Fmoc-4-氨基苯丙氨酸 | 174132-31-1

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 苯丙氨酸类衍生物
• 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: Fmoc-4-氨基苯丙氨酸
• 中文别名: 4-(Boc-氨基)-N-Fmoc-L-苯基丙氨酸；FMOC-L-4-BOC-氨基苯丙氨酸
• 英文名称: N-α-(9-fluoromethoxycarbonyl)-L-4-tert-butoxycarbonylaminophenylalanine
• 英文别名: Fmoc-p-amino-L-phenylalanine(tert-butyloxycarbonyl)-OH；Fmoc-4-(Boc-amino)-L-phenylalanine；Fmoc-p-amino(Boc)-L-Phe-OH；Fmoc-p-amino(Boc)-L-Phe；Fmoc-Phe(p-NH-Boc)-OH；Fmoc-4-(Boc-amino)-L-phenylalanine-OH；(S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-((tert-butoxycarbonyl)amino)phenyl)propanoic acid；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]propanoic acid
• CAS: 174132-31-1
• 化学式: C₂₉H₃₀N₂O₆
• 分子量: 502.567
• InChiKey: KVUAOWDVYMUKPE-VWLOTQADSA-N

物化性质

• 沸点：
  671.0±55.0 °C(Predicted)
• 密度：
  1.280±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  29225090
• 危险类别：
  IRRITANT
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -15°C

制备方法与用途

(-2-((9H-芴-9-基)甲氧基)羰基氨基)-3-(4-(叔丁氧羰基氨基)苯基)丙酸是一种苯丙氨酸衍生物[1]。

反应信息

• 作为反应物：
  描述：

  Fmoc-4-氨基苯丙氨酸 在 lithium aluminium tetrahydride 、 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 水 、 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 18.67h， 生成 (2S)-2-[[(2S)-3-[4-(aminomethyl)phenyl]-2-[[(2S)-2-azido-3-phenylpropanoyl]amino]propanoyl]amino]-N-[(E,2S)-1-(4-aminophenyl)-4-methylsulfonylbut-3-en-2-yl]-4-methylpentanamide
  参考文献：
  名称：

  Incorporation of Non-natural Amino Acids Improves Cell Permeability and Potency of Specific Inhibitors of Proteasome Trypsin-like Sites

  摘要：

  Proteasomes degrade the majority of proteins in mammalian cells by a concerted action of three distinct pairs of active sites. The chymotrypsin-like sites are targets of antimyeloma agents bortezomib and carfilzomib. Inhibitors of the trypsin-like site sensitize multiple myeloma cells to these agents. Here we describe systematic effort to develop inhibitors with improved potency and cell permeability, yielding azido-Phe-Leu-Leu-4-aminomethyl-Phe-methyl vinyl sulfone (4a, LU-102), and a fluorescent activity-based probe for this site. X-ray structures of 4a and related inhibitors complexed with yeast proteasomes revealed the structural basis for specificity. Nontoxic to myeloma cells when used as a single agent, 4a sensitized them to bortezomib and carfilzomib. This sensitizing effect was much stronger than the synergistic effects of histone acetylase inhibitors or additive effects of doxorubicin and dexamethasone, raising the possibility that cornbinations of inhibitors of the trypsin-like site with bortezomib or carfilzomib would have stronger antincoplastic activity than combinations currently used clinically.

  DOI：

  10.1021/jm3016987
• 作为产物：
  描述：

  Fmoc-对硝基-L-苯丙氨酸 在 palladium 10% on activated carbon 、 甲酸铵 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 28.0h， 生成 Fmoc-4-氨基苯丙氨酸
  参考文献：
  名称：

  Incorporation of Non-natural Amino Acids Improves Cell Permeability and Potency of Specific Inhibitors of Proteasome Trypsin-like Sites

  摘要：

  Proteasomes degrade the majority of proteins in mammalian cells by a concerted action of three distinct pairs of active sites. The chymotrypsin-like sites are targets of antimyeloma agents bortezomib and carfilzomib. Inhibitors of the trypsin-like site sensitize multiple myeloma cells to these agents. Here we describe systematic effort to develop inhibitors with improved potency and cell permeability, yielding azido-Phe-Leu-Leu-4-aminomethyl-Phe-methyl vinyl sulfone (4a, LU-102), and a fluorescent activity-based probe for this site. X-ray structures of 4a and related inhibitors complexed with yeast proteasomes revealed the structural basis for specificity. Nontoxic to myeloma cells when used as a single agent, 4a sensitized them to bortezomib and carfilzomib. This sensitizing effect was much stronger than the synergistic effects of histone acetylase inhibitors or additive effects of doxorubicin and dexamethasone, raising the possibility that cornbinations of inhibitors of the trypsin-like site with bortezomib or carfilzomib would have stronger antincoplastic activity than combinations currently used clinically.

