1-(2-Fluoroethyl)azetidin-3-ol | 1500555-19-0

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 1-(2-Fluoroethyl)azetidin-3-ol
• CAS: 1500555-19-0
• 化学式: C₅H₁₀FNO
• 分子量: 119.139
• InChiKey: BQNVHFDSQVDMIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-Fluoroethyl)azetidin-3-ol 、 (1R,3R)-1-[4-(azetidin-3-yloxy)-2,6-difluorophenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline formate salt 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 (1R,3R)-1-[2,6-difluoro-4-(1-prop-2-ynylazetidin-3-yl)oxyphenyl]-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole
  参考文献：
  名称：

  Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer

  摘要：

  Estrogen receptor alpha (ER alpha) is a well-validated drug target for ER-positive (ER+) breast cancer. Fulvestrant is FDA-approved to treat ER+ breast cancer and works through two mechanisms.as a full antagonist and selective estrogen receptor degrader (SERD).but lacks oral bioavailability. Thus, we envisioned a "best-in-class" molecule with the same dual mechanisms as fulvestrant, but with significant oral exposure. Through lead optimization, we discovered a tool molecule 12 (GNE-149) with improved degradation and antiproliferative activity in both MCF7 and T47D cells. To illustrate the binding mode and key interactions of this scaffold with ER alpha, we obtained a cocrystal structure of 6 that showed ionic interaction of azetidine with Asp351 residue. Importantly, 12 showed favorable metabolic stability and good oral exposure. 12 exhibited antagonist effect in the uterus and demonstrated robust dose-dependent efficacy in xenograft models.

  DOI：

  10.1021/acsmedchemlett.0c00224