tert-butyl N-[(2S)-1-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-7-[[benzyl(methyl)amino]methyl]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]carbamate | 1151560-44-9

• 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,7R,9aS)-3-(benzhydrylcarbamoyl)-7-[[benzyl(methyl)amino]methyl]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]carbamate
• CAS: 1151560-44-9
• 化学式: C₄₁H₅₃N₅O₅
• 分子量: 695.902
• InChiKey: IJIHWNFVOVNWDK-IXPCKDSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  51
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S)-1-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-7-[[benzyl(methyl)amino]methyl]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]carbamate 在 盐酸 、 甲醇 作用下， 以96%的产率得到(3S,6S,7R,9aS)-6-[[(2S)-2-aminobutanoyl]amino]-N-benzhydryl-7-[[benzyl(methyl)amino]methyl]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxamide;hydrochloride
  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：

  聚合甲醛 、 tert-butyl N-[(2S)-1-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-7-[(benzylamino)methyl]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]carbamate 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 以92%的产率得到tert-butyl N-[(2S)-1-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-7-[[benzyl(methyl)amino]methyl]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]carbamate
  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

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。
• [EN] SMAC MIMETIC COMPOUNDS AS APOPTOSIS INDUCERS<br/>[FR] NOUVEAUX COMPOSÉS MIMÉTIQUES DE SMAC EN TANT QU'INDUCTEURS DE L'APOPTOSE
  申请人：UNIV DEGLI STUDI MILANO

  公开号：WO2009060292A3

  公开（公告）日：2009-06-25
• 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.
• [EN] NEW SMAC MIMETIC COMPOUNDS AS APOPTOSIS INDUCERS<br/>[FR] NOUVEAUX COMPOSÉS MIMÉTIQUES DE SMAC EN TANT QU'INDUCTEURS DE L'APOPTOSE
  申请人：UNIV DEGLI STUDI MILANO

  公开号：WO2009060292A2

  公开（公告）日：2009-05-14

  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.
• Rational design, synthesis and characterization of potent, non-peptidic Smac mimics/XIAP inhibitors as proapoptotic agents for cancer therapy
  作者：Pierfausto Seneci、Aldo Bianchi、Cristina Battaglia、Laura Belvisi、Martino Bolognesi、Andrea Caprini、Federica Cossu、Elena de Franco、Marilenia de Matteo、Domenico Delia、Carmelo Drago、Amira Khaled、Daniele Lecis、Leonardo Manzoni、Moira Marizzoni、Eloise Mastrangelo、Mario Milani、Ilaria Motto、Elisabetta Moroni、Donatella Potenza、Vincenzo Rizzo、Federica Servida、Elisa Turlizzi、Maurizio Varrone、Francesca Vasile、Carlo Scolastico

  DOI：10.1016/j.bmc.2009.07.009

  日期：2009.8

  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.