(4-(2-ethoxyethyl)piperazin-1-yl)(2-(4-((5-fluoropyrimidin-2-ylamino)methyl)benzylamino)-4-(trifluoromethyl)pyrimidin-5-yl)methanone | 1002158-59-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (4-(2-ethoxyethyl)piperazin-1-yl)(2-(4-((5-fluoropyrimidin-2-ylamino)methyl)benzylamino)-4-(trifluoromethyl)pyrimidin-5-yl)methanone
• 英文别名: [4-(2-Ethoxyethyl)piperazin-1-yl]-[2-[[4-[[(5-fluoropyrimidin-2-yl)amino]methyl]phenyl]methylamino]-4-(trifluoromethyl)pyrimidin-5-yl]methanone
• CAS: 1002158-59-9
• 化学式: C₂₆H₃₀F₄N₈O₂
• 分子量: 562.57
• InChiKey: HKDAUWBQNJQYOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  1-(N-Boc-氨基甲基)-4-(氨基甲基)苯 在 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (4-(2-ethoxyethyl)piperazin-1-yl)(2-(4-((5-fluoropyrimidin-2-ylamino)methyl)benzylamino)-4-(trifluoromethyl)pyrimidin-5-yl)methanone
  参考文献：
  名称：

  双嘧啶胺：一类具有高特异性的新型趋化因子受体 4 型拮抗剂

  摘要：

  CXC 趋化因子受体 4 (CXCR4)/基质细胞衍生因子-1（SDF-1 或 CXCL12）相互作用和由此产生的细胞信号级联反应在转移和炎症中起关键作用。在先前发表的 CXCR4 拮抗剂5 (WZ811)的基础上，设计并合成了一系列新型非肽类抗 CXCR4 小分子以提高效力。根据大约5的结构-活性特征，发现了N , N '-(1, 4-亚苯基双(亚甲基)) dipyrimidin-2-amines 系列中更先进的化合物，并且显示出比5具有更高的 CXCR4 结合潜力和特异性。化合物26(508MCl) 是先导化合物，在三种体外试验中表现出亚纳摩尔的效力，包括竞争性结合、基质胶侵入和 Gα i环磷酸腺苷 (cAMP) 调节信号。此外，化合物26通过干扰三种小鼠模型中的 CXCR4 功能显示出有希望的效果：爪子炎症、Matrigel 栓塞血管生成和葡萄膜黑色素瘤微转移。这些数据表明，双嘧啶胺是独特的具有高效力和特异性的

  DOI：

  10.1021/jm100786g

文献信息

• Inhibition of chemokine CCL7 or receptor CCR3 of same for the treatment and diagnosis of prostate cancer
  申请人：Universite Paul Sabatier (Toulouse III)

  公开号：US10401365B2

  公开（公告）日：2019-09-03

  The invention concerns an inhibitor of the expression of chemokine CCL7 or an inhibitor of the expression of the receptor CCR3 or an inhibitor of CCL7/CCR3 interaction for the use of same to prevent or treat the extension of prostate cancer outside the prostatic capsule in a subject. The invention also concerns a method for determining the degree of aggressiveness of a prostate cancer tumor in a subject suffering from prostate cancer, comprising a step of determining the concentration or level of expression of the receptor CCR3 in a sample of prostate tumor cells obtained from said subject.

  本发明涉及一种趋化因子CCL7表达抑制剂或受体CCR3表达抑制剂或CCL7/CCR3相互作用抑制剂，用于预防或治疗受试者的前列腺癌向前列腺囊外延伸。本发明还涉及一种确定前列腺癌患者前列腺癌肿瘤侵袭程度的方法，该方法包括一个步骤，即确定从所述患者处获得的前列腺肿瘤细胞样本中受体CCR3的浓度或表达水平。
• CXCR4 Antagonists Including Diazine And Triazine Structures For The Treatment Of Medical Disorders
  申请人：Liotta Dennis C.

  公开号：US20090099194A1

  公开（公告）日：2009-04-16

  The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor for the treatment of proliferative conditions mediated by CXCR4 receptors or for the treatment of viral infections. The compounds provided interfere with the binding of SDF 1 to the receptor. These compounds are particularly useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis, or for reducing entry of HIV in to a cell while not reducing the capacity of the stem cells to proliferate. The compounds may be useful for long term treatment regimes.
• Inhibition of Chemokine CCL7 or Receptor CCR3 of Same for the Treatment and Diagnosis of Prostate Cancer
  申请人：Universite Paul Sabatier (Toulouse III)

  公开号：US20170131282A1

  公开（公告）日：2017-05-11

  The invention concerns an inhibitor of the expression of chemokine CCL7 or an inhibitor of the expression of the receptor CCR3 or an inhibitor of CCL7/CCR3 interaction for the use of same to prevent or treat the extension of prostate cancer outside the prostatic capsule in a subject. The invention also concerns a method for determining the degree of aggressiveness of a prostate cancer tumour in a subject suffering from prostate cancer, comprising a step of determining the concentration or level of expression of the receptor CCR3 in a sample of prostate tumour cells obtained from said subject.
• US8080659B2
  申请人：——

  公开号：US8080659B2

  公开（公告）日：2011-12-20
• [EN] CXER4 ANTAGONISTS INCLUDING DIAZINE AND TRIAZINE STRUCTURES FOR THE TREATMENT OF MEDICAL DISORDERS<br/>[FR] ANTAGONISTES DE CXCR4 COMPRENANT DES STRUCTURES DE DIAZINE ET DE TRIAZINE POUR LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：UNIV EMORY

  公开号：WO2008008854A2

  公开（公告）日：2008-01-17

  (EN) The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor for the treatment of proliferative conditions mediated by CXCR4 receptors or for the treatment of viral infections. The compounds provided interfere with the binding of SDFl to the receptor. These compounds are particularly useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis, or for reducing entry of HIV in to a cell while not reducing the capacity of the stem cells to proliferate. The compounds may be useful for long term treatment regimes.(FR) L'invention concerne des composés, des compositions pharmaceutiques et des procédés d'utilisation de certains composés qui sont antagonistes du récepteur CXCR4 de la chémokine pour le traitement de conditions prolifératives à médiation par les récepteurs CXCR4 ou pour le traitement d'infections virales. Les composés fournis gênent la liaison de SDF1 au récepteur. Ces composés sont particulièrement utiles pour le traitement ou la diminution de la gravité de maladies hyperprolifératives par l'inhibition des métastases, ou pour freiner l'entrée du VIH dans une cellule, sans diminuer la capacité des cellules souches à proliférer. Les composés peuvent être utiles pour des régimes de traitement à long terme.