6-aryl-4-oxohexanoic acids: synthesis, effects on eicosanoid biosynthesis, and anti-inflammatory in vivo-activities.
The synthesis of a series of 6-aryl-4-oxohexanoic acids is described: This involves condensation of an appropriate aldehyde (Ia-f) and levulenic acid using catalytic amounts of piperidine and acetic acid in toluene to afford the 6-aryl-4-oxohex-5-enoic acids (IIa-f). The arylidene derivatives (IIa-d) were reduced by hydrogen at room temperature using palladium (10 %/carbon) as catalyst to produce 6-aryl-4-oxohexanoic acids (IIIa-d) as target compounds. In certain instances, the lactone derivative (IVd) was obtained as a low-melting by-product. These compounds were tested in two models used for evaluating the activity of non-steroidal anti-inflammatory drugs (NSAIDs). The first test is the effect of the synthesized compounds on arachidonic acid metabolism in vitro using human whole blood assay. The second is the in vivo carrageenan induced rat paw edema test. Compound IIe showed higher in vivo-activity compared to fenbufen at the same dose level (50mg/kg).
Abouzid
Khaled
K
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. abouzid@yahoo.com
Frohberg
Petra
P
Lehmann
Jochen
J
Decker
Michael
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D002208:Caproates / Q000138:chemical synthesis* / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015777:Eicosanoids / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002208:Caproates; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D016859:Lipoxygenase Inhibitors