1-(3-chloro-4-fluoro-phenyl)-3-{3-[8-(2-isopropyl-imidazol-1-yl)-imidazo[1,2-a]pyrazin-6-yl]-phenyl}-urea

• 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-(3-chloro-4-fluoro-phenyl)-3-{3-[8-(2-isopropyl-imidazol-1-yl)-imidazo[1,2-a]pyrazin-6-yl]-phenyl}-urea
• 英文别名: 1-(3-Chloro-4-fluorophenyl)-3-[3-[8-(2-propan-2-ylimidazol-1-yl)imidazo[1,2-a]pyrazin-6-yl]phenyl]urea
• 化学式: C₂₅H₂₁ClFN₇O
• 分子量: 489.939
• InChiKey: QHXFNKDAQBHEHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  89.1
• 氢给体数：
  2
• 氢受体数：
  5

文献信息

• [EN] CERTAIN 8-HETEROARYL-6-PHENYL-IMIDAZO[1,2-A]PYRAZINES AS MODULATORS OF HSP90 COMPLEX ACTIVITY<br/>[FR] 8-HETEROARYLE-6-PHENYLE-IMIDAZO[1,2-A]PYRAZINES COMME MODULATEURS DE L'ACTIVITE DU COMPLEXE HSP90
  申请人：CELLULAR GENOMICS INC

  公开号：WO2004072080A1

  公开（公告）日：2004-08-26

  This invention pertains to compounds of Formula (I) and the pharmaceutically-acceptable forms thereof. The variables R1, R2, R3, Z1, Z2, W, and X shown in Formula I are defined herein. The invention also provides pharmaceutical compositions containing one or more compound of Formula I, or pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents. The invention further comprises methods of treating patients suffering from certain diseases and disorders responsive to Hsp90 complex 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. These diseases include cancer, including chronic myeloid leukemia, melanoma, breast, ovarian, brain, thyroid, colorectal, prostate, and bladder cancer, heart disease, stroke, autoimmune/inflammatory diseases, and neurodegenerative diseases. Thus methods of treatment include administering a sufficient amount of a compound of Formula I or form thereof to decrease the symptoms or slow the progression of these diseases or disorders. The invention also encompasses methods of treating non-human patients, including livestock and domesticated companion animals, suffering from a disease or disorder responsive to Hsp90 complex modulation. 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 agent. The invention also includes a method for determining the presence of certain kinases or Hsp90 complex in a sample, comprising contacting the sample with a compound of Formula I or form thereof, and detecting Hsp90 complex activity in the sample.

  本发明涉及Formula（I）的化合物及其药用可接受形式。在Formula I中显示的变量R1、R2、R3、Z1、Z2、W和X在此处被定义。该发明还提供含有一个或多个Formula I化合物或其药用可接受形式以及一个或多个药用可接受载体、辅料或稀释剂的药物组合物。该发明进一步包括治疗对Hsp90复合物调节敏感的某些疾病和紊乱的方法，包括向这些患者施用Formula I化合物的有效量，以减少疾病或紊乱的症状。这些疾病包括癌症，包括慢性髓细胞白血病、黑色素瘤、乳腺癌、卵巢癌、脑癌、甲状腺癌、结肠直肠癌、前列腺癌和膀胱癌、心脏病、中风、自身免疫/炎症性疾病和神经退行性疾病。因此，治疗方法包括施用足够量的Formula I化合物或其形式以减轻这些疾病或紊乱的症状或减缓其进展。该发明还包括治疗非人类患者，包括家畜和驯养伴侣动物，患有对Hsp90复合物调节敏感的疾病或紊乱的方法。治疗方法包括以单一活性剂形式施用Formula I化合物或与一个或多个其他治疗剂联合施用Formula I化合物。该发明还包括一种用于确定样本中某些激酶或Hsp90复合物存在的方法，包括将样本与Formula I化合物或其形式接触，并检测样本中的Hsp90复合物活性。
• Certain 8-heteroaryl-6-phenyl-imidazo[1,2-A]pyrazines as modulators of Hsp90 complex activity
  申请人：Currie S. Kevin

  公开号：US20050054649A1

  公开（公告）日：2005-03-10

  This invention pertains to compounds of Formula I: and the pharmaceutically-acceptable forms thereof. The variables R 1 , R 2 , R 3 , Z 1 , Z 2 , W, and X shown in Formula I are defined herein. The invention also provides pharmaceutical compositions containing one or more compound of Formula I, or pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents. The invention further comprises methods of treating patients suffering from certain diseases and disorders responsive to Hsp90 complex 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. These diseases include cancer, including chronic myeloid leukemia, melanoma, breast, ovarian, brain, thyroid, colorectal, prostate, and bladder cancer, heart disease, stroke, autoimmune/inflammatory diseases, and neurodegenerative diseases. Thus methods of treatment include administering a sufficient amount of a compound of Formula I or form thereof to decrease the symptoms or slow the progression of these diseases or disorders. The invention also encompasses methods of treating non-human patients, including livestock and domesticated companion animals, suffering from a disease or disorder responsive to Hsp90 complex modulation. 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 agent. The invention also includes a method for determining the presence of certain kinases or Hsp90 complex in a sample, comprising contacting the sample with a compound of Formula I or form thereof, and detecting Hsp9O complex activity in the sample.

  本发明涉及公式I的化合物及其药学上可接受的形式。公式I中所示的变量R1、R2、R3、Z1、Z2、W和X在此定义。本发明还提供包含一个或多个公式I化合物或其药学上可接受的形式以及一个或多个药学上可接受的载体、辅料或稀释剂的制药组合物。本发明还包括治疗对Hsp90复合物调节有反应的某些疾病和疾病的患者的方法，其中包括向这些患者投予足够的公式I化合物剂量，以减轻疾病或疾病的症状。这些疾病包括癌症，包括慢性髓细胞白血病、黑色素瘤、乳腺、卵巢、脑、甲状腺、结肠直肠、前列腺和膀胱癌、心脏疾病、中风、自身免疫/炎症性疾病和神经退行性疾病。因此，治疗方法包括投予足够的公式I化合物或其形式以减轻这些疾病或疾病的症状或减缓其进展。本发明还包括治疗非人类患者，包括家畜和驯养的伴侣动物，患有对Hsp90复合物调节有反应的疾病或疾病的方法。治疗方法包括将公式I化合物作为单一活性剂投予或将公式I化合物与一个或多个其他治疗剂联合使用。本发明还包括一种确定样品中某些激酶或Hsp90复合物存在的方法，包括将样品与公式I化合物或其形式接触，并检测样品中的Hsp9O复合物活性。
• US7160885B2
  申请人：——

  公开号：US7160885B2

  公开（公告）日：2007-01-09