6-methoxy-3-{4-[2-(1-piperidinyl)ethoxy]phenoxy}-2-(4-methoxyphenyl)benzo[b]thiophene S-oxide | 182133-03-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-methoxy-3-{4-[2-(1-piperidinyl)ethoxy]phenoxy}-2-(4-methoxyphenyl)benzo[b]thiophene S-oxide
• 英文别名: 6-Methoxy-2-(4-methoxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophene 1-oxide
• CAS: 182133-03-5
• 化学式: C₂₉H₃₁NO₅S
• 分子量: 505.635
• InChiKey: VAYPKCWRKVXTLV-UHFFFAOYSA-N

物化性质

• 沸点：
  711.4±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  76.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-methoxy-3-{4-[2-(1-piperidinyl)ethoxy]phenoxy}-2-(4-methoxyphenyl)benzo[b]thiophene S-oxide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 [6-methoxy-3-[4-[2-(1-piperidinyl)ethoxy]-phenoxy]-2-(4-methoxyphenyl)]benzo[b]thiophene
  参考文献：
  名称：

  Discovery and Synthesis of [6-Hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]- 2-(4-hydroxyphenyl)]benzo[b]thiophene:  A Novel, Highly Potent, Selective Estrogen Receptor Modulator

  摘要：

  Raloxifene,[2-(4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]-methanone hydrochloride (2), is representative of a class of compounds known as selective estrogen receptor modulators (SERMs) that possess estrogen agonist-like actions on bone tissues and serum lipids while displaying potent estrogen antagonist properties in the breast and uterus. As part of ongoing SAR studies with raloxifene, we found that replacement of the carbonyl group with oxygen ([6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene hydrochloride, 4c) resulted in a substantial (10-fold) increase in estrogen antagonist potency relative to raloxifene in an in vitro estrogen dependent cell proliferation assay (IC50 = 0.05 nM) in which human breast cancer cells (MCF-7) were utilized. In vivo, 4c potently inhibited the uterine proliferative response to exogenous estrogen in immature rats following both sc and oral dosing (ED50 of 0.006 and 0.25 mg/kg, respectively). In ovariectomized aged rats, 4c produced a significant maximal decrease (45%) in total cholesterol at 1.0 mg/kg (po) and showed a protective effect on bone relative to controls with maximal efficacy at 1.0 mg/kg (po). These data identify 4c as a novel SERM with greater potency to antagonize estrogen in uterine tissue and in human mammary cancer cells compared to raloxifene, tamoxifen or ICI-182,780.

  DOI：

  10.1021/jm970167b
• 作为产物：
  描述：

  4-苄氧基苯酚 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hydride 、 potassium carbonate 、 caesium carbonate 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 51.25h， 生成 6-methoxy-3-{4-[2-(1-piperidinyl)ethoxy]phenoxy}-2-(4-methoxyphenyl)benzo[b]thiophene S-oxide
  参考文献：
  名称：

  Discovery and Synthesis of [6-Hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]- 2-(4-hydroxyphenyl)]benzo[b]thiophene:  A Novel, Highly Potent, Selective Estrogen Receptor Modulator

  摘要：

  Raloxifene,[2-(4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]-methanone hydrochloride (2), is representative of a class of compounds known as selective estrogen receptor modulators (SERMs) that possess estrogen agonist-like actions on bone tissues and serum lipids while displaying potent estrogen antagonist properties in the breast and uterus. As part of ongoing SAR studies with raloxifene, we found that replacement of the carbonyl group with oxygen ([6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene hydrochloride, 4c) resulted in a substantial (10-fold) increase in estrogen antagonist potency relative to raloxifene in an in vitro estrogen dependent cell proliferation assay (IC50 = 0.05 nM) in which human breast cancer cells (MCF-7) were utilized. In vivo, 4c potently inhibited the uterine proliferative response to exogenous estrogen in immature rats following both sc and oral dosing (ED50 of 0.006 and 0.25 mg/kg, respectively). In ovariectomized aged rats, 4c produced a significant maximal decrease (45%) in total cholesterol at 1.0 mg/kg (po) and showed a protective effect on bone relative to controls with maximal efficacy at 1.0 mg/kg (po). These data identify 4c as a novel SERM with greater potency to antagonize estrogen in uterine tissue and in human mammary cancer cells compared to raloxifene, tamoxifen or ICI-182,780.

  DOI：

  10.1021/jm970167b

文献信息

• Discovery and Synthesis of [6-Hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]- 2-(4-hydroxyphenyl)]benzo[<i>b</i>]thiophene:  A Novel, Highly Potent, Selective Estrogen Receptor Modulator
  作者：Alan D. Palkowitz、Andrew L. Glasebrook、K. Jeff Thrasher、Kenneth L. Hauser、Lorri L. Short、D. Lynn Phillips、Brian S. Muehl、Masahiko Sato、Pamela K. Shetler、George J. Cullinan、Tina R. Pell、Henry U. Bryant

  DOI：10.1021/jm970167b

  日期：1997.5.1

  Raloxifene,[2-(4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]-methanone hydrochloride (2), is representative of a class of compounds known as selective estrogen receptor modulators (SERMs) that possess estrogen agonist-like actions on bone tissues and serum lipids while displaying potent estrogen antagonist properties in the breast and uterus. As part of ongoing SAR studies with raloxifene, we found that replacement of the carbonyl group with oxygen ([6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene hydrochloride, 4c) resulted in a substantial (10-fold) increase in estrogen antagonist potency relative to raloxifene in an in vitro estrogen dependent cell proliferation assay (IC50 = 0.05 nM) in which human breast cancer cells (MCF-7) were utilized. In vivo, 4c potently inhibited the uterine proliferative response to exogenous estrogen in immature rats following both sc and oral dosing (ED50 of 0.006 and 0.25 mg/kg, respectively). In ovariectomized aged rats, 4c produced a significant maximal decrease (45%) in total cholesterol at 1.0 mg/kg (po) and showed a protective effect on bone relative to controls with maximal efficacy at 1.0 mg/kg (po). These data identify 4c as a novel SERM with greater potency to antagonize estrogen in uterine tissue and in human mammary cancer cells compared to raloxifene, tamoxifen or ICI-182,780.