3α-hydroxy-3β-phenylmethyl-5α-androstan-17-one

• 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: 3α-hydroxy-3β-phenylmethyl-5α-androstan-17-one
• 英文别名: 3β-benzyl-3α-Hydroxy-5α-androstane-17-one；(3R,5S,8R,9S,10S,13S,14S)-3-benzyl-3-hydroxy-10,13-dimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-one
• 化学式: C₂₆H₃₆O₂
• 分子量: 380.571
• InChiKey: XOWPNPDBHWAXCS-OQHHGKSNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  雄诺龙 在 咪唑 、 盐酸 、 jones' reagent 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 3.5h， 生成 3α-hydroxy-3β-phenylmethyl-5α-androstan-17-one
  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

文献信息

• [EN] INHIBITORS OF 17ß-HSD1, 17ß-HSD3 AND 17ß-HSD10<br/>[FR] INHIBITEURS DE 17SS-HSD1, 17SS-HSD3 ET 17SS-HSD10
  申请人：UNIV LAVAL

  公开号：WO2012129673A1

  公开（公告）日：2012-10-04

  The present application discloses 17β hydroxy steroid dehydrogenase (17β HSD) type 1, 3, 10 inhibitors and use thereof (alone and in combination) in the treatment of cancer and other afflictions. 17β HSDl inhibitors include estradiol derivatives with a nieta-carbamoylbenzyl substituent at C 16. 17β HSD3/HSD10 inhibitors include androsterone derivatives substituted at the C3 position with a sulfonamide piperazine. Also disclosed are compounds that are inhibitors of both 17β HSDl and 17β HSD3 that have a spiro-morpholine substituent at C20.

  该申请公开了17β羟基类固醇脱氢酶（17β HSD）类型1、3、10的抑制剂及其在癌症和其他疾病治疗中的使用（单独和组合使用）。17β HSD1抑制剂包括在C16处带有尼达-氨甲酰苯甲基取代基的雌二醇衍生物。17β HSD3/HSD10抑制剂包括在C3位置用磺胺基哌嗪取代的雄甾酮衍生物。还公开了既是17β HSD1又是17β HSD3抑制剂的化合物，其在C20处带有螺环吗啡基取代基。
• Inhibitors of type 5 and type 3 17beta-hydroxysteroid dehydrogenase and methods for their use
  申请人：Endorecherche, Inc.

  公开号：US20040082556A1

  公开（公告）日：2004-04-29

  Novel methods of medical treatment and/or inhibition of development of diseases are disclosed for diseases that are sensitive to androgenic or estrogenic activity. The treatments utilize inhibitors of type 5 and/or type 3 17&bgr;-hydroxysteroid dehydrogenase. Novel inhibitors of type 5 17&bgr;-hydroxysteroid dehydrogenase are also disclosed, as are novel inhibitors of type 3 17&bgr;-hydroxysteroid dehydrogenase.

  本发明揭示了一种针对对雄激素或雌激素活性敏感的疾病的新型医疗治疗和/或抑制疾病发展的方法。这些治疗方法利用了类型5和/或类型3的17β-羟基类固醇脱氢酶的抑制剂。本发明还揭示了新型的类型5 17β-羟基类固醇脱氢酶抑制剂，以及新型的类型3 17β-羟基类固醇脱氢酶抑制剂。
• INHIBITORS OF 17Beta-HSD1, 17Beta-HSD3 AND 17Beta-HSD10
  申请人：Poirier Donald

  公开号：US20140088053A1

  公开（公告）日：2014-03-27

  The present application discloses 17β hydroxy steroid dehydrogenase (17β HSD) type 1, 3, 10 inhibitors and use thereof (alone and in combination) in the treatment of cancer and other afflictions. 17β HSD1 inhibitors include estradiol derivatives with a nieta-carbamoylbenzyl substituent at C 16. 17β HSD3/HSD10 inhibitors include androsterone derivatives substituted at the C3 position with a sulfonamide piperazine. Also disclosed are compounds that are inhibitors of both 17β HSD1 and 17β HSD3 that have a spiro-morpholine substituent at C20.

  本申请公开了17β羟基类固醇脱氢酶(17β HSD)类型1、3、10的抑制剂及其使用(单独或联合)治疗癌症和其他疾病的方法。17β HSD1抑制剂包括在C16处具有一个尼龙-氨基甲酰苯基取代基的雌二醇衍生物。17β HSD3/HSD10抑制剂包括在C3位被磺酰胺哌嗪取代的雄甾酮衍生物。还公开了既抑制17β HSD1又抑制17β HSD3的化合物，其在C20处具有一个螺环吡啶取代基。
• Inhibitors of type 5 and 3 17beta-hydroxysteroid dehydrogenase and methods for their use
  申请人：Endorecherche Inc.

  公开号：EP1321146A2

  公开（公告）日：2003-06-25

  Novel methods of medical treatment and/or inhibition of development of diseases are disclosed for diseases that are sensitive to androgenic or estrogenic activity. The treatments utilize inhibitors of type 5 and/or type 3 17β-hydroxysteroid dehydrogenase. Novel inhibitors of type 5 17β-hydroxysteroid dehydrogenase are also disclosed, as are novel inhibitors of type 3 17β-hydroxysteroid dehydrogenase.

  针对对雄激素或雌激素活性敏感的疾病，公开了新的医疗和/或抑制疾病发展的方法。这些治疗方法利用了 5 型和/或 3 型 17β- 羟类固醇脱氢酶的抑制剂。还公开了 5 型 17β- 羟类固醇脱氢酶的新型抑制剂，以及 3 型 17β- 羟类固醇脱氢酶的新型抑制剂。
• Inhibitors of 17β-HSD1, 17β-HSD3 and 17β-HSD10
  申请人：Poirier Donald

  公开号：US11072632B2

  公开（公告）日：2021-07-27

  The present application discloses 17β hydroxy steroid dehydrogenase (17β HSD) type 1, 3, 10 inhibitors and use thereof (alone and in combination) in the treatment of cancer and other afflictions. 17β HSD1 inhibitors include estradiol derivatives with a nieta-carbamoylbenzyl substituent at C 16. 17β HSD3/HSD10 inhibitors include androsterone derivatives substituted at the C3 position with a sulfonamide piperazine. Also disclosed are compounds that are inhibitors of both 17β HSD1 and 17β HSD3 that have a spiro-morpholine substituent at C20.

  本申请公开了17β羟基类固醇脱氢酶（17β HSD）1、3、10型抑制剂及其在治疗癌症和其他疾病中的用途（单独或联合使用）。17β HSD1 抑制剂包括雌二醇衍生物，其 C 16 位具有尼他-氨基甲酰基苄基取代基。17β HSD3/HSD10 抑制剂包括在 C3 位被磺酰胺哌嗪取代的雄甾酮衍生物。还公开了同时作为 17β HSD1 和 17β HSD3 抑制剂的化合物，这些化合物在 C20 位具有螺吗啉取代基。