3,3-ethylenedioxy-5α-hydroxy-11β-{4'-[1',1'-(ethylenedioxy)-ethyl]phenyl}-estr-9-ene-17-one | 151424-85-0

• 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: 3,3-ethylenedioxy-5α-hydroxy-11β-{4'-[1',1'-(ethylenedioxy)-ethyl]phenyl}-estr-9-ene-17-one
• 英文别名: 3,3-ethylenedioxy-5α-hydroxy-11β-{4'-[1',1'-(ethylenedioxy)ethyl]phenyl}estra-9-ene-17-one；3-ethylenedioxy-5α-hydroxy-11β-{4'-[1',1'-(ethylenedioxy)-ethyl]phenyl}-estra-9-ene-17-one；3,3-ethylenedioxy-5a-hydroxy-11β-{4'-[1',1'(ethylenedioxy)-ethyl]phenyl}-estra-9-ene-17-one；(5'R,8'S,11'R,13'S,14'S)-5'-hydroxy-13'-methyl-11'-[4-(2-methyl-1,3-dioxolan-2-yl)phenyl]spiro[1,3-dioxolane-2,3'-2,4,6,7,8,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene]-17'-one
• CAS: 151424-85-0
• 化学式: C₃₀H₃₈O₆
• 分子量: 494.628
• InChiKey: IAUWPFBGMLCWOD-RHCHIPKVSA-N

物化性质

• 熔点：
  183-188 °C
• 沸点：
  666.5±55.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  36
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,3-ethylenedioxy-5α-hydroxy-11β-{4'-[1',1'-(ethylenedioxy)-ethyl]phenyl}-estr-9-ene-17-one 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 0.33h， 以76%的产率得到11β-(4'-acetyl-phenyl)-estra-4,9-diene-3,17-dione
  参考文献：
  名称：

  Hydrolytic behavior of 5α-hydroxy-11β- and 5β-hydroxy-11α-substituted 19-norsteroids

  摘要：

  Teutsch G. and Belanger A. treated 5alpha,10alpha epoxides with Grignard-reagents catalyzed by copper(l) ions. The reaction with steroidal epoxides proceeded with complete regio- and stereospecificity, leading exclusively to the 11beta-substituted compounds. According to our synthetic strategy, the 5, 10 epoxide isomers were not separated; instead, the pure 11beta, and in some cases, 11alpha-substituted molecules were isolated after the conjugate addition of the Grignard-reagents, followed by deketalization and dehydration. Surprisingly, appearance of a third compound was generally observed beside the expected deprotected products, and this compound turned out to have a 3-keto-5(10),9(11) structural unit. Starting from pure 3-ethylenedioxy-5alpha,10alpha-epoxy-estr-9(11)-ene-17-one and 3-ethylenedioxy-5beta,10beta-epoxy-estr-9(11)-ene-17-one, four model compounds were synthesized (11alpha- and 11beta-{4-[1,1-(ethylenedioxy)-ethyl]phenyl}-estra-, as well as 11alpha- and 11beta-cyclohexyl-estra-derivatives) to study the process of deprotection and dehydration. 3-keto-5(10),9(11)-derivatives were found to form after deketalization and dehydration only from 11alpha-substituted derivatives, while 11beta-derivatives resulted in only the expected 3-keto-5,9-diene structure. After observing this remarkable difference between the behavior of 11alpha-, 11beta-substituted isomers we decided to take a closer look at the processes of deketalization and dehydration. In order to carry out the hydrolysis under mild conditions, pyridinium paratoluenesulfonate, a weakly acidic salt, was applied. All the intermediate products observed by TLC were isolated. The outcome of the deprotection and elimination reactions can be rationalized by two factors: conjugation of olefins (with the 3-oxo-group or the 11-phenyl group) and orientation of groups to be eliminated. (C) 2003 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2003.07.003
• 作为产物：
  描述：

  3-缩酮 在 disodium hydrogenphosphate 、 双氧水 、 六氟丙酮 、 copper(l) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 21.5h， 生成 3,3-ethylenedioxy-5α-hydroxy-11β-{4'-[1',1'-(ethylenedioxy)-ethyl]phenyl}-estr-9-ene-17-one
  参考文献：
  名称：

  New 11β-aryl-substituted steroids exhibit both progestational and antiprogestational activity

  摘要：

  The syntheses of three 11 beta-aryl-19-norpregna-4,9-dien-3-one derivatives with 17-spirolactone and 17 beta-hydroxy-17 alpha-cyanoethyl substitutions are described. The progesterone agonist/antagonist activities of the new compounds are investigated using a recently developed tissue culture system,that relies on the progesterone agonist up-regulation of the prostate-specific antigen (PSA) gene in female breast tumor cell lines. Two of the newly synthesized compounds exhibit mixed agonistic/antagonistic progestational activity. (Steroids 63:523-530, 1998) (C) 1998 by Elsevier Science Inc.

