STUDIES ON THE LAXATIVE ACTIVITY OF TRIPHENYLMETHANE DERIVATIVES

I. Relationship between Structure and Activity of Phenolphthalein Congeners

¹ Department of Pharmacology, University of Utah School of Medicine, Salt Lake City, Utah

1 . By a study of the laxative potency in the monkey of 46 isomers, homologs and analogs of phenolphthalein, some light is shed upon the structural factors which vary the laxophoric character of the basic two-ring skeleton and govern the modification of cathartic activity by substituents.

2. In the class of isomers and homologs of phenolphthalein, the variation of laxative activity by hydroxyl and other substituents at the free benzene rings, and of blocking of hydroxyl groups, could be expressed by a series of rules which are compatible with certain concepts of spatial arrangement and intramolecular kinetics. Maximum potency in the series, 1.63 times that of phenolphthalein, was embodied in the racemic trihydric pyrogallolbenzenephthalein, which suggests the possibility of still higher potency in an optical isomer.

3. In the analogs of phenolphthalein, the laxophoric character of the skeletal two-ring system was decreased in those compounds studied in which the benzene part of the skeleton was enlarged by substitution, and when the phthalide was replaced by phthalimide, N-methylphthalimide or anthrone, but greatly increased when it was replaced by isatin, N-acetylisatin or naphthalide. Phenolnaphthalein had 5 and the isatins up to 17 times the potency of phenolphthalein.

4. Reasons are presented for discarding certain older views concerning the mechanism of laxative action of phenolphthalein and its congeners.