4-(4-bromo-1-methyl-1H-pyrazol-3-yl)-4-hydroxy-cyclohexanone | 1228652-48-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-(4-bromo-1-methyl-1H-pyrazol-3-yl)-4-hydroxy-cyclohexanone
• 英文别名: 4-(4-bromo-1-methylpyrazol-3-yl)-4-hydroxycyclohexan-1-one
• CAS: 1228652-48-9
• 化学式: C₁₀H₁₃BrN₂O₂
• 分子量: 273.129
• InChiKey: KVZUNHROWWYEQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  15
• 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-(4-bromo-1-methyl-1H-pyrazol-3-yl)-4-hydroxy-cyclohexanone 在 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-({1-[4-hydroxy-4-(1-methyl-1H-pyrazol-3-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide
  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
• 作为产物：
  描述：

  1,4-环己二酮单乙二醇缩酮 在 盐酸 、 正丁基锂 作用下， 以 正己烷 、 丙酮 为溶剂， 反应 6.5h， 生成 4-(4-bromo-1-methyl-1H-pyrazol-3-yl)-4-hydroxy-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

• 4-AZETIDINYL-1-HETEROARYL-CYCLOHEXANOL ANTAGONISTS OF CCR2
  申请人：Zhang Xuqing

  公开号：US20100144695A1

  公开（公告）日：2010-06-10

  The present invention comprises compounds of Formula (I). wherein: R 1 , R 2 , R 3 , and R 4 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).

  本发明涉及式（I）的化合物。其中：R1、R2、R3和R4如规范中所定义。该发明还涉及包含式（I）化合物的药物组合物，以及通过给予式（I）化合物来预防、治疗或改善CCR2介导的综合症、疾病或疾病的方法，例如II型糖尿病、肥胖或哮喘。
• 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。
• US8450304B2
  申请人：——

  公开号：US8450304B2

  公开（公告）日：2013-05-28
• [EN] 4-AZETIDINYL-1-HETEROARYL-CYCLOHEXANOL ANTAGONISTS OF CCR2<br/>[FR] ANTAGONISTES DE CCR2 À BASE DE 4-AZÉTIDINYL-1-HÉTÉROARYL-CYCLOHEXANOL
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2010068663A1

  公开（公告）日：2010-06-17

  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).