(5S,5'S,8S,8'S,10aR,10a'R)-3,3'-dodecanedioylbis(N-benzhydral-5-((S)-2-(methylamino)propanamido)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide) | 957187-72-3

• 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: (5S,5'S,8S,8'S,10aR,10a'R)-3,3'-dodecanedioylbis(N-benzhydral-5-((S)-2-(methylamino)propanamido)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide)
• 英文别名: (5S,8S,10aR)-3-[12-[(5S,8S,10aR)-8-(benzhydrylcarbamoyl)-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-3-yl]-12-oxododecanoyl]-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide
• CAS: 957187-72-3
• 化学式: C₆₆H₈₈N₁₀O₈
• 分子量: 1149.49
• InChiKey: DXCPTXCRBFZDAZ-JRNDJQCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  84
• 可旋转键数：
  25
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  222
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 生成 (5S,5'S,8S,8'S,10aR,10a'R)-3,3'-dodecanedioylbis(N-benzhydral-5-((S)-2-(methylamino)propanamido)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide)
  参考文献：
  名称：

  Bivalent Smac Mimetics with a Diazabicyclic Core as Highly Potent Antagonists of XIAP and cIAP1/2 and Novel Anticancer Agents

  摘要：

  Nonpeptidic, bivalent Smac mimetics designed based upon monovalent Smac mimetics with a diazabicyclic core structure bind to XIAP, cIAP1, and cIAP2 with low to subnanomolar affinities and are highly effective in antagonizing XIAP in cell-free functional assays. They efficiently induce the degradation of cIAP1 and cIAP2 in cancer cells at concentrations as low as 1 nM, activate caspase-3 and -8, and cleave PARP at 3-10 nM. The most potent compounds in the series have IC50 of 3-5 nM in inhibition of cell growth in both MDA-MB-231and SK-OV-3 cell lines and are promising lead compounds for the development of a new class of cancer therapy.

  DOI：

  10.1021/jm201072x

文献信息

• [EN] BIVALENT SMAC MIMETICS AND THE USES THEREOF<br/>[FR] AGENTS MIMÉTIQUES BIVALENTS DE LA SMAC ET LEURS UTILISATIONS
  申请人：UNIV MICHIGAN

  公开号：WO2007130626A2

  公开（公告）日：2007-11-15

  [EN] The invention relates to bivalent mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.
  [FR] L'invention concerne des agents mimétiques bivalents de la protéine Smac qui agissent en tant qu'inhibiteurs de l'inhibiteur des protéines de l'apoptose. L'invention concerne également l'utilisation de ces agents mimétiques pour induire une mort cellulaire programmée et pour sensibiliser les cellules à des inducteurs de l'apoptose.