4-Chloro-2-methyl-6-(trifluoromethyl)quinazoline | 1422284-63-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-Chloro-2-methyl-6-(trifluoromethyl)quinazoline
• CAS: 1422284-63-6
• 化学式: C₁₀H₆ClF₃N₂
• 分子量: 246.619
• InChiKey: BCMNEUWJAPJFIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(2-aminoacetamido)azetidine-1-carboxylate 、 4-Chloro-2-methyl-6-(trifluoromethyl)quinazoline 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 C₂₀H₂₄F₃N₅O₃
  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

• 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。
• 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
• A novel series of N-(azetidin-3-yl)-2-(heteroarylamino)acetamide CCR2 antagonists
  作者：Nalin L. Subasinghe、James Lanter、Thomas Markotan、Evan Opas、Sandra McKenney、Carl Crysler、Cuifen Hou、John O’Neill、Dana Johnson、Zhihua Sui

  DOI：10.1016/j.bmcl.2012.12.017

  日期：2013.2

  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.