Description
Loxoprofen sodium i s an antiinflammatory/analgesic agent useful in the management of rheumatoid arthritis and related disorders. It is converted in vivo to the corresponding trans-hydroxycyclopentane analog, through which it appears to exert its activity.
Originator
Sankyo (Japan)
Definition
ChEBI: A hydrate that is the dihydrate form of loxoprofen sodium. The parent acid, loxoprofen, is a prodrug that is rapidly converted to its active trans-alcohol metabolite following oral administration.
Mechanism of action
As most NSAIDs, loxoprofen is a non-selective cyclooxygenase inhibitor, and works by reducing the synthesis of prostaglandins from arachidonic acid.
Side effects
Adverse effects include anorexia, nausea, vomiting, bleeding, anemia, diarrhea, and constipation.
Synthesis
General procedure for the synthesis of sodium 2-(4-((2-oxocyclopentyl)methyl)phenyl)propionate from 2-(4-((2-oxocyclopentyl)methyl)phenyl)propionic acid: 2-(4-((2-oxocyclopentyl)methyl)phenyl)propionic acid and methanol were added into a round-bottomed flask, and 1 equivalent of aqueous sodium hydroxide was added to the above solution drop by drop, and the reaction was stirred for 1 hour at room temperature. Upon completion of the reaction, a decompression distillation was carried out at 50-55°C to remove the solvent. Subsequently, a 5% aqueous solution of ethyl acetate was added to the residue, heated until dissolved and then slowly cooled to room temperature. Crystallization was induced by the addition of crystal seeds during cooling and stirring was continued for 5-6 hours at 0-5°C until a suspension was formed. Finally, the solid was collected by filtration to give loxoprofen sodium dihydrate in 95% yield and 99.1% HPLC purity.
References
[1] Journal of Medicinal Chemistry, 2010, vol. 53, # 21, p. 7879 - 7882
[2] Patent: CN107176942, 2017, A. Location in patent: Paragraph 0067; 0068; 0069
[3] Patent: CN108440274, 2018, A. Location in patent: Paragraph 0076; 0077; 0078; 0079; 0080
