Comparison of the Bromureide Sedative-Hypnotic Drugs, Bromvaletone (Bromisoval) and Carbromal, and Their Chloro Analogues in Mice

Abstract

1. The central depressant effects of bromvaletone, carbromal and six non-bromo analogues were compared in mice. 2. The chloro analogues of bromvaletone and carbromal were slightly less potent as central depressant agents than the bromo compounds. 3. The chloro analogue of bromvaletone had the greatest margin between central depressant and lethal doses. 4. Lipophilicity (octanol-water partition coefficient) did not provide a unifying relationship for potency within this group of eight acylureas. However, within each of the two subsets of compounds, a linear relationship was found between relative potency and lipophilicity.

A Study in Mice of Bromo and Chloro Acylurea Analogues of the Sedative‐hypnotic Bromureides

“…However, there is indirect evidence to suggest that the relationship is parabolic with a peak corresponding to halo acylureas of six acyl carbons. First, the peak of potency for homologous nonhalogenated acylureas has been found with compounds of seven acyl carbons (Mrongovius, 1975) and the lipophilic effect of a 2-chloro (or 2-bromo) substituent is about the same as that of an additional acyl carbon (Mrongovius et al, 1976). Second, the 8 acyl carbon compound 1 -(2-bromo-2-ethylhexanoyl)urea is less potent than its 6 acyl carbon homologue, carbromal (Nelson, Lyster & Cartland, 1941).…”

“…The 2-chloro analogues of bromvaletone and carbromal may offer some advantages over the bromureides as sedative-hypnotic drugs since they have almost the same depressant activity as the bromo compounds in mice, but can not give rise to bromism (Mrongovius, Gaff & Rand, 1976). Changes in the branching of isomeric halogen substituted acylureas can produce large differences in their central depressant activities (Eeckhout, 1907;Fourneau & Florence, 1927, 1928a.…”