N2-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidine-2,5-diamine | 925897-77-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N2-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidine-2,5-diamine
• 英文别名: 2-N-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidine-2,5-diamine
• CAS: 925897-77-4
• 化学式: C₁₅H₂₀N₆
• 分子量: 284.364
• InChiKey: BQJZZCUVYAPVEQ-UHFFFAOYSA-N

物化性质

• 沸点：
  524.8±60.0 °C(Predicted)
• 密度：
  1.249±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  70.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N2-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidine-2,5-diamine 、 2,6-二氯苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以79%的产率得到2,6-dichloro-N-(2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl)benzamide
  参考文献：
  名称：

  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

  摘要：

  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).

  DOI：

  10.1021/jm7010996
• 作为产物：
  描述：

  N-[4-(4-methylpiperazin-1-yl)phenyl]-5-nitropyrimidin-2-amine 在 palladium 10% on activated carbon 氢气 作用下， 以 乙醇 为溶剂， 反应 48.0h， 生成 N2-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidine-2,5-diamine
  参考文献：
  名称：

  Bis-aryl amide compounds and methods of use

  摘要：

  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。

  公开号：

  US20070072862A1

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。
• 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
• [EN] BIS-ARYL AMIDE COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSES BIS-ARYL AMIDE ET PROCEDES D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2007022380A2

  公开（公告）日：2007-02-22

  [EN] 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 A1, A2, A3, A4, L, R1, R2 and R3 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.
  [FR] L'invention concerne une nouvelle classe de composés utilisés pour la prophylaxie et le traitement de maladies médiées par la protéine kinase, telles que les maladies auto-immunes et l'inflammation. Dans un mode de réalisation, les composés possèdent la formule générale (I) dans laquelle A1, A2, A3, A4, L, R1, R2 et R3 sont tels que définis dans la spécification. L'invention se rapporte également à des compositions pharmaceutiques renfermant un ou plusieurs composés de l'invention, à des procédés d'utilisation destinés à traiter des maladies médiées par la Lck et/ou la c-Kit kinase par l'administration des composés précités ou de compositions renfermant un ou plusieurs des composés précités, et à des intermédiaires et procédés utilisés dans la préparation des composés de l'invention.