1,1a(2)-Diethyl (2E,2a(2)E)-4,4a(2)-[(3,6-dioxo-2,5-piperazinediyl)bis(4,1-butanediylimino)]bis[4-oxo-2-butenoate] | 1013385-28-8

• 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: 1,1a(2)-Diethyl (2E,2a(2)E)-4,4a(2)-[(3,6-dioxo-2,5-piperazinediyl)bis(4,1-butanediylimino)]bis[4-oxo-2-butenoate]
• 英文别名: ethyl (E)-4-[4-[5-[4-[[(E)-4-ethoxy-4-oxobut-2-enoyl]amino]butyl]-3,6-dioxopiperazin-2-yl]butylamino]-4-oxobut-2-enoate
• CAS: 1013385-28-8
• 化学式: C₂₄H₃₆N₄O₈
• 分子量: 508.572
• InChiKey: QLVUUTXYMBJJSA-PHEQNACWSA-N

物化性质

• 沸点：
  845.4±65.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  36
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  169
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1,1a(2)-Diethyl (2E,2a(2)E)-4,4a(2)-[(3,6-dioxo-2,5-piperazinediyl)bis(4,1-butanediylimino)]bis[4-oxo-2-butenoate] 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 3,4-bis(N-fumaryl-N-(n-butyl)amino)-2,5-diketopiperazine
  参考文献：
  名称：

  Methods for the synthesis of activated ethylfumarates and their use as intermediates

  摘要：

  揭示的实施例涉及改进的方法，用于合成活性富马酸中间体，并将其用于化学合成。揭示的实施例描述了活化富马酸酯的合成，包括那些来自激活基团的酯，例如：4-硝基苯基、二苯基磷酸酰叠氮化物、皮瓦酰氯、氯磺酰异氰酸酯、对硝基苯酚、MEF、三氟乙酰和氯等，例如，乙酰基富马酰氯和随后在原位使用活化酯。进一步的实施例描述了从未分离和未纯化的中间体改进合成取代氨基烷基二酮哌嗪，从而实现了更高的产量和反应器吞吐量。

  公开号：

  US20130289278A1
• 作为产物：
  描述：

  富马酸单乙酯 在 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 0.33h， 生成 1,1a(2)-Diethyl (2E,2a(2)E)-4,4a(2)-[(3,6-dioxo-2,5-piperazinediyl)bis(4,1-butanediylimino)]bis[4-oxo-2-butenoate]
  参考文献：
  名称：

  Methods for the synthesis of activated ethylfumarates and their use as intermediates

  摘要：

  揭示的实施例涉及改进的方法，用于合成活性富马酸中间体，并将其用于化学合成。揭示的实施例描述了活化富马酸酯的合成，包括那些来自激活基团的酯，例如：4-硝基苯基、二苯基磷酸酰叠氮化物、皮瓦酰氯、氯磺酰异氰酸酯、对硝基苯酚、MEF、三氟乙酰和氯等，例如，乙酰基富马酰氯和随后在原位使用活化酯。进一步的实施例描述了从未分离和未纯化的中间体改进合成取代氨基烷基二酮哌嗪，从而实现了更高的产量和反应器吞吐量。

  公开号：

  US20130289278A1

文献信息

• Dry powder inhaler and system for drug delivery
  申请人：MannKind Corporation

  公开号：US11185645B2

  公开（公告）日：2021-11-30

  A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided.

  提供了一种呼吸驱动的干粉吸入器、一个药盒和一个肺部给药系统。
• Azithromycin-loaded respirable microparticles for targeted pulmonary delivery for the treatment of pneumonia
  作者：Qiyue Wang、Gujie Mi、Daniel Hickey、Yanan Li、Jiasheng Tu、Thomas J. Webster、Yan Shen

  DOI：10.1016/j.biomaterials.2018.01.022

  日期：2018.4

  Pneumonia is a major contributor to infection-based hospitalizations and deaths in the United States. Antibiotics such as azithromycin (AZM), although effective at managing pneumonia, often suffer from off-target diffusion and poor bioavailability when administered orally or via intravenous injection. The formation of biofilms at the disease sites makes the treatment more complicated by protecting bacteria from antimicrobial agents and thus necessitating a much higher dosage of antibiotics to eradicate the biofilms. As such, targeted pulmonary delivery of antibiotics has emerged as a promising alternative by providing direct access to the lung while also allowing higher local therapeutic concentrations but minimal systemic exposure. In this study, AZM was encapsulated in N-fumaroylated diketopiperazine (FDKP) microparticles for efficient pulmonary delivery. Both in vitro and in vivo results demonstrated that AZM@FDKP-MPs administered via intratracheal insufflation achieved at least a 3.4 times higher local concentration and prolonged retention times compared to intravenous injection and oral administration, suggesting their potential to better manage bacterial pneumonia. (C) 2018 Elsevier Ltd. All rights reserved.
• DRY POWDER INHALER AND SYSTEM FOR DRUG DELIVERY
  申请人：MannKind Corporation

  公开号：US20150045295A1

  公开（公告）日：2015-02-12

  A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable.
• US8912193B2
  申请人：——

  公开号：US8912193B2

  公开（公告）日：2014-12-16
• US9192675B2
  申请人：——

  公开号：US9192675B2

  公开（公告）日：2015-11-24