3-[(Dimethylamino)methyl]azetidin-3-ol | 1373446-64-0

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 3-[(Dimethylamino)methyl]azetidin-3-ol
• CAS: 1373446-64-0
• 化学式: C₆H₁₄N₂O
• 分子量: 130.19
• InChiKey: YECJWPNDHRDXFI-UHFFFAOYSA-N

物化性质

• 沸点：
  210.2±15.0 °C(Predicted)
• 密度：
  1.051±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  9
• 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：
  35.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride 、 3-[(Dimethylamino)methyl]azetidin-3-ol 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(dimethylamino)methyl]azetidin-3-ol
  参考文献：
  名称：

  Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973)

  摘要：

  The ERK/MAP kinase cascade is a key mechanism subject to dysregulation in cancer and is constitutively activated or highly upregulated in many tumor types. Mutations associated with upstream pathway components RAS and Raf occur frequently and contribute to the oncogenic phenotype through activation of MEK and then ERK. Inhibitors of MEK have been shown to effectively block upregulated ERK/MAPK signaling in a range of cancer cell lines and have further demonstrated early evidence of efficacy in the clinic for the treatment of cancer. Guided by structural insight, a strategy aimed at the identification of an optimal diphenylamine-based MEK inhibitor with an improved metabolism and safety profile versus PD-0325901 led to the discovery of development candidate 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol (XL518, GDC-0973) (1). XL518 exhibits robust in vitro and in vivo in preclinical models with sustained duration of action and is currently in early stage clinical trials. potency and efficacy in preclinical models with sustained duration of action and is currently in early stage clinical trials.

  DOI：

  10.1021/ml300049d

文献信息

• Discovery of a potent respiratory syncytial virus RNA polymerase inhibitor
  作者：Hui Xiong、Melinda Foulk、Lisa Aschenbrenner、Jun Fan、Choi-Lai Tiong-Yip、Kenneth D. Johnson、Demetri Moustakas、Paul R. Fleming、Dean G. Brown、Minli Zhang、Douglas Ferguson、Dedong Wu、Qin Yu

  DOI：10.1016/j.bmcl.2013.10.018

  日期：2013.12

  Targeting viral polymerases has been a proven and attractive strategy for antiviral drug discovery. Herein we describe our effort in improving the antiviral activity and physical properties of a series of benzothienoazepine compounds as respiratory syncytial virus (RSV) RNA polymerase inhibitors. The antiviral activity and spectrum of this class was significantly improved by exploring the amino substitution of the pyridine ring, resulting in the discovery of the most potent RSV A polymerase inhibitors reported to date. (C) 2013 Published by Elsevier Ltd.