3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile | 40962-89-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile
• 英文别名: 2-[(1S,2S,4aS,4bR,7S,10aR)-2-formyl-7-hydroxy-2,4b-dimethyl-1,3,4,4a,5,6,7,8,10,10a-decahydrophenanthren-1-yl]acetonitrile
• CAS: 40962-89-8
• 化学式: C₁₉H₂₇NO₂
• 分子量: 301.429
• InChiKey: LCXSLYVRBLMOHW-VIUKOLAESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  61.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile 在 Jones reagent 作用下， 以 丙酮 为溶剂， 反应 2.5h， 以38%的产率得到15-cyano-16,17-seco-17-norandrost-4-ene-3,6-dione-13-carboxylic acid
  参考文献：
  名称：

  Synthesis and antitumor activity of new d-seco and d-homo androstane derivatives

  摘要：

  Starting from 30-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 4-9 were synthesized. On the other hand, 3 beta-hydroxy-17-oxa-D-homoandrost-5-ene-16-one (10) yielded the new D-horno derivatives 12, 13 and 15. In vitro antiproliferative activity of selected compounds against three tumor cell lines (human breast ade- nocarcinoma ER+, MCF-7, human breast adenocarcinoma ER-, MDA-MB-231, prostate cancer AR-, PC-3, and normal fetal lung fibroblasts, MRC-5) was evaluated. Compounds 3 and 12 showed strong antiproliferative activity against PC-3 cells, the IC50 values being 2 mu M and 0.55 mu M, respectively. Compounds 6 (10 mu M) and 14 (9 mu M) showed moderate activity against MDA-MB-231 cells. The synthesized compounds 1-3, 5-8, 10 and 12-15 were not toxic to normal fetal lung fibroblasts cells, MRC-5. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2009.07.007
• 作为产物：
  描述：

  3β,17β-dihydroxy-16-oximinoandrost-5-ene 在 吡啶 、 对甲苯磺酰氯 作用下， 生成 3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile
  参考文献：
  名称：

  Synthesis and antitumor activity of new d-seco and d-homo androstane derivatives

  摘要：

  Starting from 30-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 4-9 were synthesized. On the other hand, 3 beta-hydroxy-17-oxa-D-homoandrost-5-ene-16-one (10) yielded the new D-horno derivatives 12, 13 and 15. In vitro antiproliferative activity of selected compounds against three tumor cell lines (human breast ade- nocarcinoma ER+, MCF-7, human breast adenocarcinoma ER-, MDA-MB-231, prostate cancer AR-, PC-3, and normal fetal lung fibroblasts, MRC-5) was evaluated. Compounds 3 and 12 showed strong antiproliferative activity against PC-3 cells, the IC50 values being 2 mu M and 0.55 mu M, respectively. Compounds 6 (10 mu M) and 14 (9 mu M) showed moderate activity against MDA-MB-231 cells. The synthesized compounds 1-3, 5-8, 10 and 12-15 were not toxic to normal fetal lung fibroblasts cells, MRC-5. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2009.07.007

文献信息

• Heterocyclic androstane and estrane d-ring modified steroids: Microwave-assisted synthesis, steroid-converting enzyme inhibition, apoptosis induction, and effects on genes encoding estrogen inactivating enzymes
  作者：Ágnes Erika Kulmány、Bianka Edina Herman、István Zupkó、Masa Sinreih、Tea Lanišnik Rižner、Marina Savić、Aleksandar Oklješa、Andrea Nikolić、Viktória Nagy、Imre Ocsovszki、Mihály Szécsi、Suzana Jovanović-Šanta

  DOI：10.1016/j.jsbmb.2021.105997

  日期：2021.11

  of the substrate estrone; its inhibition against NADPH-complexed 17β-HSD1 was markedly weaker. Compound 24 also significantly and selectively reduced proliferation of cancer cell lines of gynecological origin. This estrane triazole changed the cell cycle and induced apoptosis of HeLa, SiHa, and MDA-MB-231 cancer cells, measured by both increased subG1 fraction of cells and activation of caspase-independent

