N-FMOC-L-金刚烷甘氨酸 | 1221793-29-8

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N-FMOC-L-金刚烷甘氨酸
• 英文名称: (2S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-(adamantan-1-yl)acetic acid
• 英文别名: (S)-Fmoc-1-adamantyl-glycine；(2S)-2-(1-adamantyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)acetic acid
• CAS: 1221793-29-8
• 化学式: C₂₇H₂₉NO₄
• 分子量: 431.532
• InChiKey: YKDNBNMLFPFDRJ-FUVUBJJASA-N

物化性质

• 沸点：
  642.7±38.0 °C(Predicted)
• 密度：
  1.291±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-FMOC-L-金刚烷甘氨酸 在 1H-咪唑-1-磺酰叠氮盐酸盐 、 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 copper(II) sulfate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (2S,4R)-1-((2S)-2-(adamantan-1-yl)-2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)acetyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  具有改善口服生物利用度的效力增强的拟肽 VHL 配体

  摘要：

  von Hippel-Lindau (VHL) 蛋白在调节缺氧应激反应中发挥着关键作用，并已在靶向蛋白质降解领域，特别是在二价降解剂的背景下得到广泛研究和利用。在这项研究中，我们提出了一种全面的拟肽结构-活性关系（SAR）方法，结合细胞 NanoBRET 靶点结合测定，以增强现有的 VHL 配体。通过对该分子的系统修饰，我们确定 1,2,3-三唑基团是左侧酰胺键的最佳替代品，其结合活性高出 10 倍。此外，在甲基噻唑苯甲胺部分上纳入构象限制的改变导致开发出具有皮摩尔结合亲和力的高效VHL配体，并显着提高了口服生物利用度。我们预计，我们优化的 VHL 配体GNE7599将作为研究 VHL 途径和推进靶向蛋白质降解领域的有价值的工具化合物。

  DOI：

  10.1021/acs.jmedchem.3c02203

文献信息

• [EN] TUMOUR-TARGETING PEPTIDE VARIANTS<br/>[FR] VARIANTS PEPTIDIQUES CIBLANT DES TUMEURS
  申请人：CANCER RESEARCH TECH LTD

  公开号：WO2018197490A1

  公开（公告）日：2018-11-01

  The present invention provides a peptide that selectively binds ανβ6 integrin, the peptide having an amino acid sequence comprising the motif X1BnRGDLX2X3X4 ZmX5, wherein X1 is any D-amino acid, Bn is a sequence of any n amino acids, which may be natural or unnatural, D- or L-, and may be the same or different, wherein n is a number between 1 and 10, X2 and X3 are independently selected from any amino acid, X4 is Leu or Ile, Zm is a sequence of any m amino acids, which may be natural or unnatural, D- or L-, and may be the same or different, wherein m is a number between 1 and 10, X5 is any L- or D-amino acid. Also provided are conjugates comprising said peptide, pharmaceutical compositions comprising said peptide or said conjugates, and uses of said peptide, conjugate or composition, for example, in the treatment, imaging and/or diagnosis of an ανβ6- expressing tumour in a mammalian subject.

  本发明提供了一种选择性结合ανβ6整合素的肽，该肽具有氨基酸序列，包括基序X1BnRGDLX2X3X4 ZmX5，其中X1是任何D-氨基酸，Bn是任何n个氨基酸的序列，可以是天然的或非天然的，D-或L-，可以相同也可以不同，其中n是1到10之间的数字，X2和X3分别选自任何氨基酸，X4是Leu或Ile，Zm是任何m个氨基酸的序列，可以是天然的或非天然的，D-或L-，可以相同也可以不同，其中m是1到10之间的数字，X5是任何L-或D-氨基酸。还提供了包括所述肽的结合物，包括所述肽或所述结合物的药物组合物，以及所述肽，结合物或组合物的用途，例如，在治疗、成像和/或诊断哺乳动物主体中表达ανβ6的肿瘤。
• An Adamantyl Amino Acid Containing Gramicidin S Analogue with Broad Spectrum Antibacterial Activity and Reduced Hemolytic Activity
  作者：Varsha V. Kapoerchan、Annemiek D. Knijnenburg、Miquel Niamat、Emile Spalburg、Albert J. de Neeling、Peter H. Nibbering、Roos H. Mars-Groenendijk、Daan Noort、José M. Otero、Antonio L. Llamas-Saiz、Mark J. van Raaij、Gijs A. van der Marel、Herman S. Overkleeft、Mark Overhand

