Pharmacological profile of 4-(2',4'-difluorobiphenyl-4-yl)-2-methylbutyric acid (deoxoflobufen).
4-(2',4'- Difluorobiphenyl-4-yl)-2-methylbutyric acid (deoxoflobufen, VUFB 19053, CAS 847475-35-8) has been developed as a new omega-biphenyl-alkanoic acid and studied in comparison with the racemic form of 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (flobufen, CAS 112344-52-2). The compounds were tested in a series of models including acute inflammation induced by carrageenan, adjuvant arthritis, in vitro inhibition of the leuktotriene B4 (LTB4) production, reaction of the graft versus the host (GVHR), production of specific antibodies against ovalbumin, peritoneal exudate formation induced by thioglycollate and phagocytosis of thioglycollate-stimulated mouse peritoneal macrophages. Deoxoflobufen exhibited strong anti-inflammatory, antiarthritic and immunomodulatory effects in most of the performed tests. Anti-inflammatory and antiarthritic effects are fully comparable with those of flobufen, however, the compound is less toxic and has apparently stronger immunomodulating effects.
Bulej
Petr
P
IVAX Pharmaceuticals, R&D, Opava-Komárov, Czech Republic.
Kuchar
Miroslav
M
Panajotova
Vladimíra
V
Jegorov
Alexandr
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000917:Antibody Formation / Q000187:drug effects; D019540:Area Under Curve; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000633:toxicity; D002087:Butyrates / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D002448:Cell Adhesion / Q000187:drug effects; D005122:Exudates and Transudates / Q000187:drug effects; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007975:Leukotriene B4 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy; D010587:Phagocytosis / Q000187:drug effects; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship; D013864:Thioglycolates
C504193:4-(2',4'-difluorobiphenyl-4-yl)-2-methylbutyric acid; D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D002087:Butyrates; D013864:Thioglycolates; D007975:Leukotriene B4; D002351:Carrageenan; D010047:Ovalbumin