Z-苯丙氨酰-丙氨酰-重氮基甲基甲酮 | 71732-53-1

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丙氨酸类衍生物
• 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
• 中文名称: Z-苯丙氨酰-丙氨酰-重氮基甲基甲酮
• 中文别名: 苄氧甲酰基-L-苯丙酰氨基-L-丙氨酸-D-二氮甲烷
• 英文名称: Z-Phe-Ala-diazomethylketone
• 英文别名: Benzyloxycarbonylphenylalanylalanine diazomethyl ketone；benzyl N-[(2S)-1-[[(2S,4E)-4-diazo-3-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 71732-53-1
• 化学式: C₂₁H₂₂N₄O₄
• mdl: MFCD00077029
• 分子量: 394.43
• InChiKey: QMPATRQNERZOMF-YJBOKZPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.238
• 拓扑面积：
  86.5
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 储存条件：
  -15°C

制备方法与用途

Z-Phe-Ala-二甲基卡托内与Aβ42单体和小低聚物直接结合。它还能抑制溶液中Aβ42十二聚体及原纤维的形成，展现出在神经退行性疾病研究方面的潜在价值。

反应信息

• 作为反应物：
  描述：

  Z-苯丙氨酰-丙氨酰-重氮基甲基甲酮 在 氢溴酸 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 0.02h， 生成 Cbz-Phe-Ala-CH2Br
  参考文献：
  名称：

  Modulation of the inhibitor properties of dipeptidyl (acyloxy)methyl ketones toward the CaaX proteases

  摘要：

  Dipeptidyl (acyloxy) methyl ketones (AOMKs) have been identified as mechanism-based inhibitors of certain cysteine proteases. These compounds are also inhibitors of the integral membrane proteins Rce1p and Ste24p, which are proteases that independently mediate a cleavage step associated with the maturation of certain isoprenylated proteins. The enzymatic mechanism of Rce1p is ill-defined, whereas Ste24p is a zinc metalloprotease. Rce1p is required for the proper processing of the oncoprotein Ras and is viewed as a potential target for cancer therapy. In this study, we synthesized a small library of dipeptidyl AOMKs to investigate the structural elements that contribute to the inhibitor properties of this class of molecules toward Rce1p and Ste24p. The compounds were evaluated using a fluorescence-based in vitro proteolysis assay. The most potent dipeptidyl AOMKs contained an arginine residue and the identity of the benzoate group strongly influenced potency. A 'warhead' free AOMK inhibited Rce1p and Ste24p. The data suggest that the dipeptidyl AOMKs are not mechanism-based inhibitors of Rce1p and Ste24p and corroborate the hypothesis that Rce1p is not a cysteine protease. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.041
• 作为产物：
  描述：

  (S)-methyl 2-((S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanamido)propanoate 在 N-甲基吗啉 、 lithium hydroxide monohydrate 、 水 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 生成 Z-苯丙氨酰-丙氨酰-重氮基甲基甲酮
  参考文献：
  名称：

  有效的阿扎肽肽腈抑制剂和基于活性的探针作为有希望的抗布鲁氏锥虫药物的设计，合成和生物学评估

  摘要：

  克鲁氏锥虫和布鲁氏锥虫分别是引起南美锥虫病和非洲昏睡病的寄生虫。由于缺乏足够的治疗方法和新出现的耐药性，迫切需要开发针对这两种疾病的新药。发现针对寄生虫疾病的小分子疗法的一种有前途的策略是针对主要的半胱氨酸蛋白酶，例如克鲁氏杆菌（T. cruzi）的克鲁萨因（cruzin）和布鲁氏杆菌（T. brucei）的rhodesain / TbCatB 。。Azadipeptide腈属于一类新型的强力半胱氨酸蛋白酶抑制剂，可抵抗木瓜蛋白酶。我们在此报告了一系列含氮杂腈的化合物的设计，合成和评估，其中大多数化合物在低纳摩尔/皮摩尔范围内均能有效抑制重组克鲁萨因和罗德萨因。观察到罗丹素的抑制作用（即基于靶标的筛查）和该化合物的锥虫杀灭活性（即基于全生物的筛查）之间具有很强的相关性。为便于对该重要抑制剂类别的详细研究，我们将从筛选中选择的命中化合物化学转化为基于活性的探针（ABP），布氏锥虫。总体而言，

