N-[1-(3-amino-3-oxopropyl)-5-[benzoyl(methyl)amino]benzimidazol-2-yl]-4-cyanobenzamide

• 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-(3-amino-3-oxopropyl)-5-[benzoyl(methyl)amino]benzimidazol-2-yl]-4-cyanobenzamide
• 化学式: C₂₆H₂₂N₆O₃
• 分子量: 466.499
• InChiKey: UPBLLWLBMPEKKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-[2-amino-1-(3-amino-3-oxopropyl)-1H-benzimidazol-5-yl]-N-methylbenzamide 、 对氰基苯甲酸 在 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 24.0h， 以51%的产率得到N-[1-(3-amino-3-oxopropyl)-5-[benzoyl(methyl)amino]benzimidazol-2-yl]-4-cyanobenzamide
  参考文献：
  名称：

  [EN] SUBSTITUTED BENZIMIDAZOLE COMPOUNDS
  [FR] COMPOSES BENZIMIDAZOLE SUBSTITUES

  摘要：

  揭示了一种化学式（I）中的取代苯并咪唑化合物，其中R1、R2、R3、R4和Xa在此处定义。该发明的化合物抑制Itk激酶，因此可用于治疗涉及炎症、免疫紊乱和过敏性疾病的疾病和病理状况。还揭示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。

  公开号：

  WO2004014905A1

文献信息

• Discovery of potent inhibitors of interleukin-2 inducible T-cell kinase (ITK) through structure-based drug design
  作者：Brian N. Cook、Jörg Bentzien、Andre White、Peter A. Nemoto、Ji Wang、Chuk C. Man、Fariba Soleymanzadeh、Hnin Hnin Khine、Mohammed A. Kashem、Stanley Z. Kugler、John P. Wolak、Gregory P. Roth、Stéphane De Lombaert、Steven S. Pullen、Hidenori Takahashi

  DOI：10.1016/j.bmcl.2008.12.028

  日期：2009.2

  Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inflammatory therapy. This work describes the discovery of ITK inhibitors through structure-based design where high-resolution crystal structural information was used to optimize interactions within the kinase specificity pocket of the enzyme to improve both potency and selectivity. (C) 2009 Elsevier Ltd. All rights reserved.
• 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.
• Itk kinase inhibitors: Initial efforts to improve the metabolical stability and the cell activity of the benzimidazole lead
  作者：Kevin J. Moriarty、Michael Winters、Lei Qiao、Declan Ryan、Renee DesJarlis、Darius Robinson、Brian N. Cook、Mohammed A. Kashem、Paul V. Kaplita、Lisa H. Liu、Thomas M. Farrell、Hnin Hnin Khine、Josephine King、Steven S. Pullen、Gregory P. Roth、Ronald Magolda、Hidenori Takahashi

  DOI：10.1016/j.bmcl.2008.09.017

  日期：2008.10

  Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency and selectivity to the original series and with a potential for improved microsome stability was identified. (c) 2008 Elsevier Ltd. All rights reserved.
• Crystal structure of the ITK kinase domain
  申请人：Bentzien Martin Joerg

  公开号：US20070032403A1

  公开（公告）日：2007-02-08

  Disclosed are polypeptides encoding the ITK kinase domain and nucleic acids encoding such polypeptides, crystal structures of various polypeptide-ligand complexes comprising the ITK kinase domain bound to a ligand, methods of producing the aforementioned polypeptides and nucleic acids which encode them and methods of producing crystal structures of the aforementioned polypeptides comprising the ITK kinase domain bound to a ligand.
• EXPANSION OF TUMOR INFILTRATING LYMPHOCYTES FROM LIQUID TUMORS AND THERAPEUTIC USES THEREOF
  申请人：Iovance Biotherapeutics, Inc.

  公开号：US20200224161A1

  公开（公告）日：2020-07-16

  Methods of expanding tumor infiltrating lymphocytes (TILs), including peripheral blood lymphocytes and marrow infiltrating lymphocytes, from blood and/or bone marrow of patients with hematological malignancies, such as liquid tumors, including lymphomas and leukemias, and uses of such expanded TILs in the treatment of diseases such as cancers and hematological malignancies are disclosed herein.