[3AS-(3AALPHA,4BETA,6AALPHA)]-N-[3-[2-[2-(3-氨基丙氧基)乙氧基]乙氧基]丙基]六氢-2-氧代-1H-噻吩并[3,4-D]咪唑-4-戊酰胺单(三氟乙酸)盐 | 194920-43-9

• 物质功能分类: 催化剂及助剂 - 聚合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 中文名称: [3AS-(3AALPHA,4BETA,6AALPHA)]-N-[3-[2-[2-(3-氨基丙氧基)乙氧基]乙氧基]丙基]六氢-2-氧代-1H-噻吩并[3,4-D]咪唑-4-戊酰胺单(三氟乙酸)盐
• 英文名称: biotin-PEG-NH₂·TFA
• 英文别名: 13-N-biotinamide-4,7,10-trioxatridecaneamine trifluoroacetic acid salt；Biotin-C1-PEG3-C3-amine (TFA)；5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[3-[2-[2-(3-aminopropoxy)ethoxy]ethoxy]propyl]pentanamide;2,2,2-trifluoroacetic acid
• CAS: 194920-43-9
• 化学式: C₂HF₃O₂*C₂₀H₃₈N₄O₅S
• 分子量: 560.635
• InChiKey: NFXGRJSOZRCYLM-QMBKNIKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.25
• 重原子数：
  37
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  187
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  [3AS-(3AALPHA,4BETA,6AALPHA)]-N-[3-[2-[2-(3-氨基丙氧基)乙氧基]乙氧基]丙基]六氢-2-氧代-1H-噻吩并[3,4-D]咪唑-4-戊酰胺单(三氟乙酸)盐 、 棕榈酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以30 mg的产率得到
  参考文献：
  名称：

  凝血酶抑制抗凝脂质体：发展和特征。

  摘要：

  许多肽和拟肽药物在体内具有快速清除的缺点。可以通过低聚或与聚合物共价键合增加其尺寸来减少这种情况。作为原理证明，描述了药物低聚的替代策略，其中将拟肽凝血酶抑制剂掺入脂质体表面。为此目的，通过短的双官能化的乙二醇间隔基将抑制剂部分与棕榈酸残基共价偶联。将这些分子直接加入用于脂质体制备的脂质混合物中。所获得的脂质体在酶动力学测量和血浆抗凝活性方面具有很强的凝血酶抑制能力。它们的强效价和正ζ电位表明，大量苯甲‐衍生的抑制剂位于脂质体的表面。该概念应适用于遭受快速消除并允许用合适的脂肪酸残基进行共价修饰的其他药物分子。

  DOI：

  10.1002/cmdc.201500489
• 作为产物：
  描述：

  N-Boc-4,7,10-三氧杂-1,13-十三烷二胺 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 N,N-二异丙基乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 [3AS-(3AALPHA,4BETA,6AALPHA)]-N-[3-[2-[2-(3-氨基丙氧基)乙氧基]乙氧基]丙基]六氢-2-氧代-1H-噻吩并[3,4-D]咪唑-4-戊酰胺单(三氟乙酸)盐
  参考文献：
  名称：

  A cell-permeable inhibitor and activity-based probe for the caspase-like activity of the proteasome

  摘要：

  The ubiquitin-proteasome pathway degrades the majority of proteins in mammalian cells and plays an essential role in the generation of antigenic peptides presented by major histocompatibility class I molecules. Proteasome inhibitors are of great interest as research tools and drug candidates. Most work on proteasome inhibitors has focused on the inhibition of the chymotryptic-like (beta 5) sites; little attention has been paid to the inhibition of two other types of active sites, the trypsin-like (beta 2) and the caspase-like (beta 1). We report here the development of the first cell-permeable and highly selective inhibitors (4 and 5) of the proteasome's caspase-like site. The selectivity of the compounds is directly and unambiguously established by Staudinger-Bertozzi labeling of proteasome subunits covalently modified with azide-functionalized inhibitor 5. This labeling reveals that the caspase-like site of the immunoproteasome (beta 1i) is a preferred target of this compound. These compounds can be used as tools to study roles of beta 1 and beta 1i sites in generation of specific antigenic peptides and their potential role as co-targets of anti-cancer drugs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.092

文献信息

• Water soluble multi-biotin-containing compounds
  申请人：Wilbur Scott D.

  公开号：US20060228325A1

  公开（公告）日：2006-10-12

  Water-soluble discrete multi-biotin-containing compounds with at least three (3) biotin moieties are disclosed. The water-soluble biotin-containing compounds may additionally comprise one or more moieties that confer resistance to cleavage by biotinidase or that is cleavable in vitro or in vivo. The discrete multi-biotin-containing compounds may include a reactive moiety that provides a site for reaction with yet another moiety, such as a targeting, diagnostic or therapeutic functional moiety. Biotinylation reagents comprising water-soluble linker moieties are also disclosed and may additionally comprise a biotinidase protective group. Methods for amplifying the number of sites for binding biotin-binding proteins at a selected target using multi-biotin compounds also are disclosed.

