STUDIES OF PHENANTHRENE DERIVATIVES III. DI-SUBSTITUTION PRODUCTS

¹ From the Laboratory of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Twenty di-substitution phenanthrene compounds are described in comparison with mono-substitution derivatives containing the same groups attached to the phenanthrene nucleus.

In general the di-substitution products are less active than the related single substitution phenanthrenes. Exceptions are noted in which the two groups are attached in the 9- and 10-, or in the 3- and 4- positions. Not all of the phenanthrenes containing groups in these positions, however, show increased activity.

The most active compounds encountered in this series are 3-4-dihydroxyphenanthrene, and 3-hydroxy-4-aminophenanthrene. Both exhibit considerable toxicity and well-marked analgesic, depressant and emetic effects. Muzzling both hydroxyls of 3-4-dihydroxyphenanthrene by acetyl groups decreases effectiveness just as did muzzling the single hydroxyl of 2- or 3-hydroxyphenanthrene.

The introduction of a 4-5-oxygen bridge in the formation of the morphenols does not increase the activity of hydroxy- and alkoxyphenanthrenes.