N''-{3-(R)-[2-(S)-(1H-indol-3-yl)-1-(methylcarbamoyl)-ethylcarbamoyl]-5-methylhexanoyl}-hydrazide | 573976-91-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N''-{3-(R)-[2-(S)-(1H-indol-3-yl)-1-(methylcarbamoyl)-ethylcarbamoyl]-5-methylhexanoyl}-hydrazide
• 英文别名: (2R)-2-(2-hydrazinyl-2-oxoethyl)-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-4-methylpentanamide
• CAS: 573976-91-7
• 化学式: C₂₀H₂₉N₅O₃
• 分子量: 387.482
• InChiKey: UQQMFHHUUGVIPE-DYVFJYSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  129
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  十六烷基磺酰氯 、 N''-{3-(R)-[2-(S)-(1H-indol-3-yl)-1-(methylcarbamoyl)-ethylcarbamoyl]-5-methylhexanoyl}-hydrazide 在 碳酸氢钠 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 6.0h， 以25%的产率得到N'-{3-(R)-[2-(S)-(1H-indol-3-yl)-1-(methylcarbamoyl)-ethylcarbamoyl]-5-methylhexanoyl}-N-hexadecanesulfonylhydrazide
  参考文献：
  名称：

  Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with improved selectivity

  摘要：

  Hydrazide derivatives of Ilomastat, carrying either aryl groups or distinct alkyl and arylsulfonyl moieties were synthesized and evaluated for their MMP inhibitory activity. Potent and selective MMP-9 inhibition (IC50 = 3 nM) was observed for compound 3m (arylsulfonyl group: 4-(4-Br-C6H4)-C6H4-SO2-). Interaction with the S-2 enzyme subsite is mainly responsible for the inhibitory properties of this derivative as confirmed by molecular docking computation. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.041
• 作为产物：
  描述：

  (R)-3-[(S)-2-(1H-Indol-3-yl)-1-methylcarbamoyl-ethylcarbamoyl]-5-methyl-hexanoic acid 在 N-甲基吗啉 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 、 肼 作用下， 以 四氢呋喃 为溶剂， 以45%的产率得到N''-{3-(R)-[2-(S)-(1H-indol-3-yl)-1-(methylcarbamoyl)-ethylcarbamoyl]-5-methylhexanoyl}-hydrazide
  参考文献：
  名称：

  Improved gelatinase a selectivity by novel zinc binding groups containing galardin derivatives

  摘要：

  The synthesis of several analogues of galardin, a MMP inhibitor, are presented with their in vitro inhibitory activity against MMP-1 and MMP-2. These compounds contain a distinct Zinc Binding Group (ZBG). Those having a 2-acylated-heterocycle as well as a 2-arylamide function do not exhibit a good inhibition/selectivity against the enzymes tested. On the contrary, those that are based on a hydrazide scaffold present potent selectivity for MMP-2 versus MMP-1. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00214-2

文献信息

• Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with improved selectivity
  作者：Gwennaël LeDour、Gautier Moroy、Matthieu Rouffet、Erika Bourguet、Dominique Guillaume、Martine Decarme、Haquima ElMourabit、Franck Augé、Alain J.P. Alix、Jean-Yves Laronze、Georges Bellon、William Hornebeck、Janos Sapi

  DOI：10.1016/j.bmc.2008.07.041

  日期：2008.9

  Hydrazide derivatives of Ilomastat, carrying either aryl groups or distinct alkyl and arylsulfonyl moieties were synthesized and evaluated for their MMP inhibitory activity. Potent and selective MMP-9 inhibition (IC50 = 3 nM) was observed for compound 3m (arylsulfonyl group: 4-(4-Br-C6H4)-C6H4-SO2-). Interaction with the S-2 enzyme subsite is mainly responsible for the inhibitory properties of this derivative as confirmed by molecular docking computation. (C) 2008 Elsevier Ltd. All rights reserved.
• Improved gelatinase a selectivity by novel zinc binding groups containing galardin derivatives
  作者：Franck Augé、William Hornebeck、Martine Decarme、Jean-Yves Laronze

  DOI：10.1016/s0960-894x(03)00214-2

  日期：2003.5

  The synthesis of several analogues of galardin, a MMP inhibitor, are presented with their in vitro inhibitory activity against MMP-1 and MMP-2. These compounds contain a distinct Zinc Binding Group (ZBG). Those having a 2-acylated-heterocycle as well as a 2-arylamide function do not exhibit a good inhibition/selectivity against the enzymes tested. On the contrary, those that are based on a hydrazide scaffold present potent selectivity for MMP-2 versus MMP-1. (C) 2003 Elsevier Science Ltd. All rights reserved.