benzyl (S)-(1-oxo-1-((2-oxoethyl)amino)-3-phenylpropan-2-yl)carbamate | 64361-10-0

• 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
• 英文名称: benzyl (S)-(1-oxo-1-((2-oxoethyl)amino)-3-phenylpropan-2-yl)carbamate
• 英文别名: AQ625173；benzyl N-[(2S)-1-oxo-1-(2-oxoethylamino)-3-phenylpropan-2-yl]carbamate
• CAS: 64361-10-0
• 化学式: C₁₉H₂₀N₂O₄
• 分子量: 340.379
• InChiKey: HGCGAOORAMFLTO-KRWDZBQOSA-N

物化性质

• 沸点：
  606.1±55.0 °C(Predicted)
• 密度：
  1.209±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (S)-(1-oxo-1-((2-oxoethyl)amino)-3-phenylpropan-2-yl)carbamate 在 盐酸羟胺 、 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以56%的产率得到benzyl (S)-(1-((2-(hydroxyimino)ethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate
  参考文献：
  名称：

  设计半胱氨酸蛋白酶抑制剂的战斗部的比较研究

  摘要：

  探索了用替代性战斗部取代腈基对克鲁萨因抑制效能的影响。肟的效力几乎比相应的腈强一个数量级，并具有提供进入催化部位主要部分的潜力。发现二肽醛和氮杂二肽腈是比相应的二肽腈有效的克鲁萨因抑制剂高两个数量级，尽管通过P1和P3处的取代来调节效力差异。用环丙烷代替二肽醛的α亚甲基导致效能损失几乎三个数量级。被表征为可逆抑制剂的乙烯基酯和酰胺的效力比相应的腈差一两个数量级。

  DOI：

  10.1016/j.bmcl.2017.10.002
• 作为产物：
  描述：

  N-苄氧羰基-L-苯丙氨酸 N-羟基琥珀酰亚胺酯 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 benzyl (S)-(1-oxo-1-((2-oxoethyl)amino)-3-phenylpropan-2-yl)carbamate
  参考文献：
  名称：

  Development of α-keto-based inhibitors of cruzain, a cysteine protease implicated in Chagas disease

  摘要：

  Trypanosoma cruzi, a protozoan parasite, is the causative agent of Chagas disease, a major cause of cardiovascular disease in many Latin American countries. There is an urgent need to develop an improved therapy due to the toxicity of existing drugs and emerging drug resistance. Cruzain, the primary cysteine protease of T cruzi, is essential for the survival of the parasite in host cells and therefore is an important target for the development of inhibitors as potential therapeutics. A novel series of alpha-ketoamide-, alpha-ketoacid-, alpha-ketoester-, and aldehyde-based inhibitors of cruzain has been developed. The inhibitors were identified by screening protease targeted small molecule libraries and systematically optimizing the P1, P2, P3, and P1 ' residues using specific structure-guided methods. A total of 20 compounds displayed picomolar potency in in vitro assays and three inhibitors representing different alpha-keto-based inhibitor scaffolds demonstrated anti-trypanosomal activity in cell culture. A 2.3 angstrom crystallographic structure of cruzain bound with one of the alpha-ketoester analogs is also reported. The structure and kinetic assay data illustrate the covalent binding, reversible inhibition mechanism of the inhibitor. Information on the compounds reported here will be useful in the development of new lead compounds as potential therapeutic agents for the treatment of Chagas disease and as biological probes to study the role that cruzain plays in the pathology. This study also demonstrates the validity of structure-guided approaches to focused library design and lead compound optimization. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.12.053

文献信息

• Construction of Thioamide Peptide via Sulfur-Involved Amino Acids/Amino Aldehydes Coupling
  作者：Yanyan Liao、Xuefeng Jiang

