfur, nitrogen, amino, carbonyl, methylene, or a carbon-to-carbon bond; with the proviso that R4 and R5 are different from Z; and R6 is hydrogen or amino. Such carboxylic acids of Formula IIc include, for example: 2-(3-benzoylphenyl)propionic acid 2-(3-phenoxyphenyl)propionic acid 2-(2fluorenyl)propionic acid 2-(6-chloro-2-carbazolyl)propionic acid 2-(6-oxo-3-xanthenyl)propionic acid 10-methyl-2-phenothiazinylacetic acid 2-(9-aza-3-xanthenyl)propionic acid 4-(3-diphenyloxidyl)-4-oxobutyric acid ...While all of the compounds encompassed by the formula 1 essentially satisfy the objectives of the present investigation, preferred compounds include those derived from the following compounds: ... Lonazolac Fenbufen Carprofen Loxoprofen ...Compounds according to claim 1 wherein R1-CO- is derived from the group of compounds selected from ... Lonazolac Fenbufen Carprofen Loxoprofen ...EXAMPLE 4 Preparation of 6-chloro-alpha-methylcarbazole-2-acetic acid Into a 5 l. 3-neck flask equipped with a stirrer, thermometer, condenser and nitrogen atmosphere is placed 247 g. of diethyl-[6-chloro-2-carbazolyl]methyl malonate, 1.9 l. of glacial acetic acid and 1.9 l. of 6 N hydrochloric acid. The mixture is stirred and refluxed overnight and the resulting black solution allowed to cool to room temperature. The solid formed is filtered, washed with three 200 ml. portions of 1:1 acetic acid-water, followed by four 300 ml. portions of water, and dried at reduced pressure. The crude 6-chloro-alpha-methylcarbazole-2-acetic acid (approximately 192 g.) is dissolved in 1.2 l. of cold (10) 1 N potassium hydroxide, and the solution is extracted with four 300 ml. portions of ether, and then while cooling in an ice bath, under nitrogen, is acidified by the addition of 100 ml. of concentrated hydrochloric acid. Stirring is continued for 15 minutes, the precipitated solid is filtered, washed with three 100 ml. portions of water, and dried at reduced pressure to give 167.7 g.

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 .

Molecular Weight:273.71
XLogP3:4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:273.0556563
Monoisotopic Mass:273.0556563
Topological Polar Surface Area:53.1
Heavy Atom Count:19
Complexity:362
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes