13α,17α-estradiol

• 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: 13α,17α-estradiol
• 英文别名: (13α,17α)-estra-1(10),2,4-triene-3,17-diol；18-epi-17α-E2；(8R,9S,13R,14S,17R)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
• 化学式: C₁₈H₂₄O₂
• 分子量: 272.387
• InChiKey: VOXZDWNPVJITMN-UYTYNIKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

代谢

已知的雌二醇是人类(13alpha)-3-甲氧基-雌甾-1,3,5(10)-三烯-17alpha-醇的代谢物。

Estradiol is a known human metabolite of (13alpha)-3-methoxy-estra-1,3,5(10)-triene-17alpha-ol.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  Acetic acid (8S,9S,13R,14S,17R)-17-acetyl-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl ester 生成 13α,17α-estradiol
  参考文献：
  名称：

  Syntheses of C<SUB>20</SUB> 13α-Steroidal Progestagens

  摘要：

  为了研究生理活性，进行了3, 17-二羟基-19-去甲基-13α-孕-1, 3, 5 (10)-三烯-20-酮 17-乙酸酯（IIId, IXc）的制备。13α-雌酮（I）与乙炔镁溴化物的格氏反应生成了两种表异构体17-乙炔基-17-醇（II, VIIIa），经过水合反应转化为3, 17-二羟基-19-去甲基-13α-孕三烯-20-酮（IIIa, IXa）。通过降解的方法阐明了C-17的立体化学。首先，对IIIa进行金属氢化物还原，随后进行常规的乙酰化和Serini反应，得到19-去甲基-13α-孕三烯-20-酮（V）。在碱的处理下，V迅速转化为热力学上更加稳定的17α-表异构体（VIb），其结构通过Baeyer-Villiger反应生成已知的13α-雌三烯-3, 17α-二醇（VIIa）得到确认。所需化合物通过部分水解3, 17-二乙酸酯（IIIc, IXb）明确获得。

  DOI：

  10.1248/cpb.22.1140

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。
• Impact of estradiol structural modifications (18-methyl and/or 17-hydroxy inversion of configuration) on the in vitro and in vivo estrogenic activity
  作者：Diana Ayan、Jenny Roy、René Maltais、Donald Poirier

  DOI：10.1016/j.jsbmb.2011.07.009

  日期：2011.11

  of 17β-E2 (1) and 17α-estradiol (17α-E2; 2). The two epimers 18-epi-17β-E2 (3) and 18-epi-17α-E2 (4) were obtained in two chemical steps by inversion of the C18-methyl of estrone using 1,2-phenylendiamine in refluxing acetic acid and reduction of ketone at position C17 with LiAlH(4). The new E2 isomers were tested on estrogen-sensitive cell lines (MCF-7 and T-47D), on estrogen-sensitive tissues (uterus

  众所周知，大多数乳腺癌最初都是激素依赖性的，而17β-雌二醇（17β-E2）在其发展和进程中起着至关重要的作用。因此，使用能够阻断参与17β-E2生物合成最后一步的特定酶的化合物仍然是治疗雌激素依赖性疾病（如乳腺癌）的合理方法。本研究描述了17β-E2（1）和17α-雌二醇（17α-E2; 2）的结构修饰（13位C18甲基从β到α面的转化）的生物学和体内生物学评估。 。两种差向异构体18-epi-17β-E2（3）和18-epi-17α-E2（4）是在两个化学步骤中通过在回流的乙酸中使用1,2-苯二胺将雌酮的C18-甲基转化而得到的。用LiAlH（4）还原C17处的酮。在雌激素敏感的细胞系（MCF-7和T-47D），雌激素敏感的组织（小鼠的子宫和阴道）和雌激素受体（ER）上测试了新的E2异构体，以确定它们相对于天然雌激素的雌激素效力17β-E2（1）。结果显示18-epi-17β-E2（3）对ER的亲和力较低（RBA
• 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。
• Synthesis and biological evaluation of 13α-estrone derivatives as potential antiproliferative agents
  作者：Johanna Szabó、Zoltán Pataki、János Wölfling、Gyula Schneider、Noémi Bózsity、Renáta Minorics、István Zupkó、Erzsébet Mernyák

  DOI：10.1016/j.steroids.2016.05.010

  日期：2016.9

  13 alpha-Estrone derivatives containing various substituents on C-3 and C-17 were synthesized, and evaluated by means of MU assays for in vitro antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A2780 and A431). Compounds with N-benzyltriazolylmethoxy moieties on C-3 proved to be more potent than their 3-hydroxy or 3-ether counterparts. Some triazoles exerted substantial cytostatic effects against particular tumor cell lines, with submicromolar IC50 values. (C) 2016 Elsevier Inc. All rights reserved.