1-isopropyl-1H-benzoimidazole-4-carboxylic acid | 832099-53-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-isopropyl-1H-benzoimidazole-4-carboxylic acid
• 英文别名: 1-(Propan-2-yl)-1H-benzimidazole-4-carboxylic acid；1-propan-2-ylbenzimidazole-4-carboxylic acid
• CAS: 832099-53-3
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: STXPNSPVZQVSMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  3-(氨基甲基)-4,6-二甲基-1,2-二氢吡啶-2-酮 、 1-isopropyl-1H-benzoimidazole-4-carboxylic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 二甲基亚砜 为溶剂， 生成 N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-benzo[d]imidazole-4-carboxamide
  参考文献：
  名称：

  The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat

  摘要：

  Posttranslational methylation of histones plays a critical role in gene regulation. Misregulation of histone methylation can lead to oncogenic transformation. Enhancer of Zeste homologue 2 (EZH2) methylates histone 3 at lysine 27 (H3K27) and abnormal methylation of this site is found in many cancers. Tazemetostat, an EHZ2 inhibitor in clinical development, has shown activity in both preclinical models of cancer as well as in patients with lymphoma or INI1-deficient solid tumors. Herein we report the structure activity relationships from identification of an initial hit in a high-throughput screen through selection of tazemetostat for clinical development. The importance of several methyl groups to the potency of the inhibitors is highlighted as well as the importance of balancing pharmacokinetic properties with potency.

  DOI：

  10.1021/acs.jmedchem.5b01501
• 作为产物：
  描述：

  苯并咪唑-4-羧酸乙酯 在 caesium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-isopropyl-1H-benzoimidazole-4-carboxylic acid
  参考文献：
  名称：

  The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat

  摘要：

  Posttranslational methylation of histones plays a critical role in gene regulation. Misregulation of histone methylation can lead to oncogenic transformation. Enhancer of Zeste homologue 2 (EZH2) methylates histone 3 at lysine 27 (H3K27) and abnormal methylation of this site is found in many cancers. Tazemetostat, an EHZ2 inhibitor in clinical development, has shown activity in both preclinical models of cancer as well as in patients with lymphoma or INI1-deficient solid tumors. Herein we report the structure activity relationships from identification of an initial hit in a high-throughput screen through selection of tazemetostat for clinical development. The importance of several methyl groups to the potency of the inhibitors is highlighted as well as the importance of balancing pharmacokinetic properties with potency.

  DOI：

  10.1021/acs.jmedchem.5b01501

文献信息

• Nicotinamide derivatives useful as PDE4 inhibitors
  申请人：Mathias Paul John

  公开号：US20050020626A1

  公开（公告）日：2005-01-27

  This invention relates to nicotinamide derivatives of general formula (I): in which R 1 , R 2 and R 3 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.

  这项发明涉及一般式（I）的烟酰胺衍生物： 其中R1、R2和R3具有本文中定义的含义，并且涉及用于制备、用于制备的中间体、含有这种衍生物的组合物以及这种衍生物的用途的过程。
• Compounds
  申请人：Barber Gordon Christopher

  公开号：US20050020611A1

  公开（公告）日：2005-01-27

  This invention relates to nicotinamide derivatives of general formula (I): in which R 1 , Z and R 2 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.

  这项发明涉及一般式(I)的烟酰胺衍生物： 其中R1、Z和R2具有本文所定义的含义，并涉及用于制备、用于制备的中间体、含有和使用这种衍生物的组合物的过程。
• Nicotinamide derivatives useful as pde4 inhibitors
  申请人：Barber Gordon Christopher

  公开号：US20060178408A1

  公开（公告）日：2006-08-10

  This invention relates to nicotinamide derivatives of general formula (I): in which R 1 , Z and R 2 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.

  本发明涉及通式（I）的烟酰胺衍生物，其中R1，Z和R2具有在此定义的含义，并涉及用于制备、制备中间体、含有和使用这种衍生物的组合物的过程。
• Spiroketone Acetyl-CoA Carboxylase Inhibitors
  申请人：Corbett Jeffrey Wayne

  公开号：US20090270435A1

  公开（公告）日：2009-10-29

  The invention provides compounds of Formula (1) or a pharmaceutically acceptable salt of said compound, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating mammals suffering from the condition of being overweight.

  本发明提供了式（1）的化合物或其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8和R9如本文所述；其药物组成物；以及将其用于治疗患有超重症的哺乳动物。
• NICOTINAMIDE DERIVATIVES USEFUL AS PDE4 INHIBITORS
  申请人：Pfizer Limited

  公开号：EP1651640B1

  公开（公告）日：2007-02-14