N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-phenethylglycine | 540483-58-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-phenethylglycine
• 英文别名: Fmoc-N-phenethyl-Gly-OH；N-Fmoc-N-(2-phenylethyl)-glycine；2-[9H-fluoren-9-ylmethoxycarbonyl(2-phenylethyl)amino]acetic acid
• CAS: 540483-58-7
• 化学式: C₂₅H₂₃NO₄
• 分子量: 401.462
• InChiKey: LFQGEVARORMAGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-苯乙胺 、 N-alpha-芴甲氧羰基-N-in-叔丁氧羰基-D-色氨酸 、 N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-phenethylglycine 以2.7 mg的产率得到(R)-3-(1H-Indol-3-yl)-N-phenethyl-2-(2-phenethylamino-acetylamino)-propionamide
  参考文献：
  名称：

  Design of Selective Peptidomimetic Agonists for the Human Orphan Receptor BRS-3

  摘要：

  New tool substances may help to unravel the physiological role of the human orphan receptor BRS-3 and its possible use as a drug target for the treatment of obesity and cancer. In continuation of our work on BRS-3, the solid- and solution-phase synthesis of a library of low molecular weight peptidomimetic agonists based on the recently developed short peptide agonist 4 is described. Functional potencies of the compounds were determined measuring calcium mobilization in a fluorometric imaging plate reader (FLIPR) assay. Focusing on the N-terminus, the D-Phe-Gln moiety of 4 was modified in a combinatorial. SAR-oriented medicinal chemistry approach. With the incorporation of N-arylated glycine and alanine building blocks azaglycine, piperazine, or piperidine and the synthesis of semicarbazides and semicarbazones, a number of highly potent and selective compounds with a reduced number of peptide bonds were obtained, which also should have enhanced metabolic stability.

  DOI：

  10.1021/jm0210921
• 作为产物：
  描述：

  tert-butyl N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-phenethylglycinate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-phenethylglycine
  参考文献：
  名称：

  [EN] MACROCYCLES AS CFTR MODULATORS
  [FR] MACROCYCLES EN TANT QUE MODULATEURS DE CFTR

  摘要：

  本发明涉及公式（I）的大环化合物，其中Ar1，Ar2，R1，R2，R3，R4和X如描述中所述，它们的制备方法，其药学上可接受的盐以及它们作为药物的用途，包括含有一个或多个公式（I）化合物的药物组合物，特别是它们作为CFTR调节剂的用途。

  公开号：

  WO2022194399A1

文献信息

• Discovery of Highly Potent and Neurotensin Receptor 2 Selective Neurotensin Mimetics
  作者：Jürgen Einsiedel、Cornelia Held、Maud Hervet、Manuel Plomer、Nuska Tschammer、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm200006c

  日期：2011.4.28

  The neurotensin receptor subtype 2 (NTS2) is involved in the modulation of tonic pain sensitivity and psychiatric diseases and is, therefore, regarded as a highly attractive pharmacological target protein. Aiming to discover NTS2 selective ligands, we herein describe the identification of screening hits and the chemical synthesis of structural variants leading to the highly potent and NTS2 selective

  神经降压素受体亚型2（NTS2）参与调节强直性疼痛敏感性和精神疾病，因此被认为是极具吸引力的药理靶蛋白。旨在发现NTS2选择性配体，我们在本文描述的筛选命中的鉴定和结构变体导致高度有效的化学合成和选择性NTS2类型的肽-类肽杂合体3的神经降压素模拟物3A和3E -克结合有ñ - （4-羟苯乙基）甘氨酸亚结构表现出一位数纳摩尔亲和力（K i= 4.3-8.8 nM）和1900-12000倍于神经降压素受体亚型1（NTS1）的选择性。根据功能实验，受试化合物3a和3e - g表现出对组成型有丝分裂原激活的蛋白激酶（MAPK）活性的抑制作用，是内源性配体神经降压素逆激动剂活性的2.6-4.6倍。
• Peptide/Peptoid Hybrid Oligomers: The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity
  作者：Nicki Frederiksen、Paul R. Hansen、Fredrik Björkling、Henrik Franzyk

