A study in mice of bromo and chloro acylurea analogues of the sedative-hypnotic bromureides.
1. A series of 1-(2-chloroacyl)ureas, related to the sedative-hypnotic drugs bromvaletone and carbromal, was synthesized and tested in mice to determine central depressant and acute toxic effects. Four 1-(2-bromoacyl)ureas and two 3-halo compounds were included for comparison. 2. Large variations in potency were seen between the compounds. Much of this can be ascribed to differences in lipophilicity. Among homologous 1-(2-chloroacyl)ureas, those with 6 acyl carbons had maximal potency. Among groups of structural isomers, the most potent were 2-halo, 3-alkyl substituted compounds. 3. The most potent compounds were also those with the largest ratios of hypnotic to lethal activity. 4. The variation in the onset and duration of action of these compounds enables a choice to be made for a compound with a particular set of characteristics.
D000818:Animals; D001968:Bromisovalum / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
D006993:Hypnotics and Sedatives; D001968:Bromisovalum; D014508:Urea