Studies on the relationship between chemical constitution and physiological action

Abstract

IN Part I of this series, the author [1926] synthesised, and tested for miotic activity, a number of substituted phenyl esters of substituted carbamic acids, thereby demonstrating that miotic activity was frequently associated with urethanes of this type. While certain variations could be made in the urethane grouping without necessarily destroying the activity of the compounds, greatest activity was observed with those urethanes which were esters of methylcarbamic acid. It was further found that both the nature and position of the basic group, which was present in all the compounds examined, could be varied without in all cases destroying the physiological properties of the urethane grouping. Nevertheless, an examination of the isomeric dimethylaminophenyl esters of methyl-and ethyl-carbamic acids showed that the power of these compounds to produce a contraction of the pupil varied according to the relative positions of the basic and urethane groupings, and, further, that conversion of the tertiary basic group into a quaternary ammonium grouping exerted a great influence on this power, in some cases increasing, and in others diminishing, the miotic activity. By application of the polarity theory the deduction was made that, for each series of isomeric urethanes examined, greatest activity was exhibited by those urethanes derived from the phenols with the smallest acidic properties, and the same conclusion can be reached by application of the more modern electronic theories.