2-(4-fluorophenyl)-3-(4-hydroxyphenoxy)benzo[b]-thiophen-6-ol | 1275577-71-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(4-fluorophenyl)-3-(4-hydroxyphenoxy)benzo[b]-thiophen-6-ol
• 英文别名: 2-(4-Fluorophenyl)-3-(4-hydroxyphenoxy)-1-benzothiophen-6-ol；2-(4-fluorophenyl)-3-(4-hydroxyphenoxy)-1-benzothiophen-6-ol
• CAS: 1275577-71-3
• 化学式: C₂₀H₁₃FO₃S
• 分子量: 352.386
• InChiKey: MCTBDHKWASVVRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-fluorophenyl)-3-(4-hydroxyphenoxy)benzo[b]-thiophen-6-ol 、 异丁酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以80%的产率得到2-(4-fluorophenyl)-3-(4-(isobutyryloxy)phenoxy)benzo[b]thiophen-6-yl isobutyrate
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR TREATING ESTROGEN-RELATED MEDICAL DISORDERS
  [FR] COMPOSITIONS ET PROCÉDÉS DE TRAITEMENT DE TROUBLES MÉDICAUX ASSOCIÉS AUX ŒSTROGÈNES

  摘要：

  本文揭示了治疗与雌激素相关的医学疾病的方法。治疗方法可能包括向需要此类治疗的对象施用含有至少一种化合物的组合物，该化合物符合以下公式（I）或其药用可接受盐的治疗有效量。

  公开号：

  WO2014066692A1
• 作为产物：
  描述：

  3-bromo-2-(4-fluorophenyl)-6-methoxybenzo[b]thiophene 1-oxide 在 lithium aluminium tetrahydride 、 三溴化硼 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.0h， 生成 2-(4-fluorophenyl)-3-(4-hydroxyphenoxy)benzo[b]-thiophen-6-ol
  参考文献：
  名称：

  Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen-Resistant Breast Cancer

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b01276

文献信息

• COMPOSITIONS AND METHODS FOR TREATING ESTROGEN-RELATED MEDICAL DISORDERS
  申请人：THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

  公开号：US20150291552A1

  公开（公告）日：2015-10-15

  Disclosed herein are methods for treatment of estrogen-related medical disorders. The methods of treatment may comprise administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of at least one compound of formula (I) or a pharmaceutically acceptable salt thereof.

  本文公开了治疗雌激素相关医学疾病的方法。治疗方法可能包括向需要此类治疗的受试者给予一种组合物，该组合物包含至少一种式（I）化合物或其药学上可接受的盐的治疗有效量。
• Compositions and methods for treating estrogen-related medical disorders
  申请人：THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

  公开号：US10888545B2

  公开（公告）日：2021-01-12

  Disclosed herein are methods for treatment of estrogen-related medical disorders. The methods of treatment may comprise administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of at least one compound of formula (I) or a pharmaceutically acceptable salt thereof.

  本文公开了治疗雌激素相关疾病的方法。 治疗方法可包括向需要此类治疗的受试者施用一种组合物，该组合物包含治疗有效量的至少一种式（I）化合物或其药学上可接受的盐。
• US9475791B2
  申请人：——

  公开号：US9475791B2

  公开（公告）日：2016-10-25
• US9895348B2
  申请人：——

  公开号：US9895348B2

  公开（公告）日：2018-02-20
• 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.