TR100 | 1128165-86-5

• 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: TR100
• 英文别名: 2-cyano-3-[1-[3-(dimethylamino)propyl]-2-methylindol-3-yl]-N-octylprop-2-enamide
• CAS: 1128165-86-5
• 化学式: C₂₆H₃₈N₄O
• 分子量: 422.614
• InChiKey: XXRLIGWROLDOLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.29
• 重原子数：
  31.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  61.06
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  TR100 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)-2-methyl-1H-indol-3-yl)-N-octylpropylamide
  参考文献：
  名称：

  发现基于丙烯腈的小分子，对弯曲杆菌有抑制作用

  摘要：

  我们报告了一系列丙烯腈-含分子和α氨基酰胺，其导致99-100％致死的的发现捻转血矛线虫。在研究的22种丙烯腈类似物中，活性最高的是2-氰基-3- [1-（3-二甲基氨基丙基）-2-甲基-1 H-吲哚-3-基] -N-己基丙烯酰胺（13a），2-氰基-3- [1（2-二甲基氨基乙基）-2-甲基-1 H-吲哚-3-基] -N-己基丙烯酰胺（13b），2-氰基-3- {4- [3-（二甲基氨基）丙氧基]苯基} -N-辛基丙烯酰胺（21）和2-氰基-3- {1- [3- [二甲基氨基）丙基] -1 H-吡咯-2-基} -N-辛基丙烯酰胺（22）分别显示LD 50值<15μM，而α-氨基酰胺甲基-2- [2-（2-（2-苯甲酰基苯基氨基）-2-（4-甲氧基苯基）乙酰胺基]乙酸酯（12a）的LD 50值为10μM 。丙烯腈类似物（13a，13b，21和22）对9种癌细胞系的细胞毒性筛选显示中等至高细

  DOI：

  10.1039/c3md00255a
• 作为产物：
  描述：

  1-(3-(dimethylamino)propyl)-2-methyl-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， 反应 3.0h， 以52%的产率得到TR100
  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.
• Discovery of acrylonitrile-based small molecules active against Haemonchus contortus
  作者：Christopher P. Gordon、Lacey Hizartzidis、Mark Tarleton、Jennette A. Sakoff、Jayne Gilbert、Bronwyn E. Campbell、Robin B. Gasser、Adam McCluskey

  DOI：10.1039/c3md00255a

  日期：——

  99–100% lethality in H. contortus. Of the 22 acrylonitrile analogues investigated, the most active were 2-cyano-3-[1-(3-dimethylaminopropyl)-2-methyl-1H-indol-3-yl]-N-hexylacrylamide (13a), 2-cyano-3-[1(2-dimethylaminoethyl)-2-methyl-1H-indol-3-yl]-N-hexylacrylamide (13b), 2-cyano-3-4-[3-(dimethylamino)propoxy]phenyl}-N-octylacrylamide (21), and 2-cyano-3-1-[3-(dimethylamino)propyl]-1H-pyrrol-2-yl}-N-octylacrylamide

  我们报告了一系列丙烯腈-含分子和α氨基酰胺，其导致99-100％致死的的发现捻转血矛线虫。在研究的22种丙烯腈类似物中，活性最高的是2-氰基-3- [1-（3-二甲基氨基丙基）-2-甲基-1 H-吲哚-3-基] -N-己基丙烯酰胺（13a），2-氰基-3- [1（2-二甲基氨基乙基）-2-甲基-1 H-吲哚-3-基] -N-己基丙烯酰胺（13b），2-氰基-3- 4- [3-（二甲基氨基）丙氧基]苯基} -N-辛基丙烯酰胺（21）和2-氰基-3- 1- [3- [二甲基氨基）丙基] -1 H-吡咯-2-基} -N-辛基丙烯酰胺（22）分别显示LD 50值<15μM，而α-氨基酰胺甲基-2- [2-（2-（2-苯甲酰基苯基氨基）-2-（4-甲氧基苯基）乙酰胺基]乙酸酯（12a）的LD 50值为10μM 。丙烯腈类似物（13a，13b，21和22）对9种癌细胞系的细胞毒性筛选显示中等至高细