(8S,11S,13S,14R,17S)-17-(2-bromophenylethynyl)-11-(4-dimethylaminophenyl)-17-hydroxy-13-methyl-1,2,8,11,12,13,14,15,16,17-decahydro-6H-7-oxacyclopenta[a]phenanthren-3-one

• 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: (8S,11S,13S,14R,17S)-17-(2-bromophenylethynyl)-11-(4-dimethylaminophenyl)-17-hydroxy-13-methyl-1,2,8,11,12,13,14,15,16,17-decahydro-6H-7-oxacyclopenta[a]phenanthren-3-one
• 英文别名: (8S,11R,13S,14R,17S)-17-(2-bromo-phenylethynyl)-11-(4-dimethylamino-phenyl)-17-hydroxy-13-methyl-1,2,8,11,12,13,14,15,16,17-decahydro-6H-7-oxa-cyclopenta[a]phenanthren-3-one；(1S,3aR,3bS,10R,11aS)-1-[2-(2-bromophenyl)ethynyl]-10-[4-(dimethylamino)phenyl]-1-hydroxy-11a-methyl-3,3a,3b,5,8,9,10,11-octahydro-2H-indeno[4,5-c]isochromen-7-one
• 化学式: C₃₃H₃₄BrNO₃
• 分子量: 572.542
• InChiKey: KJNIFDGJGBMXTN-TUNFDJIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-溴苯乙炔 在 盐酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 8.25h， 生成 (8S,11S,13S,14R,17S)-17-(2-bromophenylethynyl)-11-(4-dimethylaminophenyl)-17-hydroxy-13-methyl-1,2,8,11,12,13,14,15,16,17-decahydro-6H-7-oxacyclopenta[a]phenanthren-3-one
  参考文献：
  名称：

  Parallel synthesis and SAR study of novel oxa-steroids as potent and selective progesterone receptor antagonists

  摘要：

  Efficient parallel synthesis of novel 7-oxa-steroids 4 has been achieved from the key intermediate 3 via a one-pot four-step sequence. oxa-Steroids 4 with various ortho-, meta-, and para-monosubstituents on the phenyl ring, as well as disubstituted phenyl and heterocycles, were evaluated for progesterone receptor (PR) and glucocorticoid receptor (GR) antagonist activities. SAR study demonstrated that the para-fluorinated substituents on the phenyl ring not only increased the potency for PR in a T47D cell functional assay, but also improved the selectivity over GR in an A549 cell functional assay. The para-fluorophenyl oxa-steroid 41 and the para-trifluoromethylphenyl oxa-steroid 4p were found to be remarkably more potent and more selective PR antagonists than mifepristone, with subnanomolar potency and about 140-fold selectivity over GR. Molecular modeling of the oxa-steroid bound to PR provided meaningful insight for the SAR study. oxa-Steroids 4a and 4b were found to be more efficacious than mifepristone in vivo in a rat uterine complement C3 assay via the oral route, although they were less than or equally potent to mifepristone in the T47D assay. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.013

文献信息

• OXA-STEROIDS DERIVATIVES AS SELECTIVE PROGESTERONE RECEPTOR MODULATORS
  申请人：Kang Fu-An

  公开号：US20070197635A1

  公开（公告）日：2007-08-23

  The present invention is directed to novel 7-oxa-estra-4,9-diene-3,17-dione derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by at least one progesterone or glucocorticoid receptor.

  本发明涉及新颖的7-氧杂雌甾-4,9-二烯-3,17-二酮衍生物，含有它们的药物组合物以及它们在治疗至少受孕激素或糖皮质激素受体调节的疾病和症状中的应用。
• US7763648B2
  申请人：——

  公开号：US7763648B2

  公开（公告）日：2010-07-27
• Parallel synthesis and SAR study of novel oxa-steroids as potent and selective progesterone receptor antagonists
  作者：Fu-An Kang、Jihua Guan、Nareshkumar Jain、George Allan、Olivia Linton、Pamela Tannenbaum、Xin Chen、Jun Xu、Peifang Zhu、Joseph Gunnet、Keith Demarest、Scott Lundeen、Zhihua Sui

  DOI：10.1016/j.bmcl.2007.02.013

  日期：2007.5

  Efficient parallel synthesis of novel 7-oxa-steroids 4 has been achieved from the key intermediate 3 via a one-pot four-step sequence. oxa-Steroids 4 with various ortho-, meta-, and para-monosubstituents on the phenyl ring, as well as disubstituted phenyl and heterocycles, were evaluated for progesterone receptor (PR) and glucocorticoid receptor (GR) antagonist activities. SAR study demonstrated that the para-fluorinated substituents on the phenyl ring not only increased the potency for PR in a T47D cell functional assay, but also improved the selectivity over GR in an A549 cell functional assay. The para-fluorophenyl oxa-steroid 41 and the para-trifluoromethylphenyl oxa-steroid 4p were found to be remarkably more potent and more selective PR antagonists than mifepristone, with subnanomolar potency and about 140-fold selectivity over GR. Molecular modeling of the oxa-steroid bound to PR provided meaningful insight for the SAR study. oxa-Steroids 4a and 4b were found to be more efficacious than mifepristone in vivo in a rat uterine complement C3 assay via the oral route, although they were less than or equally potent to mifepristone in the T47D assay. (c) 2007 Elsevier Ltd. All rights reserved.