Estrogen receptor agonists

Watanabe N, Ikeno A, Minato H, et al. Discovery and preclinical characterisation of (-l-)-3-[4-(l-piperidinoethoxy)phenyl]spiro[indene-l,l -indane]-5,5 -diol hydrochloride a promising nonsteroidal estrogen receptor agonist for hot flush. / Med Chem 2003 46 3961-4. 

ERB-041 and ERB-196 are estrogen receptor agonists in early clinical development for treatment of rheumatoid arthritis. 

Thomas, K.V, Balaam, J., Hurst, M., Nedyalkova, Z., Mekenyan, O. (2004). Potency and characterization of estrogen-receptor agonists in United Kingdom estuarine sediments. Environmental Toxicology and Chemistry. 23 471-479. 

Figure 17.6 Estrogen receptor agonists. Molecules are presented in a low-energy state that may represent their natural three-dimensional conformation.

Rastall, A.C., D. Getting, J. Goddard, D.R. Roberts, and L. Erdinger. 2006. A biomimetic approach to the detection and identification of estrogen receptor agonists in surface waters using semipermeable membrane devices (SPMDs) and bioassay-directed chemical analysis. Environ. Sci. Pollut. Res. 13 256-267. 

Organization for Economic Cooperation and Development (2012) Performance-based test guideline for stably transfected transactivation in vitro assays to detect estrogen receptor agonists 455... 

Wilson VS, Bobseine K, Gray LE Jr (2004) Development and characterization of a cell line that stably expresses an estrogen-responsive luciferase reporter for the detection of estrogen receptor agonist and antagonists. Toxicol Sci 81(l) 69-77... 

Rosati, R.L. and Da Silva, J.P. (1998) Discovery and predinical pharmacology of a novel, potent, nonsteroidal estrogen receptor agonist/antagonist, CP-336156, a diaryltetrahydronaphfhalene. Journal of Medicinal Chemistry, 41, 2928—2931. 

FIGURE 36 Clomiphene, an ovulation stimulant, is a partial estrogen receptor agonist. 

Impact of isotype-selective estrogen receptor agonists on ovarian function, Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5129-5134. 

Why is the administration of a partial estrogen receptor agonist beneficial ... 

A partial estrogen receptor agonist better mimics normal physiological milieu. Reduced incidence of adverse effects can also result, because of the antagonist component of the drug. 

Estrogen Estrogen receptor agonist which counteracts endogenous testosterone (testosterone enhances tumor growth) in patients with prostate cancer. 

Coronary heart disease and atherosclerosis are major contributors to morbidity and mortality in the United States and other developed countries. Epidemiological studies suggest that decreased mortality from coronary heart disease is associated with moderate consumption of alcohol, and especially of red wine [7], Numerous studies indicate that resveratrol inhibits platelet aggregation [8-10, 12, 16, 54, 55], alters eicosanoid synthesis [15, 55], modulates lipoprotein mechanisms [14, 56-58], inhibits vascular smooth muscle cell proliferation [59], and acts as an estrogen receptor agonist [60]. On the other hand, at least one earlier study indicated that it promoted atherosclerotic development, rather than protected against it, by a mechanism that appeared to be independent of observed... 

FIGURE 3.74 Synthesis of a fluorinated pyrazole as an estrogen receptor agonist. 

Some of the interest in Z is-indolylmethanes comes from the purported biological activity of trimeric and tetrameric analogs. A cyclic trimer derived from indole-3-methanol has attracted attention in connection with the antitumor activity associated with vegetables of the species Brassica. The chemical lability of indole-3-methanol and its condensation products are the source, however, of considerable complication in interpreting the metabolism of these compounds [182, 183]. Under acidic conditions, indole-3-methanol is converted to the trimer, but also to the bis-(3 -indolyl) methane and an isomer [184—186]. The trimer is reported to be an estrogen receptor agonist and to stimulate the function of an estrogen-dependent cell line (MCF-7) [187]. 

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