  DOI：

  10.1021/jm3016987

文献信息

• NON-NUCLEOSIDE ANTI-HEPACIVIRUS AGENTS AND USES THEREOF
  申请人：Boyd A. Vincent

  公开号：US20070021434A1

  公开（公告）日：2007-01-25

  The present dislcosure provides amide-based, non-nucleoside compounds having antiviral activity against Hepacivirus, such as hepatitis C virus (HCV), methods and intermediates for synthesizing such compounds, and methods of using the compounds in a variety of contexts, including in the treatment and prevention of viral infections. The present dislcosure also provides methods for identifying amide-based, non-nucleoside compounds having antiviral activity.

  本公开提供了基于酰胺的非核苷类化合物，具有抗Hepacivirus活性，例如丙型肝炎病毒（HCV），合成这类化合物的方法和中间体，以及在各种情境中使用这些化合物的方法，包括在治疗和预防病毒感染中的应用。本公开还提供了识别具有抗病毒活性的基于酰胺的非核苷类化合物的方法。
• COMPOSITIONS AND METHODS FOR TREATING HYPERPROLIFERATIVE DISEASE
  申请人：Cameron Dale Russell

  公开号：US20080171783A1

  公开（公告）日：2008-07-17

  The present disclosure provides amide-based, non-nucleoside compounds having an inhibitory activity against endogenous polymerases, such as polymerase alpha and polymerase gamma. This disclosure further provides uses of treating hyperproliferative diseases or disorders, such as benign or malignant neoplasms, and more specifically cancers that are sensitive to inhibition of polymerase alpha and polymerase gamma.

  本公开提供了基于酰胺的非核苷类化合物，具有对内源聚合酶（如聚合酶α和聚合酶γ）的抑制活性。本公开进一步提供了用于治疗过度增殖性疾病或疾病的用途，例如良性或恶性肿瘤，更具体地是对聚合酶α和聚合酶γ抑制敏感的癌症。
• 一种诱导BRD4蛋白降解的双功能化合物
  申请人：成都先导药物开发股份有限公司

  公开号：CN113387932A

  公开（公告）日：2021-09-14

  本发明提供一种新的双功能化合物及其在制备药物中的用途。本发明的双功能化合物是一种蛋白靶向联合体，通过连接链将BRD4蛋白抑制剂和E3泛素连接酶配体连接而得到，能够选择性诱导BRD4蛋白降解。
• Synthesis and in Vitro Screening of New Series of 2,6-Dipeptidyl-anthraquinones: Influence of Side Chain Length on HIV-1 Nucleocapsid Inhibitors
  作者：Francesco Frecentese、Alice Sosic、Irene Saccone、Elia Gamba、Kristina Link、Angelica Miola、Marta Cappellini、Massimiliano Gianni Cattelan、Beatrice Severino、Ferdinando Fiorino、Elisa Magli、Angela Corvino、Elisa Perissutti、Dan Fabris、Barbara Gatto、Giuseppe Caliendo、Vincenzo Santagada

  DOI：10.1021/acs.jmedchem.5b01494

  日期：2016.3.10

  2,6-Dipeptidyl-anthraquinones are a promising class of nucleic acid-binding compounds that act as NC inhibitors in vitro. We designed, synthesized, and tested new series of 2,6-disubstituted-anthraquinones, which are able to bind viral nucleic acid substrates of NC. We demonstrate here that these novel derivatives interact preferentially with noncanonical structures of TAR and cTAR, stabilize their

