N-(3-(((6-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)methyl)phenyl)acrylamide

• 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: N-(3-(((6-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)methyl)phenyl)acrylamide
• 英文别名: N-[3-[[[6-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide
• 化学式: C₂₅H₂₉N₇O
• 分子量: 443.552
• InChiKey: AIFRWGWZEZORFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  85.4
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(4-甲基哌嗪)苯胺 在 palladium 10% on activated carbon 、 一水合肼 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙醇 、 正丁醇 为溶剂， 反应 8.5h， 生成 N-(3-(((6-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)methyl)phenyl)acrylamide
  参考文献：
  名称：

  Structure-based design and synthesis of pyrimidine-4,6-diamine derivatives as Janus kinase 3 inhibitors

  摘要：

  Janus kinases (JAKs) play a key role in the proliferation, apoptosis and differentiation of immune cells, and JAKs are considered as an attractive target for the treatment of inflammatory and autoimmune diseases. Here we show the design and optimization of pyrimidine-4,6-diamine derivatives as selectivity JAK3 inhibitors. Compound 11e, which might interact with unique cysteine (Cys909) residue in JAK3, exhibited excellent JAK3 inhibitory activity (IC50 = 2.1 nM) and high JAK kinase selectivity. In cellular assay, 11e showed moderate potency inhibiting IL-2-stimulated T cell proliferation. The data supports the further development of novel JAKs inhibitors.

  DOI：

  10.1016/j.bmc.2019.03.009

文献信息

• [EN] JANUS KINASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE JANUS KINASE ET LEURS UTILISATIONS
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2015164614A1

  公开（公告）日：2015-10-29

  The present invention provides kinase inhibitors, such as compounds of Formula (I) and Formula (II). The compounds may covalently or non-covalently bind a kinase (e.g., Janus kinase 3 (JAK3)). Also provided are pharmaceutical compositions, kits, methods, and uses that involve the compounds for reducing the activity of a kinase and/or treating and/or preventing a condition associated with aberrant activity of a kinase (e.g., a proliferative disease, inflammatory disorder, autoimmune disorder, painful condition, and/or viral infection). (I) (II)

  本发明提供了激酶抑制剂，如化合物的化学式(I)和化学式(II)。这些化合物可以与激酶（例如Janus激酶3（JAK3））发生共价结合或非共价结合。还提供了涉及这些化合物用于减少激酶活性和/或治疗和/或预防与激酶异常活性相关的疾病状态的药物组合物、试剂盒、方法和用途（例如增殖性疾病、炎症性疾病、自身免疫性疾病、疼痛症状和/或病毒感染）。
• Janus kinase inhibitors and uses thereof
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10017477B2

  公开（公告）日：2018-07-10

  The present invention provides kinase inhibitors, such as compounds of Formula (I) and Formula (II). The compounds may covalently or non-covalently bind a kinase (e.g., Janus kinase 3 (JAK3)). Also provided are pharmaceutical compositions, kits, methods, and uses that involve the compounds for reducing the activity of a kinase and/or treating and/or preventing a condition associated with aberrant activity of a kinase (e.g., a proliferative disease, inflammatory disorder, autoimmune disorder, painful condition, and/or viral infection). (I) (II)

  本发明提供激酶抑制剂，如式（I）和式（II）化合物。这些化合物可共价或非共价地结合激酶（如 Janus 激酶 3 (JAK3)）。还提供了涉及这些化合物的药物组合物、试剂盒、方法和用途，这些化合物用于降低激酶活性和/或治疗和/或预防与激酶异常活性相关的病症（如增殖性疾病、炎症性疾病、自身免疫性疾病、疼痛病症和/或病毒感染）。(I) (II)
• JANUS KINASE INHIBITORS AND USES THEREOF
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US20170044111A1

  公开（公告）日：2017-02-16

  The present invention provides kinase inhibitors, such as compounds of Formula (I) and Formula (II). The compounds may covalently or non-covalently bind a kinase (e.g., Janus kinase 3 (JAK3)). Also provided are pharmaceutical compositions, kits, methods, and uses that involve the compounds for reducing the activity of a kinase and/or treating and/or preventing a condition associated with aberrant activity of a kinase (e.g., a proliferative disease, inflammatory disorder, autoimmune disorder, painful condition, and/or viral infection). (I) (II)
• Structure-based design and synthesis of pyrimidine-4,6-diamine derivatives as Janus kinase 3 inhibitors
  作者：Ru-Nan Yu、Cheng-Juan Chen、Lei Shu、Yuan Yin、Zhi-Jian Wang、Tian-Tai Zhang、Da-Yong Zhang

  DOI：10.1016/j.bmc.2019.03.009

  日期：2019.4

  Janus kinases (JAKs) play a key role in the proliferation, apoptosis and differentiation of immune cells, and JAKs are considered as an attractive target for the treatment of inflammatory and autoimmune diseases. Here we show the design and optimization of pyrimidine-4,6-diamine derivatives as selectivity JAK3 inhibitors. Compound 11e, which might interact with unique cysteine (Cys909) residue in JAK3, exhibited excellent JAK3 inhibitory activity (IC50 = 2.1 nM) and high JAK kinase selectivity. In cellular assay, 11e showed moderate potency inhibiting IL-2-stimulated T cell proliferation. The data supports the further development of novel JAKs inhibitors.