[2-(4-Trifluoromethylphenyl)-6-hydroxybenzo[b]thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]phenyl]methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-(4-Trifluoromethylphenyl)-6-hydroxybenzo[b]thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
• 英文别名: [2-(4-Trifluoromethylphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone；[6-hydroxy-2-[4-(trifluoromethyl)phenyl]-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone
• 化学式: C₂₉H₂₆F₃NO₃S
• 分子量: 525.592
• InChiKey: ATWOTNVLNKZCHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-三氟甲基苯基溴化镁 在 三溴化硼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 73.5h， 生成 [2-(4-Trifluoromethylphenyl)-6-hydroxybenzo[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, and compositions for treating bone loss,
  申请人：Eli Lilly and Company

  公开号：US05998442A1

  公开（公告）日：1999-12-07

  The invention provides benzo[b]thiophene compounds, formulations, and methods of inhibiting bone loss or bone resorption, particularly osteoporosis, and cardiovascular-related pathological conditions including hyperlipidemia and related cardiovascular pathologies.

  这项发明提供了苯并[b]噻吩化合物、配方和抑制骨质流失或骨吸收的方法，特别是针对骨质疏松症和与心血管相关的病理条件，包括高脂血症和相关的心血管病理条件。
• Benzo[B]thiophene compounds, intermediates, processes, compositions, and methods
  申请人：ELI LILLY AND COMPANY

  公开号：EP0826683A1

  公开（公告）日：1998-03-04

  The invention provides benzo[b]thiophene compounds, formulations, and methods of inhibiting bone loss or bone resorption, particularly osteoporosis, and cardiovascular-related pathological conditions including hyperlipidemia and related cardiovascular pathologies. The benzo[b]thiophenes have the following formula: wherein: X is -CH2-, -CH(OH)-, or -CO-; R1 is -H, -OH, -O(C1-C4 alkyl), -OCOAr where Ar is phenyl or substituted phenyl, -OCO(C1-C6 alkyl), or -OSO2(C4-C6 alkyl); R2, R3, and R4 are, independently, -R1, -F, -Cl, C1-C4 alkyl, or -CF3, with the proviso that R3 and R4 are not both hydrogen unless R2 is CF3, and with the further proviso that when X is -CH2-, then R3 is -H, -Cl, -F, C1-C4 alkyl, or CF3; n is 2 or 3; and R5 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt or solvate thereof.

  本发明提供了苯并[b]噻吩化合物、制剂以及抑制骨丢失或骨吸收（尤其是骨质疏松症）和心血管相关病症（包括高脂血症和相关心血管病症）的方法。 苯并[b]噻吩具有下式： 其中 X是-CH2-、-CH(OH)-或-CO-； R1 是-H、-OH、-O（C1-C4 烷基）、-OCOAr（其中 Ar 是苯基或取代苯基）、-OCO（C1-C6 烷基）或 -OSO2（C4-C6 烷基）； R2、R3 和 R4 独立地是-R1、-F、-Cl、C1-C4 烷基或-CF3，但 R3 和 R4 不能都是氢，除非 R2 是 ，而且当 X 是- -时，R3 是-H、-Cl、-F、C1-C4 烷基或 ； n 是 2 或 3；以及 R5 是 1-哌啶基、1-吡咯烷基、甲基-1-吡咯烷基、二甲基-1-吡咯烷基、4-吗啉基、二甲基氨基、二乙基氨基或 1-六亚甲基亚氨基；或其药学上可接受的盐或溶液。
• Benzo[b]thiophene compounds, intermediates, processes, compositions and methods
  申请人：Eli Lilly & Company

  公开号：EP1493741A2

  公开（公告）日：2005-01-05

  The invention provides benzo[b]thiophene compounds, formulations, and methods of inhibiting bone loss or bone resorption, particularly osteoporosis, and cardiovascular-related pathological conditions including hyperlipidemia and related cardiovascular pathologies.

  本发明提供了苯并[b]噻吩化合物、制剂和抑制骨质流失或骨吸收（尤其是骨质疏松症）以及心血管相关病症（包括高脂血症和相关心血管病症）的方法。
• US5998442A
  申请人：——

  公开号：US5998442A

  公开（公告）日：1999-12-07