3,9-Bis[[tert-butyl(dimethyl)silyl]oxy]-[1]benzofuro[3,2-c]chromen-6-one | 185254-71-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 3,9-Bis[[tert-butyl(dimethyl)silyl]oxy]-[1]benzofuro[3,2-c]chromen-6-one
• CAS: 185254-71-1
• 化学式: C₂₇H₃₆O₅Si₂
• 分子量: 496.751
• InChiKey: JUGWIOGVYRJZCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.46
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  57.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,9-Bis[[tert-butyl(dimethyl)silyl]oxy]-[1]benzofuro[3,2-c]chromen-6-one 在 四丁基氟化铵 、 二异丁基氢化铝 、 magnesium sulfate 作用下， 以 甲苯 为溶剂， 生成 6-[4-(2-piperidin-1-ylethoxy)phenyl]-6H-[1]benzofuro[3,2-c]chromene-3,9-diol
  参考文献：
  名称：

  Conversion of the phytoestrogen coumestrol into a selective estrogen receptor modulator (SERM) by attachment of an amine-containing sidechain

  摘要：

  The naturally occurring estrogen mimetic coumestrol has been shown to stimulate proliferation of MCF-7 mammary tumor cells and to cause uterotrophic effects in ovariectomized (OVX) rats. Attachment of a basic amine-containing sidechain to C-6 of coumestrol converts this estrogen agonist into an antagonist in breast and uterine tissue, while maintaining its estrogen-like activity as a hypocholesterolemic agent. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00502-1
• 作为产物：
  描述：

  考迈斯托醇 、 叔丁基二甲基氯硅烷 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以77%的产率得到3,9-Bis[[tert-butyl(dimethyl)silyl]oxy]-[1]benzofuro[3,2-c]chromen-6-one
  参考文献：
  名称：

  Conversion of the phytoestrogen coumestrol into a selective estrogen receptor modulator (SERM) by attachment of an amine-containing sidechain

  摘要：

  The naturally occurring estrogen mimetic coumestrol has been shown to stimulate proliferation of MCF-7 mammary tumor cells and to cause uterotrophic effects in ovariectomized (OVX) rats. Attachment of a basic amine-containing sidechain to C-6 of coumestrol converts this estrogen agonist into an antagonist in breast and uterine tissue, while maintaining its estrogen-like activity as a hypocholesterolemic agent. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00502-1

文献信息

• Synthesis and Pharmacology of Conformationally Restricted Raloxifene Analogues:  Highly Potent Selective Estrogen Receptor Modulators
  作者：Timothy A. Grese、Lewis D. Pennington、James P. Sluka、M. Dee Adrian、Harlan W. Cole、Tina R. Fuson、David E. Magee、D. Lynn Phillips、Ellen R. Rowley、Pamela K. Shetler、Lorri L. Short、Murali Venugopalan、Na N. Yang、Masahiko Sato、Andrew L. Glasebrook、Henry U. Bryant

  DOI：10.1021/jm970688z

  日期：1998.4.1

  The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator (SERM) which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. In vivo structure-activity relationships and molecular modeling studies have indicated that the orientation of the basic amine-containing side chain of 1, relative to the stilbene plane, is an important discriminating factor for the maintenance of tissue selectivity. We have constructed a series of analogues of 1 in which this side chain is held in an orientation which is orthogonal to the stilbene plane, similar to the low-energy conformation predicted for raloxifene. Herein, we report on the synthesis of these compounds and on their activity in a series of in vitro and in vivo biological assays reflective of the SERM profile. In particular, we describe their ability to (I) bind the estrogen receptor, (2) antagonize estrogen-stimulated proliferation of MCF-7 cells in vitro, (3) stimulate TGF-beta 3 gene expression in cell culture, (4) inhibit the uterine effects of ethynyl estradiol in immature rats, and (5) potently reduce serum cholesterol and protect against osteopenia in ovariectomized (OVX) rats without estrogen-like stimulation of uterine tissue. These data demonstrate that one of these compounds, LY357489, 4, is among the most potent SERMs described to date with in vivo efficacy on bone and cholesterol metabolism in OVX rats at doses as low as 0.01 mg/kg/d.