17β-[(tert-butyldimethylsilyl)oxy]-3β-hydroxy-3α-propyl-5α-androstane | 225244-96-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子
• 英文名称: 17β-[(tert-butyldimethylsilyl)oxy]-3β-hydroxy-3α-propyl-5α-androstane
• 英文别名: (3S,5S,8R,9S,10S,13S,14S,17S)-17-[tert-butyl(dimethyl)silyl]oxy-10,13-dimethyl-3-propyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-ol
• CAS: 225244-96-2
• 化学式: C₂₈H₅₂O₂Si
• 分子量: 448.805
• InChiKey: LNLBOFSRMDGVBG-LZHPGDNASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.95
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  17β-[(tert-butyldimethylsilyl)oxy]-3β-hydroxy-3α-propyl-5α-androstane 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Androsterone 3α-Ether-3β-Substituted and Androsterone 3β-Substituted Derivatives as Inhibitors of Type 3 17β-Hydroxysteroid Dehydrogenase:  Chemical Synthesis and Structure−Activity Relationship

  摘要：

  Type 3 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is involved in the biosynthesis of androgen testosterone. To produce potent inhibitors of this key steroidogenic enzyme, we prepared a series of androsterone (ADT) derivatives by adding a variety of substituents at position 3. The 3 beta-substituted ADT derivatives proved to be good inhibitors (IC50 = 57-147 nM) with better inhibitory activities obtained for compounds bearing a propyl, s-butyl, cyclohexylalkyl, or phenylalkyl group. With an IC50 value of 57 nM, the 3 beta-phenylmethyl-ADT was 6-fold more potent than ADT, the lead compound, and 13-fold more potent than 4-androstene-3,17-dione, the natural enzyme substrate used itself as inhibitor. The 3 alpha-ether-3 beta-substituted ADT derivatives had a lower inhibitory activity compared to the 3 beta-substituted ADT analogues except for the 3 beta-phenylethyl-3 alpha-methl-O-ADT (IC50 = 73 nM), which proved to be a more potent inhibitor than 3 beta-phenylethyl-ADT (IC50 = 99 nM). The results of our study identified potent type 3 17 beta-HSD inhibitors for potential use in the treatment of androgen-sensitive diseases.

  DOI：

  10.1021/jm058179h
• 作为产物：
  描述：

  雄诺龙 在 咪唑 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 17β-[(tert-butyldimethylsilyl)oxy]-3β-hydroxy-3α-propyl-5α-androstane
  参考文献：
  名称：

  Androsterone 3β-substituted derivatives as inhibitors of type 3 17β-hydroxysteroid dehydrogenase

  摘要：

  Androsterone derivatives substituted at position 3 were synthesized starting from dihydrotestosterone in a short sequence of reactions. They proved to be potent inhibitors (IC50 = 57-147 nM) of type 3 17beta-hydroxysteroid dehydrogenase, a key enzyme of steroidogenesis, which catalyzes the transformation of androstenedione to steroid active androgen testosterone.

  DOI：

  10.1016/s0960-894x(00)00517-5

文献信息

• Diastereoselective Addition of Organomagnesium Reagents to 17β-TBDMS-Dihydrotestosterone
  作者：BÉAtrice Tchédam Ngatcha、Donald Poirier

  DOI：10.1080/00397919908086075

  日期：1999.4

  Abstract Several alkylations of the C3-carbonyl of 17p-TBDMS-DHT (1) with Grignard reagents were performed to obtain a series of potential inhibitors of androgen formation. It has been found that, depending on the nucleophilicity of the Grignard reagent used, there was a difference in the diastereoselectivity. The stronger reagents proceeded preferentially through the equatorial attack, while the weaker ones

  摘要 用格氏试剂对 17p-TBDMS-DHT (1) 的 C3-羰基进行了几次烷基化，以获得一系列潜在的雄激素形成抑制剂。已经发现，根据所用格氏试剂的亲核性，非对映选择性存在差异。较强的试剂优先通过赤道攻击，而较弱的试剂则通过轴向攻击。