[2-(4-methoxyphenyl)-6-methylbenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone | 780733-80-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-(4-methoxyphenyl)-6-methylbenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
• 英文别名: [2-(4-Methoxyphenyl)-6-methyl-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone
• CAS: 780733-80-4
• 化学式: C₃₀H₃₁NO₃S
• 分子量: 485.647
• InChiKey: CTCKTPBHXSATOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  67
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [2-(4-methoxyphenyl)-6-methylbenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone 在 三氯化铝 、 丙烷-1-硫醇 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 5.0h， 生成 [2-(4-Hydroxy-phenyl)-6-methyl-benzo[b]thiophen-3-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone
  参考文献：
  名称：

  Structure−Activity Relationships of Selective Estrogen Receptor Modulators:  Modifications to the 2-Arylbenzothiophene Core of Raloxifene

  摘要：

  The 8-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in, vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.

  DOI：

  10.1021/jm9606352
• 作为产物：
  描述：

  2-(4-methoxyphenyl)-6-methylbenzo[b]thiophene 、 4-[2-(piperidin-1-yl)ethoxy]benzoyl chloride hydrochloride 在 三氯化铝 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 48.0h， 生成 [2-(4-methoxyphenyl)-6-methylbenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
  参考文献：
  名称：

  Structure−Activity Relationships of Selective Estrogen Receptor Modulators:  Modifications to the 2-Arylbenzothiophene Core of Raloxifene

  摘要：

  The 8-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in, vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.

  DOI：

  10.1021/jm9606352

文献信息

• Benzo [b] thiophene compounds, intermediates, formulations, and methods
  申请人：ELI LILLY AND COMPANY

  公开号：EP0835872B1

  公开（公告）日：2006-03-01
• JPH10130259A
  申请人：——

  公开号：JPH10130259A

  公开（公告）日：1998-05-19
• US9751852B1
  申请人：——

  公开号：US9751852B1

  公开（公告）日：2017-09-05
• US9790199B1
  申请人：——

  公开号：US9790199B1

  公开（公告）日：2017-10-17