5-(2-methyl-oxazol-5-yl)-thiophene-2-carboxylic acid [5-[(cyclohexyl-methyl-amino)-methyl]-1-(2-hydroxy-2-methyl-propyl)-1H-benzoimidazol-2-yl]-amide

• 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: 5-(2-methyl-oxazol-5-yl)-thiophene-2-carboxylic acid [5-[(cyclohexyl-methyl-amino)-methyl]-1-(2-hydroxy-2-methyl-propyl)-1H-benzoimidazol-2-yl]-amide
• 英文别名: N-(5-((cyclohexyl(methyl)amino)methyl)-1-(2-hydroxy-2-methylpropyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-5-(2-methyloxazol-5-yl)thiophene-2-carboxamide；N-[5-[[cyclohexyl(methyl)amino]methyl]-1-(2-hydroxy-2-methylpropyl)benzimidazol-2-yl]-5-(2-methyl-1,3-oxazol-5-yl)thiophene-2-carboxamide
• 化学式: C₂₈H₃₅N₅O₃S
• 分子量: 521.684
• InChiKey: VZWIFOMPMPZKRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-(2-methyl-oxazol-5-yl)-thiophene-2-carboxylic acid [5-formyl-1-(2-hydroxy-2-methyl-propyl)-1H-benzoimidazol-2-yl]-amide 、 环己甲胺 在 MP-BH(OAc)3 、 PS-Isocyanate resin 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以46%的产率得到5-(2-methyl-oxazol-5-yl)-thiophene-2-carboxylic acid [5-[(cyclohexyl-methyl-amino)-methyl]-1-(2-hydroxy-2-methyl-propyl)-1H-benzoimidazol-2-yl]-amide
  参考文献：
  名称：

  [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
  [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

  摘要：

  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。

  公开号：

  WO2005079791A1

文献信息

• 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。
• 5-Aminomethylbenzimidazoles as potent ITK antagonists
  作者：Doris Riether、Renée Zindell、Jennifer A. Kowalski、Brian N. Cook、Jörg Bentzien、Stéphane De Lombaert、David Thomson、Stanley Z. Kugler、Donna Skow、Leslie S. Martin、Ernest L. Raymond、Hnin Hnin Khine、Kathy O’Shea、Joseph R. Woska、Deborah Jeanfavre、Rosemarie Sellati、Kerry L.M. Ralph、Jennifer Ahlberg、Gabriel Labissiere、Mohammed A. Kashem、Steven S. Pullen、Hidenori Takahashi

  DOI：10.1016/j.bmcl.2009.02.012

  日期：2009.3

  Benzamide 1 demonstrated good potency as a selective ITK inhibitor, however the amide moiety was found to be hydrolytically labile in vivo, resulting in low oral exposure and the generation of mutagenic aromatic amine metabolites. Replacing the benzamide with a benzylamine linker not only addressed the toxicity issue, but also improved the cellular and functional potency as well as the drug-like properties. SAR studies around the benzylamines and the identification of 10n and 10o as excellent tools for proof-of-concept studies are described. (C) 2009 Elsevier Ltd. All rights reserved.
• [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。