Benoxaprofen 42

Chemical Name 2-(2-p-Chlorophenyl-5-benzoxazolyl)propionic acid 

Ethyl-2-(3-hydroxy-4-amlnophenyl)propionate p-Chlorobenzoyl Chloride 

The 6-benzoxazolyl analog of the 5-benzoxazolyl product Is prepared as follows  

Therapeutic Function Antiinflammatory,analgesic Chemical Name 2-(2-p-Chlorophenyl-5-benzoxazolyl)propionic acid Common Name -Structural Formula , ,  

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N-p-Chlorobenzohydryl piperazine Hydroxyzine HCI o-Chlorobenzo nitrile Ketamine HCI o-Chlorobenzophenone Chlophedianol 4-Chlorobenzophenone Chlorphenoxamine HCI p-Chlorobenzoyl chloride Benoxaprofen... 

Ethy I-2-(3-hydroxy-4-ami nophenyl) propio nate Benoxaprofen Ethyl p-hydroxybenzoate Cyclomethycaine... 

The selectivity of another cellulose-based CSP, Chiralcel OJ, has also been examined in SFC [60]. Separations of racemic drugs such as benoxaprofen, temazepam, and mephobarbital were obtained. Acetonitrile proved to be a better modifier than methanol for some of the compounds investigated. The four optical isomers of a calcium channel blocker were resolved by Siret et al. on the Chiralcel OJ CSP [30]. In LC, two CSPs were required to perform the same separation. 

C7H4CI2O 122-01-0) see Acemetacin Benoxaprofen Bezafibrate Feclobuzone Fenofibrate Indometacin Moclobemide Progabide Rebamipide Zomepirac (2-chlorobenzoyi)cyciopentane (C12H13CIO 6740-85-8) see Ketamine... 

CyHyNO 21850-61-3) see Benoxaprofen Flunoxaprofen 2 -hydroxy-3-phenylpropiophenone (C15H14O2 3516-95-8) see Etafenone Propafenone (2S-cw)-4-hydroxy-4-phenyI-l,2-pyrroIidinedicarboxyIic acid l-(phenylmethyl) ester (CiyHiyN05 78464-03-6) see Fosinopril a hydroxy-a-phenyl-2-thiopheneacetic acid 2-diethylami-noethyl ester... 

Probably inspired by ibuprofen and its analogues, the nonsteroidal antiinflammatory agent benoxaprofen... 

Cashin, C. H., Dawson, W. and Kitchen, E.A. (1977). The pharmacology of benoxaprofen (2-[4-chlorophynl]-a-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with anti-inflammatory activity apparently unrelated to inhibition of prostaglandin synthesis. J. Pharm. Pharmacol. 29 330-336. 

When the real problems with benoxaprofen emerged, however, they were more serious It was apparently killing elderly patients with hepatic disorders, inducing massive photosensitivity, and causing oncholysis (separation of the nail plate from the bed) in about 15% of patients. It seems probable that at least 70 elderly patients died, and many more people suf-fered. ° Shortly after its well-publicized entry into the U.S. market, the manufacturer of benoxaprofen voluntarily withdrew its product as it caused fatal cholestatic hepatitis. " This action immediately followed news of suspension of the license to sell benoxaprofen in the United Kingdom. ... 

Taggart, H., Fatal cholestatic jaundice in elderly patients taking benoxaprofen, Br. Med. /., 284, 1372,1982. 

Committee on Safety of Medicines, Suspension of products licenses for benoxaprofen. Lancet, 2, 396,1982. 

One of the first compounds reported to inhibit 5-LO was the NSAID benox-aprofen (167) (reviewed in [405]). This drug (marketed by Lilly as Oraflex ) was effective in rheumatoid arthritis, but was withdrawn because of phototoxicity, liver toxicity and reports of drug-related deaths [406]. The typical NSAID anti-inflammatory profile of this compound was remarkable for its very weak seminal vesicle CO activity [407]. Additional in vivo activities were found for benoxaprofen which were not shared by other NSAIDs, particularly inhibition of leukocyte influx in the carrageenan sponge, carrageenan pleurisy, and rat Arthus pleurisy models monocytes were affected more than neutrophils [408-411]. More recently, benoxaprofen was reported to inhibit the adhesion of monocytes to endothelium [412]. 

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