1-((1S,4r)-4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3- yl)cyclohexyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile | 1437789-90-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-((1S,4r)-4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3- yl)cyclohexyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile
• 英文别名: 1-((1S,4r)-4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohexyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile
• CAS: 1437789-90-6
• 化学式: C₂₅H₂₅FN₄O₃
• 分子量: 448.497
• InChiKey: GTRSBOPVOQICBF-SPEDKVCISA-N

物化性质

• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  91.12
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 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 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 7.75h， 生成 1-((1S,4r)-4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3- yl)cyclohexyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile
  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。
• ANTIVIRAL AXIN STABLIZER
  申请人：The Board of Regents for Oklahoma State University

  公开号：US20170065587A1

  公开（公告）日：2017-03-09

  Methods and compositions for preventing and/or treating viral infections are provided. The methods involve administering an agent that stabilizes or enhances Axin1 activity, e.g. and agent that inhibits tankyrase. Administration of the agent stimulates or increases interferon activity, thereby preventing or lessening at least one symptom of virus infection. The virus infection may be caused by a respiratory virus such as influenza vims.
• 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).