7683-30-9

Upstream product

• 186581-53-3 diazomethane 
• 362-06-1 2-hydroxyestrone 
• 65932-53-8 3-(2-benzoyl-4-nitro-phenoxy)-2-methoxy-estra-1,3,5⁽¹⁰⁾-trien-17-one 
• 83274-89-9 (13S,17S)-17-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl acetate 
• 26357-05-1 Acetic acid (8R,9S,13S,14S)-3-benzyloxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-2-yl ester 
• 26357-04-0 2-acetyl-3-benzyloxyestra-1,3,5⁽¹⁰⁾-trien-17-one 
• 26357-06-2 (8R,9S,13S,14S)-3-Benzyloxy-2-hydroxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one 
• 1624-62-0 estrone 3-methyl ether 
• 26357-03-9 2-acetyl-3-methoxy-estra-1,3,5⁽¹⁰⁾-trien-17-one 
• 26357-02-8 2-acetyl-3-hydroxyestra-1,3,5⁽¹⁰⁾-trien-17-one 
• 901-93-9 estrone acetate 
• 217792-90-0 (8R,9S,13S,14S,17S)-2-methoxy-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene 
• 217792-89-7 (8R,9S,13S,14S,17S)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-2-ol 
• 113680-55-0 (8R,9S,13S,14S,17S)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene 

Downstream Products

• 22415-44-7 17a-Ethynyl-2-methoxyestradiol 
• 26357-07-3 3-(benzyloxy)-2-methoxyestra-1,3,5⁽¹⁰⁾-trien-17-one 
• 401479-65-0 3,17β-dihydroxy-17α-(4-tert-butylbenzyl)-2-methoxyestra-1,3,5(10)-triene 
• 127349-68-2 (4-(tert-butyl)benzyl)magnesium bromide 
• 1620909-80-9 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-phenyl-1H-1,2,3-triazol-4-yl)estradiol 
• 1620909-84-3 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl)estradiol 
• 1620909-87-6 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-(4-(tert-butyl)phenyl)-1H-1,2,3-triazol-4-yl)estradiol 
• 1620909-91-2 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-(4-hydroxyphenyl)-1H-1,2,3-triazol-4-yl)estradiol 
• 1620909-94-5 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)estradiol 
• 1620909-96-7 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)estradiol 
• 1620909-99-0 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)estradiol 
• 1620910-02-2 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)estradiol 
• 1620910-05-5 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-4-yl)estradiol 
• 1620910-07-7 3-O-(tert-butyl)dimethylsilyl-2-methoxy-17-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)estradiol 

Relevant academic research and scientific papers

Synthesis, molecular modeling and biological evaluation of potent analogs of 2-methoxyestradiol

The endogenous steroid 2-methoxyestradiol (1) has attracted a great interest as a lead compound towards the development of new anti-cancer drugs. Herein, the synthesis, molecular modeling, anti-proliferative and anti-angiogenic effects of ten 2-ethyl and four 2-methoxy analogs of estradiol are reported. The ethyl group was introduced to the steroid A-ring using a novel Friedel-Crafts alkylation protocol. Several analogs displayed potent anti-proliferative activity with IC50-values in the submicromolar range towards the CEM human leukemia cancer cell line. As such, all of these compounds proved to be more active than the lead compound 2-methoxyestradiol (1) in these cells. The six most cytostatic analogs were also tested as anti-angiogenic agents using an in vitro tube formation assay. The IC50-values were determined to be in the range of 0.1 μM ± 0.03 and 1.1 μM ± 0.2. These six compounds were also modest inhibitors against tubulin polymerization with the most potent inhibitor was 14b (IC50 = 2.1 ± 0.1 μM). Binding studies using N,N′-ethylene-bis(iodoacetamide) revealed that neither14a or 14b binds to the colchicine binding site in the tubulin protein, in contrast to 2-methoxyestradiol (1). These observations were supported by molecular modeling studies. Results from a MDA-MB-231 cell cycle assay showed that both 10e and 14b gave accumulation in the G2/M phase resulting in induction of apoptosis. The results presented herein shows that the novel analogs reported exhibit their anticancer effects via several modes of action.

Discovery of chalcone-modified estradiol analogs as antitumour agents that Inhibit tumour angiogenesis and epithelial to mesenchymal transition

Angiogenesis plays an essential role in tumourigenesis and tumour progression, and anti-angiogenesis therapies have shown promising antitumour effects in solid tumours. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, has been regarded as a potential antitumour agent mainly targeting angiogenesis. Here we synthesized a novel series of chalcones based on 2-methoxyestradiol and evaluated their potential activities against tumours. Compound 11e was demonstrated to have potent antiangiogenic activity. Further studies showed that 11e suppressed tumour growth in human breast cancer (MCF-7)xenograft models without obvious side effects. Evaluation of the mechanism revealed that 11e targeted the epithelial to mesenchymal transition (EMT)process in MCF-7 cells and inhibited HUVEC migration and then contributed to hindrance of angiogenesis. Thus, 11e may be a promising antitumour agent with excellent efficacy and low toxicity.

