302-97-6Relevant articles and documents
Syntheses of [21-11C] and (21-13C)progesterone
Lidstroem, Pelle,Neu, Henrik,Langstroem, Bengt
, p. 695 - 704 (1997)
[21-11C]Progesterone was synthesised via the cross-coupling 17β-carboxylic acid chloride-4-androsten-3-one with lithium [11C]methyl(2-thienyl)cuprate (LiCN). The title compound was obtained in 30-35% decay corrected radiochemical yield, based on [11C]methyl iodide, within 35 minutes after end of radionuclide production. The specific radioactivity was 14 GBq/μmole. (21-13C)Progesterone was synthesised using the same procedure for determination of the position of the label.
Discovery of novel steroidal-chalcone hybrids with potent and selective activity against triple-negative breast cancer
Bai, Chengfeng,Hou, Qiangqiang,Lin, Xin,Lu, Xiang,Luo, Guoshun,Wei, Hanlin,Xiang, Hua
, (2020/10/02)
A series of novel steroidal-chalcone derivates were designed and synthesized based on the molecular hybridization strategy and further evaluated for their growth inhibitory activity against three human cancer cell lines. The MTT results indicated that most compounds were apparently more sensitive to human breast cancer cells MDA-MB-231. Compounds 8 and 18 exerted the best cytotoxic activity against triple-negative MDA-MB-231 cells with the IC50 values of 0.42 μM and 0.52 μM respectively, which were 23-fold increase or more compared with 5-Fu. Further mechanism studies demonstrated that compound 8 could induce cells apoptosis through regulating Bcl-2/Bax proteins and activating caspase-3 signaling pathway. Moreover, compound 8 could upregulate the cellular ROS levels which accelerated the apoptosis of MDA-MB-231 cells. In addition, interestingly, cell cycle assay showed that compound 8 could arrest MDA-MB-231 cells at S phase but not commonly anticipated G2/M phase. These evidences fully confirmed that compound 8 could be a potential candidate that deserves further development as an antitumor agent against triple-negative breast cancer.
Steroid compound as well as preparation method and application thereof (by machine translation)
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, (2020/10/29)
The compounds have the structure shown in the general formula (I) or the general formula (II); and experiments prove that the compounds can treat three-negative breast cancer by promoting apoptosis. (by machine translation)
Design, synthesis, and biological evaluation of two series of novel a-ring fused steroidal pyrazines as potential anticancer agents
Li, Na,Qian, Hao,Wang, Junru,Wang, Shijun,Yuan, Xiaorong
, (2020/03/06)
Background: Increasingly, different heterocyclic systems have been introduced into the steroid nucleus to significantly enhance the antitumor activities of steroid molecules. However, in this study, few literature precedents describing the pyrazine heterocyclic-condensed modification to an A-ring of steroid monomers were found, although the pyrazine group is thought to be essential for the potent anticancer activity of clinically relevant drugs and natural steroid dimers. Methods and Results: Two series of novel A-ring fused steroidal pyrazines were designed and efficiently synthesized from commercially available progesterone via key α-ketoenol intermediates. Through a cell counting kit-8 cytotoxic assay of 36 derivatives for three tumor cells, 14 compounds displayed significant antiproliferative activity compared to 5-fluorouracil, especially for human prostatic tumor cells (PC-3) in vitro. Further mechanistic studies indicated that the most active compound, 12n (IC50, 0.93 μM; SI, 28.71), could induce the cell apoptosis of PC-3 cells in a dose-dependent manner and cause cell cycle arrest in the G2/M phase. The molecular docking study suggested that compound 12n fitted the active sites of cytochrome P450 17A1 (6CIZ) well. Conclusions: 12n might serve as a promising lead compound for the development of novel anticancer drugs. This facile ring-closing strategy may provide a novel and promising avenue for the cycloaddition reaction of the steroidal skeleton through α-ketoenol intermediates.
