3-{(E)-[(13α,16E)-3-hydroxy-17-oxoestra-1(10),2,4-trien-16-ylidene]methyl}benzamide | 1401939-09-0

• 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-{(E)-[(13α,16E)-3-hydroxy-17-oxoestra-1(10),2,4-trien-16-ylidene]methyl}benzamide
• 英文别名: 3-[(E)-[(8R,9S,13R,14S)-3-hydroxy-13-methyl-17-oxo-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-16-ylidene]methyl]benzamide
• CAS: 1401939-09-0
• 化学式: C₂₆H₂₇NO₃
• 分子量: 401.505
• InChiKey: QBMREOWTJGDVKI-ZKKJPMSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  80.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-{(E)-[(13α,16E)-3-hydroxy-17-oxoestra-1(10),2,4-trien-16-ylidene]methyl}benzamide 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 3-{[(13α)-3-hydroxy-17-oxoestra-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：

  13α-estrone 、 3-甲酰基苯并酰胺 在 potassium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 0.5h， 以54%的产率得到3-{(E)-[(13α,16E)-3-hydroxy-17-oxoestra-1(10),2,4-trien-16-ylidene]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

文献信息

• 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。
• Impact of structural modifications at positions 13, 16 and 17 of 16β-(m-carbamoylbenzyl)-estradiol on 17β-hydroxysteroid dehydrogenase type 1 inhibition and estrogenic activity
  作者：René Maltais、Alexandre Trottier、Xavier Barbeau、Patrick Lagüe、Martin Perreault、Jean-François Thériault、Sheng-Xiang Lin、Donald Poirier

  DOI：10.1016/j.jsbmb.2015.10.020

  日期：2016.7

  The chemical synthesis of four stereoisomers (compounds 5a-d) of 16 beta-(m-carbamoylbenzyl)-estradiol, a potent reversible inhibitor of 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1), and two intermediates (compounds 3a and b) was performed. Assignment of all nuclear magnetic resonance signals confirmed the stereochemistry at positions 13,16 and 17. Nuclear overhauser effects showed clear correlations supporting a C-ring chair conformation for 5a and b and a C-ring boat conformation for 5c and d. These compounds were tested as 17 beta-HSD1 inhibitors and to assess their proliferative activity on estrogen-sensitive breast cancer cells (T-47D) and androgen-sensitive prostate cancer cells (LAPC-4). Steroid derivative 5a showed the best inhibitory activity for the transformation of estrone to estradiol (95, 82 and 27%, at 10,1 and 0.1 mu M, respectively), but like the other isomers 5c and d, it was found to be estrogenic. The intermediate 3a, however, was weakly estrogenic at 1 mu M, not at all at 0.1 mu M, and showed an interesting inhibitory potency on 17 beta-HSD1 (90, 59 and 22%, at 10, 1 and 0.1 mu M, respectively). As expected, no compound showed an androgenic activity. The binding modes for compounds 3a and b,5a-d and CC-156 were evaluated from molecular modeling. While the non-polar interactions were conserved for all the inhibitors in their binding to 17 beta-HSD1, differences in polar interactions and in binding conformational energies correlated to the inhibitory potencies. (C) 2015 Elsevier Ltd. All rights reserved.
• [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。