N-[[1-[3-(dimethylamino)propyl]indol-3-yl]methyl]tetradecan-1-amine | 1416313-74-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-[[1-[3-(dimethylamino)propyl]indol-3-yl]methyl]tetradecan-1-amine
• CAS: 1416313-74-0
• 化学式: C₂₈H₄₉N₃
• 分子量: 427.717
• InChiKey: FHXHUSJGTRNFBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  31
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 50.0 ℃ 、5.0 MPa 条件下， 以0.54 mg的产率得到N-[[1-[3-(dimethylamino)propyl]indol-3-yl]methyl]tetradecan-1-amine
  参考文献：
  名称：

  Development of Second-Generation Indole-Based Dynamin GTPase Inhibitors

  摘要：

  Focused library development of our lead 2-cyano-3-(1-(3-(dimethylamino)-propyl)-2-methyl-1H-indol-3-yl)-N-octylacrylamide (2) confirmed the tertiary dimethylamino-propyl moiety as critical for inhibition of dynamin GTPase. The cyanoamide moiety could be replaced with a thiazole-4(5H)-one isostere (19, IC50(dyn I) = 7.7 mu M), reduced under flow chemistry conditions (20, IC50(dyn I) = 5.2 mu M) or replaced by a simple amine. The latter provided a basis for a high yield library of compounds via a reductive amination by flow hydrogenation. Two compounds, 24 (IC50(dyn I) = 0.56 mu M) and 25 (IC50(dyn I) = 0.76 mu M), stood out. Indole 24 is nontoxic and showed increased potency against dynamin I and II in vitro and in cells (IC50(CME) = 1.9 mu M). It also showed 4.4-fold selectivity for dynamin I. The indole 24 compound has improved isoform selectivity and is the most active in-cell inhibitor of clathrin-mediated endocytosis reported to date.

  DOI：

  10.1021/jm300844m

文献信息

• Development of Second-Generation Indole-Based Dynamin GTPase Inhibitors
  作者：Christopher P. Gordon、Barbara Venn-Brown、Mark J. Robertson、Kelly A. Young、Ngoc Chau、Anna Mariana、Ainslie Whiting、Megan Chircop、Phillip J. Robinson、Adam McCluskey

  DOI：10.1021/jm300844m

  日期：2013.1.10

  Focused library development of our lead 2-cyano-3-(1-(3-(dimethylamino)-propyl)-2-methyl-1H-indol-3-yl)-N-octylacrylamide (2) confirmed the tertiary dimethylamino-propyl moiety as critical for inhibition of dynamin GTPase. The cyanoamide moiety could be replaced with a thiazole-4(5H)-one isostere (19, IC50(dyn I) = 7.7 mu M), reduced under flow chemistry conditions (20, IC50(dyn I) = 5.2 mu M) or replaced by a simple amine. The latter provided a basis for a high yield library of compounds via a reductive amination by flow hydrogenation. Two compounds, 24 (IC50(dyn I) = 0.56 mu M) and 25 (IC50(dyn I) = 0.76 mu M), stood out. Indole 24 is nontoxic and showed increased potency against dynamin I and II in vitro and in cells (IC50(CME) = 1.9 mu M). It also showed 4.4-fold selectivity for dynamin I. The indole 24 compound has improved isoform selectivity and is the most active in-cell inhibitor of clathrin-mediated endocytosis reported to date.