(R)-(9H-fluoren-9-yl)methyl 4-((tert-butyldisulfanyl)methyl)-5-oxooxazolidine-3-carboxylate | 1013096-02-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (R)-(9H-fluoren-9-yl)methyl 4-((tert-butyldisulfanyl)methyl)-5-oxooxazolidine-3-carboxylate
• 英文别名: 9H-fluorene-9-ylmethyl (4R)-4-[(tert-butyldisulfanyl)methyl]-5-oxo-1,3-oxazolidine-3-carboxylate；(9H-fluoren-9-yl)methyl (R)-4-((tert-butyldisulfaneyl)methyl)-5-oxooxazolidine-3-carboxylate；4R-tert-butyldisulfanylmethyl-5-oxo-oxazolidine-3-carboxylic acid 9H-fluoren-9-ylmethyl ester；(R)-Fmoc-4-((tert-butyldisulfanyl)methyl)-5-oxooxazolidine-3-carboxylate；9H-fluoren-9-ylmethyl (4R)-4-[(tert-butyldisulfanyl)methyl]-5-oxo-1,3-oxazolidine-3-carboxylate
• CAS: 1013096-02-0
• 化学式: C₂₃H₂₅NO₄S₂
• 分子量: 443.588
• InChiKey: NVODGMYRITYWBO-FQEVSTJZSA-N

物化性质

• 沸点：
  629.5±45.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  106
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-(9H-fluoren-9-yl)methyl 4-((tert-butyldisulfanyl)methyl)-5-oxooxazolidine-3-carboxylate 在 三乙基硅烷 、 三丁基膦 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 47.16h， 生成 2-[(2R)-3-(dimethylamino)-2-[9H-fluorene-9-ylmethoxycarbonyl(methyl)amino]-3-oxopropyl]sulfanylacetic acid
  参考文献：
  名称：

  JP6880352

  摘要：

  公开号：
• 作为产物：
  描述：

  聚合甲醛 、 亚芴甲氧羰基半胱胺酸 在 camphorsulfonic acid 作用下， 以 苯 为溶剂， 以87%的产率得到(R)-(9H-fluoren-9-yl)methyl 4-((tert-butyldisulfanyl)methyl)-5-oxooxazolidine-3-carboxylate
  参考文献：
  名称：

  N-甲基化环脑啡肽类似物保持高阿片受体结合亲和力

  摘要：

  为了提高非选择性环状脑啡肽类似物 H-Dmt-c[ d -Cys-Gly-Phe- d (or L )-Cys]NH 2 (Dmt = 2',6'-二甲基酪氨酸)，合成了在 Phe 4和/或 Cys 5残基处 N 甲基化的类似物。与非甲基化亲本肽相比，所有单甲基化和 N-二甲基化类似物通常在所有三种阿片受体上均保持高结合亲和力，并在功能阿片活性测定中保持高阿片激动剂效力。结果表明，这些化合物对单和二 N 甲基化的渐进构象限制没有显着影响体外阿片类药物活性概况。为该系列中构象最受限的类似物 H-Dmt-c[ D -Cys-Gly-Phe(NMe) -L -Cys (NMe)]NH 2 (6)鉴定的低能量构象异构体显示出良好的空间重叠与μ选择性阿片肽JOM-6[H-Tyr-c(S-Et-S)[ D - Cys -Phe- D - Pen]NH的拟议μ受体结合构象中的基本药效部分2 ] (Pen

  DOI：

  10.1111/j.1747-0285.2009.00919.x
• 作为试剂：
  描述：

  聚合甲醛 、 亚芴甲氧羰基半胱胺酸 在 混旋樟脑磺酸 silica gel 、 ethyl acetate n-hexane 、 (R)-(9H-fluoren-9-yl)methyl 4-((tert-butyldisulfanyl)methyl)-5-oxooxazolidine-3-carboxylate 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以to afford (R)-(9H-fluoren-9-yl)methyl 4-((tert-butyldisulfanyl)methyl)-5-oxooxazolidine-3-carboxylate (Compound 2b-B) (1.936 g, 94%)的产率得到(R)-(9H-fluoren-9-yl)methyl 4-((tert-butyldisulfanyl)methyl)-5-oxooxazolidine-3-carboxylate
  参考文献：
  名称：

  PEPTIDE-COMPOUND CYCLIZATION METHOD

  摘要：

  本发明的目的是提供一种发现对于难以处理的靶点有效的药物的方法，这些药物通常很难被发现。本发明涉及新型的环化肽化合物的方法，以及包含这些化合物的新型肽库，以实现上述目的。

  公开号：

  US20150080549A1

文献信息

• Peptide-compound cyclization method
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US09409952B2

  公开（公告）日：2016-08-09

  An object of the present invention is to provide methods of discovering drugs effective for tough targets, which have conventionally been discovered only with difficulty. The present invention relates to novel methods for cyclizing peptide compounds, and novel peptide compounds and libraries comprising the same, to achieve the above object.

