3-[2-(benzyloxy)ethyl]estra-1,3,5(10)-trien-17-one | 1318265-23-4

• 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: 3-[2-(benzyloxy)ethyl]estra-1,3,5(10)-trien-17-one
• 英文别名: 3-[2-(benzyloxy)ethyl]estra-1(10),2,4-trien-17-one；(8R,9S,13S,14S)-13-methyl-3-(2-phenylmethoxyethyl)-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 1318265-23-4
• 化学式: C₂₇H₃₂O₂
• 分子量: 388.55
• InChiKey: FDBYDETVWNYWFP-QUUPDEESSA-N

物化性质

• 沸点：
  525.4±50.0 °C(Predicted)
• 密度：
  1.109±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-[2-(benzyloxy)ethyl]estra-1,3,5(10)-trien-17-one 在 甲醇 、 sodium tetrahydroborate 、 水 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 3-{[(16β,17β)-17-hydroxy-3-[2-(methylamino)-2-oxoethyl]estra-1(10),2,4-trien-16-yl]methyl}benzamide
  参考文献：
  名称：

  [EN] INHIBITORS OF 17ß-HSD1, 17ß-HSD3 AND 17ß-HSD10
  [FR] INHIBITEURS DE 17SS-HSD1, 17SS-HSD3 ET 17SS-HSD10

  摘要：

  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。

  公开号：

  WO2012129673A1
• 作为产物：
  描述：

  3-(2-hydroxyethyl)estra-1(10),2,4-trien-17-dioxolane 在 盐酸 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 为溶剂， 反应 23.0h， 生成 3-[2-(benzyloxy)ethyl]estra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Crucial Role of 3-Bromoethyl in Removing the Estrogenic Activity of 17β-HSD1 Inhibitor 16β-(m-Carbamoylbenzyl)estradiol

  摘要：

  17 beta-Hydroxysteroid dehydrogenase type 1 (17 beta-HSD1) represents a promising therapeutic target for breast cancer treatment. To reduce the undesirable estrogenic activity of potent 17 beta-HSD1 inhibitor 16 beta-(m-carbamoylbenzyl)estradiol (1) (IC(50) = 27 nM), a series of analogues with a small functionalized side chain at position 3 were synthesized and tested. The 3-(2-bromoethyl)-16 beta-(m-carbamoylbenzy1)-estra-1,3,5(10)-trien-17 beta-ol (5) was found to be a potent inhibitor (IC(50) = 68 nM) for the transformation of estrone (E1) into estradiol (E2) and, most importantly, did not stimulate the proliferation of estrogen-sensitive MCF-7 cells, suggesting no estrogenic activity. From these results, the crucial role of a bromoalkyl side chain at carbon 3 was identified for the first time. Thus, this new inhibitor represents a good candidate with an interesting profile suitable for further studies including pharmacokinetic and in vivo studies.

  DOI：

  10.1021/ml200093v

文献信息

• Development of a Gram-Scale Synthesis of PBRM, an Irreversible Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 1
  作者：René Maltais、Donald Poirier

  DOI：10.1021/acs.oprd.8b00402

  日期：2019.11.15

  PBRM with a high-HPLC-grade purity (99.7%) after recrystallization. Important improvements have been achieved in this sequence from previously reported routes (A and B). Notably, we used a palladium-catalyzed Suzuki–Miyaura cross-coupling reaction to rapidly install the requested C3 chain on estrone. Also, catalytic hydrogenation of the C16-enone was shortened by half using Pearlman’s catalyst. Finally

  致力于开发可靠的克级规模的3-[（16β，17β）-3-（2-溴乙基）-17-羟基雌二醇1,3,5（10）-三烯-16-基]甲基的克级合成}描述了苯甲酰胺（PBRM），这是一种有效的选择性17β-羟基类固醇脱氢酶的类固醇共价抑制剂。在本文开发的三种合成路线（C–E）中，路线E是最有效的路线，距市售雌酮仅六个化学步骤，总收率为13％，从而获得了具有HPLC级纯度的PBRM（99.7）重结晶后）。从先前报告的路线（A和B）开始，此顺序已实现了重要的改进。值得注意的是，我们使用钯催化的Suzuki-Miyaura交叉偶联反应将所需的C3链快速安装在雌酮上。还，使用Pearlman催化剂，C16-烯酮的催化加氢缩短了一半。最后，我们在序列的最后一步使用了通过乙醇脱氧进行的选择性溴化，以提供PBRM而不会使其羧酰胺官能团脱水，这是在其他途径中观察到的一个持久性问题。通过在乙腈中重结晶也获得了PBR
• [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。
• 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。
• Crucial Role of 3-Bromoethyl in Removing the Estrogenic Activity of 17β-HSD1 Inhibitor 16β-(<i>m</i>-Carbamoylbenzyl)estradiol
  作者：René Maltais、Diana Ayan、Donald Poirier

  DOI：10.1021/ml200093v

  日期：2011.9.8

  17 beta-Hydroxysteroid dehydrogenase type 1 (17 beta-HSD1) represents a promising therapeutic target for breast cancer treatment. To reduce the undesirable estrogenic activity of potent 17 beta-HSD1 inhibitor 16 beta-(m-carbamoylbenzyl)estradiol (1) (IC(50) = 27 nM), a series of analogues with a small functionalized side chain at position 3 were synthesized and tested. The 3-(2-bromoethyl)-16 beta-(m-carbamoylbenzy1)-estra-1,3,5(10)-trien-17 beta-ol (5) was found to be a potent inhibitor (IC(50) = 68 nM) for the transformation of estrone (E1) into estradiol (E2) and, most importantly, did not stimulate the proliferation of estrogen-sensitive MCF-7 cells, suggesting no estrogenic activity. From these results, the crucial role of a bromoalkyl side chain at carbon 3 was identified for the first time. Thus, this new inhibitor represents a good candidate with an interesting profile suitable for further studies including pharmacokinetic and in vivo studies.