(S,3S,3'S,6S,6'S,10aS,10a'S)-N,N'-((1S,1'S)-(1,1'-(dodecane-1,12-diyl)bis(1H-1,2,3-triazole-4,1-diyl))bis(phenylmethylene))bis(6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[ 1,2-a]azocine-3-carboxamide) | 1298048-66-4

• 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: (S,3S,3'S,6S,6'S,10aS,10a'S)-N,N'-((1S,1'S)-(1,1'-(dodecane-1,12-diyl)bis(1H-1,2,3-triazole-4,1-diyl))bis(phenylmethylene))bis(6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[ 1,2-a]azocine-3-carboxamide)
• 英文别名: (3S,6S,10aS)-N-[(S)-[1-[12-[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]dodecyl]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: 1298048-66-4
• 化学式: C₆₀H₈₈N₁₄O₆
• 分子量: 1101.45
• InChiKey: WPLLBQSMIJWPPJ-LGDBJAKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  80
• 可旋转键数：
  27
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  243
• 氢给体数：
  6
• 氢受体数：
  12

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 为溶剂， 生成 (S,3S,3'S,6S,6'S,10aS,10a'S)-N,N'-((1S,1'S)-(1,1'-(dodecane-1,12-diyl)bis(1H-1,2,3-triazole-4,1-diyl))bis(phenylmethylene))bis(6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[ 1,2-a]azocine-3-carboxamide)
  参考文献：
  名称：

  Potent Bivalent Smac Mimetics: Effect of the Linker on Binding to Inhibitor of Apoptosis Proteins (IAPs) and Anticancer Activity

  摘要：

  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.

  DOI：

  10.1021/jm101651b