(8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde | 123715-79-7

• 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: (8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde
• 英文别名: 3,17β-dihydroxyestra-1,3,5(10)-trien-4-carboxaldehyde；3,17β-dihydroxyestra-1,3,5(10)-triene-4-carbaldehyde；4-formylestradiol；3,17β-dihydroxyestra-1,3,5(10)-triene-4-carboxaldehyde；3,17beta-Dihydroxyestra-1,3,5(10)-triene-4-carboxaldehyde；(8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-4-carbaldehyde
• CAS: 123715-79-7
• 化学式: C₁₉H₂₄O₃
• 分子量: 300.398
• InChiKey: GUJSHAHJIQWGNF-AFTVQHQSSA-N

物化性质

• 熔点：
  150-151 °C(Solv: chloroform (67-66-3))
• 沸点：
  460.3±45.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde 在 chromium(VI) oxide 、 硫酸 作用下， 以 丙酮 为溶剂， 反应 0.17h， 以93%的产率得到(8R,9S,13S,14S)-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde
  参考文献：
  名称：

  Steroidal oxathiazine inhibitors of estrone sulfatase

  摘要：

  The presence of estrone sulfatase in breast tumors and the high levels of circulating estrone sulfate may contribute the major portion of estrogen synthesized locally in breast tissues through conversion of estrone sulfate to estrone by the enzyme. Using inhibitors of estrone sulfatase for the treatment of estrogen-dependent (estrogen receptor positive, ER+) breast cancer could be a very effective therapeutic strategy for the treatment of estrogen-dependent breast tumors in postmenopausal women. Therefore, we designed and synthesized several steroidal 2',3-oxathiazines that inhibit estrone sulfatase and have greatly reduced estrogenic side effects. Our in vitro studies indicate that the oxathiazine compounds have inhibitory activity on estrone sulfatase in MCF-7 human breast cancer cells. These estrone sulfatase inhibitors (ESIs) also inhibit the growth of MCF-7 cells induced by estrone sulfate. In addition, our in vivo experiments demonstrate that our ESIs have moderate antitumor activity against MCF-7 breast cancer xenografts in Balb/c athymic nude mice. The synthesis and biological activity of a number of these unique steroidal ESIs are described. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(02)00118-6
• 作为产物：
  描述：

  (8R,9S,13S,14S,17S)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以78 mg的产率得到(8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde
  参考文献：
  名称：

  Pert, Derek J.; Ridley, Damon D., Australian Journal of Chemistry, 1989, vol. 42, # 3, p. 405 - 419

  摘要：

  DOI：

文献信息

• Steroid inhibitors of estrone sulfatase and associated pharmaceutical
  申请人：SRI International

  公开号：US05861388A1

  公开（公告）日：1999-01-19

  Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have the structural formula (I) ##STR1## wherein X and Y, or Y and Z, form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, and the other various substituents are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat estrogen-dependent disorders are provided as well.

  本发明提供了一种作为雌酮磺酸酶抑制剂有用的新化合物。该化合物具有结构式（I）##STR1##其中X和Y，或Y和Z，形成一个噁唑二氧杂环或二氢噁唑二氧杂环，其他各种取代基的定义如本文所述。还提供了制备药物组合物和使用式（I）化合物治疗雌激素依赖性疾病的方法。
• ESTRATRIENE DERIVATIVES COMPRISING HETEROCYCLIC BIOISOSTERES FOR THE PHENOLIC A-RING
  申请人：Blume Thorsten

  公开号：US20110190246A1

  公开（公告）日：2011-08-04

  The present invention is directed to novel pyrazolo-estrien and triazolo-estrien-derivatives, pharmaceutical compositions containing them and their use in the treatment or prevention of disorders and diseases mediated by an estrogen receptor such as hot flashes, vaginal dryness, osteopenia, osteoporosis, hyperlipidemia, loss of cognitive function, degenerative brain diseases, cardiovascular diseases, cerebrovascular diseases, hormone sensitive cancers and hyperplasia (in tissues including breast, endometrium, and cervix in women and prostate in men), endometriosis, uterine fibroids, osteoarthritis; and as contraceptive agents either alone or in combination with a progestogen or progestogen antagonist. The compounds of the invention are selective estrogen receptor modulators.