  DOI：10.1021/acs.orglett.1c03370

  日期：2021.11.19

  A sulfur-involved ligation for thioamide quasi-peptides was developed via amino acids and amino aldehydes coupling. The key to the transformation was the chelation of copper with imines for chiral activation and fixation. In this environment, linear polysulfur decreased the alkalinity of single sulfur anions to prevent racemization caused by the interaction between sulfur and sodium sulfide. Dipeptides

  通过氨基酸和氨基醛偶联开发了硫代酰胺准肽的硫参与连接。转化的关键是铜与亚胺的螯合，以实现手性激活和固定。在这种环境下，线性多硫降低了单一硫阴离子的碱度，以防止硫与硫化钠相互作用引起的外消旋化。成功获得二肽、三肽、四肽以及药物与氨基酸的键合。
• Peroxides as oxidative enzyme inhibitors: Mechanism-based inhibition of a cysteine protease by an amino acid ozonide
  作者：Patrick H. Dussault、A. Denise George、Tony K. Trullinger

  DOI：10.1016/s0960-894x(99)00563-6

  日期：1999.11

  ozonide derived from Cbz-L-Phe accomplishes rapid and stoichiometric inhibition of papain at less than 100 microM concentration under conditions where formation of the corresponding aldehyde is negligible. Oxidation of the active site thiolate by the bound peroxide is believed to lead to formation of an inactive sulfenate or sulfenic acid. Reduction of the ozonide in excess DMSO provides a convenient method

  衍生自Cbz-L-Phe的稳定的臭氧化物可以在可忽略不计相应醛的条件下，以低于100 microM的浓度快速，化学计量地抑制木瓜蛋白酶。结合位的过氧化物对活性位点硫醇盐的氧化被认为导致形成惰性的亚磺酸盐或亚磺酸。过量的DMSO中的ozonide还原为原位生成肽醛提供了一种方便的方法。
• 一种含硫酰胺的多肽类化合物及其合成方法
  申请人：华东师范大学

  公开号：CN113912524A

  公开（公告）日：2022-01-11

  本发明公开了一种如式3,4所示的含硫酰胺的多肽类化合物及其合成方法，以氨基醛、无机硫和和氨基酸为反应原料，在催化剂和添加剂的作用下，在溶剂中反应得到一系列含硫酰胺的多肽类化合物。本发明通过催化条件，以无机硫试剂作为硫源，一锅法构建含硫酰胺的多肽类化合物且手性保持，避免传统以劳森试剂为代表的一类磷硫试剂的弊端；通过本发明发展的合成策略可以顺利得到二肽、三肽、四肽以及肽‑药物偶联类化合物，在未来的药物开发领域具有巨大的潜力。
• 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.
• A comparative study of warheads for design of cysteine protease inhibitors
  作者：Daniel G. Silva、Jean F.R. Ribeiro、Daniela De Vita、Lorenzo Cianni、Caio Haddad Franco、Lucio H. Freitas-Junior、Carolina Borsoi Moraes、Josmar R. Rocha、Antonio C.B. Burtoloso、Peter W. Kenny、Andrei Leitão、Carlos A. Montanari

  DOI：10.1016/j.bmcl.2017.10.002

  日期：2017.11

  replacing a nitrile group with alternative warheads were explored. The oxime was almost an order of magnitude more potent than the corresponding nitrile and has the potential to provide access to the prime side of the catalytic site. Dipeptide aldehydes and azadipeptide nitriles were found to be two orders of magnitude more potent cruzain inhibitors than the corresponding dipeptide nitriles although potency

  探索了用替代性战斗部取代腈基对克鲁萨因抑制效能的影响。肟的效力几乎比相应的腈强一个数量级，并具有提供进入催化部位主要部分的潜力。发现二肽醛和氮杂二肽腈是比相应的二肽腈有效的克鲁萨因抑制剂高两个数量级，尽管通过P1和P3处的取代来调节效力差异。用环丙烷代替二肽醛的α亚甲基导致效能损失几乎三个数量级。被表征为可逆抑制剂的乙烯基酯和酰胺的效力比相应的腈差一两个数量级。