1-(2-amino-1H-benzo[d]imidazol-1-yl)-2-methylpropan-2-ol

• 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-(2-amino-1H-benzo[d]imidazol-1-yl)-2-methylpropan-2-ol
• 英文别名: 1-(2-aminobenzimidazol-1-yl)-2-methylpropan-2-ol
• 化学式: C₁₁H₁₅N₃O
• 分子量: 205.26
• InChiKey: VZOSKYJDPBEHDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-苯基-吡啶-4-甲酸 、 1-(2-amino-1H-benzo[d]imidazol-1-yl)-2-methylpropan-2-ol 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-[1-(2-hydroxy-2-methyl-propyl)-1H-benzoimidazol-2-yl]-2-phenyl-isonicotinamide
  参考文献：
  名称：

  Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors

  摘要：

  The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors. While tumor responses to tyrosine kinase inhibitors (TKIs) are accompanied by marked tumor shrinkage, the response is usually not durable. Most patients relapse within two years of therapy often due to acquisition of an additional mutation in EGFR kinase domain that confers resistance to TKIs. Crucially, oncogenic EGFR harboring both resistance mutations, T790M and C797S, can no longer be inhibited by currently approved EGFR TKIs. Here, we describe the discovery of BI-4020, which is a noncovalent, wild-type EGFR sparing, macro-cyclic TKI. BI-4020 potently inhibits the above-described EGFR variants and induces tumor regressions in a cross-resistant EGFR(del19 T790M C797S) xenograft model. Key was the identification of a highly selective but moderately potent benzimidazole followed by complete rigidification of the molecule through macrocyclization.

  DOI：

  10.1021/acs.jmedchem.9b01169
• 作为产物：
  描述：

  2-methyl-1-[(2-nitrophenyl)amino]propan-2-ol 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、500.01 kPa 条件下， 反应 32.0h， 生成 1-(2-amino-1H-benzo[d]imidazol-1-yl)-2-methylpropan-2-ol
  参考文献：
  名称：

  [EN] NEW BENZIMIDAZOLE COMPOUNDS AND DERIVATIVES AS EGFR INHIBITORS
  [FR] NOUVEAUX COMPOSÉS DE BENZIMIDAZOLE ET LEURS DÉRIVÉS EN TANT QU'INHIBITEURS D'EGFR

  摘要：

  本发明涵盖了式（I）（I）的化合物，其中基团R1至R5具有权利要求和说明书中给出的含义，它们作为突变EGFR的抑制剂的用途，含有这种化合物的药物组合物以及它们作为药物/医用品的用途，特别是作为治疗和/或预防肿瘤疾病的药剂。

  公开号：

  WO2019162323A1

文献信息

• HETEROCYCLIC COMPOUNDS CONTAINING AN INDOLE CORE
  申请人：Boyer Stephen James

  公开号：US20130109679A1

  公开（公告）日：2013-05-02

  Disclosed are novel compounds which inhibit RSK, methods of making such compounds and pharmaceutical compositions comprising such compounds. Also disclosed are methods of treating RSK2 regulated disorders using compounds of the invention.

  本发明揭示了一种新型化合物，可抑制RSK，制备这种化合物的方法以及包含这种化合物的药物组合物。本发明还揭示了使用本发明化合物治疗RSK2调节的疾病的方法。
• Benzimidazole compounds and derivatives as EGFR inhibitors
  申请人：Boehringer Ingelheim International GmbH

  公开号：US11174245B2

  公开（公告）日：2021-11-16

  The present invention encompasses compounds of formula (I) (I), wherein the groups R1 to R5 have the meanings given in the claims and specification, their use as inhibitors of mutant EGFR, pharmaceutical compositions which contain compounds of this kind and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

  本发明包括式(I)(I)化合物（其中基团R1至R5具有权利要求书和说明书中给出的含义）、它们作为突变型表皮生长因子受体抑制剂的用途、含有此类化合物的药物组合物以及它们作为药物/医疗用途的用途，特别是作为治疗和/或预防肿瘤疾病的制剂的用途。
• NEW BENZIMIDAZOLE COMPOUNDS AND DERIVATIVES AS EGFR INHIBITORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20200377476A1

  公开（公告）日：2020-12-03

  The present invention encompasses compounds of formula (I) (I), wherein the groups R 1 to R 5 have the meanings given in the claims and specification, their use as inhibitors of mutant EGFR, pharmaceutical compositions which contain compounds of this kind and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.
• US9150577B2
  申请人：——

  公开号：US9150577B2

  公开（公告）日：2015-10-06
• [EN] NEW BENZIMIDAZOLE COMPOUNDS AND DERIVATIVES AS EGFR INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS DE BENZIMIDAZOLE ET LEURS DÉRIVÉS EN TANT QU'INHIBITEURS D'EGFR
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2019162323A1

  公开（公告）日：2019-08-29

  The present invention encompasses compounds of formula (I) (I), wherein the groups R1 to R5 have the meanings given in the claims and specification, their use as inhibitors of mutant EGFR, pharmaceutical compositions which contain compounds of this kind and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

  本发明涵盖了式（I）（I）的化合物，其中基团R1至R5具有权利要求和说明书中给出的含义，它们作为突变EGFR的抑制剂的用途，含有这种化合物的药物组合物以及它们作为药物/医用品的用途，特别是作为治疗和/或预防肿瘤疾病的药剂。