  DOI：10.1002/chem.201001686

  日期：2010.10.25

  peptide gramicidin S (GS) is an effective topical antibacterial agent that is toxic for human red blood cells (hemolysis). Herein, we present a series of amphiphilic derivatives of GS with either two or four positive charges and characteristics ranging between very polar and very hydrophobic. Screening of this series of peptide derivatives identified a compound that combines effective antibacterial activity

  环状阳离子抗菌肽短杆菌肽S（GS）是一种有效的局部抗菌剂，对人的红血球有毒（溶血作用）。在本文中，我们介绍了一系列具有两个或四个正电荷且特性介于极极性和极疏水性之间的GS两亲衍生物。对这一系列肽衍生物的筛选确定了一种化合物，该化合物在相同浓度范围内将有效的抗菌活性与几乎没有毒性结合在一起。该肽可同时对抗革兰氏阴性菌和革兰氏阳性菌，包括多种MRSA菌株，并代表了开发广泛适用抗生素的有趣线索。
• Novel Furin Inhibitors with Potent Anti-infectious Activity
  作者：Kornelia Hardes、Gero L. Becker、Yinghui Lu、Sven O. Dahms、Susanne Köhler、Wolfgang Beyer、Kirsten Sandvig、Hiroyuki Yamamoto、Iris Lindberg、Lisa Walz、Veronika von Messling、Manuel E. Than、Wolfgang Garten、Torsten Steinmetzer

  DOI：10.1002/cmdc.201500103

  日期：2015.7

  peptidomimetic furin inhibitors with unnatural amino acid residues in the P3 position were synthesized. The most potent compound 4‐guanidinomethyl‐phenylacteyl‐Arg‐Tle‐Arg‐4‐amidinobenzylamide (MI‐1148) inhibits furin with a Ki value of 5.5 pM. The derivatives also strongly inhibit PC1/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against

  合成了在P3位具有非天然氨基酸残基的新型拟肽弗林蛋白酶抑制剂。最有效的化合物4-胍基甲基苯基乙酰基-Arg-Tle-Arg-4-ami基苄基酰胺（MI-1148）抑制弗林蛋白酶的K i值为5.5 p M。衍生物也强烈抑制PC1 / 3，而PC2受影响较小。在细胞培养物中测试了选定的抑制剂对已知依赖弗林蛋白酶活性的传染剂的抗菌和抗病毒活性。在弗林蛋白酶抑制剂的存在下，观察到了对炭疽和白喉毒素的显着保护作用。此外，强烈抑制了高致病性的H5N1和H7N1禽流感病毒的传播以及犬瘟热病毒的传播。抑制剂MI-1148与人弗林蛋白酶复合后结晶。P5苯环对位的N端胍基甲基的位置与先前发现的在结构上相关的抑制剂之间的位置相同，该抑制剂在间位含有该取代基位置，从而维持所有重要的P5互动。我们的结果证实，弗林蛋白酶的抑制是短期治疗急性传染病的有前途的策略。
• The Discovery of Potent, Selective, and Reversible Inhibitors of the House Dust Mite Peptidase Allergen Der p 1: An Innovative Approach to the Treatment of Allergic Asthma
  作者：Gary K. Newton、Trevor R. Perrior、Kerry Jenkins、Meriel R. Major、Rebekah E. Key、Mark R. Stewart、Stuart Firth-Clark、Steven M. Lloyd、Jihui Zhang、Nicola J. Francis-Newton、Jonathan P. Richardson、Jie Chen、Pei Lai、David R. Garrod、Clive Robinson

  DOI：10.1021/jm501102h

  日期：2014.11.26

  Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma.
• [EN] ANTIMICROBIAL CYCLIC PEPTIDES<br/>[FR] PEPTIDES CYCLIQUES ANTIMICROBIENS
  申请人：UNIV LEIDEN

  公开号：WO2010113042A1

  公开（公告）日：2010-10-07

  The present invention relates to antimicrobial cyclic peptides, which display a reduced hemolytic activity and optionally antimicrobial activity in comparison to parent antimicrobial cyclic peptides from which they are derived. In one embodiment the parent cyclic peptide is gramicidin S. There is also provided a method of providing novel derivative antimicrobial cyclic peptides which have been developed from a parent antimicrobial cyclic peptide and which display a reduced haemolytic activity and/or antimicrobial activity compared to the parent molecule from which they are derived.