- Prodigiosenes conjugated to tamoxifen and estradiol
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We report the synthesis of the first click-appended prodigiosene conjugates. Four prodigiosene conjugates of estradiol functionalised at the 7α-position were prepared, as were three prodigiosene conjugates of tamoxifen. The coupling between a prodigiosene and an 11-hydroxy estradiol derivative via an ether linkage was investigated, as was the 11- and 7-functionalisation of the estradiol core. The robustness of estradiol protecting groups was severely challenged by reactions typically used to equip such frameworks for 11- and 7-functionalisation. Specifically, and important to synthesis involving estradiol, TBS, TMS and THP are not useful protecting groups for the functionalisation of this core. When the chemical features of the therapeutic agent limit the choice of protecting group (in this case, prodigiosenes bearing aryl, NH, alkenyl and ester groups), click chemistry becomes an attractive synthetic strategy. The anti-cancer activity of the seven click prodigiosene conjugates was evaluated.
- Marchal, Estelle,Figliola, Carlotta,Thompson, Alison
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- Estra -1, 3, 5 (10) - triene compound and preparation method and medical application thereof
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Disclosed are estrone I,1, 3 (5) 10 triene compounds having a structure represented by general formula (-). The preparation method and the application thereof are provided. The compounds are especially suitable for treating estrogen receptor related diseases, such as estrogen-dependent cell proliferation, breast cancer, ovarian cancer, endometrial cancer and the like.
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- Compound for targeted ubiquitination degradation of ERalpha protein and application thereof
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The invention provides a compound with estrogen receptor alpha (ERalpha) activity, and particularly provides a 1,3,5-triazine compound with a general formula (I) or a general formula (II) or a pharmaceutically acceptable salt thereof. The definitions of the groups are as described in the specification. The compound disclosed by the invention has ERalpha degradation activity and can be used for preparing medicines for treating human breast cancer and endometrial cancer.
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- Design, synthesis and biological evaluation of novel 2-methoxyestradiol analogs as dual selective estrogen receptor modulators (SERMs) and antiangiogenic agents
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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
- Lao, Kejing,Wang, Yejun,Chen, Mingqi,Zhang, Jingjing,You, Qidong,Xiang, Hua
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p. 390 - 400
(2017/08/22)
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- Novel steroid selective estrogen receptor modulator as well as preparation method and pharmaceutical application thereof
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The invention relates to the field of pharmaceutical chemistry, and discloses a novel steroid selective estrogen receptor modulator as well as a preparation method and a pharmaceutical application thereof, in particular to steroid derivatives of a general formula (I), a preparation method thereof, pharmaceutical compositions containing the compounds and a pharmaceutical application thereof. The steroid derivatives can be applicable to treat a plurality of medical indications related to postmenopausal symptoms, in particular to treat ER-(+) type breast cancer. Meanwhile, the compounds can be used to prepare medicaments as angiogenesis inhibitors. The general formula (I) is shown in the description.
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Paragraph 0036; 0037; 0038
(2017/01/26)
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- An environmentally friendly and cost effective synthesis of estradiol featuring two novel reagents: Si(0)/KF and PMHS/hexamethyldisiloxane/pTSA
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Si(0)/KF is introduced as a strong, inexpensive, environmentally friendly, and safe reagent for 'dissolving metal'-type reduction. PMHS/hexamethyldisiloxane/pTSA is introduced as an inexpensive substitute for Et3SiH/TFA for 'ionic hydrogenation', where the hexamethyldisiloxane functions as a capping agent to block the oligomeric silicone by-product from cross-linking to a gel, rubber, or plastic. An environmentally friendly and cost effective synthesis of estradiol is described which showcases these new reagents.
- Lim, Chongsoo,Evenson, Gerald N.,Perrault, William R.,Pearlman, Bruce A.
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p. 6417 - 6420
(2007/10/03)
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- 17β-Hydroxy-11α-(3'-sulfanylpropyl)oxy-estra-1,3,5(10)-trien-3-yl sulfamate - A novel hapten structure: Toward the development of a specific enzyme immunoassay (EIA) for estra-1,3,5(10)-triene-3-yl sulfamates
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The title compound 17 has been synthesized for the use as hapten in the development of a competitive enzyme immunoassay for estrogen sulfamates. The synthesis started from estradiol diacetate 2. Oxyfunctionalization at C-11 to give 11α-hydroxy steroid 8 was accomplished by hydroboration/alkaline hydrogen peroxide oxidation of the 9(11)-dehydro derivative 7, which was obtained from compound 2 via 9-hydroxylation with dimethyldioxirane. After transformation of compound 8 into the allyl ether 9, the side chain was thio- functionalized at the ω-position affording the thioate 11 in two steps. Selective silylether deprotection at position 3 followed by sulfamoylation gave the sulfamate 19, which in turn was demasked at position 17 and treated with sodium borohydride/aluminum chloride to liberate the side chain thiol. Alternatively, title compound 17 was synthesized via the disulfides 13-16. For the preparation of the immunogen the title compound 17 was coupled to bovine gamma globulin in a two-step procedure using an amine and thiol specific bifunctional crosslinker. The immunization of rabbits resulted in the formation of antibodies which clearly discriminated the sulfamoylated estrogens from the non-esterified estrogens. The use of a biotinylated hapten derivative as a tracer in combination with a streptavidin-peroxidase- tetramethylbenzidine based detection system allowed the measurement of estradiol 3-sulfamate (1) in the range of about 1 to 1000 pg/well.
- Schwarz, Sigfrid,Schumacher, Matthias,Nanninga, Anita,Weber, Gisela,Thieme, Ina,Undeutsch, Bernd,Elger, Walter
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p. 460 - 471
(2007/10/03)
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