N-(4-bromo-2-fluorobenzyl)-2-(3-methyl-1,2-dioxaspiro[4.5]decan-3-yl)acetamide | 1194839-43-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-bromo-2-fluorobenzyl)-2-(3-methyl-1,2-dioxaspiro[4.5]decan-3-yl)acetamide
• 英文别名: N-[(4-bromo-2-fluorophenyl)methyl]-2-(3-methyl-1,2-dioxaspiro[4.5]decan-3-yl)acetamide
• CAS: 1194839-43-4
• 化学式: C₁₈H₂₃BrFNO₃
• 分子量: 400.288
• InChiKey: KJBIXUOGFIZTTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(3-methyl-1,2-dioxaspiro[4.5]decan-3-yl)acetic acid 、 4-溴-2-氟苄胺 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以58%的产率得到N-(4-bromo-2-fluorobenzyl)-2-(3-methyl-1,2-dioxaspiro[4.5]decan-3-yl)acetamide
  参考文献：
  名称：

  Synthesis and in vitro DMPK profiling of a 1,2-dioxolane-based library with activity against Plasmodium falciparum

  摘要：

  A 43-member 1,2-dioxolane library was synthesized by coupling a 1,2-dioxolane-3-acetic acid derivative to a range of amines. Ten compounds had EC(50)s <= 30 nM against Plasmodium falciparum 3D7 and Dd2 strains, and another 15 compounds had EC(50)s <= 50 nM against both 3D7 and Dd2. The library was then subjected to a range of in vitro DMPK assays, which revealed that side chains with a heteroatom were required for favorable solubility, Log D and membrane permeability. CYP450 inhibition was isoform dependent, with 2C19 and 3A4 particularly susceptible, and the majority of compounds tested against rat and human microsomes were metabolized rapidly. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.024

文献信息

• Synthesis and in vitro DMPK profiling of a 1,2-dioxolane-based library with activity against Plasmodium falciparum
  作者：Derek C. Martyn、Galina Beletsky、Joseph F. Cortese、Erin Tyndall、Hanlan Liu、Maria M. Fitzgerald、Thomas J. O’Shea、Beirong Liang、Jon Clardy

  DOI：10.1016/j.bmcl.2009.08.024

  日期：2009.10

  A 43-member 1,2-dioxolane library was synthesized by coupling a 1,2-dioxolane-3-acetic acid derivative to a range of amines. Ten compounds had EC(50)s <= 30 nM against Plasmodium falciparum 3D7 and Dd2 strains, and another 15 compounds had EC(50)s <= 50 nM against both 3D7 and Dd2. The library was then subjected to a range of in vitro DMPK assays, which revealed that side chains with a heteroatom were required for favorable solubility, Log D and membrane permeability. CYP450 inhibition was isoform dependent, with 2C19 and 3A4 particularly susceptible, and the majority of compounds tested against rat and human microsomes were metabolized rapidly. (C) 2009 Elsevier Ltd. All rights reserved.