- NOVEL AND REGIOSPECIFIC SYNTHESIS OF 2-AMINO ESTROGENS VIA ZINCKE NITRATION
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An efficient synthesis of 2-aminoestrone (14), 2-aminoestradiol (15), 2-amino-16α-hydroxyestrone (16) and 2-aminoestriol (17) is described. 2,4-Dibromo estrogens 1 - 4 were regiospecifically converted to the corresponding 2-nitro-4-bromo derivatives 5 - 8 in quantitative yields, with Zincke nitration using sodium nitrite.Catalytic hydrogenation of the 2-nitro-4-bromides 5 - 8 over palladium-on-charcoal gave directly the desired 2-amino estrogens 14 - 17 in high yields.The 2-amino compounds 15 and 17 were also obtained by the reduction of the corresponding 2-nitro-4-bromides 6 and 8 with sodium borohydride in the presence of palladium chloride.
- Numazawa, Mitsuteru,Kimura, Katsuhiko
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- COMPOUNDS, COMPOSITIONS, AND METHODS FOR TREATMENT OF ANDROGEN-MEDIATED DISEASE
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Provided herein are steroid sulfatase inhibitor compounds and androgen receptor inhibitor compounds that can be useful in, for example, the treatment of cancers such as prostate cancer and breast cancer. Pharmaceutical compositions and kits including the
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- New selenosteroids as antiproliferative agents
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Starting from natural steroids (diosgenin, hecogenin, smilagenin, estrone), we have prepared a wide panel of selenoderivatives, including benzoselenazolones, selenosemicarbazones, isoselenocyanates, selenoureas, selenocyanates and diselenides, with the aim of developing new families of potential chemotherapeutic agents. The modification of the organoselenium moieties, and their position on the steroid provided valuable information concerning the antiproliferative activities. Among all the families accessed herein, the best profile was achieved for selenoureas on the A ring of estrone, which exhibited GI50 values in the range 2.0-4.1 μM for all the tested tumor cell lines, with increased potency compared with commonly used chemotherapeutic agents, like 5-fluorouracil and cisplatin. Cell cycle analysis revealed that selenoureas induced accumulation of cells in the G1 phase of the cell cycle in the breast cancer cell lines HBL-100 and T-47D; therefore, a different mechanism than cisplatin, that induces cell cycle accumulation in the S phase as a result of DNA damage, must be involved. In the rest of the tumor cells, a slight increase of the S compartment was observed. Moreover, selenosteoids turned out to be excellent glutathione peroxidase (GPx) mimics for the catalytic removal of deleterious H2O2 (t1/2 8.0-22.5 min) and alkyl peroxides (t1/2 23.0-38.9 min) when used in substoichiometric amounts (1% molar ratio), thus providing a valuable tool for reducing the intrinsic oxidative stress in tumor progression.
- Fuentes-Aguilar, Alma,Romero-Hernández, Laura L.,Arenas-González, Ailed,Merino-Montiel, Penélope,Montiel-Smith, Sara,Meza-Reyes, Socorro,Vega-Báez, José Luis,Plata, Gabriela B.,Padrón, José M.,López, óscar,Fernández-Bola?os, José G.
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p. 5041 - 5054
(2017/07/11)
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- Synthesis and evaluation of analogues of estrone-3-O-sulfamate as potent steroid sulfatase inhibitors
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Estrone sulfamate (EMATE) is a potent irreversible inhibitor of steroid sulfatase (STS). In order to further expand SAR, the compound was substituted at the 2- and/or 4-positions and its 17-carbonyl group was also removed. The following general order of p
- Lawrence Woo,Leblond, Bertrand,Purohit, Atul,Potter, Barry V.L.
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p. 2506 - 2519
(2012/06/01)
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- Synthesis of W-acetylcysteine conjugates of catechol estrogens
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The synthesis of N-acetylcysteine conjugates of 2-hydroxyestrone (2-OHE1) and 4-hydroxyestrone (4-OHE1) is described. The reaction of estrone 2,3-quinone with N-acetylcysteine provided 2-OHE1 and its C-4 and C-1 thioether conjugates in a ratio of 1:1, while estrone 3,4-quinone with N-acetylcysteine gave 4-OHE, and its C-2 thioether conjugate as a sole product. Their structures were characterized by inspection of NMR spectra, chemical derivatization (methylation and acetylation), and comparison with the reactivity of 4-bromoestrone 2,3-quinone or 2-bromoestrone 3,4-quinone toward N-acetylcysteine.
- Suzuki, Emako,Iwasaki, Ryo,Goto, Junichi,Matsuki, Yasuhiko,Nambara, Toshio
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p. 296 - 301
(2007/10/03)
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- Potential antineoplastics. 4th Communication: N-mustard derivatives of estrone
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Two nitrogen mustard compounds (differing by the location of the radical N(CH2-CH2Cl)2 are synthesized as potential mammatropic antineoplastic agents from estrone (respective reaction roots shown). Both compounds show a binding affinity to the cytoplasmic estrogen receptor of the rat uterus of 1-10% compared to that of estrone. Both mustard compounds are irreversibly bound to the estrogen receptor.
- Hamacher
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p. 463 - 466,465, 466
(2007/10/13)
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