- 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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p. 4212 - 4217
(2017/08/23)
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- Epristeride intermediate, preparation method of Epristeride intermediate, and preparation method of Epristeride
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The invention relates to the field of medicine, in particular to an Epristeride intermediate, a preparation method of the Epristeride intermediate, and a preparation method of Epristeride. The preparation method of the Epristeride intermediate comprises the following steps that a compound 3 takes a sulfonation reaction with an alkaline reagent to produce a compound 4; the reaction conversion is single; the column chromatography isolation is avoided; the alkaline reagent used in the reaction process can be easily obtained; the reaction conditions are mild. The unit operation is reduced; the production period is shortened; the production efficiency is improved; the production efficiency is high; the economic benefits are improved.
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Paragraph 0059; 0096; 0100; 0106-0108
(2018/03/24)
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- PROCESS FOR THE PREPARATION OF 17?-SUBSTITUTED-3-OXO-4-AZA-5ALPHA-ANDROSTANE DERIVATIVES
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Process for the preparation of 17?-substituted-3-oxo-4-aza-5α-androstane derivatives, which are useful intermediates for the synthesis of 3-oxo-4-aza-5α-androst-1-ene derivatives including finasteride, is provided.
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Page/Page column 7
(2008/06/13)
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- Treatment of hyperandrogenic conditions
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The invention concerns the treatment of hyperandrogenic conditions in humans by the formation of a novel mechanism-based irreversible inhibitor of human 5α-reductase enzymes from 3-oxo-4-oxa and 4-thiasteroids having a 1,2-double bond and the pyridine-nuc
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- 4-Oxa and 4-thia steroids
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The compounds of the present invention are those of structural formula (I) STR1 wherein X is oxygen or sulfur. Pharmaceutical compositions and methods of use of the compounds in the treatment of hyperandrogenic conditions are disclosed. In addition, the combination of the compounds with other active agents such as finasteride, minoxidil and retinoic acid or a derivative thereof is disclosed.
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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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- Treatment of hyperandrogenic conditions
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The invention concerns the treatment of hyperandrogenic conditions in humans by the formation of a novel mechanism-based irreversible inhibitor of human 5α-reductase enzymes from 3-oxo-4-oxa end 4-thiasteroids having a 1,2-double bond and the pyridine-nuc
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- Synthesis of N-substituted 3-oxo-17β -carboxamide-4-aza-5α-androstanes and the tautomerism of 3-oxo-4-aza-5-androstenes
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An N-aryl-3-oxo-4-aza-5α -androst-1-ene-17β carboxamide and three N-aryl or alkyl substituted 17α -hydroxy-3-oxo-4-aza-5α -androstane-17β -carboxamides were synthesized as antiandrogen candidates from 3-oxoandrost-4-ene-17β - carboxylic acid and androst-4-ene-3,17-dione respectively. The chemo- and stereoselective reduction of 3-oxo-4-aza-5-ene intermediates with formic acid and their tautomerism in a solution of chloroform and methanol were described.
- Xia, Peng,Yang, Zheng-Yu,Xia, Yi,Zhang, Hao-Bing,Zhang, Ke-Hua,Sun, Xun,Chen, Ying,Zheng, Yun-Qing
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p. 703 - 716
(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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- Steroid derivatives for the treatment of prostatic hypertrophy their preparation and uses
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The invention includes compounds of formula (I): STR1 in which R1 is hydrogen, alkyl, aryl-substituted alkyl or aromatic heterocyclic-substituted alkyl; R2 is aryl-substituted alkyl, aromatic heterocyclic-substituted alkyl or diarylamino; and R3 is carboxy or a group of formula --CONHSO2 R4 wherein R4 is alkyl; and pharmaceutically acceptable salts and esters of the compounds. The compounds have valuable 5α-reductase inhibitory activity and can thus be used for the treatment and prophylaxis of, inter alia, prostatic hypertrophy as well as other disorders arising from excess levels of 5α-dihydro-testosterone.
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- Acylimidazolides as Versatile Synthetic Intermediates for the Preparation of Sterically Congested Amides and Ketones: A Practical Synthesis of Proscar
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Acylimidazolides react with magnesium amides to produce carboxamides in excellent yields, whereas Fe(III) catalyzed cross coupling between acylimidazolide and Grignard reagents produce ketones in high yields.These methods were utilized to prepare the α-reductase inhibitor Proscar as well as various 17β-amide and ketone analogs of Δ1-4-aza-5α-androsten-3-one.
- Bhattacharya, A.,Williams, J.M.,Amato, J.S.,Dolling, U.-H.,Grabowski, E.J.J.
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p. 2683 - 2690
(2007/10/02)
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