  DOI：

  10.1016/s0039-128x(98)00060-9

文献信息

• [EN] PROGESTERONE ANTAGONISTS<br/>[FR] ANTAGONISTES DE PROGESTÉRONE
  申请人：EVESTRA INC

  公开号：WO2013016725A1

  公开（公告）日：2013-01-31

  Described herein are compounds which either act as pure antiprogestins or as antiprogestins with partial agonistic activity and methods of treating cancer using such compounds.

  本文描述了一些化合物，它们要么作为纯抗孕激素，要么作为具有部分激动活性的抗孕激素，并且使用这些化合物治疗癌症的方法。
• PROGESTERONE ANTAGONISTS
  申请人：Nickisch Klaus

  公开号：US20130029953A1

  公开（公告）日：2013-01-31

  Described herein are compounds which either act as pure antiprogestins or as antiprogestins with partial agonistic activity and methods of treating cancer using such compounds.

  本文描述了一些化合物，它们可以作为纯抗孕激素或具有部分激动活性的抗孕激素，并且使用这些化合物的方法治疗癌症。
• Synthesis and biological evaluation of partially fluorinated antiprogestins and mesoprogestins
  作者：Klaus Nickisch、Walter Elger、James Cessac、Narkunan Kesavaram、Baishakhi Das、Robert Garfield、Shao-Qing Shi、Olga Amelkina、Reinhard Meister

  DOI：10.1016/j.steroids.2012.09.010

  日期：2013.2

  A series of antiprogestins have been synthesized by partially fluorinating the steroid molecule in positions relevant for receptor binding. By introducing fluorine at the exo-methylene of the 17 spirofuran ring, we obtained partial agonists (mesoprogestins) with significant applications for antiproliferative and antiovulatory treatment strategies in gynecological therapy such as uterine fibroids, endometriosis and heavy menstrual bleeding. Compared to the standard drug RU486, our synthesized compounds exhibited considerable dissociation between antiprogestational and antiglucocorticoid PR receptors. Furthermore, our studies have shown that pure antiprogestins can be generated by partially fluorinating the 17 propenyl and propynl group or by substituting the 4' acetyl phenyl group in the 11 position using trifluromethyl group. (C) 2012 Elsevier Inc. All rights reserved.
• Synthesis and antiprogestational properties of novel 17-fluorinated steroids
  作者：Klaus Nickisch、Hareesh B. Nair、Narkunan Kesavaram、Baishakhi Das、Robert Garfield、Shao-Qing Shi、Shylesh S. Bhaskaran、Sandra L. Grimm、Dean P. Edwards

  DOI：10.1016/j.steroids.2013.04.003

  日期：2013.9

  Progesterone receptor (PR) plays a key role in reproductive functions, and compounds that inhibit progesterone action (antiprogestins) have potential use in the treatment of estrogen- and progesterone-dependent diseases, including uterine leiomyomas and breast cancer. In the present study, we chemically synthesized novel 17-fluorinated steroids and evaluated the cytotoxicity profiles of these compounds in T47D breast cancer cells compared to the activity of known antiprogestins, including ZK230 211, RU-486, CDB2914, CDB4124 and ORG33628. We analyzed in vitro receptor-binding assays and PR-transactivation assays to establish the antiprogestational activity of these molecules. The representative anti-progestin EC304 was found to inhibit in vitro tumorigenicity in a dose-dependent fashion in T47D cells by a colony formation assay at 1 and 10 nM concentrations. The potent in vivo antiprogestational activity of EC304 was also demonstrated in an antinidation assay for the interruption of early pregnancy in rats. The strong antiprogestational activity and absence of antiglucocorticoid activity in EC compounds may demonstrate their utility in the treatment of leiomyoma, endometriosis and breast cancer. (C) 2013 Elsevier Inc. All rights reserved.
• 17 BETA-NITRO-11 BETA-ARYLSTEROIDS AND THEIR DERIVATIVES HAVING AGONIST OR ANTAGONIST HORMONAL PROPERTIES
  申请人：RESEARCH TRIANGLE INSTITUTE

  公开号：EP1082338B1

  公开（公告）日：2006-07-26