Design, synthesis, and biological evaluation of novel androst-17β-amide structurally related compounds as dual 5α-reductase inhibitors and androgen receptor antagonists
Lao, Kejing,Xun, Guoliang,Gou, Xingchun,Xiang, Hua
, p. 1597 - 1606 (2019/09/07)
Prostate cancer (PCa) is the second leading cause of death in men. Apart from androgen receptor, 5α-reductase has also been recognized as a potential target. In this study, a series of androst-17β-amide compounds have been designed and synthesized targeting both AR and 5α-reductase. Their anti-proliferation activities were evaluated in AR + cell line 22RV1 and AR ? cell line PC-3. The results indicated that most of the synthesized compounds inhibited the testosterone-stimulated cell proliferation with good selectivity and safety. Among all the compounds, androst[3,2-c]pyrazole derivatives (9a–9d) displayed the best inhibition activity comparable with flutamide. Moreover, most of the synthesized compounds displayed good 5α-reductase inhibitory activities with IC50 lower than 1 μM. The docking result of 9d-AR indicated that AR was forced to expands its binding cavity and maintain an antagonistic conformation since the steric hindrance of 9d impeded H12 transposition. Overall, compound 9d can be identified as a potential dual 5α-reductase inhibitor and AR antagonist, which might be of therapeutic importance for PCa treatment.
Preparation method of 17 beta-androst-4-ene-3-one-17-carboxylic acid
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Paragraph 0012; 0013; 0016; 0020; 0024, (2018/04/02)
The invention discloses a preparation method of 17 beta-androst-4-ene-3-one-17-carboxylic acid. The preparation method comprises that 4-androstenedione (called as 4AD for short) as a raw material andtriethyl orthoformate undergo a reaction in an organic solvent under acid catalysis, the reaction product is after-treated to form an etherate, the etherate is dissolved in an organic solvent and undergoes a reaction with trimethylsulfonium iodide under strong base catalysis, the product is after-treated to form an epoxide, the epoxide is dissolved in an organic solvent and then is subjected to rearrangement under acid catalysis to form an aldehyde, and aldehyde is dissolved in an organic solvent and undergoes a catalytic oxidation reaction with hydrogen peroxide acid to produce 17 beta-androst-4-ene-3-one-17-carboxylic acid. The 17 beta-androst-4-ene-3-one-17-carboxylic acid has a melting point of 244-246 DEG C, HPLC content of 99.0% or more and a reaction weight total yield of 70-72%. Compared with the traditional method, the preparation method utilizes cheap and easily available raw materials, has simple and environmental friendly processes and a high synthesis yield, produces highquality products, reduces a cost by 30-40% and is conducive to industrial production.
Design, synthesis and biological evaluation of novel androst-3,5-diene-3-carboxylic acid derivatives as inhibitors of 5α-reductase type 1 and 2
Lao, Kejing,Sun, Jie,Wang, Chong,Lyu, Weiting,Zhou, Boshen,Zhao, Ruheng,Xu, Qian,You, Qidong,Xiang, Hua
, p. 29 - 34 (2017/06/14)
5α-Reductase is a key enzyme responsible for dihydrotestosterone biosynthesis and has been recognized as an important target for discovering new drugs against benign prostatic hyperplasia (BPH). In this study, a series of novel steroidal androst-3,5-diene-3-carboxylic acids have been designed and synthesized. Biological evaluations were performed on their 5α-reductase inhibitory activities by both in vitro enzyme inhibition assay and in vivo by prostate weighing method. Results showed that most of them displayed excellent 5α-reductase inhibitory potency. Detailed evaluation indicated that most of the compounds displayed slightly higher inhibition potency towards type 2 isozyme. Among all the compounds, 16a was found to be the most potential inhibitor with the IC50 of 0.25?μM and 0.13?μM against type 1 and 2 isozymes respectively. In vivo 5a-reductase inhibitory evaluation of 16a also showed a more significant reduction effect (p??0.001) in rat prostate weight than epristeride. Furthermore, the results of in silico ADME study indicated that compound 16a exhibited good pharmacokinetic properties. Thus, 16a could serve as promising lead candidates for further study.
