(2S)-2-(naphthalene-1-carbonylamino)-3-phenylpropanoic acid | 168831-28-5

• 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
• 英文名称: (2S)-2-(naphthalene-1-carbonylamino)-3-phenylpropanoic acid
• 英文别名: N-naphthaloyl-(s)-phenylalanine
• CAS: 168831-28-5
• 化学式: C₂₀H₁₇NO₃
• 分子量: 319.36
• InChiKey: KFPQZHGGCMDFEM-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S)-2-(naphthalene-1-carbonylamino)-3-phenylpropanoic acid 在 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 N-[(1S)-1-benzyl-2-[(3-fluoro-2-oxo-propyl)-methyl-amino]-2-oxo-ethyl]naphthalene-1-carboxamide
  参考文献：
  名称：

  Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors

  摘要：

  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.

  DOI：

  10.1021/acsmedchemlett.6b00208
• 作为产物：
  描述：

  L-苯丙氨酸甲酯盐酸盐 在 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 4.0h， 生成 (2S)-2-(naphthalene-1-carbonylamino)-3-phenylpropanoic acid
  参考文献：
  名称：

  Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors

  摘要：

  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.

  DOI：

  10.1021/acsmedchemlett.6b00208

文献信息

• 5,5′-Diamino-BIPHEP ligands bearing small selector units for non-covalent binding of chiral analytes in solution
  作者：G. Storch、M. Siebert、F. Rominger、O. Trapp

  DOI：10.1039/c5cc06306j

  日期：——

  A dynamic axially chiral BIPHEP-ligand with 3,5-dichlorobenzoyl amide selector units for non-covalent binding of phenylalanine derivatives has been developed.

  已开发出一种具有3,5-二氯苯甲酰胺选择单元的动态轴向手性BIPHEP配体，用于非共价结合苯丙氨酸衍生物。
• Novel irreversible peptidic inhibitors of transglutaminase 2
  作者：Nicholas J. Cundy、Jane Arciszewski、Eric W. J. Gates、Sydney L. Acton、Kyle D. Passley、Ernest Awoonor-Williams、Elizabeth K. Boyd、Nancy Xu、Élise Pierson、Catalina Fernandez-Ansieta、Marie R. Albert、Nicole M. R. McNeil、Gautam Adhikary、Richard L. Eckert、Jeffrey W. Keillor

  DOI：10.1039/d2md00417h

  日期：——

  vivo. Our latest efforts in inhibitor optimization involve the modification of a previous lead compound's scaffold by insertion of various amino acid residues into the peptidomimetic backbone, and derivatization of the N-terminus with substituted phenylacetic acids, resulting in 28 novel irreversible inhibitors. These inhibitors were evaluated for their ability to inhibit TG2 in vitro and their pharmacokinetic

  转谷氨酰胺酶 2 (TG2)，也称为组织转谷氨酰胺酶，在蛋白质交联和细胞信号传导中发挥着至关重要的作用。它既能催化转酰胺基作用，又能充当 G 蛋白，这些活性依赖于构象、相互排斥且受到严格调控。这两种活动的失调与许多病理学有关。 TG2 在人类中普遍表达，并且定位于细胞内和细胞外。靶向 TG2 疗法已经开发出来，但面临着许多障碍，包括体内疗效下降。我们在抑制剂优化方面的最新努力包括通过将各种氨基酸残基插入拟肽主链来修饰先前先导化合物的支架，并用取代的苯乙酸对N末端进行衍生化，从而产生 28 种新型不可逆抑制剂。评估了这些抑制剂在体外抑制 TG2 的能力及其药代动力学特性，并在癌症干细胞模型中测试了最有希望的候选药物35 ( k inact / K I = 760 × 10 3 M -1 min -1 )。尽管这些抑制剂与TG2 相比表现出卓越的效力，其k inact / K I比率比其母体化
• Composition containing a penem or carbapenem antibiotic
  申请人：SANKYO COMPANY LIMITED

  公开号：EP0178911A2

  公开（公告）日：1986-04-23

  57 Administration of an N-acylated amino acid (ornithine, lysine, phenylglycine or phenylalanine) in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially. A pharmaceutical composition may be prepared simply by mixing the two components.

  57 将 N-酰化氨基酸（鸟氨酸、赖氨酸、苯甘氨酸或苯丙氨酸）与培南类或碳青霉烯类抗生素联合给药，可缓解或消除与单独给药抗生素相关的肾脏问题。 氨基酸和抗生素可一起配制成组合物，也可同时或依次单独给药。 只需将两种成分混合即可制备成药物组合物。
• US4757066A
  申请人：——

  公开号：US4757066A

  公开（公告）日：1988-07-12
• 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.