2,5-dioxopyrrolidin-1-yl 2-(diethoxyphosphoryl)acetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: 2,5-dioxopyrrolidin-1-yl 2-(diethoxyphosphoryl)acetate
• 英文别名: phosphonoacetic acid N-hydroxysuccinimide ester；(2,5-Dioxopyrrolidin-1-yl) 2-diethoxyphosphorylacetate
• 化学式: C₁₀H₁₆NO₇P
• 分子量: 293.213
• InChiKey: NKGSYJQRPQJTIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  99.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,5-dioxopyrrolidin-1-yl 2-(diethoxyphosphoryl)acetate 在 N-羟基丁二酰亚胺 、 sodium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 36.5h， 生成 tert-butyl ((S)-6-(2-(diethoxyphosphoryl)acetamido)-1-(((S)-1-hydroxypropan-2-yl)amino)-1-oxohexan-2-yl)carbamate
  参考文献：
  名称：

  Syntheses and cytotoxicity of syringolin B-based proteasome inhibitors

  摘要：

  The concise and modular total synthesis of the bacterial natural product and irreversible proteasome inhibitor syringolin B has been achieved. This synthesis has enabled the ready preparation of three diverse, structurally modified syringolin derivatives. The actions of these compounds in inhibiting the proliferation of neuroblastoma cell lines was evaluated, and significant enhancements in potency compared to the natural product were realized. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.09.048
• 作为产物：
  描述：

  磷酰基乙酸三乙酯 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 2,5-dioxopyrrolidin-1-yl 2-(diethoxyphosphoryl)acetate
  参考文献：
  名称：

  클로로퀸 기반 α,β-불포화아미드 유도체 화합물을 유효성분으로 함유하는 말라리아 감염 질환의 예방 또는 치료용 조성물

  摘要：

  该专利涉及含有新结构的氯喹基α,β-不饱和酰胺衍生物化合物作为有效成分的抗疟药。通过对该新结构的氯喹基α,β-不饱和酰胺衍生物化合物进行抗疟活性P. falciparum菌株生长抑制活性和Hela细胞生长细胞毒性实验，确认了这些新化合物具有出色的抗疟活性，可用于治疗和预防疟疾感染疾病的药学组合物中。

  公开号：

  KR101653677B1

文献信息

• 페닐알라닌-클로로퀸 유도체 화합물을 유효성분으로 함유하는 말라리아 감염 질환의 예방 또는 치료용 조성물
  申请人：Wonkwang University Center for Industry-Academy Cooperation 원광대학교산학협력단(220040233365) BRN ▼403-82-09152

  公开号：KR20180071069A

  公开（公告）日：2018-06-27

  본 발명은 상기 일반식 (I)으로 표기되는 신규 구조의 페닐알라닌-클로로퀸 유도체 화합물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 말라리아감염 질환 치료 및 예방용 조성물로서, 본 발명의 신규 구조의 페닐알라닌-클로로퀸 유도체 화합물들을 대상으로 항-말라리아 활성을 균주(Plasmodium falciparum)를 이용한 in vitro 항말라리아 효능검색(실험예 1); 및 말라리아 감염 마우스를 이용한 동물실험 (실험예 2)을 통하여 확인한 결과, 상기 신규 화합물들의 항-말라리아 활성이 탁월함을 확인하여 신규 규조의 페닐알라닌-클로로퀸 유도체 화합물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 항말라리아제를 제공한다.

  This invention provides an antimalarial agent containing a phenylalanine-chloroquine derivative compound with a novel structure represented by the general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient for the treatment and prevention of malaria infection diseases. Through in vitro antimalarial efficacy screening using Plasmodium falciparum as the target for the novel phenylalanine-chloroquine derivative compounds of the present invention (Experimental Example 1), and animal experiments using malaria-infected mice (Experimental Example 2), it was confirmed that the antimalarial activity of the novel compounds is excellent, thus providing an antimalarial agent containing a phenylalanine-chloroquine derivative compound with a novel structure or a pharmacologically acceptable salt thereof as an effective ingredient.
• [EN] NOVEL SYRINGOLIN ANALOGUES AND METHODS OF MAKING AND USING SAME<br/>[FR] NOUVEAUX ANALOGUES DE SYRINGOLINE ET PROCÉDÉS DE FABRICATION ET D'UTILISATION DE CEUX-CI
  申请人：UNIV BROWN