Design, synthesis and biological evaluation of novel 3-oxo-4-oxa-5α-androst-17β-amide derivatives as dual 5α-reductase inhibitors and androgen receptor antagonists
Lao, Kejing,Sun, Jie,Wang, Chong,Wang, Ying,You, Qidong,Xiao, Hong,Xiang, Hua
, p. 4212 - 4217 (2017/08/23)
Prostate cancer (PCa) is the second leading cause of death in men. Recently, some researches have showed that 5α-reductase inhibitors were beneficial in PCa treatment as well. In this study, a series of novel 3-oxo-4-oxa-5α-androst-17β-amide derivatives have been designed and synthesized in a more simple and convenient method. Most of the synthesized compounds displayed good 5α-reductase inhibitory activities and androgen receptor binding affinities. Their anti-proliferation activities in PC-3 and LNCaP cell lines were also evaluated and the results indicated that most of the synthesized compounds exhibited potent anti-proliferative activities. It is obvious that the androgen-dependent cell line LNCaP was much more sensitive than the androgen-independent cell line PC-3. Among all the synthesized compounds, 11d and 11k displayed the best inhibition activity with 4-fold more sensitive toward LNCaP than PC-3, which was consistent with their high affinities observed in AR binding assay. Molecular modeling studies suggested that 11k could bind to AR in a manner similar to the binding of dihydrotestosterone to AR. Compared to the finasteride, 11k showed a longer plasma half-life (4 h) and a better bioavailability. Overall, based on biological activities data, compound 11d and 11k can be identified as potential dual 5α-reductase inhibitors and AR antagonists which might be of therapeutic importance for prostate cancer treatment.
Synthesis method of 3-ketone-4-androstene-17 beta carboxylic acid
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Paragraph 0036; 0037, (2016/10/27)
The invention belongs to the field of organic chemistry and provides a synthesis method of 3-ketone-4-androstene-17 beta carboxylic acid, which comprises the following steps: (1) slowly adding 2-ethyl chloroacetate into 3 beta-ethyl ether-3,5-androst-diene-17-ketone to generate addition reaction and cyclization reaction to obtain 3 beta-ethyl ether-3,5-androst-diene-17,20-epoxy-20-carboxylic acid ethyl ester; (2) carrying out high-temperature decarboxylation and hydrolysis reaction on 3 beta-ethyl ether-3,5-androst-diene-17,20-epoxy-20-carboxylic acid ethyl ester to obtain 3-ketone-4-androstene-20-aldehyde; and (3) carrying out oxidation reaction on 3-ketone-4-androstene-20-aldehyde to obtain 3-ketone-4-androstene-17 beta carboxylic acid. According to the method provided by the invention, a synthetic route and initial synthetic raw materials are changed, low-cost 4AD derivative raw material 3 beta-ethyl ether-3,5-androst-diene-17-ketone is adopted, synthetic reaction steps are reduced, and reaction conditions are mild. The synthesis method provided by the invention is relatively simple, economical and environment-friendly and is convenient for industrialized implementation.
Preparation method of 17beta-androst-4-ene-3-one-17-carboxylic acid
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, (2016/10/07)
The invention discloses a preparation method of 17beta-androst-4-ene-3-one-17-carboxylic acid. The preparation method comprises the following specific operation steps of performing acid catalyzed reaction on 4AD (Androstenedione) and triethyl orthoformate in low-carbon alcohol organic solvent to obtain etherate 3-ethyoxyl-androst-3,5-diene-17-one; performing 17-situ addition on the obtained etherate and nitromethane in the organic solvent under the catalysis of ethanediamine to obtain a nitro compound; reducing the obtained nitro compound in the organic solvent with zinc powder, and hydrolyzing with acid to obtain 17beta-androst-4-ene-3-one-17-formaldehyde; oxidizing an intermediate obtained by hydrolyzing in the organic solvent with hydrogen peroxide to obtain a 17beta-androst-4-ene-3-one-17-formic acid crude product; recrystallizing the crude product through methyl alcohol to obtain a finished product. According to the preparation method, total yield of synthesis weight is 70 to 72 percent, and the content of HPLC (High Performance Liquid Chromatography) is 99.0 percent or over 99.0 percent. The method disclosed by the invention has the advantages of high production yield, low cost, good purity, stable quality, high recovery rate of solvent, economy and environment friendliness.
