(3S,6S,10aS)-6-((S)-2-(methylamino)propanamido)-N-((1-(2-(2-(2-(2-(4-((S)-((3S,6S,10aS)-6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamido)(phenyl)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)(phenyl)methyl)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide | 957135-36-3

• 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: (3S,6S,10aS)-6-((S)-2-(methylamino)propanamido)-N-((1-(2-(2-(2-(2-(4-((S)-((3S,6S,10aS)-6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamido)(phenyl)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)(phenyl)methyl)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide
• 英文别名: (3S,6S,1''aS)-6-((S)-2-(Methylamino)propanamido)-N-((1-(2-(2-(2-(2-(4-((S)-((3S,6S,1''aS)-6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamido)(phenyl)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)(phenyl)methyl)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide；(3S,6S,10aS)-N-[(S)-[1-[2-[2-[2-[2-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide
• CAS: 957135-36-3
• 化学式: C₅₆H₈₀N₁₄O₉
• 分子量: 1093.34
• InChiKey: BJTRDZRWFOFYFN-QHNAYFJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  79
• 可旋转键数：
  26
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  270
• 氢给体数：
  6
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  在 ascorbic acid sodium salt 、 盐酸 作用下， 以 水 、 正丁醇 、 1,4-二氧六环 、 甲醇 为溶剂， 以63%的产率得到(3S,6S,10aS)-6-((S)-2-(methylamino)propanamido)-N-((1-(2-(2-(2-(2-(4-((S)-((3S,6S,10aS)-6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamido)(phenyl)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)(phenyl)methyl)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide
  参考文献：
  名称：

  WO2007/130626

  摘要：

  公开号：

文献信息

• Potent Bivalent Smac Mimetics: Effect of the Linker on Binding to Inhibitor of Apoptosis Proteins (IAPs) and Anticancer Activity
  作者：Haiying Sun、Liu Liu、Jianfeng Lu、Longchuan Bai、Xiaoqin Li、Zaneta Nikolovska-Coleska、Donna McEachern、Chao-Yie Yang、Su Qiu、Han Yi、Duxin Sun、Shaomeng Wang

  DOI：10.1021/jm101651b

  日期：2011.5.12

  We have synthesized and evaluated a series of nonpeptidic, bivalent Smac mimetics as antagonists of the inhibitor of apoptosis proteins and new anticancer agents. All these bivalent Smac mimetics bind to full-length XIAP with low nanomolar affinities and function as ultrapotent antagonists of XIAP. While these Smac mimetics bind to cIAP1/2 with similar low nanomolar affinities, their potencies to induce degradation of cIAP1/2 proteins in cells differ by more than 100-fold. The most potent bivalent Smac mimetics inhibit cell growth with IC(50) from 1 to 3 nM in the MDA-MB-231 breast cancer cell line and are 100 times more potent than the least potent compounds. Determination of intracellular concentrations for several representative compounds showed that the linkers in these bivalent Smac mimetics significantly affect their intracellular concentrations and hence the overall cellular activity. Compound 27 completely inhibits tumor growth in the MDA-MB-231 xenografts while causing no signs of toxicity in the animals.
• INTERMEDIATES FOR THE PREPARATION OF BIVALENT SMAC MIMETICS
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：EP2019671B1

  公开（公告）日：2014-09-24
• Bivalent SMAC mimetics and the uses thereof
  申请人：Wang Shaomeng

  公开号：US20080089896A1

  公开（公告）日：2008-04-17

  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.
• BIVALENT SMAC MIMETICS AND THE USES THEREOF
  申请人：Wang Shaomeng

  公开号：US20090123480A1

  公开（公告）日：2009-05-14

  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.
• US7960372B2
  申请人：——

  公开号：US7960372B2

  公开（公告）日：2011-06-14