Characterization of 5-[5-(4-chlorophenyl-2-furanyl)]dihydro-2(3H)-furanone as a nonsteroidal antiinflammatory drug.
5-[5-(4-Chlorophenyl-2-furanyl)]dihydro-2(3H)-furanone (F-1044), a nonsteroidal antiinflammatory drug related to orpanoxin, lacks the usual acid moiety of such agents. F-1044 had antiinflammatory activity equivalent to ibuprofen's and orpanoxin's in the carrageenin-induced paw edema model in normal and adrenalectomized rats. Antiinflammatory activity was also expressed in the guinea pig UV-induced erythema and rat established arthritis models. F-1044 was a more potent analgesic than ibuprofen and orpanoxin in the rat paw pressure assay. In contrast to the reference agents, F-1044 raised the pain threshold of both the yeast-injected and non-injected paws, suggesting a central component to its analgesic action. F-1044 was more potent than ibuprofen and orpanoxin in the rat brewer's yeast pyresis model. Based on its low activity in inhibiting bradykinin-induced bronchoconstriction in guinea pigs and low gastric irritation activity in rats. F-1044 appears to have a mechanisms of action that involves more than simple inhibition of prostaglandin synthesis. Thus F-1044 is a nonsteroidal antiinflammatory agent with unique chemical and pharmacological features.
Brooks
R R
RR
Norwich Eaton Pharmaceuticals, Inc., a Procter & Gamble Company, Norwich, NY.
Miller
K E
KE
Pelosi
S S
SS
Pong
S F
SF
Anthony
D R
DR
Goldenberg
M M
MM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000517:prevention & control; D001993:Bronchodilator Agents; D005663:Furans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D007166:Immunosuppressive Agents; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced; D014528:Uricosuric Agents
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001993:Bronchodilator Agents; D005663:Furans; D007166:Immunosuppressive Agents; D014528:Uricosuric Agents; C055611:5-(5-(4-chlorophenyl-2-furanyl))dihydro-2(3H)-furanone