raloxifene | 188823-98-5

• 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: raloxifene
• 英文别名: 6-[4-(2-piperidin-1-ylethoxy)phenyl]-6H-[1]benzothiolo[3,2-c]chromene-3,9-diol
• CAS: 188823-98-5
• 化学式: C₂₈H₂₇NO₄S
• 分子量: 473.593
• InChiKey: TXINWSAFRMHRJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  90.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  raloxifene 在 palladium diacetate 、 四(三苯基膦)钯 、 甲酸 、 1,3-双(二苯基膦)丙烷 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 108.0h， 生成 6-[4-[2-(1-piperidinyl)ethoxy]phenyl]-6-H-[1]benzothieno[3,2-c][1]benzopyran
  参考文献：
  名称：

  Synthesis and Pharmacology of Conformationally Restricted Raloxifene Analogues:  Highly Potent Selective Estrogen Receptor Modulators

  摘要：

  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.

  DOI：

  10.1021/jm970688z
• 作为产物：
  描述：

  tert-butyl-[[3-[tert-butyl(dimethyl)silyl]oxy-6-phenoxy-6H-[1]benzothiolo[3,2-c]chromen-9-yl]oxy]-dimethylsilane 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.5h， 生成 raloxifene
  参考文献：
  名称：

  Synthesis and Pharmacology of Conformationally Restricted Raloxifene Analogues:  Highly Potent Selective Estrogen Receptor Modulators

  摘要：

  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.

  DOI：

  10.1021/jm970688z

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.