2,8-bis(tert-butyldimethylsilyloxy)-5-[4-(2-(piperidin-1-yl)ethoxy)phenyl]-5,11-dihydrochromeno[4,3-c]chromene | 554430-39-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2,8-bis(tert-butyldimethylsilyloxy)-5-[4-(2-(piperidin-1-yl)ethoxy)phenyl]-5,11-dihydrochromeno[4,3-c]chromene
• 英文别名: 1-(2-{4-[2,8-Bis-(tert-butyl-dimethyl-silyloxy)-5,11-dihydro-chromeno[4,3-c]-chromen-5-yl]-phenoxy}-ethyl)-piperidine；tert-butyl-[[2-[tert-butyl(dimethyl)silyl]oxy-5-[4-(2-piperidin-1-ylethoxy)phenyl]-5,11-dihydrochromeno[4,3-c]chromen-8-yl]oxy]-dimethylsilane
• CAS: 554430-39-6
• 化学式: C₄₁H₅₇NO₅Si₂
• 分子量: 700.078
• InChiKey: LRNOLDGKTQRRHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.76
• 重原子数：
  49
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  49.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,8-bis(tert-butyldimethylsilyloxy)-5-[4-(2-(piperidin-1-yl)ethoxy)phenyl]-5,11-dihydrochromeno[4,3-c]chromene 在 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 2,2-dimethyl-propionic acid 8-(2,2-dimethyl-propionyloxy)-5-[4-(2-piperidin-1-yl-ethoxy)phenyl]-5,11-dihydro-chromeno[4,3-c]chromen-2-yl ester
  参考文献：
  名称：

  Novel Chromene-Derived Selective Estrogen Receptor Modulators Useful for Alleviating Hot Flushes and Vaginal Dryness

  摘要：

  A novel SERM (selective estrogen receptor modulators), 1-(R), a chromene-derived bisbenzopyran, was discovered to alleviate hot flushes and effectively increase vaginal fluidity in rats. Moreover, 1-(R) was found to have beneficial effects on plasma cholesterol and bone metabolism while maintaining antiestrogenic activity in the uterus. The biological profile of its enantiomer 1-(S) was also evaluated.

  DOI：

  10.1021/jm060353u
• 作为产物：
  描述：

  2,8-dihydroxy-11H-chromeno[4,3-c]chromen-5-one 在 盐酸 、 正丁基锂 、 二异丁基氢化铝 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 、 正戊烷 为溶剂， 反应 25.5h， 生成 2,8-bis(tert-butyldimethylsilyloxy)-5-[4-(2-(piperidin-1-yl)ethoxy)phenyl]-5,11-dihydrochromeno[4,3-c]chromene
  参考文献：
  名称：

  Novel Chromene-Derived Selective Estrogen Receptor Modulators Useful for Alleviating Hot Flushes and Vaginal Dryness

  摘要：

  A novel SERM (selective estrogen receptor modulators), 1-(R), a chromene-derived bisbenzopyran, was discovered to alleviate hot flushes and effectively increase vaginal fluidity in rats. Moreover, 1-(R) was found to have beneficial effects on plasma cholesterol and bone metabolism while maintaining antiestrogenic activity in the uterus. The biological profile of its enantiomer 1-(S) was also evaluated.

  DOI：

  10.1021/jm060353u

文献信息

• Novel heteroatom containing tetracyclic derivatives as selective estrogen receptor modulators
  申请人：——

  公开号：US20030216463A1

  公开（公告）日：2003-11-20

  The present invention is directed to novel heteroatom containing tetracyclic derivatives, pharmaceutical compositions containing them, their use in the treatment and/or prevention of disorders mediated by one or more estrogen receptors and processes for their preparation. The compounds of the invention are useful in the treatment and/or prevention of disorders associated with the depletion of estrogen such as hot flashes, vaginal dryness, osteopenia and osteoporosis; hormone sensitive cancers and hyperplasia of the breast, endometrium, cervix and prostate; endometriosis, uterine fibroids, osteoarthritis and as contraceptive agents, alone or in combination with a progestogen or progestogen antagonist.

