excrete a variety of equine estrogens, including equilenin (5.25), a steroid containing
the naphthalene ring system, and equilin (5.26); these equine estrogens are not synthe-
sized in humans but readily bind to human estrogen receptors. All of these equine
steroids have an aromatic A-ring and therefore lack a 19-methyl group. These estro-
genic substances are excreted in very large quantities in equine urine and can be recov-
ered and used for medicinal applications in human patients.
Today, a variety of therapeutic estrogens are produced semisynthetically from estro-
gen intermediates synthesized from diosgenin and other natural precursors. Two semi-
synthetic, orally active estrogens are ethinyl estradiol (5.27) and its 3-methyl ether
(5.28, mestranol). Both of these are used in oral contraceptives (see section 5.8.3).
Quinestrol (5.29) is another semisynthetic estrogen. The most important property of the
semisynthetic estrogens is their increased oral effectiveness.
5.8.2 Nonsteroidal EstrogensIn addition to estrogen agonists based on steroid structures, a variety of nonsteroidal
estrogens have also been synthesized and used clinically: dienestrol (5.30), diethyl-
stilbestrol (5.31), benzestrol (5.32), hexestrol (5.33), methestrol (5.34), methallenestril
(5.35), and chlorotrianisene (5.36).
Of these various nonsteroidal compounds, the first were trans-diethylstilbestrol
(DES) (5.31) and its reduced derivative hexestrol (5.33). The way in which these non-
steroidal stilbene (diphenylethylene) derivatives are usually drawn suggests a resem-
blance to the steroid skeleton. However, this resemblance is purely incidental, since the
two ethyl groups are not indispensable for estrogenic activity. For example, four methyl
groups will give comparable pharmacological activity. It seems, however, that the
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