  本发明的目的是提供发现对于难以发现的药物目标有效的药物的方法，这些药物目标通常很难被发现。本发明涉及新型的循环肽化合物的方法，以及包含这些化合物的新型肽库，以达到上述目的。
• A Pro‐Fluorescent Ubiquitin‐Based Probe to Monitor Cysteine‐Based E3 Ligase Activity
  作者：David A. Pérez Berrocal、Thimmalapura M. Vishwanatha、Daniel Horn‐Ghetko、J. Josephine Botsch、Laura A. Hehl、Sebastian Kostrhon、Mohit Misra、Ivan Ðikić、Paul P. Geurink、Hans van Dam、Brenda A. Schulman、Monique P. C. Mulder

  DOI：10.1002/anie.202303319

  日期：2023.8.7

  Protein post‐translational modification with ubiquitin (Ub) is a versatile signal regulating almost all aspects of cell biology, and an increasing range of diseases is associated with impaired Ub modification. In this light, the Ub system offers an attractive, yet underexplored route to the development of novel targeted treatments. A promising strategy for small molecule intervention is posed by the final components of the enzymatic ubiquitination cascade, E3 ligases, as they determine the specificity of the protein ubiquitination pathway. Here, we present UbSRhodol, an autoimmolative Ub‐based probe, which upon E3 processing liberates the pro‐fluorescent dye, amenable to profile the E3 transthiolation activity for recombinant and in cell‐extract E3 ligases. UbSRhodol enabled detection of changes in transthiolation efficacy evoked by enzyme key point mutations or conformational changes, and offers an excellent assay reagent amenable to a high‐throughput screening setup allowing the identification of small molecules modulating E3 activity.

  摘要 用泛素（Ub）对蛋白质进行翻译后修饰是一种调节细胞生物学几乎所有方面的多功能信号，越来越多的疾病与 Ub 修饰受损有关。有鉴于此，Ub 系统为开发新型靶向治疗方法提供了一条极具吸引力但尚未充分开发的途径。酶泛素化级联的最终组分--E3连接酶--是一种很有前景的小分子干预策略，因为它们决定了蛋白质泛素化途径的特异性。在这里，我们展示了一种基于 Ub 的自巯基探针 UbSRhodol，它在 E3 处理过程中释放出亲荧光染料，可用于分析重组和细胞提取 E3 连接酶的 E3 转硫化活性。UbSRhodol 能够检测酶的关键点突变或构象变化引起的转硫化功效的变化，是一种适用于高通量筛选装置的优良检测试剂，可以鉴定调节 E3 活性的小分子。
• [EN] COMPOUNDS AND METHODS FOR USE IN TREATING NEOPLASIA AND CANCER<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT D'UNE NÉOPLASIE OU D'UN CANCER
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2013016531A3

  公开（公告）日：2013-07-25
• Amide-modified prenylcysteine based Icmt inhibitors: Structure–activity relationships, kinetic analysis and cellular characterization
  作者：Jaimeen D. Majmudar、Heather B. Hodges-Loaiza、Kalub Hahne、James L. Donelson、Jiao Song、Liza Shrestha、Marietta L. Harrison、Christine A. Hrycyna、Richard A. Gibbs

  DOI：10.1016/j.bmc.2011.10.087

  日期：2012.1

  Human protein isoprenylcysteine carboxyl methyltransferase (hIcmt) is the enzyme responsible for the alpha-carboxyl methylation of the C-terminal isoprenylated cysteine of CaaX proteins, including Ras proteins. This specific posttranslational methylation event has been shown to be important for cellular transformation by oncogenic Ras isoforms. This finding led to interest in hIcmt inhibitors as potential anti-cancer agents. Previous analog studies based on N-acetyl-S-farnesylcysteine identified two prenylcysteine-based low micromolar inhibitors (1a and 1b) of hIcmt, each bearing a phenoxyphenyl amide modification. In this study, a focused library of analogs of 1a and 1b was synthesized and screened versus hIcmt, delineating structural features important for inhibition. Kinetic characterization of the most potent analogs 1a and 1b established that both inhibitors exhibited mixed-mode inhibition and that the competitive component predominated. Using the Cheng-Prusoff method, the K-i values were determined from the IC50 values. Analog 1a has a K-IC of 1.4 +/- 0.2 mu M and a K-IU of 4.8 +/- 0.5 mu M while 1b has a K-IC of 0.5 +/- 0.07 mu M and a K-IU of 1.9 +/- 0.2 mu M. Cellular evaluation of 1b revealed that it alters the subcellular localization of GFP-KRas, and also inhibits both Ras activation and Erk phosphorylation in Jurkat cells. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis, redox properties, and conformational analysis of vicinal disulfide ring mimics
  作者：Erik L. Ruggles、P. Bruce Deker、Robert J. Hondal

  DOI：10.1016/j.tet.2008.11.085

  日期：2009.2

  A vicinal disulfide ring (VDR) results from disulfide-bond formation between two adjacent cysteine residues. This eight-membered ring is a rare motif in protein structures and is functionally important to those few proteins that posses it. This article focuses on the construction of strained and unstrained VDR mimics, discernment of the preferred conformation of these mimics, and the determination of their respective disulfide redox potentials. (C) 2008 Elsevier Ltd. All rights reserved.