- Syntheses of [21-11C] and (21-13C)progesterone
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[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.
- Lidstroem, Pelle,Neu, Henrik,Langstroem, Bengt
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Read Online
- Design, synthesis, and biological evaluation of two series of novel a-ring fused steroidal pyrazines as potential anticancer agents
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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.
- Li, Na,Qian, Hao,Wang, Junru,Wang, Shijun,Yuan, Xiaorong
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- Discovery of novel steroidal-chalcone hybrids with potent and selective activity against triple-negative breast cancer
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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.
- Bai, Chengfeng,Hou, Qiangqiang,Lin, Xin,Lu, Xiang,Luo, Guoshun,Wei, Hanlin,Xiang, Hua
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- Steroid compound as well as preparation method and application thereof (by machine translation)
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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)
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Paragraph 0058-0059; 0066-0067
(2020/10/29)
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- Design, synthesis, and biological evaluation of novel androst-17β-amide structurally related compounds as dual 5α-reductase inhibitors and androgen receptor antagonists
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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.
- Lao, Kejing,Xun, Guoliang,Gou, Xingchun,Xiang, Hua
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p. 1597 - 1606
(2019/09/07)
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- Preparation method of 17 beta-androst-4-ene-3-one-17-carboxylic acid
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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.
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Paragraph 0012; 0013; 0016; 0020; 0024
(2018/04/02)
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- Design, synthesis and biological evaluation of novel androst-3,5-diene-3-carboxylic acid derivatives as inhibitors of 5α-reductase type 1 and 2
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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.
- Lao, Kejing,Sun, Jie,Wang, Chong,Lyu, Weiting,Zhou, Boshen,Zhao, Ruheng,Xu, Qian,You, Qidong,Xiang, Hua
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- 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
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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.
- Lao, Kejing,Sun, Jie,Wang, Chong,Wang, Ying,You, Qidong,Xiao, Hong,Xiang, Hua
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supporting information
p. 4212 - 4217
(2017/08/23)
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- Synthesis method of 3-ketone-4-androstene-17 beta carboxylic acid
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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.
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Paragraph 0036; 0037
(2016/10/27)
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- A synthetic 3-carbonyl-4-androstene -17 β carboxylic acid
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The invention provides a method for synthesizing 3-carbonyl-4-androstene-17beta carboxylic acid. The method comprises the following specific steps: (1) dissolving 3-hydroxyl-5-androstene-17beta carboxylic acid II into a dioxane water solution into which a strong base is dissolved, dropwise adding a sodium hypochlorite solution in the presence of a catalyst, and carrying out oxidative reaction; (2) adjusting the pH value of a reaction system to be 1-2 with an acid liquor, heating and refluxing, and carrying out transposition reaction; (3) carrying out atmospheric concentration on the reaction system, and recovering dioxane; and (4) cooling the reaction system, throwing and filtering to obtain a filter cake, washing the filter cake to be neutral with water, and drying in a spinning manner, so as to obtain 3-carbonyl-4-androstene-17beta carboxylic acid I. The method is simple in process, high in product purity and product yield, low in energy consumption, few in three wastes, and simple in post-treatment; the method disclosed by the invention is an economic and environment-friendly synthesis method; and industrial implementation is facilitated.
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Paragraph 0050-0059
(2017/03/14)
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- Preparation method of 17beta-androst-4-ene-3-one-17-carboxylic acid
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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.
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- Progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein- mediated multidrug efflux: Design, synthesis, characterization and biological evaluation
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Bivalent ligands were designed on the basis of the described close proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of 19 progesterone-adenine hybrids are described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone. The hybrid with a hexamethylene linker chain showed the best inhibitory potency. The efficiency of these progesterone-adenine hybrids depends on two main factors: (i) the nature of the linker and (ii) its attachment point on the steroid skeleton.
