9-(2,6-Dimethylphenyl)-4-[3-methoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]anilino]-1,3,5,9,11-pentazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,10,12,14,16-heptaen-8-one | 847950-18-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 9-(2,6-Dimethylphenyl)-4-[3-methoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]anilino]-1,3,5,9,11-pentazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,10,12,14,16-heptaen-8-one
• CAS: 847950-18-9
• 化学式: C₃₄H₃₆N₈O₃
• 分子量: 604.712
• InChiKey: UOOYLPNPSPMGPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-methoxy-4-(2-(4-methylpiperazin-1-yl)ethoxy)aniline 、 6-(2,6-dimethylphenyl)-2-methanesulfonylbenzo[4,5]imidazolo[1,2-a]pyrimido[5,6-e]pyrimidin-5-one 以 异丙醇 为溶剂， 生成 9-(2,6-Dimethylphenyl)-4-[3-methoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]anilino]-1,3,5,9,11-pentazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,10,12,14,16-heptaen-8-one
  参考文献：
  名称：

  Structure-Based Design of Novel 2-Amino-6-phenyl-pyrimido[5′,4′:5,6]pyrimido[1,2-a]benzimidazol-5(6H)-ones as Potent and Orally Active Inhibitors of Lymphocyte Specific Kinase (Lck): Synthesis, SAR, and In Vivo Anti-Inflammatory Activity

  摘要：

  Lck, or lymphocyte specific kinase, is a cytoplasmic tyrosine kinase of the Src family expressed in T-cells and NK cells. Genetic evidence from knockout mice and human mutations demonstrates that Lck kinase activity is critical for T-cell receptor-mediated signaling, leading to normal T-cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T-cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection. In this paper, we describe the structure-guided design, synthesis, structure-activity relationships, and pharmacological, characterization of 2-amino-6phenylpyrirnido[5',4':5,6]pyrimido[1,2-a]benzimidazol-5(6H)-ones, a new class of compounds that are potent inhibitors of Lck. The most promising compound of this series, 6-(2,6-dimethylphenyl)-2-((4-(4-methyl-1-piperazinyl)phenyl)amino)pyrimido[5',4':5,6]pyrimido-[1,2-a]benzimidazol-5(6H)-one (25), exhibits potent inhibition of Lck kinase activity. This activity translates into inhibition of in vitro cell-based assays and in vivo models of T-cell activation and arthritis, respectively.

  DOI：

  10.1021/jm701095m

文献信息

• [EN] SUBSTITUTED HETEROCYCLIC COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSES HETEROCYCLIQUES SUBSTITUES ET LEURS METHODES D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2005021551A1

  公开（公告）日：2005-03-10

  The present invention relates to tetracyclic pyrimidines or pyridines or pharmaceutically-acceptable salts or derivatives thereof. Also included are methods of use of the tetracyclic pyrimidines or pyridines including use related to treating inflammation, inhibiting T cell activation and proliferation, arthritis, organ transplant, ischemic or reperfusion injury, myocardial infarction, stroke, multiple sclerosis, inflammatory bowel disease and many other related disorders in a subject, the methods comprising administering a therapeutically-effective amount a compound as described above to the subject.

  本发明涉及四环嘧啶或吡啶或其药用盐或衍生物。还包括使用四环嘧啶或吡啶的方法，包括用于治疗炎症、抑制T细胞激活和增殖、关节炎、器官移植、缺血再灌注损伤、心肌梗死、中风、多发性硬化、炎症性肠病和其他相关疾病的方法，在这些方法中向受试者施用上述化合物的治疗有效量。
• Substituted heterocyclic compounds and methods of use
  申请人：Nunes J. Joseph

  公开号：US20050070554A1

  公开（公告）日：2005-03-31

  The present invention relates to tetracyclic pyrimidines or pyridines or pharmaceutically-acceptable salts or derivatives thereof. Also included are methods of use of the tetracyclic pyrimidines or pyridines including use related to treating inflammation, inhibiting T cell activation and proliferation, arthritis, organ transplant, ischemic or reperfusion injury, myocardial infarction, stroke, multiple sclerosis, inflammatory bowel disease and many other related disorders in a subject, the methods comprising administering a therapeutically-effective amount a compound as described above to the subject.

  本发明涉及四环嘧啶或吡啶或其药学上可接受的盐或衍生物。还包括使用四环嘧啶或吡啶的方法，包括用于治疗炎症、抑制T细胞活化和增殖、关节炎、器官移植、缺血或再灌注损伤、心肌梗死、中风、多发性硬化症、炎症性肠病和许多其他相关疾病的方法，在该方法中向受试者施用上述化合物的治疗有效量。
• SUBSTITUTED HETEROCYCLIC COMPOUNDS AND METHODS OF USE
  申请人：AMGEN INC.

  公开号：EP1664053A1

  公开（公告）日：2006-06-07