4-hydroxy-4-(1-methyl-1H-imidazol-2-yl)-cyclohexanone | 1228652-46-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-hydroxy-4-(1-methyl-1H-imidazol-2-yl)-cyclohexanone
• 英文别名: 4-hydroxy-4-(1-methylimidazol-2-yl)cyclohexan-1-one
• CAS: 1228652-46-7
• 化学式: C₁₀H₁₄N₂O₂
• 分子量: 194.233
• InChiKey: QLMHMMSCJRCPMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxy-4-(1-methyl-1H-imidazol-2-yl)-cyclohexanone 、 N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide 生成 N-({1-[4-hydroxy-4-(1-methyl-1H-imidazol-2-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide
  参考文献：
  名称：

  4-AZETIDINYL-1-HETEROARYL-CYCLOHEXANOL ANTAGONISTS OF CCR2

  摘要：

  本发明涉及公式(I)的化合物。其中：R1、R2、R3和R4如规范中所定义。本发明还涉及包含公式(I)化合物的药物组合物，并通过给予公式(I)化合物的方法来预防、治疗或改善CCr2介导的综合症、疾病或疾病，例如II型糖尿病、肥胖症或哮喘。

  公开号：

  US20100144695A1
• 作为产物：
  描述：

  8-(1-methyl-1H-imidazol-2-yl)-1,4-dioxa-spiro[4.5]decan-8-ol 在 盐酸 作用下， 以 丙酮 为溶剂， 反应 4.0h， 生成 4-hydroxy-4-(1-methyl-1H-imidazol-2-yl)-cyclohexanone
  参考文献：
  名称：

  Discovery of a 4-Azetidinyl-1-thiazoyl-cyclohexane CCR2 Antagonist as a Development Candidate

  摘要：

  We have discovered a novel series of 4-azetidiny1-1-aryl-cyclohexanes as CCR2 antagonists. Divergent SAR studies on hCCR2 and hERG activities led to the discovery of compound 8d, which displayed good hCCR2 binding affinity (IC50, 37 nM) and potent functional antagonism (chemotaxis IC50, 30 nM). It presented an IC50 of >50 mu M in inhibition of the hERG channel and had no effect on the QTc interval up to 10 mg/kg (i.v.) in anesthetized guinea pig and dog CV studies. It also displayed high selectivity over other chemokine receptors and GPCRs, and amendable oral bioavailability in dogs and primates. In a thioglycollate-induced inflammation model in hCCR2KI mice, it had ED50 of 3 mg/kg on inhibition of the influx of leukocytes, monocytes/macrophages, and T-lymphocytes.

  DOI：

  10.1021/ml300260s

文献信息

• CYCLOHEXYL-AZETIDINYL ANTAGONISTS OF CCR2
  申请人：Zhang Xuqing

  公开号：US20110306592A1

  公开（公告）日：2011-12-15

  The present invention comprises compounds of Formula (I). wherein: R 1 , R 2 , X, and Z 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).

  本发明包括式(I)的化合物。其中：R1、R2、X和Z如规范中所定义。该发明还包括一种预防、治疗或改善综合症、紊乱或疾病的方法，其中所述综合症、紊乱或疾病为II型糖尿病、肥胖和哮喘。该发明还包括通过给哺乳动物施用至少一种式(I)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：Zhang Xuqing

  公开号：US08436023B2

  公开（公告）日：2013-05-07

  The present invention comprises compounds of Formula (I). wherein: R1, R2, X, and Z 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).

  本发明涉及式(I)化合物，其中：R1、R2、X和Z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、肥胖症和哮喘。本发明还涉及一种通过给哺乳动物治疗有效量的至少一种式(I)化合物来抑制CCR2活性的方法。
• 4-azetidinyl-1-heteroaryl-cyclohexanol antagonists of CCR2
  申请人：Zhang Xuqing

  公开号：US08450304B2

  公开（公告）日：2013-05-28

  The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, and R4 are as defined in the specification. The invention also comprises pharmaceutical compositions comprising the compounds of formula (I) and methods of preventing, treating or ameliorating a CCR2 mediated syndrome, disorder or disease, for example, type II diabetes, obesity or asthma, by administering the compounds of formula (I).

  本发明包括式（I）的化合物。其中：R1，R2，R3和R4如规范中定义。本发明还包括包含式（I）化合物的药物组合物以及通过给予式（I）化合物预防、治疗或改善CCR2介导的综合征、紊乱或疾病的方法，例如二型糖尿病、肥胖症或哮喘。
• Design, synthesis and SAR of indazole and benzoisoxazole containing 4-azetidinyl-1-aryl-cyclohexanes as CCR2 antagonists
  作者：Xuqing Zhang、Heather Hufnagel、Cuifen Hou、Evan Opas、Sandra McKenney、Carl Crysler、John O’Neill、Dana Johnson、Zhihua Sui

  DOI：10.1016/j.bmcl.2011.08.074

  日期：2011.10

  A novel series of 4-azetidinyl-1-aryl-cyclohexanes containing indazole or benzoisoxazole moiety have been identified as potent CCR2 antagonists with high selectivity versus hERG. (C) 2011 Elsevier Ltd. All rights reserved.
• CYCLOHEXYL-AZETIDINYL ANTAGONISTS OF CCR2
  申请人：Janssen Pharmaceutica, N.V.

  公开号：EP2580208A1

  公开（公告）日：2013-04-17