  本发明涉及新型吡唑酮-雌甾烯和三唑酮-雌甾烯衍生物，包含它们的制药组合物以及它们在治疗或预防由雌激素受体介导的疾病和疾病中的应用，例如潮热、阴道干燥、骨质疏松、骨质疏松症、高脂血症、认知功能丧失、退行性脑疾病、心血管疾病、脑血管疾病、激素敏感性癌症和增生（包括女性乳房、子宫内膜和宫颈以及男性前列腺组织），子宫内膜异位症、子宫肌瘤、骨关节炎；以及作为避孕剂，单独使用或与孕激素或孕激素拮抗剂组合使用。本发明的化合物是选择性雌激素受体调节剂。
• Estratriene derivatives comprising heterocyclic bioisosteres for the phenolic a-ring
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP2147924A1

  公开（公告）日：2010-01-27

  The present invention is directed to novel pyrazolo-estrien and triazolo-estrien-derivatives, pharmaceutical compositions containing them and their use in the treatment or prevention of disorders and diseases mediated by an estrogen receptor such as hot flashes, vaginal dryness, osteopenia, osteoporosis, hyperlipidemia, loss of cognitive function, degenerative brain diseases, cardiovascular diseases, cerebrovascular diseases, hormone sensitive cancers and hyperplasia (in tissues including breast, endometrium, and cervix in women and prostate in men), endometriosis, uterine fibroids, osteoarthritis; and as contraceptive agents either alone or in combination with a progestogen or progestogen antagonist. The compounds of the invention are selective estrogen receptor modulators.

  本发明涉及新型吡唑-雌三烯和三唑-雌三烯衍生物、含有它们的药物组合物，以及它们在治疗或预防由雌激素受体介导的紊乱和疾病中的用途，如潮热、阴道干燥、骨质疏松、骨质疏松症、高脂血症、认知功能丧失、脑退化性疾病、心血管疾病、脑血管疾病、激素敏感性癌症和增生（组织中包括乳腺、子宫内膜和子宫颈）、高脂血症、认知功能丧失、退化性脑部疾病、心血管疾病、脑血管疾病、对激素敏感的癌症和增生（女性组织包括乳腺、子宫内膜和宫颈，男性组织包括前列腺）、子宫内膜异位症、子宫肌瘤、骨关节炎；以及作为避孕药物单独使用或与孕激素或孕激素拮抗剂联合使用。本发明的化合物是选择性雌激素受体调节剂。
• Synthesis, Antitubulin and Antimitotic Activity, and Cytotoxicity of Analogs of 2-Methoxyestradiol, an Endogenous Mammalian Metabolite of Estradiol That Inhibits Tubulin Polymerization by Binding to the Colchicine Binding Site
  作者：Mark Cushman、Hu-Ming He、John A. Katzenellenbogen、Chii M. Lin、Ernest Hamel

  DOI：10.1021/jm00012a003

  日期：1995.6

  In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 8-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inhibitors of tubulin polymerization and colchicine binding were determined using tubulin purified from bovine brain, and the cytotoxicities of the new compounds were studied in a variety of cancer cell cultures. Maximum antitubulin activity was observed in estradiols having unbranched chain substituents at the 2-position with three non-hydrogen atoms. 2-Ethoxyestradiol and 2-((E)-1-propenyl)-estradiol were substantially more potent than 2-methoxyestradiol itself. The tubulin polymerization inhibitors in this series displayed significantly higher cytotoxicities in the MDA-MB-435 breast cancer cell line than in the other cell lines studied. The potencies of the analogs as cytotoxic and antimitotic agents in cancer cell cultures correlated with their potencies as inhibitors;of tubulin polymerization, supporting the hypothesis that inhibition of tubulin polymerization is the mechanism of the cytotoxic action of 2-methoxyestradiol and its congeners. Several of the more potent analogs were tested in an estrogen receptor binding assay, and their affinities relative to estradiol were found to be very low.
• ortho-Formylation of estrogens. Synthesis of the anti-cancer agent 2-methoxyestradiol
  作者：Øyvind W. Akselsen、Trond Vidar Hansen

  DOI：10.1016/j.tet.2011.08.005

  日期：2011.10

  Several estrogens were mono-formylated using a mixture of paraformaldehyde. MgCl2, and Et3N in refluxing THF. In all cases, the 2-isomer was formed as the major product with high regioselectivity compared to the 4-isomer. Excellent to high yields were obtained in all examples except one. The method was applied for an efficient synthesis of the anti-cancer agent 2-methoxyestradiol. (C) 2011 Elsevier Ltd. All rights reserved.