- Zeinyeh, Wael,Mahiout, Zahia,Radix, Sylvie,Lomberget, Thierry,Dumoulin, Axel,Barret, Roland,Grenot, Catherine,Rocheblave, Luc,Walchshofer, Nadia,Matera, Eva-Laure,Dumontet, Charles
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p. 1177 - 1191,15
(2020/08/20)
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- Design and diastereoselective synthesis of C-2,C-20-diaryl steroidal derivatives
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A novel and efficient synthetic strategy to access unique C-2 substituted steroid analogues 3 and 4 is described. The unusual C-2 aryl ether analogues 3 were shown to act as virtual antagonists of LRH-1 and were prepared as single diastereoisomers, employing a fifteen-step sequence from pregnenolone (9). The key steps include the stereoconvergent nucleophilic displacement of an epimeric mixture of 3-keto 2-bromo steroids, chemoselective carbonylation of an enol triflate and conversion of a thiopyridyl ester into an aryl ketone. The related C-2 benzyl analogues 4 were prepared in a similar manner. Starting from pregnenolone, a diastereoselective fifteen-step synthesis was developed to access novel C-2-substituted steroid analogues. A range of C-2 benzyl and aryl ether analogues were prepared to probe their efficacy as antagonists of the nuclear receptor LRH-1. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
- Rey, Jullien,O'Riordan, Timothy J. C.,Hu, Haipeng,Snyder, James P.,White, Andrew J. P.,Barrett, Anthony G. M.
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supporting information; experimental part
p. 3781 - 3794
(2012/10/08)
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- Design, synthesis and evaluation of progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein-mediated multidrug efflux
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Steroidal bivalent ligands were designed on the basis of the described closer proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of seven progesterone-adenine hybrids were described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone.
- Zeinyeh, Wa?l,Alameh, Ghina,Radix, Sylvie,Grenot, Catherine,Dumontet, Charles,Walchshofer, Nadia
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scheme or table
p. 3165 - 3168
(2010/09/05)
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- PROCESS FOR THE PREPARATION OF 4-AZASTEROIDS
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The invention relates to a process for the preparation of 4-steroids of the formula (I), R1 and R2 are independently selected from the group consisting of hydrogen, F, Cl, Br, I, C1-6-alkyl and C1-6-alkoxy, and R4 is selected from the group consisting of hydrogen, (N, N-di-C1-6-alkylamino)methyl, 2-(N,N-di-C1-6-alkylamino)ethyl, C1-6alkyl, C1-6-alkoxy, phenyl and benzyl, and Q7 represents a carbonyl oxygen atom or is R7-1 and R7-2, wherein one of R7-1 and R7-2 is hydrogen and the other is selected from the group consisting of hydrogen, F, Cl, Br, I, C1-6-alkyl and C1-6-alkoxy and R9 represents hydrogen or F, and Q11 represents a carbonyl oxygen atom or is R11-1 and R11-2, wherein one of R11-1 and R11-2 is hydrogen and the other is selected from the group consisting of hydrogen, cyano, cyano-C1-3-alkyl, acetoxy, COOH and COO-M+, wherein M+ is Na+, K+ or NH+4, and R16 is selected from the group consisting of hydrogen cyano, C1-3-alkyl, cyano-C1-3-alkyl, acetoxy, COOH and COO-M+, wherein M+ is Na+, K+ or NH+4, and COOR represents COOH or COO-M+, wherein M+ is Na+, K+ or NH+4. The three step process comprises (i) a haloform reaction of a 17-acetyl steroid converting the acetyl group into a -COOR group, (ii) subsequent ozonolysis of the A-ring and (iii) re-closure of the A-ring by reaction with an appropriate nitrogen compound of formula H2NR4 to afford a compound of formula (I) above.
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Page/Page column 11-12
(2008/06/13)
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- Process to prepare androst-4-en-17-carboxylic acid
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The process of the present invention transforms a steroidal ketone of formula (III) to androst-4-en-17β-carboxylic acid (IV) by reaction with K2SO5.KHSO4.K2SO4.
