Synthesis of an active hydroxylated glutethimide metabolite and some related analogs with sedative-hypnotic and anticonvulsant properties.
Two synthetic pathways are described for the preparation of 4-hydroxy-2-ethyl-2-phenylglutarimide (2), an active hydroxylated metabolite of glutethimide (1).  Fourteen other glutethimide analogs were also synthesized and tested for biological activity.  Most of the analogs exhibited sedative-hypnotic properties and compound 2 possessed the greatest activity compared to the parent drug.  4-Amino-2-ethyl-2-phenylglutarimide and 4-hydroxy-2-ethyl-2-phenylglutaconimide (13) exhibited the greatest potential as anticonvulsant agents.  The structure-activity relationships of the series are discussed.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000633:toxicity; D002490:Central Nervous System / Q000187:drug effects; D003864:Depression, Chemical; D005984:Glutethimide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis* / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D005984:Glutethimide