(3aS,5R,7aS,9aS)-3-benzyl-4-oxo-decahydro-2-oxa-3,4a-diazacyclopenta[f]azulene-5-carboxylic acid tert-butyl ester | 851544-48-4

• 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: (3aS,5R,7aS,9aS)-3-benzyl-4-oxo-decahydro-2-oxa-3,4a-diazacyclopenta[f]azulene-5-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (3S,7S,10S,13S)-4-benzyl-2-oxo-5-oxa-1,4-diazatricyclo[8.3.0.03,7]tridecane-13-carboxylate
• CAS: 851544-48-4
• 化学式: C₂₂H₃₀N₂O₄
• 分子量: 386.491
• InChiKey: QCOKZBWEVTWVOZ-XWSJACJDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3aS,5R,7aS,9aS)-3-benzyl-4-oxo-decahydro-2-oxa-3,4a-diazacyclopenta[f]azulene-5-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以90%的产率得到(3S,4S,7S,10S)-3-amino-1-aza-2-oxo-4-hydroxymethyl-bicyclo[5.3.0]decanecarboxylic acid tert-butyl ester
  参考文献：
  名称：

  Functionalized Azabicycloalkane Amino Acids by Nitrone 1,3-Dipolar Intramolecular Cycloaddition

  摘要：

  An efficient and operationally simple method for the synthesis of functionalized azaoxobicyclo[X.3.0]alkane amino acids has been devised. The key step is an intramolecular nitrone cycloaddition on 5-allyl- or 5-homoallylproline that was found to be completely regio- and stereoselective.

  DOI：

  10.1021/jo0500683
• 作为产物：
  描述：

  (2R,5S)-5-but-3-enyl-1-methoxyoxalylpyrrolidine-2-carboxylic acid tert-butyl ester 在 锂硼氢 、 草酰氯 、 碳酸氢钠 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 7.0h， 生成 (3aS,5R,7aS,9aS)-3-benzyl-4-oxo-decahydro-2-oxa-3,4a-diazacyclopenta[f]azulene-5-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Functionalized Azabicycloalkane Amino Acids by Nitrone 1,3-Dipolar Intramolecular Cycloaddition

  摘要：

  An efficient and operationally simple method for the synthesis of functionalized azaoxobicyclo[X.3.0]alkane amino acids has been devised. The key step is an intramolecular nitrone cycloaddition on 5-allyl- or 5-homoallylproline that was found to be completely regio- and stereoselective.

  DOI：

  10.1021/jo0500683

文献信息

• 4-Connected azabicyclo[5.3.0]decane Smac mimetics-Zn 2+ chelators as dual action antitumoral agents
  作者：Leonardo Manzoni、Alessandro Samela、Stefano Barbini、Silvia Cairati、Marta Penconi、Daniela Arosio、Daniele Lecis、Pierfausto Seneci

  DOI：10.1016/j.bmcl.2017.04.032

  日期：2017.6

  compounds (DACs 3a-d) based on azabicyclo[5.3.0]decane (ABD) Smac mimetic scaffolds linked to Zn2+-chelating 2,2'-dipicolylamine (DPA) through their 4 position are reported and characterized. Their synthesis, their target affinity (cIAP1 BIR3, Zn2+) in cell-free assays, their pro-apoptotic effects, and their cytotoxicity in tumor cells with varying sensitivity to Smac mimetics are described. A limited

  报告并表征了基于氮杂双环[5.3.0]癸烷（ABD）Smac模拟支架与Zn2 +螯合的2,2'-二甲基吡啶胺（DPA）连接的推定双作用化合物（DAC 3a-d），并对其进行了表征。描述了它们的合成，它们在无细胞测定中的靶亲和力（cIAP1 BIR3，Zn2 +），它们的促凋亡作用以及在对Smac模拟物敏感的肿瘤细胞中的细胞毒性。有时可以感觉到Zn2 +螯合对DPA取代的DAC 3a-d体外活性的有限影响，但并未导致强烈的细胞协同作用。特别是，将DPA与ABD支架连接的接头似乎会影响细胞的Zn2 +螯合，较长的亲脂性接头/ DAC 3c是最佳选择。
• Dual action Smac mimetics–zinc chelators as pro-apoptotic antitumoral agents
  作者：Leonardo Manzoni、Davide Gornati、Mattia Manzotti、Silvia Cairati、Alberto Bossi、Daniela Arosio、Daniele Lecis、Pierfausto Seneci

  DOI：10.1016/j.bmcl.2016.08.065

  日期：2016.10

  Dual action compounds (DACs) based on 4-substituted aza-bicyclo[5.3.0]decane Smac mimetic scaffolds (ABDs) linked to a Zn(2+)-chelating moiety (DPA, o-hydroxy, m-allyl, N-acyl (E)-phenylhydrazone) through their 10 position are reported and characterized. Their synthesis, their target affinity (XIAP BIR3, Zn(2+)) in cell-free assays, their pro-apoptotic effects and cytotoxicity in tumor cells with varying

  基于4-取代的氮杂双环[5.3.0]癸烷Smac模拟支架（ABD）的双作用化合物（DAC），与Zn（2+）螯合部分（DPA，邻羟基，间烯丙基，N- （E）-苯基hydr）通过其10位进行了报道和表征。描述了它们的合成，它们在无细胞测定中的靶亲和力（XIAP BIR3，Zn（2+）），它们在具有对Smac模拟物敏感性的肿瘤细胞中的促凋亡作用和细胞毒性。结果被解释为评估Zn（2+）螯合剂对无细胞效能和DAC的细胞渗透性的影响，并为基于Smac模拟物和Zn（2+）螯合的更有效的抗肿瘤DAC提出新途径。
• [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
• 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.
• Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents
  作者：Aldo Bianchi、Marcello Ugazzi、Luca Ferrante、Daniele Lecis、Cinzia Scavullo、Eloise Mastrangelo、Pierfausto Seneci

  DOI：10.1016/j.bmcl.2012.01.098

  日期：2012.3

  A set of phenyl-substituted Smac mimetics/IAP inhibitor analogues of lead compound 2a was synthesized, aiming to retain its strong cell-free potency while increasing its bioavailability. Seventeen compounds 2b-r were prepared and characterized in vitro, using cell-free and cellular assays. Among them, the p-CF3 substituted analogue 2m showed the best permeability through cell membranes, and was selected for further in vitro and in vivo studies due to its strong, sub-micromolar cellular potency. (C) 2012 Elsevier Ltd. All rights reserved.