Estrogen substitution

Wildemeersch, D., et al. 2004. Endometrial safety with a low-dose intrauterine levonorgestrel-releasing system after 3 years of estrogen substitution therapy. Maturitas 48 65. 

Hannon et al. (H2) evaluated the response to estrogen substitution therapy after 6 months of treatment by comparing the measurement results with the values before treatment, with respect to the critical differences. The effectiveness of therapy was best followed by the values of osteocalcine and PINP (87% of the results with the drop below the values CD percent). Collagen degradation products U-NTx/Cr and U-CTx/Cr showed only 27% and 18% responses to the treatment, respectively BMD change was significant only for the lumbar spine area in 36% of cases. No answer was reached by measuring the total and femoral value of BMD. 

Miller MM, Franklin KB Theoretical basis for the benefit of postmenopausal estrogen substitution... 

Self-condensation of the substituted propiophenone, 15, by the pinacol reaction proceeds to give the glycol, 16, as the meso isomer. (If it is assumed that the transition state for this reaction resembles product, this stereoselectivity can be rationalized on the grounds of steric interaction compare A, which leads to the observed product, with B.) Dehydration under very specialized conditions (acetyl chloride, acetic anhydride) affords the bisstyrene-type diene (17). Removal of the acyl groups by means of base affords the synthetic estrogen, dien-... 

As noted previously, triarylethylenes substituted by a basic group, such as clomiphene, exhibit estrogen antagonist activity. Formal cyclization of that molecule to a more steroid-like, rigid conformation enhances potency in this series. 

Estrogens and progestins are diminished in menopausal or ovarectomized women. In hormone replacement therapy (HRT), these hormones are substituted to alleviate hot flushes, mood changes, sleep disorders, and osteoporosis. 

Liu, H. Liu, J. van Breemen, R. B. Thatcher, G. R. Bolton, J. L. Bioactivation of the selective estrogen receptor modulator desmethylated arzoxifene to quinoids 4 -fhioro substitution prevents quinoid formation. Chem. Res. Toxicol. 2005, 18, 162-173. 

The estrogenic properties of isoflav-3-enes are well known and consequently, several derivatives of these chromene heterocycles have been the target of medicinal chemists. Varma and coworkers uncovered a useful enamine-mediated pathway to this class of compounds [142-144], Now the group has discovered a facile and general method for the MW-expedited synthesis of isoflav-3-enes substituted with basic moieties at the 2-position (Scheme 6.42) [145], These promising results are especially appealing in view of the convergent one-pot approach to 2-substituted isoflav-3-enes... 

As reviewed by Fereira et al. [104], the reaction of estrogens, that is estrone, estradiol, and ethinylestradiol, with free chlorine occurs mainly via an electrophilic substitution at the ortho and para positions, which results eventually in cleavage of the aromatic structure. Several authors have reported that dichlorinated derivatives present less estrogenic activity than monochlorinated derivatives, and in most cases, estrogen DBFs are less potent in terms of estrogenicity than the parent compounds. 

ICI 164,384 and fulvestrant (ICI 182,780) (Fig. 13) represent the first generation of pure anti-estrogens with ER destabilising activity [146]. These compounds are 7-a-substituted analogues of 17/f-estradiol. SAR studies identified fulvestrant (ICI 182,780), a compoimd with significantly increased antiestrogenic potency. As fulvestrant has a very low bioavailabiUty when administered orally it has to be applied by intramuscular injection [146]. 

Synthetic steroid hormones retain the common steroid nucleus, but they may contain novel substituents that affect their pharmacological activity. The two most widely used synthetic steroid estrogens are ethinyl estradiol (Estinyl) and mestranol, found in oral contraceptives. Synthetic steroids containing an ethinyl substitution are metabolized more slowly. Thus, these synthetic steroid hormones have better oral absorption properties and extended biological half-lives than the natural estrogens. 

Y. Seimbille, F. Benard, J. Rousseau, E. Pepin, A. Aliaga, G. Tessier, J.E. van Lier, Impact on estrogen receptor binding and target tissue uptake of [F-18]fluorine substitution at the 16-alpha-position of fulvestrant, Nucl. Med. Biol. 31 (2004) 691-698. 

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