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2-Methoxy-3,17β-estradiol, an endogenous estrogen metabolite, showed cytotoxicity in various cancer cell lines and also has antiangiogenic and proapoptotic activities. Clinical I and II trials of 2-methoxy-3,17β- estradiol for multiple myeloma, advanced solid tumors, metastatic breast and prostate cancer are underway. We prepared 2-[11C]methoxy-3,17β- estradiol to measure the pharmacokinetics and organ distribution of 2-methoxy-3,17β-estradiol in clinical trials. 2-[11C]Methoxy-3, 17β-estradiol was synthesized from a precursor, 2-hydroxy-3,17β-O- bis(methoxymethyl)estradiol, in two steps with over 99% radiochemical purity. The overall reaction time was 45 min and the decay-corrected radiochemical yield was 32.9%. The distribution coefficient (logP7.4) of 2-[ 11C]methoxy-3,17β-estradiol at pH 7.4 was measured as 2.95. Copyright

Two rhenium '3+1' mixed-ligand complexes bearing an estradiol moiety were prepared. The small-sized rhenium chelate units were introduced by two different rhenium precursors to give stable complexes in satisfactory yields.

(Chemical Equation Presented) 2-Methoxyestradiol, a natural metabolite of estradiol and potential therapeutic agent for many types of cancers, has been synthesized successfully in three steps, starting from estradiol and cumyl methyl peroxide.

Synthetic estrogens possessing hydroxyalkyl side chains at the C-2 position of the A-ring were designed in order to further elucidate the structural and electronic requirements of the estrogen receptor to A-ring modifications. Furthermore, these compounds were envisaged as being stable analogs of the estradiol metabolite 2-hydroxyestradiol. The homologous series of 2-(hydroxy-alkyl)estradiols 1-3 has been prepared by chain extension of 2- formylestradiol 6, which, in turn, was prepared via ortholithiation of estradiol. The substituted estradiols 1-3 were assayed for their abilities to bind to the estrogen receptor in MCF-7 cells and induce estrogen-responsive gene expression. The estradiol homologs exhibited significantly weaker affinity than estradiol for the MCF-7 cell estrogen receptor, with relative binding affinities (estradiol = 100) ranging from 1.11 for 2- (hydroxymethyl)estradiol (1) to 0.073 for 2-(hydroxypropyl)estradiol (3). The relative activities for mRNA induction of the pS2 gene by the estradiol homologs closely parallel the relative binding affinities for the estrogen receptor in MCF-7 cells. 2-(Hydroxymethyl)estradiol (1) exhibited similar estrogen receptor affinity and pS2 gene induction to the catechol estrogen 2- hydroxyestradiol and may prove useful in examination of the further biological effects of 2-hydroxyestrogen homologs.

2-methoxyestradiol is a novel agent showing both anti-angiogenic and vascular disrupting properties. In this study, a series of 11α-substituted 2-methoxyestradiol analogs have been designed and synthesized targeting dual ERα and microtubulin. Biological e

Methods for modulating lipoprotein lipase (LPL) and Apoliprotein C2 (ApoC2) expression and/or activity in the treatment of peripheral and central nervous system tissue disease states with C-6 substituted estradiol derivatives are presented herein.

PROBLEM TO BE SOLVED: To provide a new steroidal compound useful as a medicine for diagnosis and a medicine comprising the same. SOLUTION: The present invention provides a steroidal compound represented by formula (1) (where R1 is a hydroxy gro

Disclosed is a method of remyelinating axons with 6-substituted estradiol compounds of the formula The methods can be used to treat a variety of demyelinating diseases.

Steroid sulfatase (STS) catalyzes the hydrolysis of steroid sulfates to estrones, the main source of estrogens in tumors. Carbonic anhydrase II (CAII) is highly expressed in red blood cells through a coordination of the monoanionic form of the sulfamate moiety to the zinc atom in the enzyme active site, and CAII is highly expressed in several tumors. 2-Methoxy-3,17β-O,O- bis(sulfamoyl)estradiol (5) is a dual-function STS-CAII inhibitor inhibited STS with 39 nM IC50 value selectively over CAII with 379 nM IC 50 value. This compound exhibited potent antiproferative activity with mean graph midpoint value of 87 nM in the NCI 60-cell-line panel, and antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model as well. The compound has been recently developed as a multitargeted anticancer agent. Both STS and CAII are over-expressed in cancers and have become attractive targets for cancer treatment and molecular imaging of cancer. Here we report the first design and synthesis of 2-[11C]methoxy-3,17β- O,O-bis(sulfamoyl)estradiol ([11C]5) as a new potential imaging agent for biomedical imaging technique positron emission tomography (PET) to image STS in cancers. The authentic standard 5 was synthesized from 17β-estradiol by published procedures in 5 steps with 40% overall chemical yield. The precursor 2-hydroxy-3,17β-O,O-bis(sulfamoyl)estradiol (14a) for radiolabeling was synthesized from 17β-estradiol in 10 steps with 5% overall chemical yield. The target tracer [11C]5 was prepared from the precursor 14a with [11C]CH3OTf through O-[ 11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) purification in 40-50% radiochemical yields based on [ 11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.

Disclosed herein are 6-substituted 13-demethyl-estradiol derivatives as selective ERβ agonists. Also disclosed is a method for treating pain by administering these 6-substituted 13-demethyl-estradiol derivatives.

Estrogen receptor (ER) pure antagonists such as ICI-182,780 (fulvestrant) are effective alternatives to tamoxifen (an ER antagonist/weak partial agonist) in the treatment of postmenopausal, receptor-positive human breast cancers. Structurally, these pure

2-Methoxyestradiol (2-MEO), a metabolite of estrogen, is an attractive lead compound for the development of novel antitumor and anti-inflammatory agents, because it embodies antiproliferative and antiangiogenic activities in one molecule. However, the aff

An homologous series of 2-substituted hydroxyalkyl and aminoalkyl estradiols have been prepared by elaboration of the formylated estradiol derivative 10.

Through careful choice of reaction conditions, alkylation of estradiol with chloromethyl methyl ether may yield either the 3,17β-bis(methoxymethyl) ether or the 3-methoxymethyl ether derivative.Treatment of either of these protected estradiols with s-butyllithium, then with trimethylsilyl chloride affords, regioselectively, the 2-trimethylsilyl derivatives which can conveniently be converted into 2-bromo- or 2-iodo-estradiol.