[6-methoxy-3-[4-[2-(1-piperidinyl)ethoxy]-phenoxy]-2-(4-methoxyphenyl)]benzo[b]thiophene

• 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
• 英文别名: 1-[2-[4-[[6-Methoxy-2-(4-methoxyphenyl)-1-benzothiophen-3-yl]oxy]phenoxy]ethyl]piperidine
• 化学式: C₂₉H₃₁NO₄S
• 分子量: 489.635
• InChiKey: JSPRFDYAEIFDJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  35
• 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：
  68.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-苄氧基苯酚 在 palladium on activated charcoal 盐酸 、 lithium aluminium tetrahydride 、 氢气 、 sodium hydride 、 potassium carbonate 、 caesium carbonate 作用下， 以 四氢呋喃 、 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 51.75h， 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

文献信息

• Treatment of central nervous system disorders with selective estrogen receptor modulators
  申请人：——

  公开号：US20020013342A1

  公开（公告）日：2002-01-31

  The present invention provides a method of treating depression, mood swings, or Alzheimer's disease in a patient in need of such treatment by administering a selective estrogen receptor modulating compound of the formula 1 in which R 1 and R 2 are independently hydroxy and alkoxy of one to four carbon atoms; and R 3 and R 4 are independently methyl or ethyl, or R 3 and R 4 , taken together with the nitrogen atom to which they are attached, form a pyrrolidino, methyl-pyrrolidino, dimethylpyrrolidino, piperidino, morpholino, or hexamethyleneimino ring.

  本发明提供了一种治疗抑郁症、情绪波动或阿尔茨海默病的方法，通过给需要该治疗的患者给予选择性雌激素受体调节化合物，该化合物的公式为1，其中R1和R2独立地为一至四个碳原子的羟基和烷氧基；R3和R4独立地为甲基或乙基，或R3和R4与它们所连接的氮原子一起形成吡咯烷基、甲基吡咯烷基、二甲基吡咯烷基、哌啶基、吗啉基或六亚甲基胺环。
• Benzothiophene compounds, intermediates, compositions and methods
  申请人：Eli Lilly & Company

  公开号：EP1113013A1

  公开（公告）日：2001-07-04

  The present invention provides pharmaceutically active compounds of formula I wherein R1 is -H, -OH, -O(C1-C4 alkyl), -OCOC6H5, -OCO(C1-C6 alkyl), or -OSO2(C2-C6 alkyl); R2 is -H, -OH, -O(C1-C4 alkyl), -OCOC6H5, -OCO(C1-C6 alkyl), -OSO2(C2-C6 alkyl), or halo; R3 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; and z is -O- or -S-; or a pharmaceutically acceptable salt thereof. Further provided are pharmaceutical compositions of compounds of formula I.

  本发明提供了具有药用活性的式 I 化合物 其中 R1是-H、-OH、-O(C1-C4烷基)、-OCOC6H5、-OCO(C1-C6烷基)或-OSO2(C2-C6烷基)； R2 是-H、-OH、-O(C1-C4 烷基)、-OCOC6H5、-OCO(C1-C6 烷基)、-OSO2(C2-C6 烷基)或卤素； R3 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、二异丙基氨基或 1-六亚甲基亚氨基； n 是 2 或 3；以及 z 是-O-或-S-； 或其药学上可接受的盐。 进一步提供了式 I 化合物的药物组合物。
• Benzothiophene compounds, intermediates, compositions, and methods
  申请人：ELI LILLY AND COMPANY

  公开号：EP0729956B1

  公开（公告）日：2001-10-31
• US5488058A
  申请人：——

  公开号：US5488058A

  公开（公告）日：1996-01-30
• US5492922A
  申请人：——

  公开号：US5492922A

  公开（公告）日：1996-02-20