3-(dimethylamino)-2-(3-(trifluoromethoxy)phenyl)acrylonitrile | 1361951-71-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(dimethylamino)-2-(3-(trifluoromethoxy)phenyl)acrylonitrile
• 英文别名: 3-(dimethylamino)-2-(3-(trifluoromethoxy)phenyl)acrylonitrlle；3-(Dimethylamino)-2-(3-(trifluoromethoxy)phenyl)acrylonitrile；3-(dimethylamino)-2-[3-(trifluoromethoxy)phenyl]prop-2-enenitrile
• CAS: 1361951-71-4
• 化学式: C₁₂H₁₁F₃N₂O
• 分子量: 256.227
• InChiKey: AMHZWDHKKKSDHD-UHFFFAOYSA-N

物化性质

• 沸点：
  372.9±42.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(dimethylamino)-2-(3-(trifluoromethoxy)phenyl)acrylonitrile 在 hydrazine hydrate 、 sodium ethanolate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 44.0h， 生成 N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-5-amine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Pyrazolo[1,5-a]pyrimidine Compounds as Potent and Selective Pim-1 Inhibitors

  摘要：

  Pim-1 has emerged as an attractive target for developing therapeutic agents for treating disorders involving abnormal cell growth, especially cancers. Herein we present lead optimization, chemical synthesis and biological evaluation of pyrazolo[1,5-a]pyrimidine compounds as potent and selective inhibitors of Pim-1 starting from a hit from virtual screening. These pyrazolo[1,5-a]pyrimidine compounds strongly inhibited Pim-1 and Flt-3 kinases. Selected compounds suppressed both the phosphorylation of BAD protein in a cell-based assay and 2-dimensional colony formation in a clonogenic cell survival assay at submicromolar potency, suggesting that cellular activity was mediated through inhibition of Pim-1. Moreover, these Pim-1 inhibitors did not show significant hERG inhibition at 30 mu M concentration. The lead compound proved to be highly selective against a panel of 119 oncogenic kinases, indicating it had an improved safety profile compared with the first generation Pim-1 inhibitor SGI-1776.

  DOI：

  10.1021/ml500300c
• 作为产物：
  描述：

  3-(三氟甲氧基)苯乙腈 、 N,N-二甲基甲酰胺二甲基缩醛 在 N,N-二异丙基乙胺 作用下， 反应 4.0h， 以72%的产率得到3-(dimethylamino)-2-(3-(trifluoromethoxy)phenyl)acrylonitrile
  参考文献：
  名称：

  [EN] HETEROCYCLIC PROTEIN KINASE INHIBITORS
  [FR] INHIBITEURS DE PROTÉINE KINASE HÉTÉROCYCLIQUES

  摘要：

  本发明提供具有以下结构之一的蛋白激酶（I）、（II）或（III）：或其立体异构体、前药、互变异构体或药用可接受盐，其中R、R1、R2和X如本文所定义。还公开了在治疗癌症、自身免疫、炎症和其他Pim激酶相关疾病中使用这些蛋白激酶的组合物和方法。

  公开号：

  WO2013013188A1

文献信息

• Substituted imidazo[1,2-b]pyridazines as protein kinase inhibitors
  申请人：Xu Yong

  公开号：US09416132B2

  公开（公告）日：2016-08-16

  The present invention provides protein kinase having one of the following structures (I), (II) or (III): or a stereoisomer, prodrug, tautomer or pharmaceutically acceptable salt thereof, wherein R, R1, R2 and X are as defined herein. Compositions and methods for using the same in the treatment of cancer, autoimmune, inflammatory and other Pim kinase-associated conditions are also disclosed.

  本发明提供具有以下结构之一的蛋白激酶（I）、（II）或（III）：或其立体异构体、前药、互变异构体或药用可接受盐，其中R、R1、R2和X如本文所定义。还公开了在治疗癌症、自身免疫、炎症和其他Pim激酶相关疾病中使用这些组合物和方法。
• [EN] HETEROCYCLIC PROTEIN KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉINE KINASE HÉTÉROCYCLIQUES
  申请人：TOLERO PHARMACEUTICALS INC

  公开号：WO2013013188A1

  公开（公告）日：2013-01-24

  The present invention provides protein kinase having one of the following structures (I), (II) or (III): or a stereoisomer, prodrug, tautomer or pharmaceutically acceptable salt thereof, wherein R, R1, R2 and X are as defined herein. Compositions and methods for using the same in the treatment of cancer, autoimmune, inflammatory and other Pim kinase-associated conditions are also disclosed.

