Diphenylacetyl-l,3-Indandione as a Potent Hypoprothrombinemic Agent

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Abstract
2-Diphenylacetyl-1,3-indandione (U-1363) was a more potent hypoprothrombinemic compound than bishydroxy-coumarin, ethyl biscoumacetate, and 17 analogs of indandione, tested by oral admn. to rabbits. Comparable prothrombinopenic responses were obtained from single doses of 50 mg./kg. of ethyl biscoumacetate, 10 mg./kg. of bishydroxycoumarin, and 0.05 mg./kg. of U-1363. In chronic studies 25-100 ug./kg. of U-1363, usually every other day, yielded plasma prothrombin levels around 30% of normal. Histopathologic examinations after prolonged admn. revealed no lesions except a few pulmonary petechiae in some of the animals. Acute oral toxicities (LD50) for U-1363 were 3 mg./kg. for rats, 340 mg./kg. for mice and 35 mg./kg. for rabbits; chronic LD50''s, were 0.25 mg./kg./day for rabbits and greater than 0.1 mg./kg./day for rats. Vit. K1 was an antidote to the hypoprothrombinemia produced by U- 1363.

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