(S)-2-(((苄氧基)羰基)氨基)-3-(3-氟苯基)丙酸 | 49759-64-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (S)-2-(((苄氧基)羰基)氨基)-3-(3-氟苯基)丙酸
• 中文别名: CBZ-L-3-氟苯丙氨酸
• 英文名称: Cbz-L-m-FPhe
• 英文别名: Z-L-Phe(3F)；N-benzyloxycarbonyl-β-(3-fluorophenyl)-L-alanine；(S)-2-(((Benzyloxy)carbonyl)amino)-3-(3-fluorophenyl)propanoic acid；(2S)-3-(3-fluorophenyl)-2-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 49759-64-0
• 化学式: C₁₇H₁₆FNO₄
• 分子量: 317.317
• InChiKey: PTHVXSGNDJTPEX-HNNXBMFYSA-N

物化性质

• 沸点：
  509.3±50.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  (S)-2-(((苄氧基)羰基)氨基)-3-(3-氟苯基)丙酸 在 palladium on activated charcoal N-乙基吗啉 、 甲醇 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 环己烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 L-m-FPhe-L-Ala
  参考文献：
  名称：

  Transport of antimicrobial agents using peptide carrier systems: anticandidal activity of m-fluorophenylalanine-peptide conjugates

  摘要：

  A series of di- and tripeptides containing D- and L-m-fluorophenylalanine was prepared and tested in vitro for the ability to inhibit the growth of the yeast Candida albicans. The results demonstrate that peptides containing L-m-fluorophenylalanine inhibited the growth of C. albicans with minimum inhibitory concentrations (MIC's) ranging from 0.5 to 63 micrograms/mL. The parent L-m-fluorophenylalanine and peptides containing D-m-fluorophenylalanine were inactive (MIC greater than 250 micrograms/mL) in these tests. The results of competitive antagonism studies support peptide transport mediated entry of the inhibitory peptides, followed by release of L-m-fluorophenylalanine inside the cell.

  DOI：

  10.1021/jm00366a013
• 作为产物：
  描述：

  3-氟溴苄 在 氢氧化钾 、 乙醇 、 sodium ethanolate 作用下， 以 1,4-二氧六环 为溶剂， 生成 (S)-2-(((苄氧基)羰基)氨基)-3-(3-氟苯基)丙酸
  参考文献：
  名称：

  通过2-苄氧基羰基氨基-2-芳基烷基丙二酸酯合成光学活性的环取代的N-苄氧基羰基苯丙氨酸†

  摘要：

  使二乙基或二甲基苄氧基羰基氨基丙二酸酯与环取代的苄基卤化物反应，并将所得的芳基烷基衍生物（3至6）半皂化为DL-单酸-单酯（7至10）。通过在二恶烷中回流脱羧得到N-苄基氧羰基-DL-氨基酸酯（11至14），其通过用枯草杆菌蛋白酶Carlsberg型酶水解该酯基而分解成它们的旋光对映体。酶水解产生N-苄氧基羰基-L-氨基酸（15至18）和相应的D-氨基酸酯。通过酯基的碱性水解将后者转化为N-苄氧基羰基-D-氨基酸（19和20）。这些衍生物可直接用于进一步的肽合成。制备下列化合物：N-苄氧基羰衍生物p -甲基-L-苯丙氨酸（15），p -甲基- d -苯丙氨酸（19），p氟-L-苯丙氨酸（16），米氟- L-苯丙氨酸（17），米氟d -苯丙氨酸（20）和五氟-L-苯丙氨酸（18）。通过在乙酸中用HBr除去苄氧羰基获得游离氨基酸。

  DOI：

  10.1002/hlca.19730560603

文献信息

• α-Chymotrypsin-catalysed peptide synthesis via the kinetically controlled approach using activated esters as acyl donors in organic solvents with low water content: incorporation of non-protein amino acids into peptides
  作者：Toshifumi Miyazawa、Shin’ichi Nakajo、Miyako Nishikawa、Kazumi Hamahara、Kiwamu Imagawa、Eiichi Ensatsu、Ryoji Yanagihara、Takashi Yamada

  DOI：10.1039/b004183l

  日期：——

  α-chymotrypsin-catalysed peptide synthesis via the kinetically controlled approach is greatly improved by the use of activated esters such as the 2,2,2-trifluoroethyl ester as acyl donors instead of the conventional methyl ester in organic solvents such as acetonitrile with low water content. This approach is useful for the incorporation of non-protein amino acids such as halogenophenylalanines into peptides.

