(S)-3-acrylamido-2-(((benzyloxy)carbonyl)amino)propanoic acid | 366780-92-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-3-acrylamido-2-(((benzyloxy)carbonyl)amino)propanoic acid
• 英文别名: (2S)-2-(phenylmethoxycarbonylamino)-3-(prop-2-enoylamino)propanoic acid
• CAS: 366780-92-9
• 化学式: C₁₄H₁₆N₂O₅
• 分子量: 292.291
• InChiKey: DYGSWURAKBTVAR-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-3-acrylamido-2-(((benzyloxy)carbonyl)amino)propanoic acid 在 二甲基二环氧乙烷 作用下， 以 丙酮 为溶剂， 以100%的产率得到N_α-carbobenzyloxy-L-2-amino-3-(oxiranecarbonylamino)propionic acid
  参考文献：
  名称：

  Synthesis of dipeptide-bound epoxides and α,β-unsaturated amides as potential irreversible transglutaminase inhibitors

  摘要：

  Herein we report the synthesis of 24 novel peptides Lis potential irreversible inactivators of transglutaminase (TGase). These peptides were designed to resemble Cbz-L-Gln-Gly, known to be a good TGase substrate, and to include either alpha,beta -unsaturated amide groups or the corresponding epoxide groups. The side chain length: of the amino acid residue bearing the inhibitor group was also varied in order to permit investigation of this effect. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00292-9
• 作为产物：
  描述：

  N-苄氧羰基-L-天冬酰胺 在 吡啶 、 三乙胺 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 (S)-3-acrylamido-2-(((benzyloxy)carbonyl)amino)propanoic acid
  参考文献：
  名称：

  Synthesis of dipeptide-bound epoxides and α,β-unsaturated amides as potential irreversible transglutaminase inhibitors

  摘要：

  Herein we report the synthesis of 24 novel peptides Lis potential irreversible inactivators of transglutaminase (TGase). These peptides were designed to resemble Cbz-L-Gln-Gly, known to be a good TGase substrate, and to include either alpha,beta -unsaturated amide groups or the corresponding epoxide groups. The side chain length: of the amino acid residue bearing the inhibitor group was also varied in order to permit investigation of this effect. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00292-9

文献信息

• [EN] TG2 INHIBITOR COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS INHIBITEURS DE TG2 ET UTILISATIONS DE CES DERNIERS
  申请人：UNIV OTTAWA

  公开号：WO2017179018A1

  公开（公告）日：2017-10-19

  There are provided Tissue Transglutaminase (TG2) inhibitor compounds, and compositions and methods of use thereof for the prevention or treatment of a cancer. Compounds of Formula I, and pharmaceutically acceptable salts thereof, are provided: Formula (I).

  提供了组织转谷氨酰胺酶（TG2）抑制剂化合物，以及其用于预防或治疗癌症的组合物和使用方法。提供了化合物I的公式，以及其药用盐：公式（I）。
• TG2 inhibitor piperazine compounds and uses thereof
  申请人：UNIVERSITY OF OTTAWA

  公开号：US10894777B2

  公开（公告）日：2021-01-19

  There are provided Tissue Transglutaminase (TG2) inhibitor compounds, and compositions and methods of use thereof for the prevention or treatment of a cancer. Compounds of Formula I, and pharmaceutically acceptable salts thereof, are provided:

  提供了组织转谷氨酰胺酶（TG2）抑制剂化合物及其用于预防或治疗癌症的组合物和使用方法。提供了式 I 的化合物及其药学上可接受的盐类：
• Structure–Activity Relationships of Potent, Targeted Covalent Inhibitors That Abolish Both the Transamidation and GTP Binding Activities of Human Tissue Transglutaminase
  作者：Abdullah Akbar、Nicole M. R. McNeil、Marie R. Albert、Viviane Ta、Gautam Adhikary、Karine Bourgeois、Richard L. Eckert、Jeffrey W. Keillor

  DOI：10.1021/acs.jmedchem.7b01070

  日期：2017.9.28

  Human tissue transglutaminase (hTG2) is a multifunctional enzyme. It is primarily known for its calcium dependent transamidation activity that leads to formation of an isopeptide bond between glutamine and lysine residues found on the surface of proteins, but it is also a GTP binding protein. Overexpression and unregulated hTG2 activity have been associated with numerous human diseases, including cancer stem cell survival and metastatic phenotype. Herein, we present a series of targeted covalent inhibitors (TCIs) based on our previously reported Cbz-Lys scaffold. From this structure activity relationship (SAR) study, novel irreversible inhibitors were identified that block the transamidation activity of hTG2 and allosterically abolish its GTP binding ability with a high degree of selectivity and efficiency (k(inact)/K-I > 10(5) M-1 min(-1)). One optimized inhibitor (VA4) was also shown to inhibit epidermal cancer stem cell invasion with an EC50 of 3.9 mu M, representing a significant improvement over our previously reported "hit" NC9.