1-(2,4-dimethoxy-5-trifluoromethyl-phenyl)-3-(3-{8-[(pyridin-4-yl-methyl)-amino]-imidazo[1,2-a]pyrazin-6-yl}-phenyl)-urea | 847024-46-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(2,4-dimethoxy-5-trifluoromethyl-phenyl)-3-(3-{8-[(pyridin-4-yl-methyl)-amino]-imidazo[1,2-a]pyrazin-6-yl}-phenyl)-urea
• 英文别名: 1-(2,4-Dimethoxy-5-(trifluoromethyl)phenyl)-3-(3-(8-(pyridin-4-ylmethylamino)imidazo[1,2-a]pyrazin-6-yl)phenyl)urea；1-[2,4-dimethoxy-5-(trifluoromethyl)phenyl]-3-[3-[8-(pyridin-4-ylmethylamino)imidazo[1,2-a]pyrazin-6-yl]phenyl]urea
• CAS: 847024-46-8
• 化学式: C₂₈H₂₄F₃N₇O₃
• 分子量: 563.539
• InChiKey: YAYODJGNSKFEGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1-isocyanato-2,4-dimethoxy-5-(trifluoromethyl)benzene 、 6-(3-aminophenyl)-N-(pyridin-4-ylmethyl)imidazo[1,2-a]pyrazin-8-amine 以 甲苯 为溶剂， 反应 0.5h， 生成 1-(2,4-dimethoxy-5-trifluoromethyl-phenyl)-3-(3-{8-[(pyridin-4-yl-methyl)-amino]-imidazo[1,2-a]pyrazin-6-yl}-phenyl)-urea
  参考文献：
  名称：

  Imidazo[1,2-a]pyrazine diaryl ureas: Inhibitors of the receptor tyrosine kinase EphB4

  摘要：

  Inhibition of receptor tyrosine kinases (RTKs) such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) has been validated by recently launched small molecules Sutent(R) and Nexavar(R), both of which display activities against several angiogenesis-related RTKs. EphB4, a receptor tyrosine kinase (RTK) involved in the processes of embryogenesis and angiogenesis, has been shown to be aberrantly up regulated in many cancer types such as breast, lung, bladder and prostate. We propose that inhibition of EphB4 in addition to other validated RTKs would enhance the anti-angiogenic effect and ultimately result in more pronounced anti-cancer efficacy. Herein we report the discovery and SAR of a novel series of imidazo[1,2-a]pyrazine diarylureas that show nano-molar potency for the EphB4 receptor, in addition to potent activity against several other RTKs. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.037

文献信息

• Certain substituted imidazo[1,2-a]pyrazines, as modulators of kinase activity
  申请人：Mitchell A. Scott

  公开号：US20050085484A1

  公开（公告）日：2005-04-21

  Certain substituted imidazo[1,2-a]pyrazines and the pharmaceutically-acceptable salts thereof, are provided herein. Pharmaceutical compositions containing one or more compound of Formula I, or a pharmaceutically acceptable salt of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents, are also provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to EphB4 kinase modulation, which comprise administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include cancer, including breast neoplasia, endometrial cancer, colon cancer, and neck squamous cell carcinoma. Thus methods of treatment include administering a sufficient amount of a compound of the invention to decrease the symptoms or slow the progression of these diseases or disorders. Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with one or more other therapeutic agents. A method for determining the presence or absence of an angiogenic kinase in a sample comprising contacting the sample with a compound of Formula I under conditions that permit detection of activity of the angiogenic kinase, detecting a level of the activity of the angiogenic kinase, and therefrom determining the presence or absence of the angiogenic kinase in the sample.