  2，6-二肽基蒽醌是一类有前途的核酸结合化合物，在体外可作为NC抑制剂。我们设计，合成和测试了新系列的2,6-二取代蒽醌，它们能够结合NC的病毒核酸底物。我们在这里证明，这些新型衍生物优先与TAR和cTAR的非规范结构相互作用，稳定其动力学，并干扰NC伴侣活性。
• Non-Natural Linker Configuration in 2,6-Dipeptidyl-Anthraquinones Enhances the Inhibition of TAR RNA Binding/Annealing Activities by HIV-1 NC and Tat Proteins
  作者：Alice Sosic、Irene Saccone、Caterina Carraro、Thomas Kenderdine、Elia Gamba、Giuseppe Caliendo、Angela Corvino、Paola Di Vaio、Ferdinando Fiorino、Elisa Magli、Elisa Perissutti、Vincenzo Santagada、Beatrice Severino、Valentina Spada、Dan Fabris、Francesco Frecentese、Barbara Gatto

  DOI：10.1021/acs.bioconjchem.8b00104

  日期：2018.7.18

  The HIV-1 nucleocapsid (NC) protein represents an excellent molecular target for the development of anti-retrovirals by virtue of its well-characterized chaperone activities, which play pivotal roles in essential steps of the viral life cycle. Our ongoing search for candidates able to impair NC binding/annealing activities led to the identification of peptidyl-anthraquinones as a promising class of nucleic acid ligands. Seeking to elucidate the inhibition determinants and increase the potency of this class of compounds, we have now explored the effects of chirality in the linker connecting the planar nucleus to the basic side chains. We show here that the non-natural linker configuration imparted unexpected TAR RNA targeting properties to the 2,6-peptidyl-anthraquinones and significantly enhanced their potency. Even if the new compounds were able to interact directly with the NC protein, they manifested a consistently higher affinity for the TAR RNA substrate and their TAR-binding properties mirrored their ability to interfere with NC-TAR interactions. Based on these findings, we propose that the viral Tat protein, sharing the same RNA substrate but acting in distinct phases of the viral life cycle, constitutes an additional druggable target for this class of peptidyl-anthraquinones. The inhibition of Tat-TAR interaction for the test compounds correlated again with their TAR-binding properties, while simultaneously failing to demonstrate any direct Tat-binding capabilities. These considerations highlighted the importance of TAR RNA in the elucidation of their inhibition mechanism, rather than direct protein inhibition. We have therefore identified anti-TAR compounds with dual in vitro inhibitory activity on different viral proteins, demonstrating that it is possible to develop multitarget compounds capable of interfering with processes mediated by the interactions of this essential RNA domain of HIV-1 genome with NC and Tat proteins.

  HIV-1 核苷酸蛋白（NC）是开发抗逆转录病毒药物的绝佳分子靶标，因为它具有特性良好的伴侣活性，在病毒生命周期的关键步骤中发挥着举足轻重的作用。我们一直在寻找能够损害 NC 结合/退火活动的候选药物，结果发现肽基蒽醌是一类很有前景的核酸配体。为了阐明抑制决定因素并提高这类化合物的效力，我们现在探索了连接平面核与碱性侧链的连接体中手性的影响。我们在此表明，非天然连接体构型赋予了 2,6-肽基蒽醌类化合物意想不到的 TAR RNA 靶向特性，并显著增强了它们的效力。即使新化合物能够直接与 NC 蛋白相互作用，它们对 TAR RNA 底物的亲和力也一直较高，其 TAR 结合特性反映了它们干扰 NC-TAR 相互作用的能力。基于这些发现，我们认为病毒 TAt 蛋白具有相同的 RNA 底物，但在病毒生命周期的不同阶段起作用，是这类肽基蒽醌类药物的另一个可治疗靶点。测试化合物对 TAt-TAR 相互作用的抑制作用再次与它们的 TAR 结合特性相关，同时也未能证明它们具有任何直接结合 TAt 的能力。这些考虑突出了 TAR RNA 在阐明其抑制机制方面的重要性，而不是直接抑制蛋白质。因此，我们发现了对不同病毒蛋白具有双重体外抑制活性的抗 TAR 化合物，这表明我们有可能开发出能够干扰 HIV-1 基因组中这一重要 RNA 结构域与 NC 和 TAt 蛋白相互作用过程的多靶点化合物。