4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yltrifluoromethanesulfonate | 1456506-71-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: 4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yltrifluoromethanesulfonate
• 英文别名: 4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yl trifluoromethanesulfonate；[4-[(4S)-5,5-dimethyl-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]cyclohexen-1-yl] trifluoromethanesulfonate
• CAS: 1456506-71-0
• 化学式: C₁₈H₂₀F₃NO₅S
• 分子量: 419.422
• InChiKey: VQEGCZINBCIXQM-WUJWULDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yltrifluoromethanesulfonate 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 100.0 ℃ 、310.27 kPa 条件下， 反应 3.08h， 生成 2-amino-5-((1S,4r)-4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohexyl)nicotinonitrile
  参考文献：
  名称：

  Structure-Based Design of 2-Aminopyridine Oxazolidinones as Potent and Selective Tankyrase Inhibitors

  摘要：

  Aberrant activation of the Wnt pathway has been implicated in the development and formation of many cancers. TNKS inhibition has been shown to antagonize Wnt signaling via Axin stabilization in APC mutant colon cancer cell lines. We employed structure-based design to identify a series of 2-aminopyridine oxazolidinones as potent and selective TNKS inhibitors. These compounds exhibited good enzyme and cell potency as well as selectivity over other PARP isoforms. Co-crystal structures of these 2-aminopyridine oxazolidinones complexed to TNKS reveal an induced-pocket binding mode that does not involve interactions with the nicotinamide binding pocket Oral dosing of lead compounds 3 and 4 resulted in significant effects on several Wnt-pathway biomarkers in a three day DLD-1 mouse tumor PD model.

  DOI：

  10.1021/ml4003315
• 作为产物：
  描述：

  (S)-1-氨基-2-甲基-1-苯丙-2-醇 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 为溶剂， 反应 23.58h， 生成 4-((S)-5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yltrifluoromethanesulfonate
  参考文献：
  名称：

  Structure-Based Design of 2-Aminopyridine Oxazolidinones as Potent and Selective Tankyrase Inhibitors

  摘要：

  Aberrant activation of the Wnt pathway has been implicated in the development and formation of many cancers. TNKS inhibition has been shown to antagonize Wnt signaling via Axin stabilization in APC mutant colon cancer cell lines. We employed structure-based design to identify a series of 2-aminopyridine oxazolidinones as potent and selective TNKS inhibitors. These compounds exhibited good enzyme and cell potency as well as selectivity over other PARP isoforms. Co-crystal structures of these 2-aminopyridine oxazolidinones complexed to TNKS reveal an induced-pocket binding mode that does not involve interactions with the nicotinamide binding pocket Oral dosing of lead compounds 3 and 4 resulted in significant effects on several Wnt-pathway biomarkers in a three day DLD-1 mouse tumor PD model.

  DOI：

  10.1021/ml4003315

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。
• Oxazolidinone compounds and derivatives thereof
  申请人：AMGEN INC.

  公开号：US09340549B2

  公开（公告）日：2016-05-17

  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tankyrase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。
• PHENICOL ANTIBACTERIALS
  申请人：Zoetis LLC

  公开号：EP2822934A1

  公开（公告）日：2015-01-14
• US9340549B2
  申请人：——

  公开号：US9340549B2

  公开（公告）日：2016-05-17