- Optimization of copper(I)-catalyzed 1,6-conjugate addition of a methyl group to 17β-acetoxy-4,6-estradien-3-one
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7α-Methyl-19-nortestosterone (1) was synthesized from 19-nortestosterone (2) via 17β-acetoxy-4,6-estradien-3-one (4). The critical parameters for the synthesis of compound (1) have been identified. An optimization procedure consisting of an iterative, two-stage reaction response surface analysis was carried out. As a result, the synthesis of the target compound (1) from the intermediate (4) was achieved under the newly determined conditions, in a repeatable manner. This afforded compound (1) in an yield of over 60%, essentially free from the 7β-Me isomer (6), under experimental conditions amenable for scale enhancement.
- Martynow, Jacek,Krupa, Malgorzata,Les, Andrzej,Kutner, Andrzej,Szelejewski, Wieslaw
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- Preparation method of 6-dehydronandrolone acetate
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The invention belongs to the technical field of steroid drug intermediates, and provides a preparation method of 6-dehydronandrolone acetate. The preparation method comprises the following steps: carrying out a catalytic reaction on estra-4-ene-3,17-dione, acetic anhydride and p-toluenesulfonic acid to obtain a compound 1; carrying out a reduction reaction on the compound 1, hydroboron and aluminum trichloride to obtain a compound 2; subjecting the compound 2 and N-bromosuccinimide to reacting with DMF to obtain a solution of a compound 3; carrying out an addition reaction on the solution of the compound 3 and alkali to obtain a compound 4; and subjecting the compound 4, acetic anhydride, triethylamine and dichloromethane to a catalytic reaction to obtain 6-dehydronandrolone acetate. By adding borohydride and the aluminum trichloride in a reasonable ratio, hydrolysis of a 3-site ester group is effectively avoided, and side reactions are few; and meanwhile, the yield and the purity of a target product are remarkably improved by reasonably setting a synthesis route and controlling a reaction temperature.
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Paragraph 0042-0049
(2021/07/01)
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- METHODS OF TREATING ADVANCED PROSTATE CANCER
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Provided herein are methods for treating metastatic prostate cancer using anti-androgen compounds and radionuclide-labeled androgens.
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- Preparation method of 6-dehydronandrolone
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The invention relates to a preparation method of 6-dehydronandrolone. The preparation method comprises the following steps: putting a No. 8 magneton into a three-necked flask, dissolving a compound, namely, 3,5-estradiene-3,17beta-ester diacetate in a DMF (Dimethyl Formamide) water mixed solution for reacting to obtain a mixed solution I, dissolving DMF in an NBS (N-bromosuccinimide) solution to obtain a mixed solution II, adding the mixed solution II into the mixed solution I dropwise for reacting, adding sodium carbonate into a reaction system firstly, adding sodium bromide after full reaction, heating to 40 DEG C, gradually heating to 80 DEG C, and continually reacting for 3 hours till the reaction ends; cooling, adding an acetic acid aqueous solution for reacting with stirring, adding an equivalent acetic acid aqueous solution, and continually stirring overnight; precipitating a solid, filtering a product, cleaning a filter cake with a cold isopropanol aqueous solution, and drying to obtain pure 6-dehydronandrolone. The preparation method is simple and convenient, is easy to operate, and is up to 80 percent in yield; the synthesized 6-dehydronandrolone as a steroid drug is one of important prodrugs of tibolone.
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Paragraph 0017; 0019; 0020; 0021; 0022; 0023; 0024; 0025
(2017/10/09)
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- PROCESS AND INTERMEDIADES FOR THE PREPARATION OF 7-ALKYLATED STEROIDS
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A process for preparing compounds of formula (I), or a salt, solvate or stereoisomer thereof, including Fulvestrant, which process comprises free radical to a compound of formula (III), or a salt, solvate or stereoisomer thereof. The invention also refers to intermediates of said process.
