Anti-inflammatory and analgesic activities of 3-imino-1-oxoisoindolines in CF1 mice.
A series of 3-imino-1-oxoisoindolines were shown to be potent anti-inflammatory and analgesic agents at 8 mg/kg, intraperitoneally in mice. The compounds were also able to protect against lipopolysaccharide induced endotoxic shock and death better than the current clinical agents. These agents appear to function by blocking the release of TNF alpha and IL-1 from macrophages as well as competition with their respective high affinity receptors on target tissue, eg. fibroblasts, and macrophages. In addition lysosomal hydrolytic enzymes were inhibited as well as leukotriene synthesis in macrophages by the agents.
Butner
L
L
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27559-7360, USA.
Huang
Y
Y
Tse
E
E
Hall
I H
IH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000493:pharmacokinetics; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000493:pharmacokinetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D006867:Hydrolases