tert-butyl N-[(2S)-1-[[(3S,6S,7S,9aS)-3-[[(1S)-2-[2-[2-[2-[2-[3-[1-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-6-[[(2S)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-7-yl]methyl]triazol-4-yl]propanoylamino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxo-1-phenylethyl]carbamoyl]-7-(hydroxymethyl)-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]-N-methylcarbamate | 1412423-64-3

• 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: tert-butyl N-[(2S)-1-[[(3S,6S,7S,9aS)-3-[[(1S)-2-[2-[2-[2-[2-[3-[1-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-6-[[(2S)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-7-yl]methyl]triazol-4-yl]propanoylamino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxo-1-phenylethyl]carbamoyl]-7-(hydroxymethyl)-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]-N-methylcarbamate
• CAS: 1412423-64-3
• 化学式: C₇₆H₁₀₉N₁₃O₁₆
• 分子量: 1460.78
• InChiKey: OUTCXAUHUVFMQF-SEPWOPGESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  105
• 可旋转键数：
  38
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  353
• 氢给体数：
  7
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S)-1-[[(3S,6S,7S,9aS)-3-[[(1S)-2-[2-[2-[2-[2-[3-[1-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-6-[[(2S)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-7-yl]methyl]triazol-4-yl]propanoylamino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxo-1-phenylethyl]carbamoyl]-7-(hydroxymethyl)-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]-N-methylcarbamate 、 三氟乙酸 以 二氯甲烷 为溶剂， 以86%的产率得到(3S,6S,7R,9aS)-7-[[4-[3-[2-[2-[2-[2-[[(2S)-2-[[(3S,6S,7S,9aS)-7-(hydroxymethyl)-6-[[(2S)-2-(methylamino)butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carbonyl]amino]-2-phenylacetyl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-3-oxopropyl]triazol-1-yl]methyl]-N-benzhydryl-6-[[(2S)-2-(methylamino)butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxamide;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  Homo- and heterodimeric Smac mimetics/IAP inhibitors as in vivo-active pro-apoptotic agents. Part I: Synthesis

  摘要：

  Novel pro-apoptotic, homo-and heterodimeric Smac mimetics/IAPs inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold were prepared from monomeric structures connected through a head-head (8), tail-tail (9) or head-tail (10) linker. The selection of appropriate decorating functions for the scaffolds, and of rigid and flexible linkers connecting them, is described. The synthesis, purification and analytical characterization of each prepared dimer 8-10 is thoroughly described. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.020
• 作为产物：
  描述：

  tert-butyl N-[(2S)-1-[[(3S,6S,7R,9aS)-7-(azidomethyl)-3-(benzhydrylcarbamoyl)-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]-N-methylcarbamate 、 tert-butyl N-[(2S)-1-[[(3S,6S,7S,9aS)-7-(hydroxymethyl)-5-oxo-3-[[(1S)-2-oxo-2-[2-[2-[2-[2-(pent-4-ynoylamino)ethoxy]ethoxy]ethoxy]ethylamino]-1-phenylethyl]carbamoyl]-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]-N-methylcarbamate 在 copper diacetate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 以80%的产率得到tert-butyl N-[(2S)-1-[[(3S,6S,7S,9aS)-3-[[(1S)-2-[2-[2-[2-[2-[3-[1-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-6-[[(2S)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-7-yl]methyl]triazol-4-yl]propanoylamino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxo-1-phenylethyl]carbamoyl]-7-(hydroxymethyl)-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]-N-methylcarbamate
  参考文献：
  名称：

  Homo- and heterodimeric Smac mimetics/IAP inhibitors as in vivo-active pro-apoptotic agents. Part I: Synthesis

  摘要：

  Novel pro-apoptotic, homo-and heterodimeric Smac mimetics/IAPs inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold were prepared from monomeric structures connected through a head-head (8), tail-tail (9) or head-tail (10) linker. The selection of appropriate decorating functions for the scaffolds, and of rigid and flexible linkers connecting them, is described. The synthesis, purification and analytical characterization of each prepared dimer 8-10 is thoroughly described. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.020

文献信息

• New Homo- and Heterodimeric SMAC Mimetic Compounds as Apoptosis Inducers
  申请人：Seneci Pierfausto

  公开号：US20150119342A1

  公开（公告）日：2015-04-30

  The present invention relates to conformationally constrained homo- and heterodimeric mimetics of Smac with function as inhibitors of Inhibitor of Apoptosis Proteins (IAPs), the invention also relates to the use of these compounds in therapy, wherein the induction of apoptotic cell death is beneficial, especially in the treatment of cancer, alone or in combination with other active ingredients.
• US9321808B2
  申请人：——

  公开号：US9321808B2

  公开（公告）日：2016-04-26
• US9730976B2
  申请人：——

  公开号：US9730976B2

  公开（公告）日：2017-08-15
• [EN] NEW HOMO- AND HETERODIMERIC SMAC MIMETIC COMPOUNDS AS APOPTOSIS INDUCERS<br/>[FR] NOUVEAUX COMPOSÉS MIMÉTIQUES DE SMAC DE TYPE HOMODIMÈRE ET HÉTÉRODIMÈRE À TITRE D'INDUCTEURS D'APOPTOSE
  申请人：UNIV DEGLI STUDI MILANO

  公开号：WO2013124701A2

  公开（公告）日：2013-08-29

  The present invention relates to conformationally constrained homo- and heterodimeric mimetics of Smac with function as inhibitors of Inhibitor of Apoptosis Proteins (IAPs), the invention also relates to the use of these compounds in therapy, wherein the induction of apoptotic cell death is beneficial, especially in the treatment of cancer, alone or in combination with other active ingredients.