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- Stereoselective synthesis of some methyl-substituted steroid hormones and their in vitro cytotoxic activity against human gastric cancer cell line MGC-803
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A series of 3-, 7-, 15-, and 16-methyl-substituted steroid analogs were synthesized via a highly stereoselective 1,6-conjugate addition. Under the catalysis of CuBr, AlMe3 reacted with four steroid dienone precursors to afford either the corresponding α-epimer of C-3 and C-7 methyl-substituted steroids as the major products, and the ratio of α/β was up to 10/1. No β-epimer has been detected for methyl addition at C-16. However, under the same reaction conditions, enantioselective methyl addition at C-15 afforded the 15β-epimer as the major product. The preliminary SAR analysis showed that the methyl substituents at C-7α and C-15β positions lead to a dramatical increase in potency against human gastric cancer cell line MGC-803.
- Li, Chun,Qiu, Wenwei,Yang, Zhengfeng,Luo, Jian,Yang, Fan,Liu, Mingyao,Xie, Juan,Tang, Jie
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experimental part
p. 859 - 869
(2010/10/18)
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- PROCESS FOR THE PRODUCTION OF TIBOLONE
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Disclosed is a process for the synthesis of 17β-hydroxy-7α-methyl- 19-nor-17α-pregn-5(10)-ene-20-yne-3-one (tibolone, 11) and intermediates useful for the synthesis thereof: (11).
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- Anti-estrogenic compounds and compositions
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Inhibitors of sex steroid activity, for example those having the general structure STR1 may be used as part of a pharmaceutical composition to provide antiestrogenic effects and/or to suppress estrogen synthesis. Such pharmaceutical compositions are useful for the treatment of breast cancer or other diseases whose progress is aided by activation of sex steroid receptors.
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- Estrogen nucleus derivatives for use in inhibition of sex steroid activity
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Novel compounds for the inhibition of sex steroid activity for the treatment of both androgen-related and estrogen-related diseases include for example 15- and 16-halo substituted compounds such as: STR1 The compounds are characterized by an estrogenic nucleus substituted with a substituent of the formula --R1 [B--R2 --]x L--G wherein at least one of L and G is a polar moiety distanced from a ring carbon of the estrogenic nucleus by a least three intervening atoms: x is an integer from 0-6; R1 and R2 are independently either absent or selected from the group consisting of straight- or branched-chain alkylene, straight- or branched-chain alkynylene, straight- or branched-chain alkenylene, phenylene, and fluoro-substituted analogs of the foregoing; and B is either absent or selected from the group consisting of --O--, --Se--, --SO--, --SO2 --, --NR3 --, --SiR32, --CR3 OR3 --, NR3 CO--, NR3 CS--, --CONR3 --, CSNR3 --, --COO--, --COS--, --SCO--, --CSS--, --SCS--, --OCO-- and phenylene (R3 being hydrogen or lower alkyl).
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- The Preparation of 7α- and 7β-Allyloestradiol, and an Unusual Titanium(IV) Chloride Mediated Dimerisation
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17β-Acetoxyoestra-4,6-dien-3-one reacts with allyltrimethylsilane in the presence of fluoride ion to give the 7α- and 7β-allyloestr-4-en-3-ones in low yield.With titanium(IV) chloride catalysis, the 7α-allyloestr-4-en-3-one is the only product at -78 deg C, but its novel 6β,6'β-'dimer' is also formed at higher temperatures.The isomeric 7-allyloestr-4-en-3-ones have been aromatised to give 7α- and 7β-allyloestradiols.
- Miller, Barry W.,Kirk, David M.
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p. 2127 - 2156
(2007/10/02)
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- Method of terminating pregnancy
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7α-methyl-estr-5-ene-3β,17β-diol and 17-acyl esters as contragestative agents.
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- Method for the control of fertility
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7α-Methylestr-4-ene-3α,17β-diol and derivatives thereof useful as antifertility agents.
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