(3α,5α)-3-hydroxy-3-(piperazin-1-ylmethyl)androstan-17-one | 1326702-42-4

• 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,5α)-3-hydroxy-3-(piperazin-1-ylmethyl)androstan-17-one
• 英文别名: (3R,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-3-(piperazin-1-ylmethyl)-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-one
• CAS: 1326702-42-4
• 化学式: C₂₄H₄₀N₂O₂
• 分子量: 388.594
• InChiKey: TWQHMDFRYDLFBH-DIPHUWLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3α,5α)-3-hydroxy-3-(piperazin-1-ylmethyl)androstan-17-one 、 3,5-双三氟甲基苄基溴 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以74%的产率得到(3α,5α)-3-((4-[3,5-bis(trifluoromethyl)benzyl]piperazin-1-yl)methyl)-3-hydroxyandrostan-17-one
  参考文献：
  名称：

  Development of 3-substituted-androsterone derivatives as potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3

  摘要：

  17Beta-hydroxysteroid dehydrogenase type 3 (17 beta-HSD3) is a steroidogenic enzyme that catalyzes the transformation of 4-androstene-3,17-dione (Delta(4)-dione) into androgen testosterone (T). To provide effective inhibitors of androgen biosynthesis, we synthesized two different series (amines and carbamates) of 3 beta-substituted-androsterone derivatives and we tested their inhibitory activity on 17 beta-HSD3. From the results of our structure-activity relationship study, we identified a series of compounds producing a strong inhibition of 17 beta-HSD3 overexpressed in HEK-293 cells (homogenized cells). The most active compound when tested in intact HEK-293 transfected cells, namely (3 alpha,5 alpha)-3-{[trans-2,5-dimethyl-4-{[2-(trifluoromethyl)phenyl] sulfonyl}piperazin-1-yl]methyl}-3-hydroxyandrostan-17-one (15b), shows an IC50 value of 6 nM, this compound is thus eight times more active than our reference compound D-5-2 (IC50 = 51 nM). This new improved inhibitor did not stimulate the proliferation of androgen-sensitive Shionogi cells, suggesting a non-androgenic profile. Compound 15b is thus a good candidate for further in vivo studies on rodents. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.003
• 作为产物：
  描述：

  哌嗪 、 spiro-3(R)-oxirane-5α-androstan-17-one 以 乙醇 为溶剂， 反应 5.0h， 以58%的产率得到(3α,5α)-3-hydroxy-3-(piperazin-1-ylmethyl)androstan-17-one
  参考文献：
  名称：

  Development of 3-substituted-androsterone derivatives as potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3

  摘要：

  17Beta-hydroxysteroid dehydrogenase type 3 (17 beta-HSD3) is a steroidogenic enzyme that catalyzes the transformation of 4-androstene-3,17-dione (Delta(4)-dione) into androgen testosterone (T). To provide effective inhibitors of androgen biosynthesis, we synthesized two different series (amines and carbamates) of 3 beta-substituted-androsterone derivatives and we tested their inhibitory activity on 17 beta-HSD3. From the results of our structure-activity relationship study, we identified a series of compounds producing a strong inhibition of 17 beta-HSD3 overexpressed in HEK-293 cells (homogenized cells). The most active compound when tested in intact HEK-293 transfected cells, namely (3 alpha,5 alpha)-3-{[trans-2,5-dimethyl-4-{[2-(trifluoromethyl)phenyl] sulfonyl}piperazin-1-yl]methyl}-3-hydroxyandrostan-17-one (15b), shows an IC50 value of 6 nM, this compound is thus eight times more active than our reference compound D-5-2 (IC50 = 51 nM). This new improved inhibitor did not stimulate the proliferation of androgen-sensitive Shionogi cells, suggesting a non-androgenic profile. Compound 15b is thus a good candidate for further in vivo studies on rodents. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.003

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 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。
• Chemical synthesis of fluorinated and iodinated 17β-HSD3 inhibitors and evaluation for imaging prostate cancer tumors and tissue biodistribution
  作者：Donald Poirier、René Maltais、Jacques A. Rousseau、Jenny Roy、Serge Phoenix、Francisco Cortés-Benítez、Roger Lecomte

  DOI：10.1016/j.bioorg.2022.106145

  日期：2022.12

  representative sulfonamide derivative (compound 1) was found to accumulate in prostate tumor tissues relatively to plasma in a mouse xenograft experiment. This finding gives us the opportunity to specifically target the prostate cancer tumors through the development of a radiolabelled version of compound 1 toward targeted molecular radiotherapy or radioimaging diagnosis. The chemical synthesis of fluorinated

  前列腺癌是男性中最常见的癌症，需要开发新的治疗剂来治疗和/或诊断前列腺癌。17β-羟基类固醇脱氢酶 3 型 (17β-HSD3) 参与雄激素的产生，从而刺激前列腺癌细胞的增殖。哌嗪基甲基-雄酮磺酰胺衍生物被开发为 17β-HSD3 抑制剂，并且在小鼠异种移植实验中发现代表性磺酰胺衍生物（化合物1）的浓度相对于血浆在前列腺肿瘤组织中积累。这一发现使我们有机会通过开发化合物1的放射性标记版本来专门针对前列腺癌肿瘤用于靶向分子放射治疗或放射影像学诊断。实现了化合物1的氟化和碘化类似物的化学合成，从而产生了一系列与初始候选化合物具有相似抑制水平的化合物。从 17β-HSD3 抑制活性、分子建模和小鼠血浆浓度研究中，选择了该系列中最有希望的化合物，合成了其18 F-放射性标记版本 ( 18 F- 3 )，并进行了成像/生物分布研究。然而，当注射到小鼠体内时，18 F- 3目标组织（LNCaP[17β-HSD3]
• 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。