3-<(tert-butylsimethylsilyl)oxy>-19-nor-17α-pregna-1,3,5(10)-triene 21,17-carbolactone | 160803-26-9

• 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: 3-<(tert-butylsimethylsilyl)oxy>-19-nor-17α-pregna-1,3,5(10)-triene 21,17-carbolactone
• 英文别名: 3-(tert-butyldimethylsilyloxy)-19-nor-17α-pregna-1,3,5(10)-triene-21,17-carbolactone；(8R,9S,13S,14S,17R)-3-[tert-butyl(dimethyl)silyl]oxy-13-methylspiro[7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-17,5'-oxolane]-2'-one
• CAS: 160803-26-9
• 化学式: C₂₇H₄₀O₃Si
• 分子量: 440.698
• InChiKey: DTHLTCWZPZASCX-VJBPQSTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.0
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-<(tert-butylsimethylsilyl)oxy>-19-nor-17α-pregna-1,3,5(10)-triene 21,17-carbolactone 在 二苯并-18-冠醚-6 、 四丁基氟化铵 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 13.67h， 生成 (8R,9S,13S,14S,17R)-3-methoxy-13-methyl-3',4',6,7,8,9,11,12,13,14,15,16-dodecahydro-5'H-spiro[cyclopenta[a]phenanthrene-17,2'-furan]-5'-one
  参考文献：
  名称：

  抑制人胎盘微粒体中17β-羟类固醇脱氢酶活性的类固醇螺-γ-内酯。

  摘要：

  已知重要的酶17β-羟基类固醇脱氢酶（17β-HSD）调节生物活性类固醇（即雄激素和雌激素）的细胞内水平。为了开发有效的17β-HSD抑制剂以降低活性类固醇的水平，我们发现类固醇螺-γ-内酯会抑制17β-HSD活性。在本报告中，我们描述了包含甾体C-18或C-19核的11个螺-γ-内酯类似物的合成，并比较了它们对人类胎盘微粒体中17β-HSD活性的相对抑制作用，该活性催化雄激素的相互转化。和雌激素。为了使特异性针对雌酮和雌二醇相互转化的胞质17β-HSD活性相互作用无效，我们使用4-雄烯二酮作为底物。这些类似物对微粒体17β-HSD活性的抑制作用分析表明，含有C-18核的螺-γ-内酯比C-19核类似物更有效。酚类螺旋-γ-内酯7（3-羟基-19-nor-17α-pregna-1,3,5（10）-三烯21,17-carbolactone）的抑制效果最佳，IC50值值为0.27 microM，

  DOI：

  10.1021/jm00022a018
• 作为产物：
  描述：

  3-(O-tert-butyl(dimethyl)silyl)estrone 在 palladium on activated charcoal 正丁基锂 、 jones' reagent 、 amberlyst 15R acidic resin 、 氢气 作用下， 反应 11.67h， 生成 3-<(tert-butylsimethylsilyl)oxy>-19-nor-17α-pregna-1,3,5(10)-triene 21,17-carbolactone
  参考文献：
  名称：

  抑制人胎盘微粒体中17β-羟类固醇脱氢酶活性的类固醇螺-γ-内酯。

  摘要：

  已知重要的酶17β-羟基类固醇脱氢酶（17β-HSD）调节生物活性类固醇（即雄激素和雌激素）的细胞内水平。为了开发有效的17β-HSD抑制剂以降低活性类固醇的水平，我们发现类固醇螺-γ-内酯会抑制17β-HSD活性。在本报告中，我们描述了包含甾体C-18或C-19核的11个螺-γ-内酯类似物的合成，并比较了它们对人类胎盘微粒体中17β-HSD活性的相对抑制作用，该活性催化雄激素的相互转化。和雌激素。为了使特异性针对雌酮和雌二醇相互转化的胞质17β-HSD活性相互作用无效，我们使用4-雄烯二酮作为底物。这些类似物对微粒体17β-HSD活性的抑制作用分析表明，含有C-18核的螺-γ-内酯比C-19核类似物更有效。酚类螺旋-γ-内酯7（3-羟基-19-nor-17α-pregna-1,3,5（10）-三烯21,17-carbolactone）的抑制效果最佳，IC50值值为0.27 microM，