  公开号：WO2016182968A1

  公开（公告）日：2016-11-17

  The present invention provides, in certain aspects, novel syringolin analogues, In certain embodiments, the compounds of the invention are proteasome inhibitors, In other embodiments, the compounds treat or prevent a cancer such as, but not limited to, leukemia in a subject,

  本发明在某些方面提供了新颖的西林类似物。在某些实施方式中，本发明的化合物是蛋白酶体抑制剂。在其他实施方式中，这些化合物用于治疗或预防主体中的癌症，如但不限于白血病。
• Total Synthesis of Syringolin A and B
  作者：Michael C. Pirrung、Goutam Biswas、Tannya R. Ibarra-Rivera

  DOI：10.1021/ol100761z

  日期：2010.5.21

  Total syntheses of two recently discovered proteasome inhibitors, syringolin A and B, are reported. The key to our approach was creation of the α,β-unsaturated 12-membered lactam via intramolecular Horner−Wadsworth−Emmons reaction. Such reactions have been broadly used to prepared macrolactones, but this work presents a rarer example of its application to macrolactams. The final steps involved attachment

  据报道，两种最近发现的蛋白酶体抑制剂丁香脂素A和丁香酚B的总合成。我们方法的关键是通过分子内Horner-Wadsworth-Emmons反应生成α，β-不饱和12元内酰胺。这种反应已被广泛用于制备大内酯，但是这项工作为大内酰胺提供了一个罕见的例子。最终步骤包括使用肽偶联方法，包括基于未保护的缬氨酸N-羧酸酐的方法连接双（戊烯基）脲侧链。通过交叉复分解产生了丁香环素A的另外的烯烃。
• [EN] IMMUNOPROTEASOME INHIBITOR ANALOGS<br/>[FR] ANALOGUES D'INHIBITEURS D'IMMUNOPROTÉASOMES
  申请人：UNIV CALIFORNIA

  公开号：WO2017156471A1

  公开（公告）日：2017-09-14

  The disclosure provides for compounds having immunoproteasome inhibitory activity, and pharmaceutical compositions made thereof. The disclosure further provides for the use of the compounds and compositions in treating various diseases and disorders in a subject that are associated with immunoproteasome activity, including inflammatory disorders, autoimmune disorders, hematological disorders, and neurodegenerative disorders.

  该披露提供了具有免疫蛋白酶体抑制活性的化合物，以及由此制成的药物组合物。该披露进一步提供了在治疗与免疫蛋白酶体活性相关的受试者中的各种疾病和紊乱中使用这些化合物和组合物，包括炎症性疾病、自身免疫性疾病、血液学疾病和神经退行性疾病。
• Immunoproteasome inhibition and bioactivity of thiasyrbactins
  作者：Nicole A. Bakas、Chad R. Schultz、Lisette P. Yco、Christopher C. Roberts、Chia-en A. Chang、André S. Bachmann、Michael C. Pirrung

  DOI：10.1016/j.bmc.2017.11.048

  日期：2018.1

  trypsin-like catalytic site, including of the immunoproteasome. Their bound and free conformations suggest special properties of the thiasyrbactin ring are responsible for this unusual preference, which may be exploited to develop drug-like immunoproteasome inhibitors. These compounds show greater selectivity than earlier compounds used to infer phenotypes of immunoproteasome inhibition, like ONX-0914.

  缩乙内酰胺天然产物家族中的喜瑞巴汀（syrbactins）是已知的蛋白酶体抑制剂。制备了一小部分的喜乐丁类似物，用硫取代碳以增强合成的可及性并促进其溶解度的调节。这些化合物中的两种令人惊讶地证明是胰蛋白酶样催化位点的抑制剂，包括免疫蛋白酶体的抑制剂。它们的结合和游离构象表明，硫代酪蛋白环的特殊性质是造成这种不寻常偏好的原因，其可用于开发类似药物的免疫蛋白酶体抑制剂。这些化合物显示出比用于推断免疫蛋白酶体抑制表型的早期化合物（如ONX-0914）更高的选择性。