N-(2-aminopyrimidin-5-yl)-2-methyl-5-(3-(trifluoromethyl)benzamido)benzamide

• 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-aminopyrimidin-5-yl)-2-methyl-5-(3-(trifluoromethyl)benzamido)benzamide
• 英文别名: N-(2-amino-5-pyrimidinyl)-2-methyl-5-(((3-(trifluoromethyl)phenyl)carbonyl)amino)benzamide；N-(2-aminopyrimidin-5-yl)-2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide
• 化学式: C₂₀H₁₆F₃N₅O₂
• 分子量: 415.375
• InChiKey: HZYVHWDHIRWTNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-三氟甲基苯甲酸 在 氯化亚砜 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 N-(2-aminopyrimidin-5-yl)-2-methyl-5-(3-(trifluoromethyl)benzamido)benzamide
  参考文献：
  名称：

  发现一系列具有体内抗肿瘤活性的布鲁顿酪氨酸激酶的2,5-二氨基嘧啶共价不可逆抑制剂

  摘要：

  Bruton的酪氨酸激酶（Btk）是治疗几种B细胞谱系癌症的引人注目的药物靶标。依鲁替尼是一流的共价不可逆Btk抑制剂，在多项临床试验中已显示出令人印象深刻的效果。在本文中，我们介绍了一系列新型的Btk 2，5-二氨基嘧啶共价不可逆抑制剂。与依鲁替尼相比，这些抑制剂对所分析的激酶表现出不同的选择性，并具有抑制Btk活化和催化活性的双重作用模式，从而抵消了Btk的负调节回路。该系列中的两种化合物31和38，显示出对多种B细胞淋巴瘤细胞系的有效抗增殖活性，包括生发中心B细胞样弥散性大B细胞淋巴瘤（GCB-DLBCL）细胞。另外，化合物31在小鼠异种移植模型中显着阻止了肿瘤的生长。

  DOI：

  10.1021/jm4017762

文献信息

• Bis-aryl amide compounds and methods of use
  申请人：Dimauro F. Erin

  公开号：US20070072862A1

  公开（公告）日：2007-03-29

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including autoimmune disease and inflammation. In one embodiment, the compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , L, R 1 , R 2 and R 3 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of the present invention, methods of use such as treatment of Lck and/or c-Kit kinase mediated diseases by administering the compounds of the invention, or compositions including one or more compounds of the invention, and intermediates and processes useful for the preparation of compounds of the present invention.

  本发明涵盖了一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括自身免疫疾病和炎症。在一个实施例中，这些化合物具有一般的化学式I，其中A1、A2、A3、A4、L、R1、R2和R3在此处定义。本发明还涵盖了包括本发明的一种或多种化合物的药物组合物，使用方法如通过给予本发明的化合物治疗Lck和/或c-Kit激酶介导的疾病，或包括本发明的一种或多种化合物的组合物，以及用于制备本发明化合物的中间体和方法。
• BIS-ARYL AMIDE COMPOUNDS AND METHODS OF USE
  申请人：Dimauro Erin F.

  公开号：US20100234373A1

  公开（公告）日：2010-09-16

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including autoimmune disease and inflammation. In one embodiment, the compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , L, R 1 , R 2 and R 3 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of the present invention, methods of use such as treatment of Lck and/or c-Kit kinase mediated diseases by administering the compounds of the invention, or compositions including one or more compounds of the invention, and intermediates and processes useful for the preparation of compounds of the present invention.

  本发明涉及一种新的化合物类别，用于预防和治疗蛋白激酶介导的疾病，包括自身免疫疾病和炎症。在一种实施例中，该化合物具有通式I，其中A1、A2、A3、A4、L、R1、R2和R3在此定义。本发明还涵盖了包括本发明中一种或多种化合物的药物组合物，使用方法，例如通过给予本发明中的化合物治疗Lck和/或c-Kit激酶介导的疾病，或包括本发明中一种或多种化合物的组合物，以及用于制备本发明化合物的中间体和过程。
• Structure-Guided Design of Aminopyrimidine Amides as Potent, Selective Inhibitors of Lymphocyte Specific Kinase: Synthesis, Structure–Activity Relationships, and Inhibition of in Vivo T Cell Activation
  作者：Erin F. DiMauro、John Newcomb、Joseph J. Nunes、Jean E. Bemis、Christina Boucher、Lilly Chai、Stuart C. Chaffee、Holly L. Deak、Linda F. Epstein、Ted Faust、Paul Gallant、Anu Gore、Yan Gu、Brad Henkle、Faye Hsieh、Xin Huang、Joseph L. Kim、Josie H. Lee、Matthew W. Martin、David C. McGowan、Daniela Metz、Deanna Mohn、Kurt A. Morgenstern、Antonio Oliveira-dos-Santos、Vinod F. Patel、David Powers、Paul E. Rose、Stephen Schneider、Susan A. Tomlinson、Yan-Yan Tudor、Susan M. Turci、Andrew A. Welcher、Huilin Zhao、Li Zhu、Xiaotian Zhu

  DOI：10.1021/jm7010996

  日期：2008.3.1

  The lymphocyte-specific kinase (Lck), a member of the Src family of cytoplasmic tyrosine kinases, is expressed in T cells and natural killer (NK) cells. Genetic evidence, including knockout mice and human mutations, demonstrates that Lck kinase activity is critical for normal T cell development, activation, and signaling. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. With the aid of X-ray structure-based analysis, aminopyrimidine amides 2 and 3 were designed from aminoquinazolines 1, which had previously been demonstrated to exhibit potent inhibition of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminopyrimidine amides 3 possessing improved cellular potency and selectivity profiles relative to their aminoquinazoline predecessors 1. Orally bioavailable compound 13b inhibited the anti-CD3-induced production of interleukin-2 (IL-2) in mice in a dose-dependent manner (ED50 = 9.4 mg/kg).
• US7754717B2
  申请人：——

  公开号：US7754717B2

  公开（公告）日：2010-07-13
• US8492404B2
  申请人：——

  公开号：US8492404B2

  公开（公告）日：2013-07-23