  可溶于水的离散多生物素含有化合物，至少含有三个（3）生物素基团。这些可溶于水的生物素含有化合物可能还包括一个或多个使其对生物素酶的裂解具有抗性的基团，或者在体外或体内可被裂解的基团。这些离散的多生物素含有化合物可能包括一个反应性基团，提供与另一个基团（如靶向、诊断或治疗功能基团）反应的位点。还公开了包含可溶于水的连接基团的生物素化试剂，可能还包括生物素酶保护基团。还公开了使用多生物素化合物扩增在选定靶点上结合生物素结合蛋白的位点数量的方法。
• Structure Guided Design and Kinetic Analysis of Highly Potent Benzimidazole Inhibitors Targeting the PDEδ Prenyl Binding Site
  作者：Gunther Zimmermann、Carsten Schultz-Fademrecht、Philipp Küchler、Sandip Murarka、Shehab Ismail、Gemma Triola、Peter Nussbaumer、Alfred Wittinghofer、Herbert Waldmann

  DOI：10.1021/jm500632s

  日期：2014.6.26

  organization of K-Ras is controlled by the prenyl binding protein PDEδ, which enhances Ras diffusion in the cytosol. Inhibition of the Ras–PDEδ interaction by small molecules impairs Ras localization and signaling. Here we describe in detail the identification and structure guided development of Ras–PDEδ inhibitors targeting the farnesyl binding pocket of PDEδ with nanomolar affinity. We report kinetic

  K-Ras是最常见的信号转导人类致癌基因之一。Ras信号传导活性需要GTPase的正确细胞定位。K-Ras的空间组织受到异戊二烯结合蛋白PDEδ的控制，异戊二烯结合蛋白PDEδ增强Ras在细胞质中的扩散。小分子抑制Ras–PDEδ相互作用会削弱Ras的定位和信号传导。在这里，我们详细描述了靶向Ras–PDEδ抑制剂的鉴定和结构指导的开发，该抑制剂靶向具有纳摩尔摩尔亲和力的PDEδ的法呢基结合袋。我们报道了表征最有效的小分子配体与PDEδ结合的动力学数据，并证明了它们与细胞裂解液中的内源PDEδ结合。
• Benzimidazoles for the treatment of cancer
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2698367A1

  公开（公告）日：2014-02-19

  The present invention relates to novel substituted benzimidazoles and stereoisomeric forms, prodrugs, solvates, hydrates and/or pharmaceutically acceptable salts of these compounds as well as pharmaceutical compositions containing at least one of these substituted benzimidazoles together with pharmaceutically acceptable carrier, excipient and/or diluents. Said novel substituted benzimidazoles binding to the prenyl binding pocket of PDEδ have been identified as useful for the prophylaxis and treatment of cancer by the inhibition of the binding of PDEδ to K-Ras and of oncogenic Ras signalling in cells by altering its localization leading to cell death or inhibition of proliferation.

  本发明涉及新型取代苯并咪唑和立体异构体形式，以及这些化合物的前药、溶剂化合物、水合物和/或药学上可接受的盐，以及含有至少一种这些取代苯并咪唑的药物组合物，与药学上可接受的载体、赋形剂和/或稀释剂一起。已确定这些新型取代苯并咪唑结合到PDEδ的藤黄素结合口袋，通过抑制PDEδ与K-Ras的结合以及通过改变其定位导致细胞死亡或抑制增殖，从而对癌症的预防和治疗有用。
• [EN] BENZIMIDAZOLES FOR THE TREATMENT OF CANCER<br/>[FR] BENZIMIDAZOLES POUR LE TRAITEMENT D'UN CANCER
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2014027053A1

  公开（公告）日：2014-02-20

  The present invention relates to novel substituted benzimidazoles and stereoisomeric forms, prodrugs, solvates, hydrates and/or pharmaceutically acceptable salts of these compounds as well as pharmaceutical compositions containing at least one of these substituted benzimidazoles together with pharmaceutically acceptable carrier, excipient and/or diluents. Said novel substituted benzimidazoles binding to the prenyl binding pocket of PDEδ have been identified as useful for the prophylaxis and treatment of cancer by the inhibition of the binding of PDEδ to K-Ras and of oncogenic Ras signalling in cells by altering its localization leading to cell death or inhibition of proliferation.

  本发明涉及新型取代苯并咪唑和立体异构体形式，以及这些化合物的前药、溶剂化合物、水合物和/或药学上可接受的盐，以及含有至少一种这些取代苯并咪唑的药物组合物，与药学上可接受的载体、赋形剂和/或稀释剂一起。已经确定这些新型取代苯并咪唑结合到PDEδ的藤黄素结合口袋，对于通过抑制PDEδ与K-Ras的结合以及通过改变其定位导致细胞死亡或抑制增殖而对癌症的预防和治疗是有用的。
• Specific protein-labeling and ligand-binding position analysis with amidopyrene probes as LDI MS tags
  作者：Rei Watanabe、Yaping Hu、Keita Iio、Kozo Yoneda、Atsunori Hattori、Atsushi Arai、Hideo Kigoshi、Masaki Kita

  DOI：10.1039/c8ob02222d

  日期：——

  Ligand-dissociation type amidopyrene probes, being useful for LDI MS, were developed for specific protein-labeling and ligand-binding position analysis.

  用于特定蛋白质标记和配体结合位点分析的配体解离型Amidopyrene探针已经被开发出来，对于LDI MS非常有用。