[2-(4-Ethenylphenyl)-6-hydroxy-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)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-Ethenylphenyl)-6-hydroxy-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone
• 化学式: C₃₀H₂₉NO₃S
• 分子量: 483.631
• InChiKey: QTRNBRCYOZEWCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [2-(4-Ethenylphenyl)-6-hydroxy-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone 在 甲酸 、 palladium 10% on activated carbon 、 camphor-10-sulfonic acid 、 氢气 、 羟胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 120.17h， 生成 N-hydroxy-5-(4-(6-hydroxy-3-(4-(2-(piperidin-1-yl)ethoxy)benzoyl)benzo[b]thiophen-2-yl)phenyl)pentanamide
  参考文献：
  名称：

  雷洛昔芬/组蛋白脱乙酰酶抑制剂杂合体的设计、合成及其在乳腺癌中的抗增殖活性

  摘要：

  抗雌激素/组蛋白脱乙酰酶抑制剂 (HDACi) 杂合体的设计是通过将雷洛昔芬与辛二酰苯胺异羟肟酸的结构合并，将 HDACi 单元纳入抗雌激素的酚环中。这些杂交体是用一系列 HDACi 链长度合成的，并评估了双功能性。四种杂交体（YW471）、（YW490）、（YW486）和（YW487）在 BRET 测定和荧光 HDACi 测定中都显示出良好的抗雌激素效力。杂合体的抗增殖活性在 ER+ MCF7 和 ER-MDA-MB-231 乳腺癌细胞系中得到证实。

  DOI：

  10.1016/j.ejmech.2024.116533
• 作为产物：
  描述：

  [4-[6-[Tert-butyl(dimethyl)silyl]oxy-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophen-2-yl]phenyl] trifluoromethanesulfonate 在 palladium diacetate 、 1,3-双(二苯基膦)丙烷 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 [2-(4-Ethenylphenyl)-6-hydroxy-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)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

• Versatile raloxifene triflates
  作者：Michael J. Martin、Timothy A. Grese、Andrew L. Glasebrook、Ken Matsumoto、Lewis D. Pennington、D.Lynn Phillips、Lorri L. Short

  DOI：10.1016/s0960-894x(97)00130-3

  日期：1997.1

  Methodology has been employed that permits the differentiation of the phenols of raloxifene. Transition metal mediated transformations of raloxifene triflates have subsequently provided a number of analogs that were evaluated further in two in vitro models predictive of estrogen receptor mediated biological activity. (C) 1997 Elsevier Science Ltd.