  DOI：

  10.1021/jm00022a018

文献信息

• Inhibition of type 2 17β-hydroxysteroid dehydrogenase by estradiol derivatives bearing a lactone on the D-ring: structure–activity relationships
  作者：Patrick Bydal、Serge Auger、Donald Poirier

  DOI：10.1016/j.steroids.2004.03.002

  日期：2004.5

  The peripheral conversion of steroid precursors into biologically active forms can be a major source of steroid synthesis, and these steroids support the growth of hormone-dependent diseases. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) enzyme family is involved in the biosynthesis of active steroids and its inhibition constitutes an interesting approach for treating estrogen- and androgen-dependent cancers. We previously found that a compound formed by the introduction of a spiro-gamma-lactone at position 17 of estradiol (E,) produces a significant inhibition of type 2 17beta-HSD. To optimize the inhibitory potency of such compounds, we synthesized a series of estradiol derivatives bearing a lactone on the D-ring and tested their ability to inhibit the type 2 17beta-HSD transformation of 4-androstenedione into testosterone. The results of our structure-activity relationship study determined the importance of the 17beta-orientation of the oxygen atom. Indeed, the 17beta-O-isomer of spiro-gamma-lactone-E, is a much more potent inhibitor than the 17alpha-O-analog (respectively 85 and 9% of inhibition at I muM). The carbonyl function is essential since the percentage of inhibition shifts from 85 to 30%, 15, or 3%, when the carbonyl group is transformed into a hydroxyl, a methoxy or a methylene (cycloether) group, respectively. Our results lead us to realize the importance of the spirolactone versus the C17beta-O/C16beta lactone (respectively 32 and 2% of inhibition at 0.1 muM, for the same size of lactone ring). The optimal size for the spirolactone was also established to be six members. All the types of substituents (methyl, dimethyl, allyl, propyl, and methoxycarbonyl) that we added on the spiro-delta-tactone moiety decreased the inhibitory activity, suggesting steric restrictions for the space that can be occupied in proximity of the spiro-delta-lactone functionality. 17-(Spiro-delta-lactone)-E-2, compound 6, was thus the most potent inhibitor of type 2 17beta-HSD with a K-i value of 29 +/- 5 nM. This compound reversibly inhibits type 2 17beta-HSD in a non-competitive manner. (C) 2004 Elsevier Inc. All rights reserved.
• Steroidal Spiro-.gamma.-lactones That Inhibit 17.beta.-Hydroxysteroid Dehydrogenase Activity in Human Placental Microsomes
  作者：Kay Mane Sam、Serge Auger、Van Luu-The、Donald Poirier

  DOI：10.1021/jm00022a018

  日期：1995.10

  effects on 17 beta-HSD activity in the human placenta microsomes that catalyze the interconversion of androgens and estrogens. To void the interaction of the cytosolic 17 beta-HSD activity that is specific for the interconversion of estrone and estradiol, we used 4-androstenedione as substrate. Analysis of the inhibitory effect exerted by these analogs on microsomal 17 beta-HSD activity indicates that spiro-gamma-lactones

  已知重要的酶17β-羟基类固醇脱氢酶（17β-HSD）调节生物活性类固醇（即雄激素和雌激素）的细胞内水平。为了开发有效的17β-HSD抑制剂以降低活性类固醇的水平，我们发现类固醇螺-γ-内酯会抑制17β-HSD活性。在本报告中，我们描述了包含甾体C-18或C-19核的11个螺-γ-内酯类似物的合成，并比较了它们对人类胎盘微粒体中17β-HSD活性的相对抑制作用，该活性催化雄激素的相互转化。和雌激素。为了使特异性针对雌酮和雌二醇相互转化的胞质17β-HSD活性相互作用无效，我们使用4-雄烯二酮作为底物。这些类似物对微粒体17β-HSD活性的抑制作用分析表明，含有C-18核的螺-γ-内酯比C-19核类似物更有效。酚类螺旋-γ-内酯7（3-羟基-19-nor-17α-pregna-1,3,5（10）-三烯21,17-carbolactone）的抑制效果最佳，IC50值值为0.27 microM，