N-benzo[1,3]dioxol-5-yl-2-(3-formylindol-1-yl)acetamide | 294889-52-4

• 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-benzo[1,3]dioxol-5-yl-2-(3-formylindol-1-yl)acetamide
• 英文别名: N-Benzo[1,3]dioxol-5-yl-2-(3-formyl-indol-1-yl)-acetamide；N-(1,3-benzodioxol-5-yl)-2-(3-formylindol-1-yl)acetamide
• CAS: 294889-52-4
• 化学式: C₁₈H₁₄N₂O₄
• mdl: MFCD01785703
• 分子量: 322.32
• InChiKey: UNHDLLXYRPABOZ-UHFFFAOYSA-N

物化性质

• 沸点：
  602.7±55.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)
• 溶解度：
  0.4 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  2-氰基-N-辛基-乙酰胺 、 N-benzo[1,3]dioxol-5-yl-2-(3-formylindol-1-yl)acetamide 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 0.33h， 以79%的产率得到3-(1-(2-benzo[d][1,3]dioxol-5-yl-amino-2-oxoethyl)-1H-indol-3-yl)-2-cyano-N-octylacrylamide
  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

• [EN] NOVEL INDOLINONE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'INDOLINONE
  申请人：LEO PHARMA AS

  公开号：WO2006105796A1

  公开（公告）日：2006-10-12

  [EN] The invention relates to novel indolinone derivatives of formula (I), wherein X, R1, R2, R3, R4, R5, Re, Ri', Ri , FV/ R4'/ FV and R6' are as shown herein, as well as their use in the treatment of inflammatory autoimmune diseases, in particular by administration via the oral route.
  [FR] La présente invention concerne de nouveaux dérivés d'indolinone de formule (I) où X, R1, R2, R3, R4, R5, Re, Ri', Ri, FV/ R4'/ FV et R6' sont tels que présentés dans la présente invention, ainsi que leur application au traitement de maladies inflammatoires auto-immunes, en particulier par administration par voie orale.
• 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.