{6-[N'-(5-acetylamino-2-methoxybenzoyl)hydrazino]-5-amino-6-oxohexyl}carbamic acid benzyl ester trifluoroacetate | 1258973-72-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: {6-[N'-(5-acetylamino-2-methoxybenzoyl)hydrazino]-5-amino-6-oxohexyl}carbamic acid benzyl ester trifluoroacetate
• CAS: 1258973-72-6
• 化学式: C₂HF₃O₂*C₂₄H₃₁N₅O₆
• 分子量: 599.564
• InChiKey: APGGUQLNRIXCPX-BDQAORGHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.47
• 重原子数：
  42.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  198.18
• 氢给体数：
  6.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  {6-[N'-(5-acetylamino-2-methoxybenzoyl)hydrazino]-5-amino-6-oxohexyl}carbamic acid benzyl ester trifluoroacetate 在 哌啶 、 N-羟基-7-氮杂苯并三氮唑 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 tert-butyl N-[(1S)-1-[(3R,4R)-3-[(2S)-2-[[(1S)-1-[[(5-acetamido-2-methoxybenzoyl)amino]carbamoyl]-5-(benzyloxycarbonylamino)pentyl]carbamoyl]pyrrolidin-1-yl]-4-(p-tolylsulfonylamino)piperidine-1-carbonyl]-2-methylpropyl]carbamate
  参考文献：
  名称：

  Structure-activity relationships of β-hairpin mimics as modulators of amyloid β-peptide aggregation

  摘要：

  Aggregation of amyloid proteins is currently involved in more than 20 serious human diseases that are actually untreated, such as Alzheimer's disease (AD). Despite many efforts made to target the amyloid cascade in AD, finding an aggregation inhibiting compound and especially modulating early oligomerization remains a relevant and challenging strategy. We report herein the first examples of small and non peptide mimics of acyclic beta-hairpins, showing an ability to delay the fibrillization of amyloid-beta (A beta(1-42)) peptide and deeply modify its early oligomerization process. Modifications providing better drugg-ability properties such as increased hydrophilicity and reduced peptidic character were performed. We also demonstrate that an appropriate balance between flexibility and stability of the beta-hairpin must be reached to adapt to the different shape of the various aggregated forms of the amyloid peptide. This strategy can be investigated to target other challenging amyloid proteins. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.05.018
• 作为产物：
  描述：

  N-(3-hydrazinocarbonyl-4-methoxyphenyl)acetamide 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 {6-[N'-(5-acetylamino-2-methoxybenzoyl)hydrazino]-5-amino-6-oxohexyl}carbamic acid benzyl ester trifluoroacetate
  参考文献：
  名称：

  寻求第一个野生型和突变的HIV-1蛋白酶二聚化的非肽类分子钳抑制剂

  摘要：

  在这里，我们描述了16种带有萘基支架的新型拟肽分子钳的合成及其对HIV-1蛋白酶（PR）的抑制活性。它们的肽特性逐渐降低。这些分子的两表现出对于被HIV-1野生型和multimutated ANAM-11蛋白酶迄今为止获得这个类分子（〜40 n中的二聚化最好抑制活性中号为野生型PR和100 n中中号为ANAM-11 PR ）。尽管一个分子钳的肽特性被完全抑制，但仍保持了对两种蛋白酶的抑制机理和抑制效力。

  DOI：

  10.1002/cmdc.201000308

文献信息

• Designed Glycopeptidomimetics Disrupt Protein–Protein Interactions Mediating Amyloid β-Peptide Aggregation and Restore Neuroblastoma Cell Viability
  作者：Julia Kaffy、Dimitri Brinet、Jean-Louis Soulier、Isabelle Correia、Nicolo Tonali、Katia Fabiana Fera、Yasmine Iacone、Anaïs R. F. Hoffmann、Lucie Khemtémourian、Benoit Crousse、Mark Taylor、David Allsop、Myriam Taverna、Olivier Lequin、Sandrine Ongeri

  DOI：10.1021/acs.jmedchem.5b01629

  日期：2016.3.10

  How anti-Alzheimer's drug candidates that reduce amyloid 1-42 peptide fibrillization interact with the most neurotoxic species is far from being understood. We report herein the capacity of sugar-based peptidomimetics to inhibit both A beta(1-42) early oligomerization and fibrillization. A wide range of bio- and physicochemical techniques, such as a new capillary electrophoresis method, nuclear magnetic resonance, and surface plasmon resonance, were used to identify how these new molecules can delay the aggregation of A beta(1-42). We demonstrate that these molecules interact with soluble oligomers in order to maintain the presence of nontoxic monomers and to prevent fibrillization. These compounds totally suppress the toxicity of A beta(1-42) toward SH-SYSY neuroblastoma cells, even at substoichiometric concentrations. Furthermore, demonstration that the best molecule combines hydrophobic moieties, hydrogen bond donors and acceptors, ammonium groups, and a hydrophilic beta-sheet breaker element provides valuable insight for the future structure-based design of inhibitors of A beta(1-42) aggregation.