Edward Charles Dodds

OEstrogenic Activity of Certain Synthetic Compounds

IN earlier communications1,2 two of us have described the œstrogenic activity of certain derivatives of diphenylethane, and in particular it was shown that the introduction of an ethylene linkage between the α and β carbon-atoms of such compounds greatly increased the potency. A number of stilbene derivatives were found to possess a marked activity. Following up this observation, the activity of p-hydroxypropylbenzene was next investigated and compared with that of p-hydroxypropenylbenzene (anol). The œstrogenic activity of some specimens of anol was found to be of a very high order, but further research indicated that this remarkable potency was probably due to the presence of a more complex substance produced as a by-product during the demethylation of anethole3. Recently, the activity of di-anol has been described4.

Synthetic Oestrogenic Compounds Related to Stilbene and Diphenylethane. III

The paper describes further experiments bearing on the relation between oestrogenic activity and chemical constitution in the synthetic series allied to stilboestrol. Certain generalizations suggested by previous work have been found to hold for the new examples. A new potent oestrogenic agent is described, namely, 3:4-di(p-hydroxyphenyl)-1:3:5-hexatriene. This substance, which we designate trienoestrol, is approximately equal to stilboestrol in activity.

Œstrogenic Activity of Anol; a Highly Active Phenol Isolated from the By-Products

IN a previous communication1, it was suggested that the œstrogenic activity of crude specimens of anol and of the mother liquor from these preparations may be due to the presence of a polymer possessing an extremely high degree of potency. The active substance has been isolated by the following procedure:

Œstrogenic Activity of some Hydrocarbon Derivatives of Ethylene

IN an earlier preliminary communication1, we reported the activity of some substituted derivatives of ethylene including the hydrocarbon diphenyl ethylene (stilbene). Before making any further publication, we decided to investigate other hydrocarbons of the same series as extensively as possible.

Œstrogenic Activity of Esters of Diethyl StilbÅ"strol

IT is a well established fact that the esterification of naturally occurring œstrogenic substances such as œstrone and œstradiol causes a marked alteration in their biological activity, particularly with regard to the duration of their action. It was therefore decided to investigate the biological activity of various double esters of the synthetic œstrogenic agent diethyl stilbcestrol previously described by us1.

Œstrogenic Activity of Di-Anol, a Dimeride of p -Propenyl-Phenol

DI-ANETHOLE or iso-anethole (I) has been described by Kraut and Schlun1 and later by Orndorff, Terrasse and Morton2 as an unsaturated liquid dimeride of anethole. Its structure was established by Goodall and Haworth3, who obtained from it, by oxidation, anisic acid and a ketone, which was identified as (II) by synthesis.

Morphine-like properties of diphenylethylamine and related compounds

Since morphine possesses the phenanthrene ring structure, experiments have been performed to investigate the possibility of producing a simple analogue with a relationship similar to that between oestrone and stilboestrol. The activity of diphenylethylamine and a number of other compounds has been investigated. Many were found to possess morphine-like activity, and of these the most promising from the clinical point of view was β-hydroxy-αβ-diphenylethylamine. This substance was found to give complete relief from pain in doses of 200-400 mg. 4-hourly.

The Nature of the Oestrogenic Substances Produced during the Demethylation of Anethole

The discovery of oestrogenic activity in synthetic substances not possessing the phenanthrene nucleus led eventually to interest in derivatives of stilbene, notably 4:4’ -dihydroxy-stilbene, and in para alkyl substituted phenols (Dodds and Lawson 1937a; Dodds, Fitzgerald and Lawson 1937). It was noted that p-propenyl phenol (anol) was a member of the latter series but in addition possessed structural similarity to the former. The substance was accordingly prepared and tested for oestrogenic activity, the potency being found of the same order as that of oestrone (Dodds and Lawson 1937b). Following this publication numerous workers repeated the preparation but reports on the activity were conflicting. Confirmation of the original announcement was forthcoming from several laboratories but others were quite unable to obtain similar results. A reinvestigation of the subject showed that while certain batches of crystalline material had high oestrogenic activity, others were very much less active.