J. Med. Chem. 1981,24,843-847
Research, National Institute of Child Health and Human Development, National Institute of Health (NO1 HD-02813), is gratefully acknowledged. Thanks are expressed to Professor Niels Andersen and Dr. Marvin J. Karten for
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useful discussions and comments. We are indebted to Professor J. Jarabak, Department of Medicine, University of Chicago, for the 15-hydroxyprostaglandin dehydrogenase inhibition assays.
A Nonmetabolized Analogue of Phenytoin’ James D. Henderson,* Peter G. Dayton, Zafar H. Israili, and Leon Mandell Departments of Medicine and Chemistry, Emory University, Atlanta, Georgia 30322. Received August 25, 1980
Nine novel analogues of 5,5-diphenylhydantoin bearing a CF3groups(s) in the meta or para position of one or both rings were synthesized. Preliminary evaluation of all the analogues (performed by the ADD Program, NIH) indicated no significant anticonvulsant activity against electrical or chemical shock in mice at doses of 1100 mg/kg. The analogue 5,5-bis[4-(trifluoromethyl)phenyl]hydantoin(1) was synthesized labeled with ‘“c in the 4 position of the hydantoin ring. Certain physicochemical properties (pK,, partition ratio, protein binding, etc.) and the LDso of 1 in mice (40 mg/kg, ip; 100 mg/kg, PO) were determined. The disposition of [“C]l was determined in rodents. The compound was excreted unchanged in rat feces (94% in 18 days), urinary excretion
