2-benzyloxycarbonylamino-3-biphenyl-4-ylpropionic acid | 270568-72-4

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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
• 英文名称: 2-benzyloxycarbonylamino-3-biphenyl-4-ylpropionic acid
• 英文别名: (S)-N-Cbz-(4-phenyl)phenylalanine；Cbz-4-biphenyl-L-ala；(2S)-2-(phenylmethoxycarbonylamino)-3-(4-phenylphenyl)propanoic acid
• CAS: 270568-72-4
• 化学式: C₂₃H₂₁NO₄
• 分子量: 375.424
• InChiKey: ZZIBVIHXEMIHEQ-NRFANRHFSA-N

物化性质

• 沸点：
  603.0±55.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-benzyloxycarbonylamino-3-biphenyl-4-ylpropionic acid 在 4-二甲氨基吡啶 、 二碳酸二叔丁酯 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 20.0~40.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 4,4-联苯丙氨酸-1,1-二甲基乙酯
  参考文献：
  名称：

  4-联苯丙氨酸和3-苯基酪氨酸衍生的异羟肟酸作为JumonjiC领域的组蛋白去甲基化酶KDM4A的抑制剂。

  摘要：

  调节H3K9和H3K36甲基化状态的组蛋白赖氨酸脱甲基酶KDM4A的过表达与几种人类癌症的病理学有关。我们发现以前报道的基于异羟肟酸酯的组蛋白脱乙酰基酶（HDAC）抑制剂（SW55）也能够以25.4μm的IC50值弱抑制这种脱甲基酶。在这里，我们报告了该铅结构的一系列衍生物的合成和生化评估，以及两个正交的体外测定。通过对前导结构进行广泛的化学修饰，还通过利用芳基重氮盐进行自由基芳基化的多功能性，我们能够将衍生物对KDM4A的效力提高至低微摩尔范围，更重要的是，获得了对KDM4A的脱甲基酶选择性。对HDAC的尊重。

  DOI：

  10.1002/cmdc.201600218
• 作为产物：
  描述：

  Boc-L-4-溴苯丙氨酸 在 碳酸氢钠 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 2-benzyloxycarbonylamino-3-biphenyl-4-ylpropionic acid
  参考文献：
  名称：

  Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors

  摘要：

  A class of tripeptidyl transition state inhibitors containing a P1 glutamine surrogate, a P2 leucine, and a P3 arylalanines, was found to potently inhibit Norwalk virus replication in enzyme and cell based assays. An array of warheads, including aldehyde, a-ketoamide, bisulfite adduct, and a-hydroxyphosphonate transition state mimic, was also investigated. Tripeptidyls 2 and 6 possess antiviral activities against noroviruses, human rhinovirus, severe acute respiratory syndrome coronavirus, and coronavirus 229E, suggesting a broad range of antiviral activities. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.070

文献信息

• Chemical and Biological Evaluation of Dipeptidyl Boronic Acid Proteasome Inhibitors for Use in Prodrugs and Pro-Soft Drugs Targeting Solid Tumors
  作者：Lawrence J. Milo、Jack H. Lai、Wengen Wu、Yuxin Liu、Hlaing Maw、Youhua Li、Zhiping Jin、Ying Shu、Sarah E. Poplawski、Yong Wu、David G. Sanford、James L. Sudmeier、William W. Bachovchin

  DOI：10.1021/jm200460q

  日期：2011.7.14

  Bortezomib, a dipeptidyl boronic acid and potent inhibitor of the 26S proteasome, is remarkably effective against multiple myeloma (MM) but not against solid tumors. Dose-limiting adverse effects from "on target" inhibition of the proteasome in normal cells and tissues appear to be a key obstacle. Achieving efficacy against solid tumors therefore is likely to require making the inhibitor more selective for tumor tissue over normal tissues. The simplest strategy that might provide such tissue specificity would be to employ a tumor specific protease to release an inhibitor from a larger, noninhibitory structure. However, such release would necessarily generate an inhibitor with a free N-terminal amino group, raising a key question: Can short peptide boronic acids with N-terminal amino groups have the requisite properties to serve as warheads in prodrugs? Here we show that dipeptides of boroLeu, the smallest plausible candidates for the task, can indeed be sufficiently potent, cell-penetrating, cytotoxic, and stable to degradation by cellular peptidases to serve in this capacity.
• Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors
  作者：Allan M. Prior、Yunjeong Kim、Sahani Weerasekara、Meghan Moroze、Kevin R. Alliston、Roxanne Adeline Z. Uy、William C. Groutas、Kyeong-Ok Chang、Duy H. Hua

  DOI：10.1016/j.bmcl.2013.09.070

  日期：2013.12

  A class of tripeptidyl transition state inhibitors containing a P1 glutamine surrogate, a P2 leucine, and a P3 arylalanines, was found to potently inhibit Norwalk virus replication in enzyme and cell based assays. An array of warheads, including aldehyde, a-ketoamide, bisulfite adduct, and a-hydroxyphosphonate transition state mimic, was also investigated. Tripeptidyls 2 and 6 possess antiviral activities against noroviruses, human rhinovirus, severe acute respiratory syndrome coronavirus, and coronavirus 229E, suggesting a broad range of antiviral activities. (C) 2013 Elsevier Ltd. All rights reserved.
• 4-Biphenylalanine- and 3-Phenyltyrosine-Derived Hydroxamic Acids as Inhibitors of the JumonjiC-Domain-Containing Histone Demethylase KDM4A
  作者：Ludovica Morera、Martin Roatsch、Michael C. D. Fürst、Inga Hoffmann、Johanna Senger、Mirjam Hau、Henriette Franz、Roland Schüle、Markus R. Heinrich、Manfred Jung

  DOI：10.1002/cmdc.201600218

  日期：2016.9.20

  Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and H3K36 methylation states, has been related to the pathology of several human cancers. We found that a previously reported hydroxamate-based histone deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this demethylase with an IC50 value of 25.4 μm. Herein we report the synthesis and biochemical evaluations

  调节H3K9和H3K36甲基化状态的组蛋白赖氨酸脱甲基酶KDM4A的过表达与几种人类癌症的病理学有关。我们发现以前报道的基于异羟肟酸酯的组蛋白脱乙酰基酶（HDAC）抑制剂（SW55）也能够以25.4μm的IC50值弱抑制这种脱甲基酶。在这里，我们报告了该铅结构的一系列衍生物的合成和生化评估，以及两个正交的体外测定。通过对前导结构进行广泛的化学修饰，还通过利用芳基重氮盐进行自由基芳基化的多功能性，我们能够将衍生物对KDM4A的效力提高至低微摩尔范围，更重要的是，获得了对KDM4A的脱甲基酶选择性。对HDAC的尊重。