  DOI：

  10.1002/chem.201103322

文献信息

• Enantiopure N-protected α-amino glyoxals 1. Synthesis from α-amino acids and some condensation reactions with amines
  作者：Paul Darkins、Michelle Groarke、M. Anthony McKervey、Hazel M. Moncrieff、Noreen McCarthy、Mark Nieuwenhuyzen

  DOI：10.1039/a907948c

  日期：——

  N-protected α-amino diazoketones has been prepared from L-amino acids and dipeptides and used as precursors in the synthesis of novel N-protected α-amino glyoxals via oxidation with distilled dimethyldioxirane (DMD) in acetone. The glyoxals have been converted, without purification, into enantiopure imines, pyrazines, quinoxalines, and pyrido[2,3-b]pyrazines via condensation with the appropriate amine or

  由L-氨基酸制备了一系列N-保护的α-氨基重氮酮。二肽并用作新颖的合成的前体Ñ -保护的α氨基乙二醛经由 氧化作用 与蒸馏的二甲基二环氧乙烷（DMD） 丙酮。乙二醛已经转化，没有纯化，变成对映体 亚胺， 吡嗪，喹喔啉和吡啶并[2,3- b ]吡嗪通过与适当的缩合反应胺 或者 二胺。吡啶并[2,3- b ]吡嗪的分子结构N -Cbz- L-苯丙氨酸 由...决定 X射线分析。
• Oxidation of α-diazoketones derived from<scp>L</scp>-amino acids and dipeptides using dimethyldioxirane. Synthesis and reactions of homochiral N-protected α-amino glyoxals
  作者：Paul Darkins、Noreen McCarthy、M. Anthony McKervey、Tao Ye

  DOI：10.1039/c39930001222

  日期：——

  Homochiral N-protected α-amino glyoxals are readily accessible by oxidation of α-diazoketones derived from natural amino acids and dipeptides using dimethyldioxirane in acetone; the glyoxals can be trapped efficiently in reactions such as Wittig olefination and condensation with amines and vicinal diamines.

  在丙酮中使用二甲基二氧环己烷氧化从天然氨基酸和二肽中提取的δ±-二氮酮，很容易获得同手性 N 保护的δ±-氨基乙二醛；乙二醛可以在诸如维蒂希油化反应以及与胺和邻位二胺的缩合反应中被有效地捕获。
• Materials for cathepsin B enhancement and methods of use
  申请人：The University of North Carolina at Pembroke

  公开号：US10702571B2

  公开（公告）日：2020-07-07

  The present invention provides methods for treating a subject afflicted with a protein accumulation disease or TBI, comprising administering to the subject at least one compound that increases the level of active cathepsin B in cells of the subject, or a pharmaceutically acceptable salt or ester thereof, in an amount that is effective to treat the subject. The present invention also provides compositions for treating a subject afflicted with a protein accumulation disease or TBI.

  本发明提供了治疗受蛋白蓄积症或创伤性脑损伤困扰的受试者的方法，包括向受试者施用至少一种可增加受试者细胞中活性酪蛋白B水平的化合物或其药学上可接受的盐或酯，其用量对治疗受试者有效。本发明还提供了用于治疗蛋白蓄积症或创伤性脑损伤患者的组合物。
• Evacuated blood collection tubes containing protease inhibitors for the assessment of contact system activation
  申请人：Dyax Corp.

  公开号：US10870115B2

  公开（公告）日：2020-12-22

  Disclosed herein are evacuated blood collection tubes comprising protease inhibitor cocktails in liquid form and uses thereof for assessing features associated with the contact system in a subject, including the endogenous level of contact system activation, the endogenous level of a drug that targets a component of contact system during treatment, and/or the immunogenicity of such a drug.

  本文公开了包含液态蛋白酶抑制剂鸡尾酒的抽真空采血管及其用途，用于评估受试者体内与接触系统相关的特征，包括接触系统活化的内源性水平、治疗过程中针对接触系统成分的药物的内源性水平和/或此类药物的免疫原性。
• Synthesis of amino acid-derived imidazoles from enantiopure N-protected α-amino glyoxals
  作者：Michelle Groarke、M.Anthony McKervey、Mark Nieuwenhuyzen

  DOI：10.1016/s0040-4039(99)02267-4

  日期：2000.2

  A range of novel imidazoles, including three histidine derivatives, with chiral side chains derived from amino acids and dipeptides have been synthesised from N-Cbz-protected alpha-amino glyoxals. (C) 2000 Elsevier Science Ltd. All rights reserved.