N-(3-amino-4-methylphenyl)-3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzamide | 851319-35-2

• 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-(3-amino-4-methylphenyl)-3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzamide
• 英文别名: n-(3-Amino-4-methyl-phenyl)-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide；N-(3-amino-4-methylphenyl)-3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzamide
• CAS: 851319-35-2
• 化学式: C₁₉H₁₇F₃N₄O
• 分子量: 374.365
• InChiKey: DYTDVDGSDLVBPF-UHFFFAOYSA-N

物化性质

• 沸点：
  487.5±45.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-amino-4-methylphenyl)-3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzamide 、 2-(3-chloroquinoxalin-2-yl)propanedinitrile 在 硫酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 2-amino-1-(2-methyl-5-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzamido)phenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carboxamide
  参考文献：
  名称：

  Pyrrolo[3,2-b]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and in Vivo Validation

  摘要：

  The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I-1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I-1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.

  DOI：

  10.1021/jm5009242
• 作为产物：
  描述：

  N-(3-nitro-4-methylphenyl)-3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 以44%的产率得到N-(3-amino-4-methylphenyl)-3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Pyrrolo[3,2-b]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and in Vivo Validation

  摘要：

  The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I-1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I-1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.

  DOI：

  10.1021/jm5009242

文献信息

• 2-Amino-1-phenyl-pyrrolo[3,2-b]quinoxaline-3-carboxamide derivates
  申请人：Universität Zürich

  公开号：EP2924039A1

  公开（公告）日：2015-09-30

  The invention relates to compound characterized by a general formula (1), wherein n of R1n is 0, 1, 2, 3 or 4, in particular n of R1n is 0 or 1, and each R1 independently from any other R1 is C1-C3 alkyl, C1-C3 haloalkyl or C1-C3 alkoxy, and DA is a Donor-Acceptor group. The invention relates further to a compound or a pharmaceutical preparation for use in a method for treatment of cancer or intraocular neovascular syndromes.

  该发明涉及一种具有一般式(1)的化合物，其中R1n的n为0、1、2、3或4，特别是R1n的n为0或1，每个R1独立于其他R1，为C1-C3烷基、C1-C3卤代烷基或C1-C3烷氧基，DA为给体-受体基团。该发明还涉及一种化合物或药物制剂，用于治疗癌症或眼内新生血管综合征的方法。
• Compounds and compositions as protein kinase inhibitors
  申请人：Ding Qiang

  公开号：US20050159391A1

  公开（公告）日：2005-07-21

  The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, Bmx, CSK, TrkB, FGFR3, Fes, Lck, B-RAF, C-RAF, MKK6, SAPK2α and SAPK2β kinases.

  本发明提供了一类新型化合物，包括这种化合物的药物组成物，以及使用这种化合物治疗或预防与异常或非调节激酶活性相关的疾病或障碍的方法，特别是涉及Abl、BCR-Abl、Bmx、CSK、TrkB、FGFR3、Fes、Lck、B-RAF、C-RAF、MKK6、SAPK2α和SAPK2β激酶异常激活的疾病或障碍。
• COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
  申请人：Ding Qiang

  公开号：US20080108616A1

  公开（公告）日：2008-05-08

  The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, Bmx, CSK, TrkB, FGFR3, Fes, Lck, B-RAF, C-RAF, MKK6, SAPK2α and SAPK2β kinases.

  本发明提供了一类新型化合物，包括这些化合物的药物组成物以及使用这些化合物治疗或预防与异常或非规则激酶活性相关的疾病或疾病或障碍的方法，尤其是涉及Abl，BCR-Abl，Bmx，CSK，TrkB，FGFR3，Fes，Lck，B-RAF，C-RAF，MKK6，SAPK2α和SAPK2β激酶异常激活的疾病或障碍。
• Compounds and Compositions as Protein Kinase Inhibitors
  申请人：Okram Barun

  公开号：US20080287432A1

  公开（公告）日：2008-11-20

  The invention provides a novel class of compounds of formula I, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the AbI, Bcr-AbI, Aurora-A, SGK, Tie-2, Trk-B, FGFR3, c-kit, b-RAF, c-RAF, DYRK2, Fms, Fyn and PDGFRalpha and PDGFR&bgr; kinases.

  本发明提供了一种新型的I类化合物，包括这些化合物的药物组合物以及使用这些化合物治疗或预防与异常或失调激酶活性相关的疾病或障碍的方法，尤其是涉及AbI、Bcr-AbI、AuroRA-A、SGK、Tie-2、Trk-B、FGFR3、c-kit、b-RAF、c-RAF、DYRK2、Fms、Fyn和PDGFRAlpha和PDGFR&bgr;激酶异常激活的疾病或障碍。
• AZAINDOLE DERIVATIVES AS MULTI KINASE INHIBITORS
  申请人：ORIBASE PHARMA

  公开号：US20150353539A1

  公开（公告）日：2015-12-10

  The present invention relates to compounds of the following formula (I) and/or the pharmaceutically acceptable addition salts, solvates, enantiomers, diastereoisomers thereof, as well as mixtures thereof. The subject matter of the present invention thus also includes the preparation of compounds of formula (I), their uses, in particular in the inhibition of protein kinases which are implicated for example in numerous diseases such as cancers or immune system disorders.

  本发明涉及以下式(I)的化合物和/或其药学上可接受的加合盐、溶剂化物、对映体、非对映异构体以及它们的混合物。因此，本发明的主题还包括制备式(I)化合物，它们的用途，特别是在抑制蛋白激酶方面的用途，这些蛋白激酶例如与许多疾病有关，如癌症或免疫系统紊乱。