Flunoxaprofen

Flunoxaprofen

Systematic (IUPAC) name
(2S)-2-[2-(4-fluorophenyl)-1,3-benzoxazol-5-yl]propanoic acid
Identifiers
CAS Number	66934-18-7 Y
ATC code	G02CC04 (WHO) M01AE15
PubChem	CID: 68869
UNII	UKU5U19W9M Y
KEGG	D07219 Y
ChEBI	CHEBI:76154 N
ChEMBL	CHEMBL1614641 N
Chemical data
Formula	C16H12FNO3
Molecular mass	285.269783 g/mol
NY (what is this?)  (verify)

Flunoxaprofen, also known as Priaxim, is a chiral non-steroidal anti-inflammatory drug. It is closely related to Naproxen, which is also an NSAID. Flunoxaprofen has been shown to significantly improve the symptoms of osteoarthritis and rheumatoid arthritis. The clinical use of flunoxaprofen has ceased due to concerns of potential hepatotoxicity.

Structure

Flunoxaprofen is a two-ring heterocyclic compound derived from benzoxazole. It also contains a fluorine atom and a propanoyl group.

Synthesis and preparation

Synthesis of flunoxaprofen can be seen here

Because flunoxaprofen has limited water-solubility, additional steps must be taken in order to prepare syrups, creams, suppositories, etc. In order to make flunoxaprofen water-soluble, yet still active and efficient, it must be mixed with lysine and then suspended in an organic solvent that is soluble in water. A salt will crystallize upon cooling. The salt must then be filtered out and dried. Pharmacological testing of this now water-soluble compound has shown that it has anti-inflammatory properties equal to flunoxaprofen by itself.

Pharmacokinetics

The efficacy and safety of flunoxaprofen has been compared with those of Naproxen in rheumatoid arthritis patients to show that the two drugs have equivalent therapeutical effects. Both drugs significantly relieve spontaneous pain which occurs both during the day and at night. Both drugs also significantly relive the pain associated with active and passive motion and aid in relieving morning stiffness. The study also showed both drugs to be equally effective at improving grip strength.

Flunoxaprofen has two enantiomers. The absorption and siposition of both enantiomers were studied in 1988. No significant differences were seen between the absorption and elimination half-lives between the two. However, further studies have shown that the S-enantiomer is the active form of the drug. Flunoxaprofen is pharmacologically activated through biotransformation of the R-enantiomer to the S-enantiomer. This highly stereoselective chiral inversion is mediated by the FLX-S-Acyl-CoA thioester.

Pharmacokinetic studies have been carried out by determining the level of propranolol enantiomers in the plasma after administering the racemic drug orally. It has been shown that the dextrorotatory form is particularly active and has a much higher therapeutic index than some other anti-inflammatories, including indomethacin and diclofenac.

It has also been shown that flunoxaprofen inhibits leukotriene rather than prostaglandin synthesis. This is similar to benoxaprofen. Flunoxaprofen and benoxaprofen have been shown to have similar absorption characteristics. However, the distribution and elimination of flunoxaprofen has been shown to be much faster than benoxaprofen.

Adverse effects

A structural analog of flunoxaprofen is benoxaprofen. The two drugs are carboxylic acid analogs that form reactive acyl glucurnonides. Benoxaprofen has been shown to be involved in rare hepatotoxicity. Because of this, benoxaprofen has been removed from the market. In response to this the clinical use of flunoxaprofen has also stopped, even though studies have shown that flunoxaprofen is less toxic than benoxaprofen.

The toxicity of these nonsteroidal antiinflammatory drugs may be related to the covalent modification of proteins in response to the drugs' reactive acyl glucuronides. The reactivity of the acyl glucoronides can affect the protein binding.