For female steroid nucleus to 2 bit or 16 substituted chalcone derivative and its preparation and use

The invention belongs to the field of medicinal chemicals, and relates to a 2/16-site-substituted chalcone derivative taking estrogen as a mother nucleus and a preparation method and application of the derivative. The preparation method comprises the following step: combining chalcone structural fragments on an estrogen body in parallel, thereby keeping or improving the activity of anti-tumor cells and inhibiting activity of tumor cell angiogenesis. The structural formula of the 2/16-site-substituted chalcone derivative is as shown in the specification. The in-vitro anti-tumor cell proliferation activity test and the chick embryo allantois test show that the derivative has certain anti-tumor cell proliferation activity and inhibiting activity of tumor cell angiogenesis; and the dose-effect relationship study shows that the tumor cell inhibition function of the derivative is prior to that of 2-methoxy estradiol with broad-spectrum anti-tumor activity, and moreover the half-life period can be prolonged.

Synthesis, cytotoxic effects and tubulin polymerization inhibition of 1,4-disubstituted 1,2,3-triazole analogs of 2-methoxyestradiol

Thirteen 1,4-disubstituted 1,2,3-triazole analogs of 2-methoxyestradiol were prepared and tested for their cytotoxic and tubulin polymerization inhibition effects. Two compounds, 11j and 11k, exhibited anti-proliferative effects at low micromolar concentr

Synthesis and biological evaluations of new analogs of 2-methoxyestradiol: Inhibitors of tubulin and angiogenesis

The synthesis, cytotoxicity, inhibition of tubulin polymerization and anti-angiogenic effects of 15 analogs of 2-methoxyestradiol (1) are reported. The biological studies revealed that the position of nitrogen atom in the heterocyclic ring is important for inhibition of both tubulin polymerization and angiogenesis. The most potent inhibitors were compounds 11f and 13e, with a 6-substituted isoquinoline ring in the 17-position of the steroid skeleton. Moreover, low estrogen activity was observed for the analogs tested at 10 μM concentrations.

Synthesis and antitumor activities of 3-modified 2-methoxyestradiol analogs

The syntheses of 2-methoxyestradiol analogs with modifications at the 3-position are described. The analogs were assessed for their antiproliferative, antiangiogenic, and estrogenic activities. Several lead substituents were identified with similar or imp

Synthesis and antimitotic activity of novel 2-methoxyestradiol analogs. Part III

The syntheses and antimitotic activity of several novel analogs of 2-methoxyestradiol are described. Structural modifications include ring-D homologation, aromatization of the six-membered ring-D to a chrysine type molecule, and introduction of unsaturation in five-membered ring-D along with substitution of alkyl and ethynyl groups for the 17β-hydroxy function. Of nine analogs synthesized, five have demonstrated superior antiproliferative activities compared to 2-methoxyestradiol.

2-ALKOXYESTRADIOL ANALOGS AND PHARMACEUTICAL PREPARATIONS

Novel 2-alkoxyestradiol analogs, pharmaceutical compositions and methods of treatment of proliferative and angiogenesis associated conditions are disclosed.

PROCESS FOR THE PREPARATION 2-SUBSTITUTED-DERIVATIVES OF ESTRONE AND ESTRADIOL

The invention provides a process for the preparation of 2- substituted-derivatives of estrone and estradiol comprising i) the preparation of a compound of general formula (II) by reacting a compound of general formula (I) in one or more steps to a compound of general formula II wherein Rl is a C1-C10 alkyl, alkenyl or aryl group; -C1, -Br, -I, -F; -CN; -OH; or a -OR2, -O(CO)R2 or -R2-OH group, wherein R2 is an alkyl or alkylene group having 1-6 C atoms; and the bonding between atoms 9 and 10 is a single or a double bond. ii) aromatization of the compound of general formula II to a compound of general formula III wherein Rl and R2 have the above defined meanings; and iii) optionally, reduction of the compound of general formula III to a compound of general formula IV wherein Rl and R2 have the above defined meanings . Furthermore the invention provides several novel compounds, which can be intermediates in the above process, and processes to prepare these novel compounds . The invention also provides 2-alkoxy-estrone, 2-alkoxy- estradiol or mixtures thereof essentially free from other estrogenic intermediates.

A-ring-substituted estrogen-3-O-sulfamates: Potent multitargeted anticancer agents

Efficient and flexible syntheses of 2-substituted estrone, estradiol and their 3-O-sulfamate (EMATE) derivatives have been developed using directed ortho-lithiation methodology. 2-Substituted EMATEs display a similar antiproliferative activity profile to the corresponding estradiols against a range of human cancer cell lines. 2-Methoxy (3, 4), 2-methylsulfanyl (20, 21) and 2-ethyl EMATEs (32, 33) proved the most active compounds with 2-ethylestradiol-3-O-sulfamate (33), displaying a mean activity over the NCI 55 cell line panel 80-fold greater than the established anticancer agent 2-methoxyestradiol (2). 2-Ethylestradiol-3-O-sulfamate (33) was also an effective inhibitor of angiogenesis using three in vitro markers, and various 2-substituted EMATEs also proved to be inhibitors of steroid sulfatase (STS), a therapeutic target for the treatment of hormone-dependent breast cancer. The potential of this novel class of multimechanism anticancer agents was confirmed in vivo with good activity observed in the NCI hollow fiber assay and in a MDA-MB-435 xenograft mouse model.