(4-chloro-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone | 1118761-69-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-chloro-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone
• 英文别名: (4-Chloro-3-methylphenyl)-(3-methylimidazol-4-yl)methanone；(4-chloro-3-methylphenyl)-(3-methylimidazol-4-yl)methanone
• CAS: 1118761-69-5
• 化学式: C₁₂H₁₁ClN₂O
• 分子量: 234.685
• InChiKey: JJDBGDAUUFGXRY-UHFFFAOYSA-N

物化性质

• 沸点：
  444.1±40.0 °C(predicted)
• 密度：
  1.24±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4-chloro-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone 、 6-bromo-4-(3-chloro-phenyl)-2-methoxy-quinoline 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 生成 (4-Chloro-3-methylphenyl)-[4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]-(3-methylimidazol-4-yl)methanol
  参考文献：
  名称：

  Rational Modification of a Candidate Cancer Drug for Use Against Chagas Disease

  摘要：

  Chagas disease is one of the major neglected diseases of the world. Existing drug therapies are limited, ineffective, and highly toxic. We describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. The protein farnesyltransferase (PFT) inhibitor tipifarnib, now in phase III anticancer clinical trials, was previously found to kill Trypanosoma cruzi by blocking sterol 14 alpha-demethylase (14DM). We rationally developed tipifarnib analogues that display reduced affinity for human PFT to reduce toxicity while increasing affinity for parasite 14DM. The lead compound has picomolar activity against cultured T. cruzi and is efficacious in a mouse model of acute Chagas disease.

  DOI：

  10.1021/jm801313t
• 作为产物：
  描述：

  C₁₈H₂₅ClN₂OSi 在 盐酸 作用下， 以 四氢呋喃 、 正己烷 、 水 为溶剂， 生成 (4-chloro-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone
  参考文献：
  名称：

  Rational Modification of a Candidate Cancer Drug for Use Against Chagas Disease

  摘要：

  Chagas disease is one of the major neglected diseases of the world. Existing drug therapies are limited, ineffective, and highly toxic. We describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. The protein farnesyltransferase (PFT) inhibitor tipifarnib, now in phase III anticancer clinical trials, was previously found to kill Trypanosoma cruzi by blocking sterol 14 alpha-demethylase (14DM). We rationally developed tipifarnib analogues that display reduced affinity for human PFT to reduce toxicity while increasing affinity for parasite 14DM. The lead compound has picomolar activity against cultured T. cruzi and is efficacious in a mouse model of acute Chagas disease.

  DOI：

  10.1021/jm801313t

文献信息

• NEW IMIDAZOLYLKETONE DERIVATIVES
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20140128429A1

  公开（公告）日：2014-05-08

  The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 and R 4 n are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般式（I）的新化合物，其中R1、R2、R3和R4n如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• IMIDAZOLYLKETONE DERIVATIVES ASD ALDOSTERONE SYNTHASE INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2814814B1

  公开（公告）日：2019-05-08
• US9464058B2
  申请人：——

  公开号：US9464058B2

  公开（公告）日：2016-10-11
• Rational Modification of a Candidate Cancer Drug for Use Against Chagas Disease
  作者：James M. Kraus、Christophe L. M. J. Verlinde、Mandana Karimi、Galina I. Lepesheva、Michael H. Gelb、Frederick S. Buckner

  DOI：10.1021/jm801313t

  日期：2009.3.26

  Chagas disease is one of the major neglected diseases of the world. Existing drug therapies are limited, ineffective, and highly toxic. We describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. The protein farnesyltransferase (PFT) inhibitor tipifarnib, now in phase III anticancer clinical trials, was previously found to kill Trypanosoma cruzi by blocking sterol 14 alpha-demethylase (14DM). We rationally developed tipifarnib analogues that display reduced affinity for human PFT to reduce toxicity while increasing affinity for parasite 14DM. The lead compound has picomolar activity against cultured T. cruzi and is efficacious in a mouse model of acute Chagas disease.