  本发明涉及包含杂原子的新型四环衍生物，包含它们的药物组合物，它们在治疗和/或预防由一个或多个雌激素受体介导的疾病中的应用，以及它们的制备过程。发明中的化合物在治疗和/或预防与雌激素耗竭相关的疾病中是有用的，如热潮红、阴道干涩、骨量减少和骨质疏松症；激素敏感性癌症和乳腺、子宫内膜、宫颈和前列腺的增生；子宫内膜异位症、子宫肌瘤、骨关节炎，并且作为避孕剂，单独使用或与孕激素或孕激素拮抗剂结合使用。
• Synthesis of Tetracyclic Heterocompounds as Selective Estrogen Receptor Modulators. Part 1. Process Development for Scale-up of 2,5,8-Substituted 5,11-Dihydrochromeno[4,3-<i>c</i>]chromene Derivatives
  作者：Xun Li、Michael Reuman、Ronald K. Russell、Richard Adams、Robert Ma、Sandra Beish,、Shawn Branum、Scott Youells、Jerry Roberts、Nareshkumar Jain、Ramesh Kanojia、Zhihua Sui

  DOI：10.1021/op700020f

  日期：2007.5.1

  compounds are novel selective estrogen receptor modulators (SERMs). A reproducible and nonchromatographic process was developed to prepare multihundred gram quantities of 5-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-5,11-dihydrochromeno[4,3-c]chromene-2,8-diyl-bis(2,2-dimethylpropanoate) (14). The overall yield of this 11-step synthesis was improved from 0.17% to 7.1% after three scale-up campaigns.

  不对称的苯并吡喃并苯并吡喃化合物是新型的选择性雌激素受体调节剂（SERM）。开发了一种可重现的非色谱方法，以制备数百克数量的5-（4-（2-（2-哌啶-1-基）乙氧基）苯基）-5,11-二氢苯并[4,3 - c ]苯二甲基-2,8 -二基-双（2，2-二甲基丙酸酯）（14）。经过三个扩大规模的推广活动后，该11步合成的总产率从0.17％提高到7.1％。
• Heteroatom containing tetracyclic derivatives as selective estrogen receptor modulators
  申请人：Janssen Pharmaceutica N.V.

  公开号：US07329654B2

  公开（公告）日：2008-02-12

  The present invention is directed to novel heteroatom containing tetracyclic derivatives, pharmaceutical compositions containing them, their use in the treatment and/or prevention of disorders mediated by one or more estrogen receptors and processes for their preparation. The compounds of the invention are useful in the treatment and/or prevention of disorders associated with the depletion of estrogen such as hot flashes, vaginal dryness, osteopenia and osteoporosis; hormone sensitive cancers and hyperplasia of the breast, endometrium, cervix and prostate; endometriosis, uterine fibroids, osteoarthritis and as contraceptive agents, alone or in combination with a progestogen or progestogen antagonist.

  本发明涉及新颖的含杂原子的四环衍生物，包含它们的制药组合物，以及它们在治疗和/或预防由一个或多个雌激素受体介导的疾病中的使用和制备过程。本发明的化合物在治疗和/或预防与雌激素耗竭相关的疾病方面具有用途，如潮热，阴道干燥，骨质疏松症；激素敏感性癌症和乳腺，子宫内膜，宫颈和前列腺的增生；子宫内膜异位症，子宫肌瘤，骨关节炎以及作为避孕剂，单独或与孕激素或孕激素拮抗剂联合使用。
• Novel Chromene-Derived Selective Estrogen Receptor Modulators Useful for Alleviating Hot Flushes and Vaginal Dryness
  作者：Nareshkumar Jain、Ramesh M. Kanojia、Jiayi Xu、Guo Jian-Zhong、Emmanuel Pacia、Muh-Tsann Lai、Fuyong Du、Amy Musto、George Allan、Hahn、Scott Lundeen、Zhihua Sui

  DOI：10.1021/jm060353u

  日期：2006.6.1

  A novel SERM (selective estrogen receptor modulators), 1-(R), a chromene-derived bisbenzopyran, was discovered to alleviate hot flushes and effectively increase vaginal fluidity in rats. Moreover, 1-(R) was found to have beneficial effects on plasma cholesterol and bone metabolism while maintaining antiestrogenic activity in the uterus. The biological profile of its enantiomer 1-(S) was also evaluated.