  本发明提供具有以下结构之一的蛋白激酶（I）、（II）或（III）：或其立体异构体、前药、互变异构体或药用可接受盐，其中R、R1、R2和X如本文所定义。还公开了在治疗癌症、自身免疫、炎症和其他Pim激酶相关疾病中使用这些蛋白激酶的组合物和方法。
• IMIDAZO[1,2-B]PYRIDAZINE AND PYRAZOLO[1,5-A]PYRIMIDINE DERIVATIVES AND THEIR USE AS PROTEIN KINASE INHIBITORS
  申请人：Xu Yong

  公开号：US20120058997A1

  公开（公告）日：2012-03-08

  The present invention provides protein kinase inhibitors comprising imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine compounds of the following structure (I) and (II): or a stereoisomer, prodrug or pharmaceutically acceptable salt thereof, wherein R, R 1 , R 2 and X are as defined herein. Compositions and methods for using the same in the treatment of cancer and other Pim kinase-associated conditions are also disclosed.

  本发明提供了蛋白激酶抑制剂，包括以下结构（I）和（II）的咪唑[1,2-b]吡啶和吡唑[1,5-a]嘧啶化合物或其立体异构体、前药或药物可接受的盐，其中R、R1、R2和X如本文所定义。还公开了将其用于治疗癌症和其他Pim激酶相关疾病的组合物和方法。
• HETEROCYCLIC PROTEIN KINASE INHIBITORS
  申请人：Xu Yong

  公开号：US20140329807A1

  公开（公告）日：2014-11-06

  The present invention provides protein kinase having one of the following structures (I), (II) or (III): or a stereoisomer, prodrug, tautomer or pharmaceutically acceptable salt thereof, wherein R, R 1 , R 2 and X are as defined herein. Compositions and methods for using the same in the treatment of cancer, autoimmune, inflammatory and other Pim kinase-associated conditions are also disclosed.

  本发明提供具有以下结构之一（I），（II）或（III）的蛋白激酶：或其立体异构体，前药，互变异构体或药学上可接受的盐，其中R，R1，R2和X如本文所定义。还公开了在治疗癌症，自身免疫，炎症和其他Pim激酶相关疾病中使用相同的组合物和方法。
• Synthesis and Biological Evaluation of Pyrazolo[1,5-<i>a</i>]pyrimidine Compounds as Potent and Selective Pim-1 Inhibitors
  作者：Yong Xu、Benjamin G. Brenning、Steven G. Kultgen、Jason M. Foulks、Adrianne Clifford、Shuping Lai、Ashley Chan、Shannon Merx、Michael V. McCullar、Steven B. Kanner、Koc-Kan Ho

  DOI：10.1021/ml500300c

  日期：2015.1.8

  Pim-1 has emerged as an attractive target for developing therapeutic agents for treating disorders involving abnormal cell growth, especially cancers. Herein we present lead optimization, chemical synthesis and biological evaluation of pyrazolo[1,5-a]pyrimidine compounds as potent and selective inhibitors of Pim-1 starting from a hit from virtual screening. These pyrazolo[1,5-a]pyrimidine compounds strongly inhibited Pim-1 and Flt-3 kinases. Selected compounds suppressed both the phosphorylation of BAD protein in a cell-based assay and 2-dimensional colony formation in a clonogenic cell survival assay at submicromolar potency, suggesting that cellular activity was mediated through inhibition of Pim-1. Moreover, these Pim-1 inhibitors did not show significant hERG inhibition at 30 mu M concentration. The lead compound proved to be highly selective against a panel of 119 oncogenic kinases, indicating it had an improved safety profile compared with the first generation Pim-1 inhibitor SGI-1776.