[2-(4-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanol | 174731-13-6

• 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-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanol
• 英文别名: [6-HYDROXY-2-(4-HYDROXYPHENYL)BENZO[B]THIEN-3-YL][4-[2-(1-PIPERIDINYL)ETHOXY]PHENYL]METHANOL；2-(4-Hydroxyphenyl)-3-[hydroxy-[4-(2-piperidin-1-ylethoxy)phenyl]methyl]-1-benzothiophen-6-ol
• CAS: 174731-13-6
• 化学式: C₂₈H₂₉NO₄S
• 分子量: 475.609
• InChiKey: KSBCHRYYEZTEJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [2-(4-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanol 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以72%的产率得到[2-(4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methane
  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：

  雷洛昔芬 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以91%的产率得到[2-(4-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanol
  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

• Benzothiophenes, formulations containing same, and methods
  申请人：Eli Lilly and Company

  公开号：US05731342A1

  公开（公告）日：1998-03-24

  This invention provides novel benzothiophene compounds.

  这项发明提供了新型苯并噻吩化合物。
• Benzothiophenes, formulations containing same, and methods for their préparation
  申请人：ELI LILLY AND COMPANY

  公开号：EP0791591B1

  公开（公告）日：2001-08-29
• 2-(4-Hydroxyphenyl)benzothiophene compounds, compositions and methods for alleviating the symptoms of post-menopause syndrome
  申请人：ELI LILLY AND COMPANY

  公开号：EP0703231B1

  公开（公告）日：2002-05-02
• US5484798A
  申请人：——

  公开号：US5484798A

  公开（公告）日：1996-01-16
• US5492921A
  申请人：——

  公开号：US5492921A

  公开（公告）日：1996-02-20