2-(4-methoxyphenyl)-6-methylbenzo[b]thiophene | 185414-71-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 2-(4-methoxyphenyl)-6-methylbenzo[b]thiophene
• 英文别名: 6-Methyl-2-(4-methoxyphenyl)benzo[b]thiophene；2-(4-methoxyphenyl)-6-methyl-1-benzothiophene
• CAS: 185414-71-5
• 化学式: C₁₆H₁₄OS
• 分子量: 254.353
• InChiKey: RTAHFAMACJXYGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  37.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-methoxyphenyl)-6-methylbenzo[b]thiophene 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 53.0h， 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：

  1-(2-溴-4-甲基苯基)-2-(4-甲氧基苯基)乙炔 在 copper(l) iodide 、 sodium sulfide nonahydrate 、 四甲基乙二胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以70%的产率得到2-(4-methoxyphenyl)-6-methylbenzo[b]thiophene
  参考文献：
  名称：

  CuI/TMEDA-Catalyzed Annulation of 2-Bromo Alkynylbenzenes with Na₂S: Synthesis of Benzo[b]thiophenes

  摘要：

  A copper-catalyzed thiolation annulation reaction of 2-bromo alkynylbenzenes with sodium sulfide has been developed. In the presence of CuI and TMEDA, a variety of 2-substituted benzo[b]thiophenes were readily prepared in moderate to good yields by the reaction of 2-bromo alkynylbenzenes and Na2S center dot 9H(2)O.

  DOI：

  10.1021/jo201081v

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
• US5948796A
  申请人：——

  公开号：US5948796A

  公开（公告）日：1999-09-07
• Structure−Activity Relationships of Selective Estrogen Receptor Modulators:  Modifications to the 2-Arylbenzothiophene Core of Raloxifene
  作者：Timothy A. Grese、Stephen Cho、Don R. Finley、Alexander G. Godfrey、Charles D. Jones、Charles W. Lugar、Michael J. Martin、Ken Matsumoto、Lewis D. Pennington、Mark A. Winter、M. Dee Adrian、Harlan W. Cole、David E. Magee、D. Lynn Phillips、Ellen R. Rowley、Lorri L. Short、Andrew L. Glasebrook、Henry U. Bryant

  DOI：10.1021/jm9606352

  日期：1997.1.1

  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.
• CuI/TMEDA-Catalyzed Annulation of 2-Bromo Alkynylbenzenes with Na₂S: Synthesis of Benzo[<i>b</i>]thiophenes
  作者：Lei-Lei Sun、Chen-Liang Deng、Ri-Yuan Tang、Xing-Guo Zhang

  DOI：10.1021/jo201081v

  日期：2011.9.16

  A copper-catalyzed thiolation annulation reaction of 2-bromo alkynylbenzenes with sodium sulfide has been developed. In the presence of CuI and TMEDA, a variety of 2-substituted benzo[b]thiophenes were readily prepared in moderate to good yields by the reaction of 2-bromo alkynylbenzenes and Na2S center dot 9H(2)O.