N-Fmoc-1,6-己二胺 氢溴酸盐 | 352351-56-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N-Fmoc-1,6-己二胺 氢溴酸盐
• 中文别名: -Fmoc-1,6-己二胺氢溴酸盐；N-Fmoc-1,6-己二胺氢溴酸盐
• 英文名称: N-Fmoc-1,6-hexanediamine hydrobromide
• 英文别名: N-Fmoc-1,6-diaminohexane hydrobromide；N-(fluoren-9-ylmethoxycarbonyl)-1,6-diaminohexane hydrobromide；9H-fluoren-9-ylmethyl N-(6-aminohexyl)carbamate;hydrobromide
• CAS: 352351-56-5
• 化学式: BrH*C₂₁H₂₆N₂O₂
• 分子量: 419.362
• InChiKey: QSBKKENLOBODIG-UHFFFAOYSA-N

物化性质

• 熔点：
  ~153°C (dec.)

计算性质

• 辛醇/水分配系数(LogP)：
  4.62
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.4
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  N-Fmoc-1,6-己二胺 氢溴酸盐 、 4-amino-6-[[2-(4-formylphenoxymethyl)benzoyl]amino]-2-methylquinoline 在 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of bivalent antagonists of the nociceptin opioid receptor

  摘要：

  Bivalent ligands constituted by two identical pharmacophores structurally related to the Nociceptin Opioid Receptor (NOPr) antagonist JTC-801 were synthesized and their binding affinities for NOPr were evaluated. The novel ligands are formed by two modified JTC-801 units linked by di-iminic and di-aminic spacers with length ranging from three to ten methylene units. Moreover, the synthesis and the pharmacological characterization were extended to the corresponding univalent ligands. The latter compounds consisted in a single modified JTC-801 unit and an alkyl or alkylamino or alkylimino tail. The purpose of this study is to feature the location and surroundings of the allosteric binding site(s) of pharmacophores containing the 4-aminoquinoline structure. Most important, the bivalent ligands were exploited to reveal the eventual occurrence of a supramolecular receptorial architecture of the NOPr.All the bivalent derivatives 4 and 5 proved to be active in the nanomolar range with no outstanding dependence on the chain length. They showed potencies from three to ten times higher than the corresponding monomers. Consequently, results clearly indicated a positive role of the second pharmacophore in the ligand-protein interaction. The pharmacological profile of I he monomers 7 and 8 clarified the contribution of the linker chain to NOP receptor affinity and suggested the presence of a lipophilic acidic site neighbouring the binding site of the JTC-like ligands.Selectivity of saturated compounds 5, 7, and 8 was tested by binding experiments on delta, kappa and mu opioid receptors. Results indicated a general loss of selectivity as compared to JTC-801. In the [(35)S]GTP gamma S binding assay, all the compounds revealed antagonistic properties at the NOP Receptor.In conclusion the present study set the basis for a systematic investigation on the structural modifications that can be introduced into novel ligands for NOPr and helped to feature the surrounds of the allosteric site of NOPr. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.040

文献信息

• HEPARAN SULFATE/HEPARIN MIMETICS WITH ANTI-CHEMOKINE AND ANTI-INFLAMMATORY ACTIVITY
  申请人：California Institute of Technology

  公开号：US20150038455A1

  公开（公告）日：2015-02-05

  The present disclosure provides for methods and compositions comprising a series of synthetic glycopolymers. The disclosure also relates to a kit which is suitable for carrying out the inventive methods.

  本公开提供了一系列合成糖聚合物的方法和组合物。该公开还涉及一种适用于执行创新方法的试剂盒。
• TAILORED GLYCOPOLYMERS AS ANTICOAGULANT HEPARIN MIMETICS
  申请人：California Institute of Technology

  公开号：US20150038436A1

  公开（公告）日：2015-02-05

  The present disclosure provides for methods and compositions comprising a series of synthetic glycopolymers. The disclosure also relates to a kit which is suitable for carrying out the inventive methods.

  本公开提供了一系列合成糖聚合物的方法和组合物。该公开还涉及一种适用于实施创新方法的试剂盒。
• Mitochondrial targeting of cyclosporin A enables selective inhibition of cyclophilin-D and enhanced cytoprotection after glucose and oxygen deprivation
  作者：Sylvanie Malouitre、Henry Dube、David Selwood、Martin Crompton

  DOI：10.1042/bj20090332

  日期：2010.1.1

  CsA (cyclosporin A) is a hydrophobic undecapeptide that inhibits CyPs (cyclophilins), a family of PPIases (peptidylprolyl cis–trans isomerases). In some experimental models, CsA offers partial protection against lethal cell injury brought about by transient ischaemia; this is believed to reflect inhibition of CyP-D, a mitochondrial isoform that facilitates formation of the permeability transition pore in the mitochondrial inner membrane. To evaluate this further, we have targeted CsA to mitochondria so that it becomes selective for CyP-D in cells. This was achieved by conjugating the inhibitor to the lipophilic triphenylphosphonium cation, enabling its accumulation in mitochondria due to the inner membrane potential. In a cell-free system and in B50 neuroblastoma cells the novel reagent (but not CsA itself) preferentially inhibited CyP-D over extramitochondrial CyP-A. In hippocampal neurons, mitochondrial targeting markedly enhanced the capacity of CsA to prevent cell necrosis brought about by oxygen and glucose deprivation, but largely abolished its capacity to inhibit glutamate-induced cell death. It is concluded that CyP-D has a major pathogenic role in ‘energy failure’, but not in glutamate excitotoxicity, where cytoprotection primarily reflects CsA interaction with extramitochondrial CyPs and calcineurin. Moreover, the therapeutic potential of CsA against ischaemia/reperfusion injuries not involving glutamate may be improved by mitochondrial targeting.

