dynole 34-2 | 1128165-88-7

• 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: dynole 34-2
• 英文别名: 2-Cyano-3-{1-[3-(dimethylamino)propyl]indol-3-YL}-N-octylprop-2-enamide；2-cyano-3-[1-[3-(dimethylamino)propyl]indol-3-yl]-N-octylprop-2-enamide
• CAS: 1128165-88-7
• 化学式: C₂₅H₃₆N₄O
• 分子量: 408.587
• InChiKey: MYIMRONQBLZJFI-UHFFFAOYSA-N

物化性质

• 熔点：
  105-106 °C(Solv: ethanol (64-17-5))
• 沸点：
  613.5±55.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  61.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P501,P270,P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313,P301+P312+P330
• 危险性描述：
  H302,H315,H319

反应信息

• 作为反应物：
  描述：

  dynole 34-2 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92%的产率得到2-cyano-3-[1-[3-(dimethylamino)propyl]indol-3-yl]-N-octylpropanamide
  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
• 作为产物：
  描述：

  1-(3-dimethylaminopropyl)-1H-indole-3-carbaldehyde 、 2-氰基-N-辛基-乙酰胺 在 哌啶 作用下， 以 乙醇 为溶剂， 以67%的产率得到dynole 34-2
  参考文献：
  名称：

  Inhibition of Dynamin Mediated Endocytosis by the Dynoles—Synthesis and Functional Activity of a Family of Indoles

  摘要：

  Screening identified two bisindolylmaleimides as 100 mu M inhibitors of the GTPase activity of dynamin I. Focused library approaches allowed development of indole-based dynamin inhibitors called dynoles. 100-Fold in vitro enhancement of potency was noted with the best inhibitor, 2-cyano-3-(1-(2-(dimethylamino)ethyl)- 1H-indol-3-yl)-N-octylacrylamide (dynole 34-2), a 1.3 +/- 0.3 mu M dynamin I inhibitor. Dynole 34-2 potently inhibited receptor mediated endocytosis (RME) internalization of Texas red-transferrin. The rank order of potency for a variety of dynole analogues on RME in U2OS cells matched their rank order for dynamin inhibition, suggesting that the mechanism of inhibition is via dynamin. Dynoles are the most active dynamin I inhibitors reported for in vitro or RME evaluations. Dynole 34-2 is 15-fold more active than dynasore against dynamin I and 6-fold more active against dynamin mediated RME (IC50 similar to 15 mu M; RME IC50 similar to 80 mu M). The dynoles represent a new series of tools to better probe endocytosis and dynamin-mediated trafficking events in a variety of cells.

  DOI：

  10.1021/jm900036m

文献信息

• Inhibition of Dynamin Mediated Endocytosis by the <i>Dynoles</i>—Synthesis and Functional Activity of a Family of Indoles
  作者：Timothy A. Hill、Christopher P. Gordon、Andrew B. McGeachie、Barbara Venn-Brown、Luke R. Odell、Ngoc Chau、Annie Quan、Anna Mariana、Jennette A. Sakoff、Megan Chircop (nee Fabbro)、Phillip J. Robinson、Adam McCluskey

  DOI：10.1021/jm900036m

  日期：2009.6.25

  Screening identified two bisindolylmaleimides as 100 mu M inhibitors of the GTPase activity of dynamin I. Focused library approaches allowed development of indole-based dynamin inhibitors called dynoles. 100-Fold in vitro enhancement of potency was noted with the best inhibitor, 2-cyano-3-(1-(2-(dimethylamino)ethyl)- 1H-indol-3-yl)-N-octylacrylamide (dynole 34-2), a 1.3 +/- 0.3 mu M dynamin I inhibitor. Dynole 34-2 potently inhibited receptor mediated endocytosis (RME) internalization of Texas red-transferrin. The rank order of potency for a variety of dynole analogues on RME in U2OS cells matched their rank order for dynamin inhibition, suggesting that the mechanism of inhibition is via dynamin. Dynoles are the most active dynamin I inhibitors reported for in vitro or RME evaluations. Dynole 34-2 is 15-fold more active than dynasore against dynamin I and 6-fold more active against dynamin mediated RME (IC50 similar to 15 mu M; RME IC50 similar to 80 mu M). The dynoles represent a new series of tools to better probe endocytosis and dynamin-mediated trafficking events in a variety of cells.
• 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.