(9H-fluoren-9-yl)methyl (2-(((4-nitrophenoxy)carbonyl)oxy)ethyl)carbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (9H-fluoren-9-yl)methyl (2-(((4-nitrophenoxy)carbonyl)oxy)ethyl)carbamate
• 英文别名: 4-nitrophenyl 2-[(9H-fluoren-9-ylmethoxy)carbonyl]aminoethylcarbonate；p-nitrophenyl 2-(9-fluorenylmethoxycarbonylamino)ethylcarbonate；4-nitrophenyl 2-(9-fluorenyloxycarbonlyamino)ethylcarbonate；Fmoc-Gly-PNOC；4-nitrophenyl 2-[(9H-fluoren-9-ylmethoxy)carbonyl]aminoethyl carbonate；2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl (4-nitrophenyl) carbonate
• 化学式: C₂₄H₂₀N₂O₇
• 分子量: 448.432
• InChiKey: ZOCNYXUBEKWNMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (9H-fluoren-9-yl)methyl (2-(((4-nitrophenoxy)carbonyl)oxy)ethyl)carbamate 、 pentachlorophenyl (E)-3-(4-phosphorylphenyl)but-2-enoate 、 (2S,5S)-5-[[(9H-芴-9-基甲氧基)羰基]氨基]-1,2,4,5,6,7-六氢-4-氧代-氮杂卓并[3,2,1-hi]吲哚-2-羧酸 在 哌啶 、 C₃₃H₃₁N₂O₆Pol 、 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以38 mg的产率得到2-[[(2S,11S)-12-oxo-11-[[(E)-3-(4-phosphonooxyphenyl)but-2-enoyl]amino]-1-azatricyclo[6.4.1.04,13]trideca-4,6,8(13)-triene-2-carbonyl]amino]ethyl carbamate
  参考文献：
  名称：

  Potent and Selective Phosphopeptide Mimetic Prodrugs Targeted to the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3

  摘要：

  Signal transducer and activator of transcription 3 (Stat3), a target for anticancer drug design, is activated by recruitment to phosphotyrosine residues on growth factor and cytokine receptors via its SH2 domain. We report here structure activity relationship studies on phosphopeptide mimics targeted to the SH2 domain of Stat3. Inclusion of a methyl group on the beta-position of the pTyr mimic 4-phosphocinnamide enhanced affinity 2- to 3-fold. Bis-pivaloyloxymethyl prodrugs containing beta-methylcinnamide, dipeptide scaffolds Haic and Nle-cis-3,4-methanoproline, and glutamine surrogates were highly potent, completely inhibiting phosphorylation of Stat3 Tyr705 at 0.5-1,mu M in a variety of cancer cell lines. The inhibitors were selective for Stat3 over Stat1, Stat5, Src, and p85 of PI3K, indicating ability to discriminate individual SH2 domains in intact cells. At concentrations that completely inhibited Stat3 phosphorylation, the prodrugs were not cytotoxic to a panel of tumor cells, thereby showing clear distinction between cytotoxicity and effects downstream of activated Stat3.

  DOI：

  10.1021/jm2000882
• 作为产物：
  描述：

  在 吡啶 、 sodium tetrahydroborate 作用下， 以 二氯甲烷 为溶剂， 反应 0.02h， 生成 (9H-fluoren-9-yl)methyl (2-(((4-nitrophenoxy)carbonyl)oxy)ethyl)carbamate
  参考文献：
  名称：

  Design and synthesis of a novel peptidomimetic inhibitor of HIV-1 Tat–TAR interactions: Squaryldiamide as a new potential bioisostere of unsubstituted guanidine

  摘要：

  By performing RNA-targeted structure-activity relationship studies, we discovered a novel peptidomimetic containing squaryldiamide as a potential bioisostere replacement for guanidine that binds transactivation responsive RNA with high affinity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.077

文献信息

• Sequencing of Sequence-Defined Oligourethanes via Controlled Self-Immolation
  作者：Samuel D. Dahlhauser、P. Rogelio Escamilla、Abigail N. VandeWalle、Jordan T. York、Rachel M. Rapagnani、Jasper S. Shei、Samuel A. Glass、Jaime N. Coronado、Sarah R. Moor、Douglas P. Saunders、Eric V. Anslyn

  DOI：10.1021/jacs.9b12818

  日期：2020.2.12

  Sequence-defined polymers show promise for biomimetics, self-assembly, catalysis, and information storage, wherein the primary structure begets complex chemical processes. Here we report the solution-phase and the high-yielding solid-phase syntheses of discrete oligourethanes and methods for their self-immolative sequencing, resulting in rapid and robust characterization of this class of oligomers

  序列定义的聚合物显示出仿生学、自组装、催化和信息存储的前景，其中一级结构引发复杂的化学过程。在这里，我们报告了离散低聚氨基甲酸酯的液相和高产固相合成及其自焚测序方法，从而在不使用 MS/MS 的情况下对此类低聚物和聚合物进行了快速和稳健的表征。测序的关键是末端醇以受控和迭代方式“解压缩”低聚物的固有反应性，将每个单体作为 2-恶唑烷酮释放。通过 LC/MS 监测自焚反应，应用算法可快速生成低聚氨基甲酸酯的序列。这个过程不仅提供了结构复杂分子的表征，
• INHIBITORS OF STAT3 AND USES THEREOF
  申请人：McMurray John S.

  公开号：US20120035114A1

  公开（公告）日：2012-02-09

  Compounds which inhibit the activity of signal transducer and activator of transcription 3 (STAT3) are provided together with methods of making and using the same. The compounds are designed to bind to the SH2 domain of STAT3, preventing STAT3 from binding to receptors for interleukin-6 family cytokines, growth factors such as the platelet-derived growth factor, the epidermal growth factor, vascular endothelial growth factor, and other signaling molecules such as leptin. Blocking these interactions prevents STAT3 from being phosphorylated on Tyr705, which is required for the dimerization of STAT3, translocation to the nucleus, binding to STAT3 response elements on promotors, and transcription of genes. In addition to these activities, binding to the SH2 domain of STAT3 breaks up pre-formed dimmers, thereby preventing the transcriptional activity of the inhibitor.

  本发明提供了抑制信号转导与激活转录因子3 (STAT3) 活性的化合物，以及制备和使用这些化合物的方法。这些化合物被设计成结合STAT3的SH2结构域，防止STAT3与白细胞介素6家族细胞因子、血小板源性生长因子、表皮生长因子、血管内皮生长因子等生长因子和瘦素等信号分子的受体结合。阻断这些相互作用可防止STAT3在Tyr705位点磷酸化，这是STAT3二聚化、向细胞核转位、结合启动子上的STAT3响应元件和基因转录所必需的。除了这些作用，结合STAT3的SH2结构域还可以分解已形成的二聚体，从而防止抑制剂的转录活性。
• [EN] INHIBITORS OF STAT3 AND USES THEREOF<br/>[FR] INHIBITEURS DU STAT3 ET LEURS UTILISATIONS
  申请人：UNIV TEXAS

  公开号：WO2010118309A3

  公开（公告）日：2011-01-13
• Structure−Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3
  作者：Pijus K. Mandal、Zhiyong Ren、Xiaomin Chen、Chiyi Xiong、John S. McMurray

  DOI：10.1021/jm901105k

  日期：2009.10.8

  In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals and is a validated target for anticancer drug design. We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gin mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4-methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date.
• US8841257B2
  申请人：——

  公开号：US8841257B2

  公开（公告）日：2014-09-23