Itk antagonist | 1149753-56-9

• 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: Itk antagonist
• 英文别名: N-[5-[[[(2S)-3,3-dimethylbutan-2-yl]amino]methyl]-1-(2-hydroxy-2-methylpropyl)benzimidazol-2-yl]-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide
• CAS: 1149753-56-9
• 化学式: C₂₆H₃₄N₆O₂S
• 分子量: 494.661
• InChiKey: MUAICZWSFWUFNA-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  、 (S)-3,3-二甲基-2-丁胺 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 生成 Itk antagonist
  参考文献：
  名称：

  5-Aminomethylbenzimidazoles as potent ITK antagonists

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2009.02.012

文献信息

• METHODS OF TREATING FIBROSIS
  申请人：Pharmacyclics LLC

  公开号：US20160199376A1

  公开（公告）日：2016-07-14

  Disclosed are methods of treating fibrosis in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of an ACK inhibitor (e.g., a BTK inhibitor, such as for example an irreversible BTK inhibitor, such as for example, ibrutinib).

  本发明涉及一种治疗患者纤维化的方法，包括向需要治疗的患者施用治疗有效量的ACK抑制剂（例如，BTK抑制剂，例如不可逆的BTK抑制剂，例如ibrutinib）。
• Methods of treating fibrosis
  申请人：Pharmacyclics LLC

  公开号：US10226466B2

  公开（公告）日：2019-03-12

  Disclosed are methods of treating fibrosis in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of an ACK inhibitor (e.g., a BTK inhibitor, such as for example an irreversible BTK inhibitor, such as for example, ibrutinib).

  公开了治疗患者纤维化的方法，包括向有需要的患者施用治疗有效量的ACK抑制剂（如BTK抑制剂，例如不可逆的BTK抑制剂，如伊布替尼）。
• Methods for treating B cell proliferative disorders
  申请人：Cornell University

  公开号：US10314842B2

  公开（公告）日：2019-06-11

  Described herein are methods for treating B cell proliferative disorders, in an individual in need thereof. The methods include administering to an individual in need thereof a Btk inhibitor (e.g., ibrutinib), in combination with a CDK4 inhibitor (e.g., palbociclib).

  本文描述了治疗有需要的个体的B细胞增殖性疾病的方法。这些方法包括向有需要的个体施用 Btk 抑制剂（如 ibrutinib）与 CDK4 抑制剂（如 palbociclib）。
• Methods of treating and preventing graft versus host disease
  申请人：Pharmacyclics LLC

  公开号：US10463668B2

  公开（公告）日：2019-11-05

  Described herein are methods for treating and preventing graft versus host disease using ACK inhibitors. The methods include administering to an individual in need thereof an ACK inhibitor such as ibrutinib for treating and preventing graft versus host disease.

  本文描述了使用ACK抑制剂治疗和预防移植物抗宿主疾病的方法。这些方法包括向有需要的个体施用ACK抑制剂，如伊布替尼，以治疗和预防移植物抗宿主疾病。
• TREATMENT USING BRUTON'S TYROSINE KINASE INHIBITORS AND IMMUNOTHERAPY
  申请人：Pharmacyclics, Inc.

  公开号：US20150118222A1

  公开（公告）日：2015-04-30

  Combinations of Bruton's tyrosine kinase (Btk) inhibitors, e.g., 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, with immunotherapy are provided. Also provided are methods of treating cancers, and autoimmune disorders by administering combinations of Bruton's tyrosine kinase (Btk) inhibitors, e.g., 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, and an immune checkpoint inhibitor.