4-((4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)-cyclohexyl)amino)-3-nitrobenzonitrile | 1437790-10-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)-cyclohexyl)amino)-3-nitrobenzonitrile
• CAS: 1437790-10-7
• 化学式: C₂₄H₂₆N₄O₄
• 分子量: 434.495
• InChiKey: YELHHRTUXINXSP-IPJJNNNSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.16
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  108.5
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-((4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)-cyclohexyl)amino)-3-nitrobenzonitrile 在 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 以73.1%的产率得到3-amino-4-((4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohexyl)amino)benzonitrile
  参考文献：
  名称：

  Discovery of Novel, Induced-Pocket Binding Oxazolidinones as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors

  摘要：

  Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates beta-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of beta-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (39, 40).

  DOI：

  10.1021/jm4000038
• 作为产物：
  描述：

  4-N-Boc-氨基环己酮 在 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 3.25h， 生成 4-((4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)-cyclohexyl)amino)-3-nitrobenzonitrile
  参考文献：
  名称：

  Discovery of Novel, Induced-Pocket Binding Oxazolidinones as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors

  摘要：

  Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates beta-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of beta-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (39, 40).

  DOI：

  10.1021/jm4000038

文献信息

• [EN] OXAZOLIDINONE COMPOUNDS AND DERIVATIVES THEREOF<br/>[FR] COMPOSÉS D'OXAZOLIDINONE ET LEURS DÉRIVÉS
  申请人：AMGEN INC

  公开号：WO2013134079A1

  公开（公告）日：2013-09-12

  Compounds of Formula (I) and Formula (II) are useful inhibitors of tankyrase. Compounds of Formula (I) and Formula (II) have the following structure: where the definitions of the variables are provided herein.

  式(I)和式(II)的化合物是坦克酶的有用抑制剂。式(I)和式(II)的化合物具有以下结构：其中变量的定义在此提供。
• OXAZOLIDINONE COMPOUNDS AND DERIVATIVES THEREOF
  申请人：AMGEN INC.

  公开号：US20150045368A1

  公开（公告）日：2015-02-12

  Compounds of Formula (I) and Formula (II) are useful inhibitors of tankyrase. Compounds of Formula (I) and Formula (II) have the following structure: where the definitions of the variables are provided herein.

  式(I)和式(II)的化合物是坦克酰酶的有用抑制剂。式(I)和式(II)的化合物具有以下结构：其中变量的定义在此提供。
• US9340549B2
  申请人：——

  公开号：US9340549B2

  公开（公告）日：2016-05-17
• Discovery of Novel, Induced-Pocket Binding Oxazolidinones as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors
  作者：Howard Bregman、Nagasree Chakka、Angel Guzman-Perez、Hakan Gunaydin、Yan Gu、Xin Huang、Virginia Berry、Jingzhou Liu、Yohannes Teffera、Liyue Huang、Bryan Egge、Erin L. Mullady、Steve Schneider、Paul S. Andrews、Ankita Mishra、John Newcomb、Randy Serafino、Craig A. Strathdee、Susan M. Turci、Cindy Wilson、Erin F. DiMauro

  DOI：10.1021/jm4000038

  日期：2013.6.13

  Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates beta-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of beta-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (39, 40).