bis(((1aR,7aS,10aS,10bS,E)-1a-methyl-8-methylene-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2‘,3‘:9,10]cyclodeca(1,2-bfuran-5-yl)methyl)4,4'-(butane-1,4-diyl)bis(azanediyl))bis(4-oxobutanoate)

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: bis(((1aR,7aS,10aS,10bS,E)-1a-methyl-8-methylene-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2‘,3‘:9,10]cyclodeca(1,2-bfuran-5-yl)methyl)4,4'-(butane-1,4-diyl)bis(azanediyl))bis(4-oxobutanoate)
• 英文别名: bis-(((1aR,7aS,10aS,10bS,E)-1a-methyl-8-methylene-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-5-yl)methyl)-4,4'-(butane-1,4-diylbis(azanediyl)) bis-(4-oxobutanoate)；[(1S,2S,4R,7E,11S)-4-methyl-12-methylidene-13-oxo-3,14-dioxatricyclo[9.3.0.02,4]tetradec-7-en-8-yl]methyl 4-[4-[[4-[[(1S,2S,4R,7E,11S)-4-methyl-12-methylidene-13-oxo-3,14-dioxatricyclo[9.3.0.02,4]tetradec-7-en-8-yl]methoxy]-4-oxobutanoyl]amino]butylamino]-4-oxobutanoate
• 化学式: C₄₂H₅₆N₂O₁₂
• 分子量: 780.913
• InChiKey: WTHJCHSLGIMXFA-ZSHKISGDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  56
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  189
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  melampomagnolide B 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 生成 bis(((1aR,7aS,10aS,10bS,E)-1a-methyl-8-methylene-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2‘,3‘:9,10]cyclodeca(1,2-bfuran-5-yl)methyl)4,4'-(butane-1,4-diyl)bis(azanediyl))bis(4-oxobutanoate)
  参考文献：
  名称：

  [EN] MELAMPOMAGNOLIDE B DIMERS
  [FR] DIMÈRES DE MÉLAMPOMAGNOLIDE B

  摘要：

  本公开提供了美拉波木内酯B（MMB）的二聚体，包括MMB的氨基甲酸酯、碳酸酯、琥珀酰胺、酯和羧酰胺二聚体。这些衍生物对于治疗人类癌症特别有用，尤其是治疗白血病，包括急性髓性白血病（AML）。一种包含如下式（1）的化合物：其中：Z独立地选自由CH2、O、C（O）和CH组成的群，当Z为CH时，Z通过双键连接到Y，而Y为N。

  公开号：

  WO2016090166A1

文献信息

• [EN] MELAMPOMAGNOLIDE B DIMERS<br/>[FR] DIMÈRES DE MÉLAMPOMAGNOLIDE B
  申请人：UNIV ARKANSAS

  公开号：WO2016090166A1

  公开（公告）日：2016-06-09

  The present disclosure provides dimers of melampomagnolide B (MMB), including carbamate, carbonate, succinic amide, ester and carboxamide dimers of MMB. These derivatives are useful for treating cancer in humans, in particular in treating leukemia, including acute myelogenous leukemia (AML). A compound comprising Formula (1 ) wherein: Z is independently selected from the group consisting of CH2, O, C(O), and CH, wherein when Z is CH, Z is connected to Y via a double bond and Y is N.

  本公开提供了美拉波木内酯B（MMB）的二聚体，包括MMB的氨基甲酸酯、碳酸酯、琥珀酰胺、酯和羧酰胺二聚体。这些衍生物对于治疗人类癌症特别有用，尤其是治疗白血病，包括急性髓性白血病（AML）。一种包含如下式（1）的化合物：其中：Z独立地选自由CH2、O、C（O）和CH组成的群，当Z为CH时，Z通过双键连接到Y，而Y为N。
• MELAMPOMAGNOLIDE B DIMERS
  申请人：BioVentures, LLC

  公开号：US20170362254A1

  公开（公告）日：2017-12-21

  The present disclosure provides dimers of melampomagnolide B (MMB), including carbamate, carbonate, succinic amide, ester and carboxamide dimers of MMB. These derivatives are useful for treating cancer in humans, in particular in treating leukemia, including acute myelogenous leukemia (AML). A compound comprising Formula (1) wherein: Z is independently selected from the group consisting of CH2, O, C(O), and CH, wherein when Z is CH, Z is connected to Y via a double bond and Y is N.
• US9981990B2
  申请人：——

  公开号：US9981990B2

  公开（公告）日：2018-05-29
• Succinamide derivatives of melampomagnolide B and their anti-cancer activities
  作者：Venumadhav Janganati、Jessica Ponder、Shraddha Thakkar、Craig T. Jordan、Peter A. Crooks

  DOI：10.1016/j.bmc.2017.05.008

  日期：2017.7

  A series of succinamide derivatives of melampomagnolide B have been synthesized by coupling MMB monosuccinate (2) with various heterocyclic amines to afford compounds 3a-3l. MMB monosuccinate was also reacted with terminal diaminoalkanes to afford dimeric succinamido analogs of MMB (4a-4h). These succinamide analogs of MMB were evaluated for their anti-cancer activity against a panel of sixty human cancer cell lines. Analogs 3d-3i and dimers 4f-4g exhibited promising anti-cancer activity with GI(50) values ranging from 0.28 to 33.5 mu M against most of the cell lines in the panel. The dimeric analogs 4f and 4g were identified as lead compounds with GI(50) values in the nanomolar range (GI(50) = 280-980 nM) against several cell lines in the panel; i.e. leukemia cell lines CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226 and SR; and solid tumor cell lines NCI-H522 (non-small cell lung cancer), SW-620 and HCT-116 (colon cancer), LOX IMVI (melanoma), RXF 393 (renal cancer), and MCF7, BT-549 and MDA-MB-468 (breast cancer). Succinamide analogs 3a, 3c-3l and 4b-4h were also evaluated for their apoptotic activity against M9-ENL1 acute myelogenous leukemia cells; compounds 3h-3j and 4g were equipotent with parthenolide, exhibiting LC50 values in the range 4.1-8.1 mu M. Molecular docking studies indicate that these molecules interact covalently with the highly conserved Cys-46 residue of the N-terminal lobe (1-109) of human IKK beta to inhibit the NF-kappa B transcription factor complex, resulting in down-regulation of anti-apoptotic genes under NF kappa B control. (C) 2017 Elsevier Ltd. All rights reserved.