  CsA（环孢素 A）是一种疏水性十一肽，可抑制 CyPs（环嗜蛋白），CyPs 是一种 PPI 酶（肽基脯氨酰顺反异构酶）家族。在一些实验模型中，CsA 对瞬时缺血造成的致命细胞损伤提供部分保护；这被认为反映了对 CyP-D 的抑制，CyP-D 是线粒体异构体，可促进线粒体内膜通透性转换孔的形成。为了进一步评估这一点，我们将 CsA 靶向线粒体，使其对细胞中的 CyP-D 具有选择性。这是通过将抑制剂与亲脂性的三苯基膦阳离子共轭来实现的，从而使抑制剂因内膜电位而在线粒体中蓄积。在无细胞系统和 B50 神经母细胞瘤细胞中，新型试剂（而非 CsA 本身）优先抑制 CyP-D 而非线粒体外 CyP-A。在海马神经元中，线粒体靶向明显增强了 CsA 预防缺氧和葡萄糖导致的细胞坏死的能力，但在很大程度上削弱了其抑制谷氨酸诱导的细胞死亡的能力。结论是，CyP-D 在 "能量衰竭 "中具有重要的致病作用，而在谷氨酸兴奋毒性中则没有，在谷氨酸兴奋毒性中，细胞保护主要反映了 CsA 与线粒体外 CyPs 和钙神经蛋白的相互作用。此外，CsA 对不涉及谷氨酸的缺血/再灌注损伤的治疗潜力可能会通过线粒体靶向得到改善。
• Functionalized Ruthenium Complexes: Selective “Turn-on” Detection of Biologically Relevant Anionic Species
  作者：Emanuela Berni、Laurent Le Henaff、Lucie Jarrige、Emeline Girard、Gediminas Jonusauskas、Isabelle Gosse、Sandra Pinet

  DOI：10.1002/ejoc.201700586

  日期：2017.7.7

  for dicarboxylates or phosphates can be switched by using guanidinium- or ammonium-functionalized probes. One of these probes turned out to be selective towards glutamate over aspartate and γ-aminobutyric acid (GABA). Another was selective towards adenosine 5′-triphosphate (ATP) over adenosine 5′-diphosphate (ADP), pyrophosphate (PPi), adenosine 5′-monophosphate (AMP), and orthophosphate (Pi). In both

  为了研究3，3'-修饰的联吡啶钌配合物的结构对其识别有机阴离子的能力的影响，已经制备了各种钌配合物。结合功能和大尺寸的修饰联吡啶配体被证明对乙腈的选择性至关重要。可以通过使用胍鎓或铵官能化的探针来切换二羧酸盐或磷酸盐的选择性。这些探针中的一种被证明对谷氨酸具有天冬氨酸和γ-氨基丁酸（GABA）的选择性。另一选择是对腺苷5'-二磷酸（ATP），焦磷酸酯（PPi），腺苷5'-单磷酸酯（AMP）和正磷酸酯（Pi）对腺苷5'-三磷酸酯（ATP）具有选择性。在这两种情况下，结合均归因于库仑相互作用和氢键。π-堆积相互作用也与核苷酸发生。用锌-二甲基吡啶胺单元代替铵使得在缓冲的水性系统中识别磷酸化的物质成为可能。令我们高兴的是，该探针显示了对ADP的选择性高于ATP，我们证明了选择性的部分原因是由于在配体的3和3'位置发生了取代。
• [EN] AN OSTEOADSORPTIVE FLUOROGENIC SUBSTRATE OF CATHEPSIN K FOR IMAGING OSTEOCLAST ACTIVITY AND MIGRATION<br/>[FR] SUBSTRAT FLUOROGÈNE OSTÉOADSORBANT DE CATHEPSINE K POUR L'IMAGERIE DE L'ACTIVITÉ ET DE LA MIGRATION DES OSTÉOCLASTES
  申请人：UNIV CALIFORNIA

  公开号：WO2019018238A1

  公开（公告）日：2019-01-24

  In certain embodiments osteoadsorptive fluorogenic substrates of cathepsin K (or other proteases) are provided. Utilizing a bisphosphonate targeting moiety, the fluorogenic substrates provide effective bone-targeted protease sensor(s). In certain embodiments the "probes" comprise cleavable fluorophore-quencher pair linked by a cathepsin K (or other protease) peptide substrate and tethered to a bisphosphonate. Unlike existing probes that are cleared within a few days in vivo, the probes described herein (e.g., OFS-1) allow for monitoring resorption over the course of longer time periods with a single dose.

  在某些实施例中，提供了钙蛋白酶K（或其他蛋白酶）的骨吸收荧光底物。利用双磷酸盐靶向基团，荧光底物提供有效的靶向骨蛋白酶传感器。在某些实施例中，“探针”包括可切割的荧光团-猝灭剂对，由钙蛋白酶K（或其他蛋白酶）肽底物连接，并与双磷酸盐相连。与现有的在体内几天内被清除的探针不同，本文所述的探针（例如OFS-1）允许在单剂量下监测骨吸收的长时间进程。