3-amino-2,6-dimethyl-N-(2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-5-yl)benzamide | 1018070-85-3

• 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: 3-amino-2,6-dimethyl-N-(2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-5-yl)benzamide
• 英文别名: 3-amino-2,6-dimethyl-N-[2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-5-yl]benzamide
• CAS: 1018070-85-3
• 化学式: C₂₄H₂₉N₇O
• 分子量: 431.541
• InChiKey: LBCHUHUJWLVRFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  99.4
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-amino-2,6-dimethyl-N-(2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-5-yl)benzamide 、 3-(三氟甲基)苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以20%的产率得到2,6-dimethyl-N-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-5-yl}-3-(3-trifluoromethyl-benzoylamino)-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：

  2,6-dimethyl-N-[2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-5-yl]-3-nitrobenzamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 以80%的产率得到3-amino-2,6-dimethyl-N-(2-(4-(4-methylpiperazin-1-yl)phenylamino)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