  DOI：10.3390/molecules24244429

  日期：——

  relationships within a subclass of oligomers displaying variation of three structural features: (i) cationic side-chain length, (ii) hydrophobic side-chain length, and (iii) type of residue that is of a flexible peptoid nature. Increased side-chain length of cationic residues led to reduced hydrophobicity till the side chains became more extended than the aromatic/hydrophobic side chains, at which point

  先前对肽/拟肽杂交体的优化研究通常包括比较显示不同寡聚体长度和不同侧链的结构相关类似物。目前的工作涉及系统构建的一系列 16 个密切相关的 12 聚体低聚物，具有交替的阳离子/疏水设计，代表了广泛的疏水性和相对侧链长度的差异。目的是探索和合理化显示三个结构特征变化的低聚物亚类内的结构 - 活性关系：（i）阳离子侧链长度，（ii）疏水侧链长度，以及（iii）残基类型具有灵活的拟肽性质。阳离子残基侧链长度的增加导致疏水性降低，直到侧链变得比芳香族/疏水性侧链更长，此时疏水性略有增加。抗菌活性评估表明，具有最低疏水性的类似物对大肠杆菌的活性降低，而具有最短阳离子侧链的低聚物对铜绿假单胞菌最有效。因此，与铜绿假单胞菌的膜破坏相互作用似乎是由低聚物的疏水表面（由保护阳离子侧链的芳族基团组成）促进的。具有短阳离子侧链的肽模拟物表现出增加的溶血特性以及降低 HepG2（肝母细胞瘤 G2 细胞系）细胞活力。
• Peptoids bearing tertiary amino residues in the n-alkyl side chains: synthesis of a potent inhibitor of Semaphorin 3A
  作者：Joaquim Messeguer、Isabel Masip、Marisol Montolio、Jose Antonio del Rio、Eduardo Soriano、Angel Messeguer

  DOI：10.1016/j.tet.2010.01.090

  日期：2010.3

  A study on the preparation of N-alkylglycines (peptoids) that contain tertiary amino residues on the N-alkyl side chains is reported. The appropriate combination of the submonomer strategy with N-alkylglycine monomer couplings depending upon the structure of the N-alkyl side chain that must be incorporated into the peptoid is determinant for the efficiency of the synthetic pathway. The application of this strategy to the preparation of SICHI, an N-alkyglycine trimer containing tertiary amino residues in the three N-alkyl branches, and that has been identified as a potent Semaphorin 3A inhibitor, is presented. (C) 2010 Elsevier Ltd. All rights reserved.
• CYCLIC PEPTIDE COMPOUND HAVING HIGH MEMBRANE PERMEABILITY, AND LIBRARY CONTAINING SAME
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US20200131669A1

  公开（公告）日：2020-04-30

  The present inventors have found that when screening for cyclic peptide compounds that can specifically bind to a target molecule, the use of a library including cyclic peptide compounds having a long side chain in the cyclic portion can improve the hit rate for cyclic peptide compounds that can specifically bind to the target molecule. Meanwhile, the present inventors have found that tryptophan and tyrosine residues, which have conventionally been used in oral low molecular-weight pharmaceuticals and are amino acid residues having an indole skeleton or a hydroxyphenyl group, are not suitable for peptides intended to attain high membrane permeability.
• [EN] PEPTIDE DERIVATIVES AND RELATED USES AS OREXIN AGONISTS<br/>[FR] DÉRIVÉS PEPTIDIQUES ET LEURS UTILISATIONS EN TANT QU'AGONISTES DE L'OREXINE
  申请人：[en]OREXIA THERAPEUTICS LIMITED

  公开号：WO2023017180A1

  公开（公告）日：2023-02-16

  The present disclosure relates to peptide having a sequence comprising: Z1X1X2X3X4X5X6X7X8X9X10X11X12-NH2(SEQ ID NO: 1), and to their isomers, pharmaceutically acceptable salts, or prodrugs thereof, methods of use, and methods for their preparation. The peptides disclosed herein are useful for modulating orexin receptor activity and may be used in the treatment of disorders in which orexin receptor activity is implicated, such as narcolepsy, a hypersomnia disorder, a neurodegenerative disorder, a symptom of a rare genetic disorder, a mental health disorder, a metabolic syndrome, osteoporosis, cardiac failure, coma, or a complication in emergence from anaesthesia.