雷洛昔芬杂质 | 175460-94-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 中文名称: 雷洛昔芬杂质
• 英文名称: 4-(6-methoxybenzo[b]thiophen-2-yl)phenol
• 英文别名: 6-methoxy-2-(4-hydroxyphenyl)benzo[b]thiophene；2-(4-hydroxyphenyl)-6-methoxybenzo[b]thiophene；4-(6-methoxy-1-benzothiophen-2-yl)phenol
• CAS: 175460-94-3
• 化学式: C₁₅H₁₂O₂S
• 分子量: 256.325
• InChiKey: PXDYWLJYLUKTQX-UHFFFAOYSA-N

物化性质

• 沸点：
  446.0±30.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  雷洛昔芬杂质 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 triisopropylsilyl methanesulfonate 为溶剂， 生成 4-(6-Methoxybenzo[b]thiophen-2-yl)phenyl Triisopropylsilyl Ether
  参考文献：
  名称：

  Thrombin inhibitors

  摘要：

  这项申请涉及到式I的新化合物（及其药学上可接受的盐），如本文所定义，用于它们的制备的过程和中间体，包含式I的新化合物的药物配方，以及将式I的特定化合物用作凝血酶抑制剂。

  公开号：

  US06391901B1
• 作为产物：
  描述：

  4-(6-methoxybenzo[b]thiophen-3-yl)phenol 在 甲烷磺酸 作用下， 以 甲苯 、 正庚烷 为溶剂， 以74 %的产率得到雷洛昔芬杂质
  参考文献：
  名称：

  Synthesis, biological evaluation, and stability studies of raloxifene mono- and bis-sulfamates as dual-targeting agents

  摘要：

  DOI：

  10.1016/j.bmc.2024.117645

文献信息

• [EN] ANTITHROMBOTIC DIAMINES<br/>[FR] DIAMINES ANTITHROMBOTIQUES
  申请人：ELI LILLY AND COMPANY

  公开号：WO1997025033A1

  公开（公告）日：1997-07-17

  (EN) This application relates to the use as thrombin inhibitors, coagulation inhibitors and thromboembolic disorder agents of diamines of formula (I) as defined herein. It also provides novel compounds of formula (I), processes and intermediates for their preparation, and pharmaceutical formulations comprising the novel compounds of formula (I).(FR) La présente invention concerne l'utilisation, comme inhibiteurs de thrombine, inhibiteurs de coagulation et agents destinés aux désordres de la thromboembolie, de diamines de formule I telle qu'elle est définie dans la description. L'invention concerne aussi des composés nouveaux de formule I, des procédés et des produits intermédiaires pour leur préparation, et des formulations pharmaceutiques comprenant les composés nouveaux de formule I.

  该应用涉及使用公式（I）所定义的二胺作为凝血酶抑制剂、凝血抑制剂和血栓栓塞疾病药物的用途。它还提供了公式（I）的新化合物、其制备过程和中间体，以及包含公式（I）的新药物配方。
• An improved process for preparing 3-(4-aminoethoxy-benzoyl)benzo beta -thiophenes
  申请人：ELI LILLY AND COMPANY

  公开号：EP0693488A1

  公开（公告）日：1996-01-24

  The invention provides a process for preparing 6-alkoxy-3-(4-alkoxyphenyl)benzo[B]thiophenes in good yield on a manufacturing scale without generating a thick, potentially yield-reducing, paste. The invention also provides methods for converting a-(-alkoxyphenylthio)-4-alkoxyacetophenones into 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-aminoethoxy)-benzoyl]benzo[B]thiophenes via acylation of a dialkoxy benzo[B]thiophene. Each of these preparations relies on an intramolecular cyclization of a dialkoxy acetophenone derivative to yield a benzo[B]thiophene without generating a thick paste that lowers overall yields on a manufacturing scale.

  本发明提供了一种在生产规模上以良好收率制备 6-烷氧基-3-(4-烷氧基苯基)苯并[B]噻吩的工艺，而不会产生粘稠的、可能降低收率的糊状物。本发明还提供了通过二烷氧基苯并[B]噻吩的酰化将 a-(-烷氧基苯硫基)-4-烷氧基苯乙酮转化为 6-羟基-2-(4-羟基苯基)-3-[4-(2-氨基乙氧基)-苯甲酰基]苯并[B]噻吩的方法。上述每种制备方法都依赖于二烷氧基苯乙酮衍生物的分子内环化来生成苯并[B]噻吩，而不会生成浓稠的糊状物，从而降低了生产规模上的总体产量。
• 2-Arylbenzo b thiophenes useful for the treatment of estrogen deprivation syndrome
  申请人：ELI LILLY AND COMPANY

  公开号：EP0920862A1

  公开（公告）日：1999-06-09

  This invention provides methods which are useful for the inhibition of the various medical conditions associated with estrogen deprivation syndrome including osteoporosis and hyperlipidemia utilizing compounds of formula I:

  本发明提供了利用式 I 化合物抑制与雌激素缺乏综合征有关的各种病症（包括骨质疏松症和高脂血症）的方法：
• Process for preparing 3-aryl-benzo{b} thiophenes
  申请人：——

  公开号：US20040132775A1

  公开（公告）日：2004-07-08

  The present invention relates to a process for preparing a compound of formula (I): which includes cyclodehydrating a compound of formula (II): in the presence of an acid activated clay or acid activated zeolite catalyst and in the presence of a suitable solvent. 1

  本发明涉及一种制备式(I)化合物的工艺，该工艺包括在酸活化粘土或酸活化沸石催化剂存在下，在合适的溶剂存在下，对式(II)化合物进行环脱水。 1
• Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen-Resistant Breast Cancer
  作者：Rui Xiong、Hitisha K. Patel、Lauren M. Gutgesell、Jiong Zhao、Loruhama Delgado-Rivera、Thao N. D. Pham、Huiping Zhao、Kathryn Carlson、Teresa Martin、John A. Katzenellenbogen、Terry W. Moore、Debra A. Tonetti、Gregory R. J. Thatcher

  DOI：10.1021/acs.jmedchem.5b01276

  日期：2016.1.14

  Almost 70% of breast cancers are estrogen receptor alpha (ER alpha) positive. Tamoxifen, a selective estrogen receptor modulator (SERM), represents the standard of care for many patients; however, 30-50% develop resistance, underlining the need for alternative therapeutics. Paradoxically, agonists at ER alpha such as estradiol (E-2) have demonstrated clinical efficacy in patients with heavily treated breast cancer, although side effects in gynecological tissues are unacceptable. A drug that selectively mimics the actions of E-2 in breast cancer therapy but minimizes estrogenic effects in other tissues is a novel, therapeutic alternative. We hypothesized that a selective human estrogen receptor partial agonist (ShERPA) at ER alpha would provide such an agent. Novel benzothiophene derivatives with nanomolar potency in breast cancer cell cultures were designed. Several showed partial agonist activity, with potency of 0.8-76 nM, mimicking E-2 in inhibiting growth of tamoxifen-resistant breast cancer cell lines. Three ShERPAs were tested and validated in xenograft models of endocrine-independent and tamoxifen-resistant breast cancer, and in contrast to E-2, ShERPAs did not cause significant uterine growth.