(5α,10α,17α)-(9CI)-5,10:17,23-diepoxy-19,24-dinorchola-9(11),20-dien-3-one cyclic 3-(1,2-ethanediyl)acetal | 155768-31-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 英文名称: (5α,10α,17α)-(9CI)-5,10:17,23-diepoxy-19,24-dinorchola-9(11),20-dien-3-one cyclic 3-(1,2-ethanediyl)acetal
• CAS: 155768-31-3
• 化学式: C₂₄H₃₂O₄
• 分子量: 384.516
• InChiKey: KZHBWXRRTYOWAW-FSQCBZKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5α,10α,17α)-(9CI)-5,10:17,23-diepoxy-19,24-dinorchola-9(11),20-dien-3-one cyclic 3-(1,2-ethanediyl)acetal 、 1,4-二碘苯 在 异丙基溴化镁 、 copper(l) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 3.08h， 以92%的产率得到3,3-ethylenedioxy-5α-hydroxy-11β-(4'-iodophenyl)-17,23-epoxy-19,24-dinor-17α-chola-9,20-diene
  参考文献：
  名称：

  Synthesis and biological evaluation of 11′ imidazolyl antiprogestins and mesoprogestins

  摘要：

  Antiprogestins with a 4 ' para imidazolylphenyl moiety were synthesized and their biochemical interactions with the progesterone and glucocorticoid receptor were investigated. Depending on the substitution pattern at the 17 position partial progesterone receptor (PR)-agonistic derivatives like compounds EC339 and E036 or pure antagonists like compound EC317 were obtained. EC317 was investigated in vivo and found to be significantly more potent than RU 486 in cycling and pregnant guinea pigs. For testing the biological action progesterone receptor modulators (PRM), guinea pigs appears as a specific model when compare to pregnant human uterus. This model correlates to human conditions such as softening and widening of the cervix, the elevation of the uterine responsiveness to prostaglandins and oxytocin, and finally to induction of labor. The use of non-pregnant guinea pigs permitted the simultaneous assessment of PR-agonistic and PR-antagonistic properties and their physiological interactions with uterine and vaginal environment. These can histologically be presumed from the presence of estrogen or progesterone dominance in the genital tract tissues. The ovarian histology indicated the effects on ovulation. Corpora lutea in guinea pigs further reflects inhibitory effects of the progesterone-dependent uterine prostaglandin secretion. PRMs are initially synthesized as analogues of RU 486. They represent a heterogeneous group of compounds with different ratios of PR-agonistic and-antagonistic properties. PR-agonistic properties may be essential for uterine anti-proliferative effects. In various clinical studies these were also attributed to RU 486 or Ulipristal [1,2]. Adjusted PR-agonistic PRMs (EC312, EC313) [3] may be more effective in achieving a mitotically resting endometrium and superior uterine tumor inhibition. For the use in termination of pregnancy, progesterone-inhibitory effects are essentially needed. Even minor PR-agonistic properties compromise the therapeutic goals. Pure PR-antagonists, as EC317, clearly exceeded the gold standard RU 486 with respect to labor inducing effects. Mechanistically it is surprising that both types of compound may be potent inhibitors of ovulation. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2014.08.017
• 作为产物：
  描述：

  3-缩酮 在 盐酸 、 二环己烷并-18-冠醚-6 、 正丁基锂 、 potassium tert-butylate 、 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 丙酮 、 甲苯 、 叔丁醇 为溶剂， 反应 1.0h， 生成 (5α,10α,17α)-(9CI)-5,10:17,23-diepoxy-19,24-dinorchola-9(11),20-dien-3-one cyclic 3-(1,2-ethanediyl)acetal 、 (5β,10β,17α)-(9CI)-5,10:17,23-diepoxy-19,24-dinorchola-9(11),20-dien-3-one cyclic 3-(1,2-ethanediyl)acetal
  参考文献：
  名称：

  New progesterone receptor antagonists: Phosphorus-containing 11β-aryl-substituted steroids

  摘要：

  A new series of phosphorus-containing 11 beta-aryl-substituted steroids have been synthesized in an eight-step sequence involving a palladium-catalyzed coupling reaction to introduce a phosphorus group onto the aromatic ring. The compounds were evaluated for progesterone receptor (PR) antagonist activity in a T47D cell-based assay and for glucocorticoid receptor (GR) antagonist activity in an A549 cell-based assay. The structure-activity relationships of these compounds are discussed. Selected compounds were tested in vivo in a rat complement C3 assay. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.05.066

文献信息

• 11-PHOSPHOROUS STEROID DERIVATIVES USEFUL AS PROGESTERONE RECEPTOR MODULATORS
  申请人：Fiordeliso J. James

  公开号：US20070232570A1

  公开（公告）日：2007-10-04

  The present invention is directed to novel 11-phosphorous steroid derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by a progesterone or glucocorticoid receptor.

  本发明涉及新颖的11-磷酸类固醇衍生物，含有它们的药物组合物以及它们在治疗受孕激素或糖皮质激素受体调节的疾病和症状中的应用。
• 17-PHOSPHOROUS STEROID DERIVATIVES USEFUL AS PROGESTERONE RECEPTOR MODULATORS
  申请人：Jiang Weiqin

  公开号：US20070207982A1

  公开（公告）日：2007-09-06

  The present invention is directed to novel 17-phosphorous steroid derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by a progesterone or glucocorticoid receptor.

  本发明涉及新颖的17-磷类固醇衍生物，含有它们的药物组合物以及它们在治疗受孕激素或糖皮质激素受体调节的疾病和症状中的用途。
• [EN] (11ß,17a)-11-(4-(2-11C-ACETYL)PHENYL)-17,23-EPOXY- 19,24-DINORCHOLA-4,9,20-TRIEN-3-ONE<br/>[FR] (11B,17A)-11-(4-(2-11C-ACETYL)PHENYL)-17,23-EPOXY-19,24-DINORCHOLA-4,9,20-TRIEN-3-ONE
  申请人：MSD OSS BV

  公开号：WO2011157443A8

  公开（公告）日：2012-08-02
• (11beta, 17alpha)-11-(4-(2-11C-ACETYL)PHENYL)-17,23-EPOXY-19,24-DINORCHOLA-4,9,20-TRIEN-3-ONE
  申请人：Brands Franciscus Theodorus Leonardus

  公开号：US20130272956A1

  公开（公告）日：2013-10-17

  The present invention relates to (11β,17α)-11-(4-(2- 11 C-acetyl)phenyl)-17,23-epoxy-19,24-dinorchola-4,9,20-trien-3-one, an 11 C-labelled ORG 33628; a process for the preparation thereof, intermediates used in this process and the use of this compound as a PET tracer for the detection of breast cancer.
• US7678781B2
  申请人：——

  公开号：US7678781B2

  公开（公告）日：2010-03-16