N-[2-amino-1-[3-(2-oxopyrrolidin-1-yl)propyl]benzimidazol-5-yl]-N-methylbenzamide | 1095269-13-8

• 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-[2-amino-1-[3-(2-oxopyrrolidin-1-yl)propyl]benzimidazol-5-yl]-N-methylbenzamide
• CAS: 1095269-13-8
• 化学式: C₂₂H₂₅N₅O₂
• 分子量: 391.473
• InChiKey: SWXVYTTZMJDFGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  84.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-乙酰基-1H-吡咯-2-羧酸 、 N-[2-amino-1-[3-(2-oxopyrrolidin-1-yl)propyl]benzimidazol-5-yl]-N-methylbenzamide 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以60%的产率得到5-acetyl-N-[5-[benzoyl(methyl)amino]-1-[3-(2-oxopyrrolidin-1-yl)propyl]benzimidazol-2-yl]-1H-pyrrole-2-carboxamide
  参考文献：
  名称：

  2-Aminobenzimidazoles as potent ITK antagonists: de novo design of a pyrrole system targeting additional hydrogen bonding interaction

  摘要：

  Based on information from molecular modeling, a series of 2-aminobenzimidazoles with pyrrole moieties were designed and synthesized as ITK antagonists. Results showed that a significant improvement of intrinsic and cell-based potency was achieved. X-ray crystallographic analysis of an inhibitor complex with ITK confirmed the prediction from the de novo design that the pyrrole moiety of the inhibitor would form an additional hydrogen bonding interaction with Glu436 in the catalytic domain, and hence improve overall binding affinity of the inhibitor. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2008.10.057
• 作为产物：
  描述：

  溴化氰 、 N-[3-amino-4-[3-(2-oxopyrrolidin-1-yl)propylamino]phenyl]-N-methylbenzamide 以 乙醇 为溶剂， 以80%的产率得到N-[2-amino-1-[3-(2-oxopyrrolidin-1-yl)propyl]benzimidazol-5-yl]-N-methylbenzamide
  参考文献：
  名称：

  2-Aminobenzimidazoles as potent ITK antagonists: de novo design of a pyrrole system targeting additional hydrogen bonding interaction

  摘要：

  Based on information from molecular modeling, a series of 2-aminobenzimidazoles with pyrrole moieties were designed and synthesized as ITK antagonists. Results showed that a significant improvement of intrinsic and cell-based potency was achieved. X-ray crystallographic analysis of an inhibitor complex with ITK confirmed the prediction from the de novo design that the pyrrole moiety of the inhibitor would form an additional hydrogen bonding interaction with Glu436 in the catalytic domain, and hence improve overall binding affinity of the inhibitor. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2008.10.057

文献信息

• [EN] THIOPHENE -2- CARBOXYLIC ACID - (1H - BENZIMIDAZOL - 2 YL) - AMIDE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE TEC KINASE ITK (INTERLEUKIN -2- INDUCIBLE T CELL KINASE) FOR THE TREATMENT OF INFLAMMATION, IMMUNOLOGICAL AND ALLERGIC DISORDERS<br/>[FR] DERIVES D'ACIDE THIOPHENE-2-CARBOXYLIQUE (1H-BENZIMIDAZOL-2 YL)-AMIDE ET COMPOSES ASSOCIES UTILISES COMME INHIBITEURS DE LA TEC KINASE ITK (KINASE DES LYMPHOCITES INDUCTIBLES PAR L'INTERLEUKINE -2) POUR TRAITER UNE INFLAMMATION ET DES TROUBLES IMMUNOLOGIQUES ET ALLERGIQUES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2005079791A1

  公开（公告）日：2005-09-01

  Disclosed are compounds of formula (I): wherein Ar1, Ar2, 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.

  揭示了式（I）的化合物：其中Ar1、Ar2、R1、R2、R3、R4和Xa在此定义。该发明的化合物抑制Itk激酶，因此对于治疗涉及炎症、免疫紊乱和过敏疾病的疾病和病理状况是有用的。还公开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。
• Tec kinase inhibitors
  申请人：Bentzien Martin Joerg

  公开号：US20050209284A1

  公开（公告）日：2005-09-22

  Disclosed are compounds of formula(I): wherein Ar 1 , Ar 2 , 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.

  本发明公开了式(I)的化合物：其中Ar1、Ar2、R1、R2、R3、R4和Xa的定义如下。本发明的化合物抑制Itk激酶，因此可用于治疗涉及炎症、免疫紊乱和过敏症的疾病和病理条件。本发明还公开了制备这些化合物的方法和包含这些化合物的药物组合物。
• 2-Aminobenzimidazoles as potent ITK antagonists: de novo design of a pyrrole system targeting additional hydrogen bonding interaction
  作者：Ho Yin Lo、Jörg Bentzien、Andre White、Chuk C. Man、Roman W. Fleck、Steven S. Pullen、Hnin Hnin Khine、Josephine King、Joseph R. Woska、John P. Wolak、Mohammed A. Kashem、Gregory P. Roth、Hidenori Takahashi

  DOI：10.1016/j.tetlet.2008.10.057

  日期：2008.12

  Based on information from molecular modeling, a series of 2-aminobenzimidazoles with pyrrole moieties were designed and synthesized as ITK antagonists. Results showed that a significant improvement of intrinsic and cell-based potency was achieved. X-ray crystallographic analysis of an inhibitor complex with ITK confirmed the prediction from the de novo design that the pyrrole moiety of the inhibitor would form an additional hydrogen bonding interaction with Glu436 in the catalytic domain, and hence improve overall binding affinity of the inhibitor. (C) 2008 Elsevier Ltd. All rights reserved.