  使用微波辅助反应条件合成了雌三烯和雄甾烷系列中的d-环稠合和d-高内酯化合物。微波辐射合成方法方便有效，收率高，反应时间短。在体外酶测定中研究了它们对 C 17,20 -裂解酶和 17β-羟基类固醇脱氢酶 1 (17β-HSD1) 活性的抑制作用。d-环融合的三唑基雌酮类似物24显示出对 NADH 复合的 17β-HSD1 的有效抑制，其结合亲和力与底物雌酮相似；它对 NADPH 复合的 17β-HSD1 的抑制作用明显减弱。化合物24还显着和选择性地减少了妇科来源的癌细胞系的增殖。这种雌二醇三唑改变了 HeLa、SiHa 和 MDA-MB-231 癌细胞的细胞周期并诱导细胞凋亡，通过增加细胞的 subG1 部分和激活不依赖于半胱天冬酶的信号通路来衡量。的抗雌激素作用的第三模式24锯增加的mRNA表达SULT1E1在HeLa细胞中的基因; 相比之下，其 3-苄氧基类似物23增加了HSD17B2基因的mRNA
• An intramolecular one-pot synthesis of steroidal triazoles via 1,3-dipolar cycloadditions of in situ generated diazo compounds
  作者：Marija N. Sakač、Andrea R. Gaković、János J. Csanádi、Evgenija A. Djurendić、Olivera Klisurić、Vesna Kojić、Gordana Bogdanović、Katarina M. Penov Gaši

  DOI：10.1016/j.tetlet.2009.04.107

  日期：2009.7

  A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular 1,3-dipolar cycloaddition of a steroidal 16,17-seco-17-diazo-16-nitrile system. The structures of the products are established by X-ray and NMR studies. The in vitro antiproliferative activity of the steroidal triazoles against three tumor cell lines was evaluated.

  据报道，通过甾体16，17-seco-17-重氮16-腈系统的分子内1，3-偶极环加成制备甾体三唑的新的合成途径。产品的结构通过X射线和NMR研究确定。评价了甾体三唑对三种肿瘤细胞系的体外抗增殖活性。
• Synthesis and Biological Evaluation of Some A,D-Ring Modified 16,17-Secoandrostane Derivatives
  作者：Evgenija A. Djurendić、Marina P. Zaviš、Marija N. Sakač、Vesna V. Kojić、Gordana M. Bogdanović、Katarina M. Penov Gaši

  DOI：10.1135/cccc20080627

  日期：——

  Starting from 3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 2-11 were synthesized. Protection of the 17-oxo function of compound 1 with ethylene glycol yielded compounds 2 and 3. The Oppenauer oxidation of 2 or oxidation with H₂O₂ in alkaline conditions gave the respective compounds 4 and 10. Epoxidation of compound 4 yielded a mixture of 4α,5α- and 4β,5β-epoxides 5 and 6 and a mixture of 4α,5α- and 4β,5β-epoxy-carboxamides 7 and 8. Opening of the oxirane ring of a mixture of compounds 5 and 6 with formic acid afforded the 4-hydroxy derivative 9. Anti-aromatase activity and in vitro cytotoxicity for three tumor cell lines (human breast adenocarcinoma ER+, MCF-7 as well as human breast adenocarcinoma ER-, MDA-MB-231, and prostate cancer, PC3) of selected compounds were evaluated. Compounds 2, 4, 9, and 10 showed a strong cytotoxicity for PC3 cells.

  从3β-羟基-17-酮基-16,17-去氢雄烯-16-腈（1）开始，合成了新的16,17-去氢雄烷衍生物2-11。用乙二醇保护化合物1的17-酮基，得到化合物2和3。在碱性条件下，用Oppenauer氧化剂氧化2或用H₂O₂氧化剂氧化，得到相应的化合物4和10。化合物4的环氧化反应生成了4α,5α-和4β,5β-环氧化物5和6的混合物，以及4α,5α-和4β,5β-环氧羧酰胺7和8的混合物。用甲酸开环氧丙烷环，得到4-羟基衍生物9的混合物5和6。选择性化合物的抗芳香化酶活性和对三种肿瘤细胞系（人乳腺腺癌ER+，MCF-7以及人乳腺腺癌ER-，MDA-MB-231和前列腺癌，PC3）的体外细胞毒性进行了评估。化合物2、4、9和10对PC3细胞显示出强烈的细胞毒性。