The anti-inflammatory activity of N-substituted indazolones in mice.
N-Substituted indazolones were shown to be potent anti-inflammatory and analgesic agents in mice at 8 mg/kg. In addition, the agents were able to protect against death caused by endotoxins similar to those found in chronic infections. In part, the ability of these agents to suppress the inflammatory process is due to their blockage of cytokine release, e.g.TNF alpha and IL-1, as well as their inhibition of high affinity binding to receptors on target cells of inflammation. Suppressing these receptors can be linked to the inhibition by the agents of lysosomal hydrolytic enzymes, prostaglandin cyclooxygenase and 5'-lipoxygenase activities. Free radical generation involved in inflammation was also stabilized in the presence of most of these agents.
Tse
E
E
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27759-7360, USA.
Butner
L
L
Huang
Y
Y
Hall
I H
IH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D007213:Indomethacin / Q000031:analogs & derivatives*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D007191:Indazoles; D007213:Indomethacin