N-(2-(pyrrolidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide

• 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: N-(2-(pyrrolidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide
• 英文别名: N-[2-(1-pyrrolidinyl)-5-(trifluoromethyl)phenyl]isonicotinamide；N-[2-pyrrolidin-1-yl-5-(trifluoromethyl)phenyl]pyridine-4-carboxamide
• 化学式: C₁₇H₁₆F₃N₃O
• 分子量: 335.329
• InChiKey: AIOMSFNPXPGQGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氟-3-硝基三氟甲苯 在 盐酸 、 三乙胺 、 tin(ll) chloride 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.5h， 生成 N-(2-(pyrrolidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide
  参考文献：
  名称：

  具有抗白血病作用和对富含丝氨酸/精氨酸的蛋白激酶（SRPK）具有细胞内抑制活性的三氟甲基芳基酰胺。

  摘要：

  在许多癌症中，经常发现富含丝氨酸/精氨酸的蛋白激酶（SRPK）的活性发生了变化，这表明它们可以作为肿瘤学中潜在的治疗靶标。在这里，我们描述了基于已知的SRPKs抑制剂N-（2-（2-哌啶-1-基）-5-（三氟甲基）苯基）异烟酰胺（SRPIN340）的一系列22种三氟甲基芳基酰胺的合成及其抗白血病的评估效果。与SRPIN340相比，某些衍生物对髓样和淋巴白血病细胞系表现出优异的细胞毒性作用。特别是，化合物24、30和36的IC50值介于6.0和35.7μM之间。另外，这三种化合物能够触发细胞凋亡和自噬，并表现出与化学治疗剂长春新碱的协同作用。此外，化合物30在削弱SR蛋白的细胞内磷酸化状态以及MAP2K1，MAP2K2，VEGF和RON致癌同工型的表达方面比SRPIN340更有效。因此，获得了具有增强的针对SRPK活性的细胞内作用的新型化合物，有助于药物化学努力开发新的抗癌剂。

  DOI：

  10.1016/j.ejmech.2017.03.078

文献信息

• Method for controlling sr protein phosphorylation, and antiviral agents whose active ingredients comprise agents that control sr protein activity
  申请人：Hagiwara Masatoshi

  公开号：US20070135367A1

  公开（公告）日：2007-06-14

  The present invention provides: (1) antiviral agents that act by reducing or inhibiting the activity of SR proteins, more specifically, (i) antiviral agents that act by enhancing dephosphorylation of SR proteins, and (ii) antiviral agents that act by inhibiting proteins that phosphorylate SR proteins; (2) antiviral agents that act by inhibiting the expression of SR proteins, and (3) antiviral agents that act by activating proteins that antagonize SR proteins. The present invention also provides compounds that inhibit SRPKs, which phosphorylate SR proteins. Such compounds inhibit the activity of SR proteins and have antiviral activities. Various new viruses including SARS have emerged, and thus the present invention provides long-lasting broad-spectrum antiviral agents applicable to new viruses.

  本发明提供了：（1）通过减少或抑制SR蛋白活性作用的抗病毒剂，更具体地，（i）通过增强SR蛋白的去磷酸化作用的抗病毒剂，和（ii）通过抑制磷酸化SR蛋白的蛋白质的抗病毒剂；（2）通过抑制SR蛋白表达的抗病毒剂，和（3）通过激活拮抗SR蛋白的蛋白质的抗病毒剂。本发明还提供了抑制磷酸化SR蛋白的SRPKs的化合物。这些化合物抑制SR蛋白的活性并具有抗病毒活性。各种新病毒，包括SARS，已经出现，因此本发明提供了适用于新病毒的持久的广谱抗病毒剂。
• METHODS FOR CONTROLLING SR PROTEIN PHOSPHORYLATION, AND ANTIVIRAL AGENTS WHOSE ACTIVE INGREDIENTS COMPRISE AGENTS THAT CONTROL SR PROTEIN ACTIVITY
  申请人：Hagiwara Masatoshi

  公开号：US20100016359A1

  公开（公告）日：2010-01-21

  The present invention provides: (1) antiviral agents that act by reducing or inhibiting the activity of SR proteins, more specifically, (i) antiviral agents that act by enhancing dephosphorylation of SR proteins, and (ii) antiviral agents that act by inhibiting proteins that phosphorylate SR proteins; (2) antiviral agents that act by inhibiting the expression of SR proteins, and (3) antiviral agents that act by activating proteins that antagonize SR proteins. The present invention also provides compounds that inhibit SRPKs, which phosphorylate SR proteins. Such compounds inhibit the activity of SR proteins and have antiviral activities. Various new viruses including SARS have emerged, and thus the present invention provides long-lasting broad-spectrum antiviral agents applicable to new viruses.

