(5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-6-oxodeca-hydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide | 1071992-83-0

• 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: (5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-6-oxodeca-hydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide
• 英文别名: (5S,8S,10aR)-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-2,3,4,5,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a][1,5]diazocine-8-carboxamide
• CAS: 1071992-83-0
• 化学式: C₂₇H₃₅N₅O₃
• 分子量: 477.607
• InChiKey: KMHMGJITTBRABL-AWDZXFJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl N-[(2S)-1-[[(5S,8S,10aR)-8-(benzhydrylcarbamoyl)-6-oxo-2,3,4,5,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a][1,5]diazocin-5-yl]amino]-1-oxopropan-2-yl]-N-methylcarbamate 在 盐酸 、 水 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 以95%的产率得到(5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-6-oxodeca-hydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide
  参考文献：
  名称：

  Potent, Orally Bioavailable Diazabicyclic Small-Molecule Mimetics of Second Mitochondria-Derived Activator of Caspases

  摘要：

  A series of small-molecule Smac mimetics containing a diazabicyclic core structure have been designed, synthesized, and evaluated. The most potent compound (6) binds to XIAP, cIAP-1, and cIA-P-2 with K-i values of 8.4, 1.5, and 4.2 nM, respectively, directly antagonizes XIAP in a cell-free functional assay and induces cIAP-1 degradation in cancer cells. It inhibits cell growth with an IC50 value of 31 nM, effectively induces apoptosis in the MDA-MB-231 cancer cell line, and has a good oral bioavailability.

  DOI：

  10.1021/jm801254r

文献信息

• DIAZO BICYCLIC SMAC MIMETICS AND THE USES THEREOF
  申请人：Wang Shaomeng

  公开号：US20100273812A1

  公开（公告）日：2010-10-28

  The invention relates to diazo bicyclic 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.

  该发明涉及一种Smac的重氮双环模拟物，其作为细胞凋亡抑制蛋白抑制剂。该发明还涉及利用这些模拟物诱导细胞凋亡死亡以及使细胞对凋亡诱导剂敏感的用途。
• US8278293B2
  申请人：——

  公开号：US8278293B2

  公开（公告）日：2012-10-02
• US8664212B2
  申请人：——

  公开号：US8664212B2

  公开（公告）日：2014-03-04
• [EN] DIAZO BICYCLIC SMAC MIMETICS AND THE USES THEREOF<br/>[FR] MIMÉTIQUES SMAC DIAZOBICYLIQUES ET UTILISATIONS DE CEUX-CI
  申请人：UNIV MICHIGAN

  公开号：WO2008128171A2

  公开（公告）日：2008-10-23

  [EN] The invention relates to diazo bicyclic 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.
  [FR] L'invention concerne des mimétiques diazobicyliques de SMAC qui servent d'inhibiteurs de protéines d'apoptose. L'invention concerne également l'utilisation de ces mimétiques pour induire la mort cellulaire apoptotique et pour sensibiliser les cellules aux inducteurs d'apoptose.
• [EN] BIVALENT INHIBITORS OF IAP PROTEINS AND THERAPEUTIC METHODS USING THE SAME<br/>[FR] INHIBITEURS BIVALENTS DE PROTÉINES IAP ET MÉTHODES THÉRAPEUTIQUES LES UTILISANT
  申请人：REGENTIS OF THE UNIVERSITY OF MICHIGAN

  公开号：WO2014031487A1

  公开（公告）日：2014-02-27

  Inhibitors of IAP proteins and compositions containing the same are disclosed. Methods of using the IAP protein inhibitors in the treatment of diseases and conditions wherein inhibition of IAP proteins provides a benefit, like cancers, also are disclosed.