methyl (3S,6S,7S,9aS)-7-(hydroxymethyl)-6-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxylate | 1099616-12-2

• 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: methyl (3S,6S,7S,9aS)-7-(hydroxymethyl)-6-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxylate
• CAS: 1099616-12-2
• 化学式: C₂₁H₃₅N₃O₇
• 分子量: 441.525
• InChiKey: GIWWONIXVMPHLR-YXMSTPNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  134
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (3S,6S,7S,9aS)-7-(hydroxymethyl)-6-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxylate 在 水 、 lithium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 以100%的产率得到(3S,6S,7S,9aS)-7-(hydroxymethyl)-6-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxylic acid
  参考文献：
  名称：

  Rational design, synthesis and characterization of potent, non-peptidic Smac mimics/XIAP inhibitors as proapoptotic agents for cancer therapy

  摘要：

  Novel proapoptotic Smac mimics/IAPs inhibitors have been designed, synthesized and characterized. Computational models and structural studies (crystallography, NMR) have elucidated the SAR of this class of inhibitors, and have permitted further optimization of their properties. In vitro characterization (XIAP BIR3 and linker-BIR2-BIR3 binding, cytotox assays, early ADMET profiling) of the compounds has been performed, identifying one lead for further in vitro and in vivo evaluation. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.009
• 作为产物：
  描述：

  methyl (3S,7S,10S,13S)-4-benzyl-2-oxo-5-oxa-1,4-diazatricyclo[8.3.0.03,7]tridecane-13-carboxylate 、 BOC-L-2-氨基丁酸 在 palladium 10% on activated carbon 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 72.0h， 以75%的产率得到methyl (3S,6S,7S,9aS)-7-(hydroxymethyl)-6-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxylate
  参考文献：
  名称：

  [EN] SMAC MIMETIC COMPOUNDS AS APOPTOSIS INDUCERS
  [FR] NOUVEAUX COMPOSÉS MIMÉTIQUES DE SMAC EN TANT QU'INDUCTEURS DE L'APOPTOSE

  摘要：

  公开号：

  WO2009060292A3

文献信息

• SMAC mimetic compounds as apoptosis inducers
  申请人：Universita' degli Studi di Milano

  公开号：EP2058312A1

  公开（公告）日：2009-05-13

  The present invention relates to compounds conformationally constrained 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.

  本发明涉及具有凋亡抑制蛋白（IAPs）抑制剂功能的 Smac 的构象受限模拟物化合物，本发明还涉及这些化合物在治疗中的应用，其中诱导细胞凋亡是有益的，特别是在单独或与其他活性成分联合治疗癌症时。
• SPION-Smac mimetic nano-conjugates: Putative pro-apoptotic agents in oncology
  作者：Pierfausto Seneci、Mattia Rizzi、Luigi Ballabio、Daniele Lecis、Annalisa Conti、Claudio Carrara、Emanuela Licandro

  DOI：10.1016/j.bmcl.2014.03.048

  日期：2014.5

  Non-covalent (NP-1/3) and covalent (NP-A-1/3) pro-apoptotic SPION-Smac mimetic nano-conjugates antitumor agents are reported. The solution synthesis of key Smac mimetics, their support onto SPIONs through non-covalent adsorption (NP-1/3) or APTES-mediated covalent binding (NP-A-1/3), the analytical characterization of SPION-Smac mimetic conjugates, their target affinity in cell-free assays, and their cytotoxicity against tumor cells are thoroughly described. (C) 2014 Elsevier Ltd. All rights reserved.
• HOMO- AND HETERODIMERIC SMAC MIMETIC COMPOUNDS AS APOPTOSIS INDUCERS
  申请人：Universita' degli Studi di Milano

  公开号：EP2817322B1

  公开（公告）日：2016-04-20
• SMAC MIMETIC COMPOUNDS AS APOPTOSIS INDUCERS
  申请人：Scolastico Carlo

  公开号：US20100267692A1

  公开（公告）日：2010-10-21

  The present invention relates to compounds conformationally constrained 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.
• 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.