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- Anti-AIDS agents. Part 36: 17-carboxylated steroids as potential anti-HIV agents
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In our search for novel anti-HIV agents, seven 17-carboxylated steroid derivatives were synthesized and evaluated as potential anti-HIV agents. Compound 13 exhibited potent anti-HIV activity in acutely infected H9 lymphocytes with EC50 and therapeutic index values of 0.8 μM and 300, respectively.
- Xia, Peng,Yang, Zheng-Yu,Xia, Yi,Zheng, Yun-Qing,Cosentino, L.Mark,Lee, Kuo-Hsiung
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p. 1907 - 1911
(2007/10/03)
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- Synthesis of 4-trifluoromethylsteroids: A novel class of steroid 5α-reductase inhibitors
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A concise synthetic approach to 4-trifluoromethyl steroids, a novel class of steroid 5α-reductase inhibitors, is described. Direct trifluoromethylation of steroid olefinic bromide with methyl fluorosulfonyldifluoroacetate was used as a key step in the synthesis. The compound 4 exhibited highly inhibitory activity than Finasteride in in vitro assay.
- Fei, Xiang-Shu,Tian, Wei-Sheng,Chen, Qing-Yun
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p. 3113 - 3118
(2007/10/03)
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- Steriod 5-alpha-reductase inhibitors
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Invented are substituted acrylate analogues of steroidal synthetic compounds, pharmaceutical compositions containing these compounds, and methods of using these compounds to inhibit steroid 5-α-reductase. Also invented are intermediates used in preparing these compounds.
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- 7-KETO OR HYDROXY 3,5-DIENE STEROIDS AS INHIBITORS OF STEROID 5-ALPHA REDUCTASE
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Invented are carboxyl and carboxyl alkyl ester substituted 7-keto and hydroxy analogues of synthetic steroidal compounds, pharmaceutical compositions containing, these compounds, and methods of using these compounds to inhibit steroid 5-alpha-reductase. Also invented are methods for preparing these compounds.
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- PHOSPHINIC ACID SUBSTITUTED STEROIDS AS INHIBITORS OF STEROID 5 ALPHA-REDUCTASE
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The invention relates to 3-phosphinic acid steroidal compounds, pharmaceutical compositions containing these compounds, and methods of using these compounds to inhibit steroid 5alpha-reductase.
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- Steroid 5-alpha-reductase inhibitors
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[From equivalent EP0289327A3] Compounds of formula (I) : ψψ in which, inter alia, R± is H or C±±±alkyl and M is O or S, processes for their preparation, pharmaceutical compositions containing then and their use as inhibitors of 5-à-reductase in the treatment in the reduction of prostate size.ψ
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- STEROID 5-ALPHA-REDUCTASE INHIBITORS
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Invented are substituted acrylate analogues of steroidal synthetic compounds, pharmaceutical compositions containing the compounds, and methods of using these compounds to inhibit steroid 5-alpha-reductase. Also invented are intermediates used in preparing these compounds
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- PHOSPHONIC ACID SUBSTITUTED STEROIDS AS STEROID 5 ALPHA-REDUCTASE INHIBITORS
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Invented are substituted acrylate analogues of steroidal synthetic compounds, pharmaceutical compositions containing the compounds, and methods of using these compounds to inhibit steroid 5 alpha-reductase. Also invented are intermediates used in preparing these compounds
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- Azasteroids as Inhibitors of Rat Prostatic 5α-Reductase
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A series of A-ring heterocyclic steroids has been prepared and tested for inhibition of rat prostatic steroid 5α-reductase in vitro.Strinkingly high inhibitory activity was found with a group of 17β-substituted 4-methyl-4-aza-5α-androstan-3-ones.These compounds were prepared from 3-keto-Δ4-precursors by oxidative (O3 or NaIO4-KMnO4) A-ring cleavage followed, in turn, by ring closure with an amine and hydrogenation over platinum catalyst.Other A-ring azasteroids were made by Beckmann rearrangement of oximes of 2-oxo-A-nor-, 3-oxo- and 4-oxo-5α-androstanes.An A-nor-2-oxo-3-azasteroid was prepared by oxidative decarbonylation of a precursor 2,3-dioxo-4-azasteroid with m-chloroperbenzoic acid.A-ring modifications of the 4-azasteroids included Δ1-unsaturation, 2- and 4-substituents, and 3-carbonyl replacements.Side chains at the 17-position were varied with an emphasis on carboxylate derivatives (salts, esters, and amides).
