4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)aniline | 943752-28-1

• 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: 4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)aniline
• 英文别名: 4-(cis-3,4,5-Trimethyl-piperazin-1-yl)-phenylamine；4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]aniline
• CAS: 943752-28-1
• 化学式: C₁₃H₂₁N₃
• 分子量: 219.33
• InChiKey: VRPRJZRWGBWKAK-PHIMTYICSA-N

物化性质

• 沸点：
  361.5±37.0 °C(Predicted)
• 密度：
  1.020±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)aniline 、 (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione 以 N,N-二甲基甲酰胺 为溶剂， 以56.7%的产率得到(4Z)-6-iodo-4-[({4-[3,4,5-trimethylpiperazin-1-yl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione
  参考文献：
  名称：

  4-(Phenylaminomethylene)isoquinoline-1,3(2H,4H)-diones as Potent and Selective Inhibitors of the Cyclin-Dependent Kinase 4 (CDK4)

  摘要：

  The cyclin-dependent kinases (CDKs), as complexes with their respective partners, the cyclins, are critical regulators of cell cycle progression. Because aberrant regulations of CDK4/cyclin D1 lead to uncontrolled cell proliferation, a hallmark of cancer, small-molecule inhibitors of CDK4/cyclin D1 are attractive as prospective antitumor agents. The series of 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)-dione derivatives reported here represents a novel class of potent inhibitors that selectively inhibit CDK4 over CDK2 and CDK1 activities. In the headpiece of the 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)dione, a basic amine substitutent is required on the aniline ring for the CDK4 inhibitory activity. The inhibitory activity is further enhanced when an aryl or heteroaryl substituent is introduced at the C-6 position of the isoquinoline-1,3(2H,4H)-dione core. We present here SAR data and a CDK4 mimic model that explains the binding, potency, and selectivity of our CDK4 selective inhibitors.

  DOI：

  10.1021/jm800072z
• 作为产物：
  描述：

  2,6-dimethylpiperazine 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 34.5h， 生成 4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)aniline
  参考文献：
  名称：

  [EN] PYRIMIDINE DERIVATIVES AS KINASE INHIBITORS AND THEIR THERAPEUTICAL APPLICATIONS
  [FR] DÉRIVÉS DE PYRIMIDINE UTILISÉS EN TANT QU'INHIBITEURS DE KINASE, ET LEURS APPLICATIONS THÉRAPEUTIQUES

  摘要：

  本发明提供了具有抗增殖活性的激酶抑制剂，包括取代嘧啶衍生物及其药用可接受的配方。此外，本发明提供了制备新化合物的方法以及使用这些化合物的方法。

  公开号：

  WO2016138527A1

文献信息

• IMIDAZO[1,2-b]PYRIMIDO[4,5-d]PYRIDAZIN-5(6H)-ONES AND THE USE THEREOF
  申请人：IMPACT THERAPEUTICS, INC.

  公开号：US20200131192A1

  公开（公告）日：2020-04-30

  Disclosed are imidazo[1,2-b]pyrimido[4,5-d]pyridazin-5(6H)-one compounds, specifically represented by the Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A and R 1 -R 5 are defined herein. Compounds having Formula I are Wee1 kinase inhibitors. Therefore, compounds of the disclosure may be used to treat diseases caused by abnormal Wee1 activity.

  本文揭示了咪唑[1,2-b]嘧啶并[4,5-d]吡啶嗪-5(6H)-酮化合物，具体由公式I表示：或其药用可接受的盐或前药，其中A和R1-R5在此定义。具有公式I的化合物是Wee1激酶抑制剂。因此，本公开的化合物可用于治疗由异常Wee1活性引起的疾病。
• Triazolopyridine compounds useful for the treatment of degenerative & inflammatory diseases
  申请人：Edwards Paul John

  公开号：US20090105242A1

  公开（公告）日：2009-04-23

  Novel triazolopyridine compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, ECM degradation, joint degradation and/or inflammation, and others.

  本发明公开了一种具有以下式子表示的新型三唑基吡啶化合物：这些化合物可以制备为药物组合物，并可用于预防和治疗哺乳动物，包括人类的各种疾病，例如ECM降解，关节降解和/或炎症等。
• Triazolopyridine compounds useful for the treatment of degenerative and inflammatory diseases
  申请人：Galapagos NV

  公开号：US07977352B2

  公开（公告）日：2011-07-12

  Novel triazolopyridine compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, ECM degradation, joint degradation and/or inflammation, and others.

  揭示了一种具有以下公式表示的新型三唑并吡啶化合物：这些化合物可以制备为药物组成物，并可用于预防和治疗哺乳动物（包括人类）的各种疾病，包括但不限于ECM降解、关节降解和/或炎症等。
• 8,9-DIHYDROIMIDAZOLE[1,2-A]PYRIMIDO[5,4-E]PYRIMIDINE-5(6H)-KETONE COMPOUND
  申请人：Impact Therapeutics, Inc

  公开号：EP3543242A1

  公开（公告）日：2019-09-25

  Disclosed are 8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one compounds, specifically represented by the Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A and R1-R7 are defined herein. Compounds having Formula I are Wee1 kinase inhibitors. Therefore, compounds of the disclosure may be used to treat diseases caused by abnormal Wee1 activity.

  所公开的是 8,9-二氢咪唑并[1,2-a]嘧啶并[5,4-e]嘧啶-5(6H)-酮化合物，具体由式 I 表示： 或其药学上可接受的盐或原药，其中 A 和 R1-R7 在此定义。具有式 I 的化合物是 Wee1 激酶抑制剂。因此，本公开的化合物可用于治疗由 Wee1 活性异常引起的疾病。
• 8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-ones
  申请人：IMPACT THERAPEUTICS, INC.

  公开号：US10703759B2

  公开（公告）日：2020-07-07

  Disclosed are 8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one compounds, specifically represented by the Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A and R1-R7 are defined herein. Compounds having Formula I are Wee1 kinase inhibitors. Therefore, compounds of the disclosure may be used to treat diseases caused by abnormal Wee1 activity.

  所公开的是 8,9-二氢咪唑并[1,2-a]嘧啶并[5,4-e]嘧啶-5(6H)-酮化合物，具体由式 I 表示： 或其药学上可接受的盐或原药，其中 A 和 R1-R7 在此定义。具有式 I 的化合物是 Wee1 激酶抑制剂。因此，本公开的化合物可用于治疗由 Wee1 活性异常引起的疾病。