N-[1-(2-Carbamoyl-ethyl)-5-(2-cyclohexyl-1-methyl-2-oxo-ethyl)-1H-benzoimidazol-2-yl]-4-cyano-benzamide

• 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: N-[1-(2-Carbamoyl-ethyl)-5-(2-cyclohexyl-1-methyl-2-oxo-ethyl)-1H-benzoimidazol-2-yl]-4-cyano-benzamide
• 英文别名: N-[1-(3-amino-3-oxopropyl)-5-(1-cyclohexyl-1-oxopropan-2-yl)benzimidazol-2-yl]-4-cyanobenzamide
• 化学式: C₂₇H₂₉N₅O₃
• 分子量: 471.559
• InChiKey: MHXCDCLABMYDSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-[2-amino-5-(2-cyclohexyl-1-methyl-2-oxo-ethyl)-benzoimidazol-1-yl]-propionamide 、 对氰基苯甲酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-[1-(2-Carbamoyl-ethyl)-5-(2-cyclohexyl-1-methyl-2-oxo-ethyl)-1H-benzoimidazol-2-yl]-4-cyano-benzamide
  参考文献：
  名称：

  Discovery, SAR and X-ray structure of 1H-benzimidazole-5-carboxylic acid cyclohexyl-methyl-amides as inhibitors of inducible T-cell kinase (Itk)

  摘要：

  A series of novel potent benzimidazole based inhibitors of interleukin-2 T-cell kinase (Itk) were prepared. In this report, we discuss the structure-activity relationship (SAR), selectivity, and cell-based activity for the series. We also discuss the SAR associated with an X-ray structure of one of the small-molecule inhibitors bound to ITK. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.015

文献信息

• Ketone substituted benzimidazole compounds
  申请人：Moriarty J. Kevin

  公开号：US20050176792A1

  公开（公告）日：2005-08-11

  Disclosed are ketone substituted benzimidazole compounds of formula(I): wherein R 1 , R 2 , R 3 , R 4 and X a are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and to pharmaceutical compositions comprising these compounds.

  披露了式(I)的酮取代苯并咪唑化合物，其中R1、R2、R3、R4和Xa在此有定义。本发明的化合物抑制Itk激酶，因此可用于治疗涉及炎症、免疫紊乱和过敏紊乱的疾病和病理条件。还披露了制备这些化合物的方法以及包含这些化合物的药物组合物。
• [EN] 1H-BENZIMIDAZOL-2-YL-BENZAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ITK INHIBITORS (INTERLEUKIN-2-INDUCIBLE T CELL KINASE) FOR THE TREATMENT OF INFLAMMATION, IMMUNOLOGICAL AND ALLERGIC DISORDERS<br/>[FR] DERIVES DE 1H-BENZIMIDAZOL-2-YL-BENZAMIDE ET COMPOSES APPARENTES EN TANT QU'INHIBITEURS DE ITK (LYMPHOCYTES KINASE INDUCTIBLES PAR INTERLEUKIN-2) POUR TRAITER DES MALADIES INFLAMMATOIRES, IMMUNOLOGIQUES ET ALLERGIQUES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2005070420A1

  公开（公告）日：2005-08-04

  Disclosed are ketone substituted benzimidazole compounds of formula (I) wherein R1, R2, R3, R4 and Xa are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and to pharmaceutical compositions comprising these compounds.
• Discovery, SAR and X-ray structure of 1H-benzimidazole-5-carboxylic acid cyclohexyl-methyl-amides as inhibitors of inducible T-cell kinase (Itk)
  作者：Kevin J. Moriarty、Hidenori Takahashi、Steven S. Pullen、Hnin Hnin Khine、Rosemarie H. Sallati、Ernest L. Raymond、Joseph R. Woska、Deborah D. Jeanfavre、Gregory P. Roth、Michael P. Winters、Lei Qiao、Declan Ryan、Renee DesJarlais、Darius Robinson、Matthew Wilson、Mark Bobko、Brian N. Cook、Ho Yin Lo、Peter A. Nemoto、Mohammed A. Kashem、John P. Wolak、André White、Ronald L. Magolda、Bruce Tomczuk

  DOI：10.1016/j.bmcl.2008.09.015

  日期：2008.10

  A series of novel potent benzimidazole based inhibitors of interleukin-2 T-cell kinase (Itk) were prepared. In this report, we discuss the structure-activity relationship (SAR), selectivity, and cell-based activity for the series. We also discuss the SAR associated with an X-ray structure of one of the small-molecule inhibitors bound to ITK. (c) 2008 Elsevier Ltd. All rights reserved.