  在α-胰凝乳蛋白酶催化下的偶联效率 肽通过使用活化的方法，通过动力学控制方法的合成得到了极大的改善酯类 例如2,2,2-三氟乙基酯 酰基供体 代替传统的有机甲酯 溶剂 如 乙腈 低 水内容。这种方法对于合并非蛋白质 氨基酸 如卤代苯丙氨酸成 肽。
• Identification of highly potent and selective HTRA1 inhibitors
  作者：David G. Dennis、Young Joo Sun、Dylan E. Parsons、Vinit B. Mahajan、Mark Smith

  DOI：10.1016/j.bmcl.2024.129814

  日期：2024.9

  Arthritis. Selective inhibition of serine protease HTRA1 therefore offers a promising new strategy for the treatment of these diseases. Herein we disclose structure–activity-relationship (SAR) studies which identify key interactions responsible for binding affinity of small molecule inhibitors to HTRA1. The study results in highly potent molecules with IC′s less than 15 nM and excellent selectivity following

  高温要求丝氨酸肽酶 1 (HTRA1) 是一种参与一系列信号传导途径的丝氨酸蛋白酶。它还负责调节蛋白质聚集体的重折叠、易位和降解。随后发现失控的 HTRA1 蛋白水解活性在多种疾病中发挥作用，包括年龄相关性黄斑变性 (AMD)、骨关节炎和类风湿关节炎。因此，选择性抑制丝氨酸蛋白酶 HTRA1 为治疗这些疾病提供了一种有前景的新策略。在此，我们公开了结构-活性-关系（SAR）研究，该研究确定了负责小分子抑制剂与 HTRA1 结合亲和力的关键相互作用。该研究在筛选 35 种蛋白酶后产生了 IC 小于 15 nM 且具有出色选择性的高效分子。
• Chemical and Biological Evaluation of Dipeptidyl Boronic Acid Proteasome Inhibitors for Use in Prodrugs and Pro-Soft Drugs Targeting Solid Tumors
  作者：Lawrence J. Milo、Jack H. Lai、Wengen Wu、Yuxin Liu、Hlaing Maw、Youhua Li、Zhiping Jin、Ying Shu、Sarah E. Poplawski、Yong Wu、David G. Sanford、James L. Sudmeier、William W. Bachovchin

  DOI：10.1021/jm200460q

  日期：2011.7.14

  Bortezomib, a dipeptidyl boronic acid and potent inhibitor of the 26S proteasome, is remarkably effective against multiple myeloma (MM) but not against solid tumors. Dose-limiting adverse effects from "on target" inhibition of the proteasome in normal cells and tissues appear to be a key obstacle. Achieving efficacy against solid tumors therefore is likely to require making the inhibitor more selective for tumor tissue over normal tissues. The simplest strategy that might provide such tissue specificity would be to employ a tumor specific protease to release an inhibitor from a larger, noninhibitory structure. However, such release would necessarily generate an inhibitor with a free N-terminal amino group, raising a key question: Can short peptide boronic acids with N-terminal amino groups have the requisite properties to serve as warheads in prodrugs? Here we show that dipeptides of boroLeu, the smallest plausible candidates for the task, can indeed be sufficiently potent, cell-penetrating, cytotoxic, and stable to degradation by cellular peptidases to serve in this capacity.
• Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors
  作者：Zongxing Qiu、Bernd Kuhn、Johannes Aebi、Xianfeng Lin、Haiyuan Ding、Zheng Zhou、Zhiheng Xu、Danqing Xu、Li Han、Cheng Liu、Hongxia Qiu、Yuxia Zhang、Wolfgang Haap、Claus Riemer、Martin Stahl、Ning Qin、Hong C. Shen、Guozhi Tang

  DOI：10.1021/acsmedchemlett.6b00208

  日期：2016.8.11

  ATG4B or autophagin-1 is a cysteine protease that cleaves ATG8 family proteins. ATG4B plays essential roles in the autophagosome formation and the autophagy pathway. Herein we disclose the design and structural modifications of a series of fluoromethylketone (FMK)-based peptidomimetics as highly potent ATG4B inhibitors. Their structure activity relationship (SAR) and protease selectivity are also discussed.
• 3,4-DISUBSTITUTED AZETIDIN-2-ONE DERIVATIVES USEFUL AS CYSTEINE PROTEINASE REGULATORS
  申请人：Naeja Pharmaceutical Inc.

  公开号：EP0950046B1

  公开（公告）日：2002-04-10