  本文提供了某些取代的咪唑并[1,2-a]吡嗪化合物及其药物可接受的盐。本文还提供了含有一种或多种I式化合物或这些化合物的药物可接受的盐和一种或多种药物可接受的载体、赋形剂或稀释剂的制药组合物。本文公开了治疗对EphB4激酶调节敏感的某些疾病和疾病的患者的方法，该方法包括向这些患者施用足够的I式化合物的量，以减少疾病或疾病的症状或迹象。这些疾病包括癌症，包括乳腺肿瘤、子宫内膜癌、结肠癌和颈部鳞状细胞癌。因此，治疗方法包括施用足够的本发明化合物的量，以减轻这些疾病或疾病的症状或减缓其进展。治疗方法包括将I式化合物作为单一活性剂或与一种或多种其他治疗剂联合使用。一种用于确定样品中是否存在血管生成激酶的方法，包括将样品与I式化合物接触，以便在允许检测血管生成激酶活性的条件下检测血管生成激酶活性水平，并从中确定样品中是否存在血管生成激酶。
• US7259164B2
  申请人：——

  公开号：US7259164B2

  公开（公告）日：2007-08-21
• [EN] SUBSTITUTED IMIDAZO[1,2-A]PYRAZINES AS MODULATORS OF KINASE ACTIVITY<br/>[FR] IMIDAZO[1,2-A]PYRAZINES SUBSTITUEES UTILISEES COMME MODULATEURS DE L'ACTIVITE D'UNE KINASE
  申请人：CELLULAR GENOMICS INC

  公开号：WO2005019220A2

  公开（公告）日：2005-03-03

  Certain substituted imidazo[1,2-a]pyrazines and the pharmaceutically-acceptable salts thereof, are provided herein. Pharmaceutical compositions containing one or more compound of Formula I, or a pharmaceutically acceptable salt of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents, are also provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to EphB4 kinase modulation, which comprise administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include cancer, including breast neoplasia, endometrial cancer, colon cancer, and neck squamous cell carcinoma. Thus methods of treatment include administering a sufficient amount of a compound of the invention to decrease the symptoms or slow the progression of these diseases or disorders. Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with one or more other therapeutic agents. A method for determining the presence or absence of an angiogenic kinase in a sample comprising contacting the sample with a compound of Formula I under conditions that permit detection of activity of the angiogenic kinase, detecting a level of the activity of the angiogenic kinase, and therefrom determining the presence or absence of the angiogenic kinase in the sample.
• [EN] MODAFINIL COMBINATION THERAPY FOR IMPROVING SLEEP QUALITY<br/>[FR] THERAPIE COMBINATOIRE AVEC LA MODAFINILE POUR AMELIORER LA QUALITE DU SOMMEIL
  申请人：SEPRACOR INC

  公开号：WO2005063248A1

  公开（公告）日：2005-07-14

  One aspect of the present invention relates to pharmaceutical compositions comprising a compound that modulates the orexin system and a sedative agent. In a preferred embodiment, the compound that modulates the orexin system is modafinil and the sedative agent is (S)-zopiclone. The pharmaceutical compositions of the invention are useful in the treatment of various sleep disorders. In addition, the present invention relates to a method of treating a patient suffering from a sleep abnormality or insomnia comprising administering a therapeutically effective amount of a pharmaceutical composition of the invention.
• Imidazo[1,2-a]pyrazine diaryl ureas: Inhibitors of the receptor tyrosine kinase EphB4
  作者：Scott A. Mitchell、Mihaela Diana Danca、Peter A. Blomgren、James W. Darrow、Kevin S. Currie、Jeffrey E. Kropf、Seung H. Lee、Steven L. Gallion、Jin-Ming Xiong、Douglas A. Pippin、Robert W. DeSimone、David R. Brittelli、David C. Eustice、Aaron Bourret、Melissa Hill-Drzewi、Patricia M. Maciejewski、Lisa L. Elkin

  DOI：10.1016/j.bmcl.2009.10.037

  日期：2009.12

  Inhibition of receptor tyrosine kinases (RTKs) such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) has been validated by recently launched small molecules Sutent(R) and Nexavar(R), both of which display activities against several angiogenesis-related RTKs. EphB4, a receptor tyrosine kinase (RTK) involved in the processes of embryogenesis and angiogenesis, has been shown to be aberrantly up regulated in many cancer types such as breast, lung, bladder and prostate. We propose that inhibition of EphB4 in addition to other validated RTKs would enhance the anti-angiogenic effect and ultimately result in more pronounced anti-cancer efficacy. Herein we report the discovery and SAR of a novel series of imidazo[1,2-a]pyrazine diarylureas that show nano-molar potency for the EphB4 receptor, in addition to potent activity against several other RTKs. (C) 2009 Elsevier Ltd. All rights reserved.