English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

In earlier publications the oestrogenic activity of a number of synthetic substances has been discussed. The first compounds to be tested contained the phenanthrene ring system, and it was shown (Cook, Dodds and Hewett 1933; Cook and Dodds 1933; Cook, Dodds, Hewett and Lawson 1934; Cook, Dodds and Greenwood 1934) that a high degree of activity is possessed by 9 : 10-dihydroxy-9 : 10-di- n -propyl-9 : 10-dihydro-1 : 2 : 5 : 6-dibenzanthracene. Potency was also observed in the highly unsaturated aliphatic acid, clupanodonic acid, whilst a feeble but definite oestrogenic action was found to be possessed by calciferol. Since neither of these compounds contains the phenanthrene ring system, it was considered that this was not essential for oestrogenic properties. A further interesting observation was made in the partial activity of 1-keto-1: 2: 3: 4: 5: 6: 7: 8-octahydroanthracene. This substance produced an advanced pro-oestrus, but full cornification could not be produced no matter how much of the material was administered. A series of derivatives of acenaphthene was studied because these compounds contain a three-ring system arranged in a manner different from that in phenanthrene. These were tested on ovariectomized rats in the manner described in the above-mentioned publications. Table I shows the results obtained with this group of substances. It will be observed that the most potent member of the series is 1 : 2-dihydroxy-1 : 2-di- α -naphthyl acenaphthene. In doses of 10 mg. this compound produces prolonged oestrus. This new substance confirmed our assumption that the phenanthrene ring system was unnecessary for oestrogenic activity and led to experiments with a number of aromatic carbinols (Table II). This series of compounds showed surprising differences in behaviour. Thus, whilst diphenyl- α -naphthyl carbinol possesses full activity in doses of 100 mg. the corresponding diphenyl- β -naphthyl carbinol and triphenyl carbinol were both without action. The effect of hydroxy groups in the aromatic nucleus was then studied and several phenolic diphenyl methane derivatives were investigated with results as shown in Table III. 3 : 3′- and 4 : 4′- dihydroxydiphenyl methane both showed activity, the latter much greater than the former, but the corresponding dicarboxylic acids were without effect. Many potent substances were found in derivatives of 4 : 4′ dihydroxy-diphenyl methane. From this series it appears that the alkyl substituents on the central carbon atom have no influence on the efficacy of the substance. A single phenyl nucleus has a distinct depressing action, and the diphenyl derivative is completely inert. The introduction of methyl groups in the 3 : 3′ positions appears to diminish the potency in some cases.

Molecular structure in relation to oestrogenic activity. Compounds without a phenanthrene nucleus