  本发明提供：（1）抗病毒剂，通过减少或抑制SR蛋白的活性发挥作用，更具体地，（i）通过增强SR蛋白的去磷酸化作用发挥作用的抗病毒剂，以及（ii）通过抑制磷酸化SR蛋白的蛋白质发挥作用的抗病毒剂；（2）通过抑制SR蛋白的表达发挥作用的抗病毒剂，以及（3）通过激活对抗SR蛋白的蛋白质发挥作用的抗病毒剂。本发明还提供抑制磷酸化SR蛋白的SRPKs的化合物。这些化合物抑制SR蛋白的活性，并具有抗病毒活性。各种新的病毒，包括SARS，已经出现，因此本发明提供适用于新病毒的持久广谱抗病毒剂。
• Method for controlling SR protein phosphorylation, and antiviral agents whose active ingredients comprise agents that control SR protein activity
  申请人：——

  公开号：US07569536B2

  公开（公告）日：2009-08-04

  The present invention provides: (1) antiviral agents that act by reducing or inhibiting the activity of SR proteins, more specifically, (i) antiviral agents that act by enhancing dephosphorylation of SR proteins, and (ii) antiviral agents that act by inhibiting proteins that phosphorylate SR proteins; (2) antiviral agents that act by inhibiting the expression of SR proteins, and (3) antiviral agents that act by activating proteins that antagonize SR proteins. The present invention also provides compounds that inhibit SRPKs, which phosphorylate SR proteins. Such compounds inhibit the activity of SR proteins and have antiviral activities. Various new viruses including SARS have emerged, and thus the present invention provides long-lasting broad-spectrum antiviral agents applicable to new viruses.

  本发明提供以下内容：（1）抗病毒剂，通过减少或抑制SR蛋白的活性来发挥作用，更具体地，（i）通过增强SR蛋白的去磷酸化作用来发挥作用的抗病毒剂，以及（ii）通过抑制SR蛋白磷酸化的蛋白质来发挥作用的抗病毒剂；（2）通过抑制SR蛋白的表达来发挥作用的抗病毒剂，以及（3）通过激活对抗SR蛋白的蛋白质来发挥作用的抗病毒剂。本发明还提供抑制磷酸化SR蛋白的SRPKs的化合物。这些化合物抑制SR蛋白的活性，并具有抗病毒活性。各种新的病毒，包括SARS，已经出现，因此本发明提供了适用于新病毒的持久的广谱抗病毒剂。
• Methods for controlling SR protein phosphorylation, and antiviral agents whose active ingredients comprise agents that control SR protein activity
  申请人：Masatoshi Hagiwara

  公开号：US08338362B2

  公开（公告）日：2012-12-25

  The present invention provides: (1) antiviral agents that act by reducing or inhibiting the activity of SR proteins, more specifically, (i) antiviral agents that act by enhancing dephosphorylation of SR proteins, and (ii) antiviral agents that act by inhibiting proteins that phosphorylate SR proteins; (2) antiviral agents that act by inhibiting the expression of SR proteins, and (3) antiviral agents that act by activating proteins that antagonize SR proteins. The present invention also provides compounds that inhibit SRPKs, which phosphorylate SR proteins. Such compounds inhibit the activity of SR proteins and have antiviral activities. Various new viruses including SARS have emerged, and thus the present invention provides long-lasting broad-spectrum antiviral agents applicable to new viruses.

  本发明提供了以下内容：（1）抗病毒剂，通过降低或抑制SR蛋白活性来发挥作用，更具体地说，（i）通过增强SR蛋白去磷酸化的抗病毒剂，和（ii）通过抑制SR蛋白磷酸化的蛋白质的抗病毒剂；（2）通过抑制SR蛋白表达的抗病毒剂，和（3）通过激活对抗SR蛋白的蛋白质的抗病毒剂。本发明还提供了抑制SR蛋白激酶（SRPKs）的化合物，这些化合物抑制SR蛋白的活性，并具有抗病毒活性。各种新的病毒，包括SARS，已经出现，因此本发明提供了适用于新病毒的长效广谱抗病毒剂。
• Method of regulating phosphorylation of sr protein and antiviral agents comprising sr protein activity regulator as the active ingredient
  申请人：HAGIWARA, Masatoshi

  公开号：EP2666481A2

  公开（公告）日：2013-11-27

  The present invention is related to an aniline derivative represented by the following formula (I): wherein, R1, R2, R3, R4, Q and W are defined elsewhere. A typical compound of the aniline derivatives of invention is depicted in the figure. The aniline derivatives of invention have antiviral activity

  本发明涉及一种由下式（I）表示的苯胺衍生物： 其中，R1、R2、R3、R4、Q 和 W 在别处定义。本发明苯胺衍生物的典型化合物如图所示。本发明的苯胺衍生物具有抗病毒活性