- Rasmusson, Gary H.,Reynolds, Glenn F.,Utne, Torleif,Jobson, Ronald B.,Primka, Raymond L.,et al.
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p. 1690 - 1701
(2007/10/02)
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- Preparation of 4-aza-17-substituted-5α-androstan-3-ones useful as 5α-reductase inhibitors
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A method of preparing a compound of the formula: STR1 where Formula (I) may also have the structure of partial Formula (III); wherein, STR2 R' is hydrogen or methyl; R" is hydrogen or β-methyl; R'" is β-methyl or hydroxy; Z is (1) oxo; (2) β-hydrogen and α-hydroxy; or α-hydrogen or α-hydroxyl and (3) (Y)n Q where n=0 or 1, Y is a straight or branched hydrocarbon chain of 1 to 12 carbon atoms and Q is STR3 where R8 is, STR4 where the dashed bond replaces the 17α hydrogen; (6) cyano; or (7) tetrazolyl; and pharmaceutically acceptable salts of the above compounds; CHARACTERIZED IN THAT (I.) a compound of the formula: STR5 , where A has the meanings above except --CH=CH--, is (1) treated with an oxidizing agent at reduced temperatures to form the corresponding 5-oxo-3,5-seco-androstan-3-oic acid compound; (2) treating the product of step (1) with an amine of formula: R1 NH2 to form the corresponding 4-aza-5-androsten-3-one compound substituted in the 4-position with R1 ; and (3) treating the product of step (2) with hydrogen under catalytic conditions to form the compound of Formula I and I & II wherein B is STR6 (II.) and where it is desired to prepare compounds of Formula I wherein B is STR7 additionally carrying out the following steps on the products prepared by the procedures in (I.) above: (1) alkylating the lactim carbonyl by treating it with trialkyloxonium tetrafluoroborate to form the corresponding alkyl iminium ether, i.e., the compound of Formula I where B is as above and R4 =OR5 ; (2) treating the product of step (1) with an amine of formula HNR6 R7 followed by treatment with a mineral acid to form the compound of Formula I where B is as above and R4 =NR6 R7 ; (III.) and where it is desired to prepare compounds of Formula I wherein A is --CH=CH--, additionally carrying out the following steps on the products prepared by the procedures in (I.) above: (1) treating the 1,2 saturated compound with lithium diisopropyl amide to form the corresponding enolate; (2) treating the enolate of step (1) in situ with diphenyldisulfide to form the corresponding α-phenylthio compound; (3) oxidizing the product of step (2) to form the corresponding sulfoxide compound; and (4) heating the product of step (3) to form the compound of Formula I wherein A is --CH=CH--.
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- Process for preparing 17β-carboxy-5-androsten-3-ones
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A process for preparing 17β-carboxy-4-androsten-3-ones comprising the steps of (1) reacting a 17β-(1-ketoethyl)-5-androsten-3-ol, for example, pregnenolene, with pyridine and iodine to form a pyridinium iodide compound; (2) reacting the pyridinium iodide compound with alkali metal methoxide in methanol to form a methyl-5-androsten-3-ol-17β carboxylate; (3) oxidizing the product of Step (2) preferably with aluminum isopropoxide to form methyl-4-androsten-3-one-17β-carboxylate; and (4) hydrolyzing the product of Step (3) to the corresponding 17β-carboxylic acid, salt, or ester. The 17β-carboxy-4-androsten-3-ones are useful as intermediates for preparation of N-substituted-17β-carbamoylandrost-4-en-3-one and 4-aza-17β-substituted-5α-androstan-3-one 5α reductase inhibitors.
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