The series of 4-(2',4'-difluorobiphenylyl)-2-methylbutyric acid (deoxoflobufen, 1) and its four amides and two salts were prepared and tested for anti-inflammatory activity in rats and mice, using as models carrageenan-induced paw oedema, pleuritis, and arachidonic acid-induced ear inflammation, and on leucotriene B4 production in cells.
deoxoflobufen; derivatives; salts; anti-inflammatory activity
Bjarnason I, Hayllar J, MacPherson AJ, Russell AS: Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 104:1832-1847, 1993.
Bulej P, Kuchar M, Husak M et al.: Crystal structure of 4-(2',4'-difluorobiphenyl-4-yl)-2- methylbutanoic acid, F2C16H15COOH, deoxoflobufen. Z Kristallogr NCS 219:297-298, 2004a.
Bulej P, Kuchar M, Husak M et al.: Crystal structure of benzylammonium 4-(2',4'- difluorobiphenyl-4-yl)-2-methylbutyrate, (F2C16H15COO)(C7H7NH3), a salt of deoxoflobufen. Z Kristallogr NCS 219:299-300, 2004b.
Bulej P, Kuchar M, Panajotova V, Jegorov A: Arzneim Forsch/Drug Res, in press 2005.
Hidaka T, Hosoe K, Katsumi I, Yamashita T, Watanabe K: The effect of alpha-(3,5-di-t-butyl- 4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory drug, on leucocyte migration in rat carrageenan pleurisy. J Pharm Pharmacol 38:244-247, 1986.
Jegorov A, Sedmera P, Havlicek V et al.: Spectroscopic and structural study of flobufen. J Fluorine Chem 73:213-219, 1995.
Jegorov A, Husak M, Ondracek J et al.: Structural study of flobufen. II. An unexpected role of packing effects on dihedral angle of phenyl rings in crystal structures of 2,4- difluorobiphenyls. J Fluorine Chem 83:111-116, 1997.
Kuchar M, Maturova E, Brunova B et al.: Quantitative relationships between structure and antiinflammatory activity of aryloxoalkanoic acids. Collect Czech Chem Commun 53:1862-1872, 1988.
Kuchar M, Poppova M, Jandera A et al.: Chiral forms of 4-(2',4'-difluorobiphenyl-4-yl)-2- methyl-4-oxobutanoic acid (Flobufen) and its metabolite. Synthesis and basic biological properties. Coll Czech Chem Commun 62:498-509, 1997.
Opas EE, Bonney RJ, Humes JL: Prostaglandin and leukotriene synthesis in mouse ears inflamed by arachidonic acid. J Invest Dermatol 84:253-256, 1985.
Palmer RMJ, Salmon JA: Release of leukotriene B4 from human neutrophils and its relationship to degranulation induced by N-formyl- methionyl-leucyl-phenylalanine, serum-treated zymosan and the ionophore A23187. Immunology 50:65-73, 1983.
Panajotova V, Anderova E, Jandera A, Kuchar M: Pharmacological profile of the novel potent antirheumatic 4-(2',4'-difluorobiphenyl-4-yl)-2- methyl-4-oxobutanoic acid. Arzneim Forsch/Drug Res 47:648-652, 1997.
Szabo S, Spill WF, Rainsford KD: Non-steroidal anti-inflammatory drug-induced gastropathy. Med Toxicol Adverse Drug Exp 4:77-94, 1989.
Winter CA, Risley EA, Nuss GN: Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs. Proc Soc Exp Biol Med 111:544-547, 1962.