(E)-3-(4-((2-(2,6-dimethylbenzoyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (E)-3-(4-((2-(2,6-dimethylbenzoyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid
• 英文别名: (E)-3-[4-[[2-(2,6-dimethylbenzoyl)-6-hydroxy-1-benzothiophen-3-yl]oxy]phenyl]prop-2-enoic acid
• 化学式: C₂₆H₂₀O₅S
• 分子量: 444.508
• InChiKey: AFKHJLINIGEQDW-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,6-二甲基溴苯 在 bis-triphenylphosphine-palladium(II) chloride 、 三氟二甲基硫醚络合物 、 碘 、 caesium carbonate 、 magnesium 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 (E)-3-(4-((2-(2,6-dimethylbenzoyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid
  参考文献：
  名称：

  Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer

  摘要：

  Resistance to the selective estrogen receptor modulator tamoxifen and to aromatase inhibitors that lower circulating estradiol occurs in up to 50% of patients, generally leading to an endocrine-independent ER+ phenotype. Selective ER downregulators (SERDs) are able to ablate ER and thus, theoretically, to prevent survival of both endocrine-dependent and -independent ER+ tumors. The clinical SERD fulvestrant is hampered by intramuscular administration and undesirable pharmacokinetics. Novel SERDs were designed using the 6-OH-benzothiophene (BT) scaffold common to arzoxifene and raloxifene. Treatment-resistant (TR) ER+ cell lines (MCF-7:5C and MCF-7:TAM1) were used for optimization, followed by validation in the parent endocrine-dependent cell line (MCF-7:WS8), in 2D and 3D cultures, using ER alpha in-cell westerns, ERE-luciferase, and cell viability assays, with 2 (GDC-0810/ARN-810) used for comparison. Two BT SERDs with superior in vitro activity to 2 were studied for bioavailability and shown to cause regression of a TR, endocrine -independent ER+ xenograft superior to that with 2.

  DOI：

  10.1021/acs.jmedchem.6b01355

文献信息

• [EN] CYCLIN-DEPENDENT KINASE INHIBITING COMPOUNDS FOR THE TREATMENT OF MEDICAL DISORDERS<br/>[FR] COMPOSÉS INHIBITEURS DE KINASE DÉPENDANT DE LA CYCLINE POUR LE TRAITEMENT D'AFFECTIONS MÉDICALES
  申请人：G1 THERAPEUTICS INC

  公开号：WO2021236650A1

  公开（公告）日：2021-11-25

  This invention is in the area of cell cycle inhibiting compounds for the treatment of disorders involving abnormal cellular proliferation, and include selective CDK2 inhibitors for medical therapy and their pharmaceutically acceptable salts and compositions.

  这项发明涉及细胞周期抑制化合物领域，用于治疗涉及异常细胞增殖的疾病，包括用于医学治疗的选择性CDK2抑制剂及其药用盐和组合物。
• Benzothiophene-based selective estrogen receptor downregulators
  申请人：The Board of Trustees of the University of Illinois

  公开号：US10118910B2

  公开（公告）日：2018-11-06

  This invention is benzothiophene-based estrogen receptor downregulators and their compositions and uses to treat estrogen-related medical disorders.

  本发明是苯并噻吩类雌激素受体下调剂及其组合物，用于治疗雌激素相关疾病。
• Benzothiophene-based selective estrogen receptor downregulator compounds
  申请人：The Board of Trustees of the University of Illinois

  公开号：US11072595B2

  公开（公告）日：2021-07-27

  This invention is benzothiophene-based estrogen receptor downregulators and their compositions and uses to treat estrogen-related medical disorders.

  本发明是苯并噻吩类雌激素受体下调剂及其组合物，用于治疗雌激素相关疾病。
• Combination therapy for treatment of cancer
  申请人：G1 Therapeutics, Inc.

  公开号：US11364222B2

  公开（公告）日：2022-06-21

  Compositions, combinations and methods comprising a CDK4/6 inhibitor of Formula D with a selective estrogen receptor downregulator of Formula A, B or C that are advantageous for the treatment of abnormal cellular proliferation, including a cancer or a tumor.

  由式D的CDK4/6抑制剂与式A、B或C的选择性雌激素受体下调剂组成的组合物、组合物和方法，有利于治疗异常细胞增殖，包括癌症或肿瘤。
• BENZOTHIOPHENE-BASED SELECTIVE ESTROGEN RECEPTOR DOWNREGULATORS
  申请人：The Board of Trustees of the University of Illinois

  公开号：EP3386500B1

  公开（公告）日：2022-09-07