Humber L G, Ferdinandi E, Demerson C A, Ahmed S, Shah U, Mobilio D, Sabatucci J, De Lange B, Labbadia F, Hughes P
Ayerst Laboratories Research, Inc., Princeton, New Jersey 08543-8000.
J Med Chem. 1988 Sep;31(9):1712-9. doi: 10.1021/jm00117a009.
The syntheses of five metabolites of the antiinflammatory drug etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid) are described, viz. 6-hydroxyetodolac, N-methyletodolac, 4-ureidoetodolac, 8-(1'-hydroxy)etodolac, and 4-oxoetodolac. These syntheses were used to confirm the identities of the metabolites. The metabolites themselves, as well as the previously reported metabolite 7-hydroxyetodolac, were tested in a rat adjuvant edema model and in vitro for their capacity to block prostaglandin production in chondrocyte cells. All either were inactive or possessed only marginal activity. The isolation of N-methyletodolac and 4-oxoetodolac from human and rat urine, respectively, is also described.
