Pharmacological profile of the novel potent antirheumatic 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid.
On the basis of basic screening for novel, more potent antiarthritics VUFB-16066 (4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid, CAS 112344-S2-2) was chosen as a compound with pronounced anti-inflammatory and immunomodulatory effects, with good gastric tolerance and relatively low toxicity. VUFB-16066 is a dual cyclooxygenase and 5-lipoxygenase inhibitor, and it suppresses alloantigen-driven cellular immune response and phagocytosis of stimulated peritoneal cells. VUFB-16066 exhibits prolonged pharmacological activity connected with its major metabolite having a very long half-life. In the model of adjuvant arthritis VUFB-16066 improves most of disease symptoms including immunopathological disturbances, which indicates possible disease-modifying activity of the drug. The beneficial antiarthritic effect of VUFB-16066 has been also confirmed in patients with rheumatoid arthritis.
Panajotova
V
V
VUFB, a.s. (Research Institute for Pharmacy and Biochemistry), Prague, Czech Republic.
Andĕrova
E
E
Jandera
A
A
Kuchar
M
M
D015746:Abdominal Pain / Q000139:chemically induced / Q000188:drug therapy; D019342:Acetic Acid; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D016718:Arachidonic Acid; D001169:Arthritis, Experimental / Q000188:drug therapy; D002087:Butyrates / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002351:Carrageenan; D004008:Diclofenac / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006087:Graft vs Host Reaction / Q000187:drug effects; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000187:drug effects; D010654:Phenylbutyrates / Q000627:therapeutic use; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D011917:Rats, Inbred Lew; D013276:Stomach Ulcer / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002087:Butyrates; D010654:Phenylbutyrates; C056474:flobufen; D004008:Diclofenac; D007975:Leukotriene B4; D016718:Arachidonic Acid; D002351:Carrageenan; C010725:fenbufen; D015232:Dinoprostone; D019342:Acetic Acid