3-Bromo-6-(trifluoromethyl)phthalide | 1352933-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3-Bromo-6-(trifluoromethyl)phthalide
• 英文别名: 3-bromo-6-(trifluoromethyl)-3H-2-benzofuran-1-one
• CAS: 1352933-98-2
• 化学式: C₉H₄BrF₃O₂
• 分子量: 281.029
• InChiKey: MKXCKQFOUUFTPB-UHFFFAOYSA-N

物化性质

• 沸点：
  318.5±42.0 °C(Predicted)
• 密度：
  1.825±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-Bromo-6-(trifluoromethyl)phthalide 在 sodium methylate 、 potassium hydroxide 作用下， 以 甲醇 、 氯仿 、 水 、 乙酸乙酯 为溶剂， 反应 45.0h， 生成 3-(trifluoromethyl)-5,6-dihydro-6-(3-(1H-imidazol-1-yl)-propyl)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  Discovery of Potent Indenoisoquinoline Topoisomerase I Poisons Lacking the 3-Nitro Toxicophore

  摘要：

  3-Nitroindenoisoquinoline human topoisomerase IB (Top1) poisons have potent antiproliferative effects on cancer cells. The undesirable nitro toxicophore could hypothetically be replaced by other functional groups that would retain the desired biological activities and minimize potential safety risks. Eleven series of indenoisoquinolines bearing 3-nitro bioisosteres were synthesized. The molecules were evaluated in the Top1-mediated DNA cleavage assay and in the National Cancer Institute's 60 cell line cytotoxicity assay. The data reveal that fluorine and chlorine may substitute for the 3-nitro group with minimal loss of Top1 poisoning activity. The new information gained from these efforts can be used to design novel indenoisoquinolines with improved safety.

  DOI：

  10.1021/acs.jmedchem.5b00303
• 作为产物：
  描述：

  6-氨基四氯苯酞 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 偶氮二异丁腈 、 sodium nitrite 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 3-Bromo-6-(trifluoromethyl)phthalide
  参考文献：
  名称：

  A novel series of N-(azetidin-3-yl)-2-(heteroarylamino)acetamide CCR2 antagonists

  摘要：

  The inflammatory response associated with the activation of C C chemokine receptor CCR2 via it's interaction with the monocyte chemoattractant protein-1 (MCP-1, CCL2) has been implicated in many disease states, including rheumatoid arthritis, multiple sclerosis, atherosclerosis, asthma and neuropathic pain. Small molecule antagonists of CCR2 have been efficacious in animal models of inflammatory disease, and have been advanced into clinical development. The necessity to attenuate hERG binding appears to be a common theme for many of the CCR2 antagonist scaffolds appearing in the literature, presumably due the basic hydrophobic motif present in all of these molecules. Following the discovery of a novel cyclohexyl azetidinylamide CCR2 antagonist scaffold, replacement of the amide bond with heterocyclic rings was explored as a strategy for reducing hERG binding and improving pharmacokinetic properties. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.017

文献信息

• [EN] CYCLOHEXYL-AZETIDINYL ANTAGONISTS OF CCR2<br/>[FR] ANTAGONISTES DU CCR2 À BASE DE CYCLOHEXYL-AZÉTIDINYLE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2011159854A1

  公开（公告）日：2011-12-22

  The present invention comprises compounds of Formula (I). Wherein: R1, R2, R4, J, Q, and A are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).

  本发明包括公式(I)的化合物。其中：R1、R2、R4、J、Q和A如说明书所述定义。本发明还包括预防、治疗或改善综合征、障碍或疾病的方法，其中所述综合征、障碍或疾病为2型糖尿病、肥胖和哮喘。本发明还包括通过管理治疗有效量的至少一种公式(I)化合物来抑制哺乳动物中的CCR2活性的方法。
• CYCLOHEXYL-AZETIDINYL ANTAGONISTS OF CCR2
  申请人：Lanter James C.

  公开号：US20110312936A1

  公开（公告）日：2011-12-22

  The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 4 , J, Q, and A are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.

  本发明涉及I式化合物，其中：R1、R2、R4、J、Q和A如规范中所定义。本发明还涉及一种预防、治疗或改善综合症、紊乱或疾病的方法，其中所述综合症、紊乱或疾病是II型糖尿病、肥胖和哮喘。本发明还涉及通过给哺乳动物施加至少一种I式化合物的治疗有效量来抑制CCR2活性的方法。
• Cyclohexyl-azetidinyl antagonists of CCR2
  申请人：Janssen Pharmaceutica NV

  公开号：US09062048B2

  公开（公告）日：2015-06-23

  The present invention comprises compounds of Formula I. wherein: R1, R2, R4, J, Q, and A are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.

  本发明涉及公式I的化合物，其中：R1、R2、R4、J、Q和A如规范中所定义。该发明还涉及一种预防、治疗或改善综合症、疾病或疾患的方法，其中所述综合症、疾病或疾患是2型糖尿病、肥胖症和哮喘。该发明还涉及通过给哺乳动物施用公式I中至少一种化合物的治疗有效量来抑制CCR2活性的方法。
• US8518969B2
  申请人：——

  公开号：US8518969B2

  公开（公告）日：2013-08-27
• US9062048B2
  申请人：——

  公开号：US9062048B2

  公开（公告）日：2015-06-23