[2-(4-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl] [4-methylphenyl]methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-(4-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl] [4-methylphenyl]methanone
• 英文别名: [2-(4-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-methylphenyl]methanone；[6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-(4-methylphenyl)methanone
• 化学式: C₂₂H₁₆O₃S
• 分子量: 360.433
• InChiKey: VBWCDXJRQBKNIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  85.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 [2-(4-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl] [4-methylphenyl]methanone
  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

• Benzothiophene compounds, and uses formulations thereof
  申请人：Eli Lilly and Company

  公开号：US05780648A1

  公开（公告）日：1998-07-14

  Benzothiophenes, and uses and formulations thereof, are provided by the present invention.

  本发明提供苯并噻吩及其用途和制剂。
• Benzothiophene compounds, and uses and formulations thereof
  申请人：ELI LILLY AND COMPANY

  公开号：EP0819686B1

  公开（公告）日：2003-10-01
• US5780648A
  申请人：——

  公开号：US5780648A

  公开（公告）日：1998-07-14
• 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.