benzyl ((S)-6-azido-1-(((S)-1-(((S)-1-hydroxy-3-(4-(prop-2-yn-1-yloxy)phenyl)propan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxohexan-2-yl)carbamate | 1359969-83-7

• 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: benzyl ((S)-6-azido-1-(((S)-1-(((S)-1-hydroxy-3-(4-(prop-2-yn-1-yloxy)phenyl)propan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxohexan-2-yl)carbamate
• 英文别名: Cbz-Nle(N3)-Phe-Tyr(prop-2-ynyl)(prop-2-ynyl)-ol；benzyl N-[(2S)-6-azido-1-[[(2S)-1-[[(2S)-1-hydroxy-3-(4-prop-2-ynoxyphenyl)propan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxohexan-2-yl]carbamate
• CAS: 1359969-83-7
• 化学式: C₃₅H₄₀N₆O₆
• 分子量: 640.739
• InChiKey: HVGDBUPOIRZTLX-GOBOWQCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  47
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  benzyl ((S)-6-azido-1-(((S)-1-(((S)-1-hydroxy-3-(4-(prop-2-yn-1-yloxy)phenyl)propan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxohexan-2-yl)carbamate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 copper(I) bromide 作用下， 以 二氯甲烷 为溶剂， 反应 7.25h， 以75%的产率得到benzyl N-[(12S,15S,18S)-15-benzyl-18-(hydroxymethyl)-13,16-dioxo-2-oxa-5,6,7,14,17-pentaazatricyclo[18.2.2.1(4,7)]pentacosa-1(22),4(25),5,20,23-pentaen-12-yl]carbamate
  参考文献：
  名称：

  New β-Strand Templates Constrained by Huisgen Cycloaddition

  摘要：

  New peptidic templates constrained into a beta-strand geometry by linking acetylene and azide containing P-1 and P-3 residues of a tripeptide by Huisgen cycloaddition are presented. The conformations of the macrocycles are defined by NMR studies and those that best define a beta-strand are shown to be potent inhibitors of the protease calpain. The beta-strand templates presented and defined here are prepared under optimized conditions that should be suitable for targeting a range of proteases and other applications requiring such a geometry.

  DOI：

  10.1021/ol3002199
• 作为产物：
  描述：

  Boc-L-酪氨酸甲酯 在 sodium tetrahydroborate 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.5h， 生成 benzyl ((S)-6-azido-1-(((S)-1-(((S)-1-hydroxy-3-(4-(prop-2-yn-1-yloxy)phenyl)propan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxohexan-2-yl)carbamate
  参考文献：
  名称：

  New β-Strand Templates Constrained by Huisgen Cycloaddition

  摘要：

  New peptidic templates constrained into a beta-strand geometry by linking acetylene and azide containing P-1 and P-3 residues of a tripeptide by Huisgen cycloaddition are presented. The conformations of the macrocycles are defined by NMR studies and those that best define a beta-strand are shown to be potent inhibitors of the protease calpain. The beta-strand templates presented and defined here are prepared under optimized conditions that should be suitable for targeting a range of proteases and other applications requiring such a geometry.

  DOI：

  10.1021/ol3002199

文献信息

• Synthesis and Extended Activity of Triazole-Containing Macrocyclic Protease Inhibitors
  作者：Ashok D. Pehere、Markus Pietsch、Michael Gütschow、Paul M. Neilsen、Daniel Sejer Pedersen、Steven Nguyen、Ondrej Zvarec、Matthew J. Sykes、David F. Callen、Andrew D. Abell

  DOI：10.1002/chem.201204260

  日期：2013.6.10

  Peptide‐derived protease inhibitors are an important class of compounds with the potential to treat a wide range of diseases. Herein, we describe the synthesis of a series of triazole‐containing macrocyclic protease inhibitors pre‐organized into a β‐strand conformation and an evaluation of their activity against a panel of proteases. Acyclic azido–alkyne‐based aldehydes are also evaluated for comparison

  肽源蛋白酶抑制剂是一类重要的化合物，具有治疗多种疾病的潜力。本文中，我们描述了一系列预组织为β-链构象的含三唑的大环蛋白酶抑制剂的合成及其对一组蛋白酶的活性评估。还评估了基于无环叠氮基-炔烃的醛作比较。大环肽模拟物对钙蛋白酶II，组织蛋白酶L和S以及20S蛋白酶体胰凝乳蛋白酶样活性表现出相当大的活​​性。鉴定了组织蛋白酶S的强效大环抑制剂的一些第一个实例。它们采用了明确定义的β链几何结构，如NMR光谱，X射线分析和分子对接研究所示。
• New β-Strand Templates Constrained by Huisgen Cycloaddition
  作者：Ashok D. Pehere、Andrew D. Abell

  DOI：10.1021/ol3002199

  日期：2012.3.2

  New peptidic templates constrained into a beta-strand geometry by linking acetylene and azide containing P-1 and P-3 residues of a tripeptide by Huisgen cycloaddition are presented. The conformations of the macrocycles are defined by NMR studies and those that best define a beta-strand are shown to be potent inhibitors of the protease calpain. The beta-strand templates presented and defined here are prepared under optimized conditions that should be suitable for targeting a range of proteases and other applications requiring such a geometry.