N-Fmoc-尸胺 氢溴酸盐 | 352351-57-6

• 物质功能分类: 有机原料 - 氨基化合物 - 无环单胺、多胺及其衍生物和盐
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N-Fmoc-尸胺 氢溴酸盐
• 中文别名: N-FMOC-尸胺氢溴酸盐；N-Fmoc-尸胺氢溴酸盐；N-FMOC-尸胺 氢溴酸盐
• 英文名称: N-Fmoc-cadaverine hydrobromide
• 英文别名: N-Fmoc-1,5-diaminopentane hydrobromide；9H-fluoren-9-ylmethyl N-(5-aminopentyl)carbamate;hydrobromide
• CAS: 352351-57-6
• 化学式: BrH*C₂₀H₂₄N₂O₂
• 分子量: 405.335
• InChiKey: FJUIIWVLGUITRD-UHFFFAOYSA-N

物化性质

• 熔点：
  ~130 °C (dec.)

计算性质

• 辛醇/水分配系数(LogP)：
  4.23
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  64.4
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  N-Fmoc-尸胺 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

• Synthesis of functional molecular rod oligomers
  作者：Casper S. Andersen、Kurt V. Gothelf

  DOI：10.1039/b815099k

  日期：——

  We are presenting the synthesis of a phenylene ethynylene-based rod containing an Fmoc protected amino group and an activated acid which can be applied to peptide couplings. This linear amino acid analogue is applied to the synthesis of di-, tri- and pentamers. The pentamer has a molecular mass of 6.5 kDa and is characterized by 1H NMR spectroscopy and MALDI-TOF MS. The method has potential for the

  我们提出了一种含有Fmoc保护的氨基和可用于肽偶联的活化酸的亚苯基乙炔基棒的合成。该线性氨基酸类似物用于二，三和五聚体的合成。五聚体的分子量为6.5 kDa，并通过1 H NMR光谱和MALDI-TOF MS进行表征。该方法具有形成长大分子低聚物的潜力。
• Triphenylbutanamines: Kinesin Spindle Protein Inhibitors with in Vivo Antitumor Activity
  作者：Fang Wang、James A. D. Good、Oliver Rath、Hung Yi Kristal Kaan、Oliver B. Sutcliffe、Simon P. Mackay、Frank Kozielski

  DOI：10.1021/jm201195m

  日期：2012.2.23

  The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-L-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit K-i(aPP) <= 10 nM and GI(50) approximate to 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.
• Synthesis and SAR of 99mTc/Re-labeled small molecule prostate specific membrane antigen inhibitors with novel polar chelates
  作者：Genliang Lu、Kevin P. Maresca、Shawn M. Hillier、Craig N. Zimmerman、William C. Eckelman、John L. Joyal、John W. Babich

  DOI：10.1016/j.bmcl.2012.09.014

  日期：2013.3

  Prostate specific membrane antigen (PSMA) is recognized as an attractive molecular target for the development of radiopharmaceuticals to image and potentially treat metastatic prostate cancer. A series of novel Tc-99m/Re-tricarbonyl radiolabeled PSMA inhibitors were therefore synthesized by the attachment of glutamate-urea-lysine (Glu-urea-Lys) and glutamate-urea-glutamate (Glu-urea-Glu) pharmacophore to single amino acid chelate (SAAC) where the SAAC ligand was either bis(pyridin-2-ylmethyl)amino (DPA), bis((1-methyl-1H-imidazol-2-yl)methyl)amino (NMI), bis((1-(carboxymethyl)-1H-imidazol-2-yl)methyl)amino (CIM) or bis((1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino (TIM). The in vitro binding affinity of the rhenium complexes was evaluated using PSMA-expressing human prostate cancer LNCaP cells. IC50 values ranged from 3.8 +/- 2 to > 2000 nM. A linker between the SAAC chelate and pharmacophore was required for high affinity binding. However, extending the length of the linker did not substantially improve binding. PSMA binding was also influenced by the nature of the SAAC chelate. One of the most potent compounds, 23b (IC50 = 4.8 +/- 2.7 nM), was radiolabeled with technetium tricarbonyl (Tc-99m(CO)(3)}(+)) to afford the Tc-99m(CO)(3)}(+) complex in excellent yield and high purity. This effort has led to the identification of a diverse series of promising high affinity Tc-99m(CO)(3)}(+) radiolabeled PSMA inhibitors. (c) 2012 Elsevier Ltd. All rights reserved.
• Synthesis and pharmacological evaluation of bivalent antagonists of the nociceptin opioid receptor
  作者：Maria Rosaria Del Giudice、Anna Borioni、Giuditta Bastanzio、Maria Sbraccia、Carlo Mustazza、Isabella Sestili

  DOI：10.1016/j.ejmech.2011.01.040

  日期：2011.4

  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.