N-(3-bromoimidazo[1,2-a]pyridin-8-yl)acetamide | 1229620-12-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: N-(3-bromoimidazo[1,2-a]pyridin-8-yl)acetamide
• CAS: 1229620-12-5
• 化学式: C₉H₈BrN₃O
• 分子量: 254.086
• InChiKey: YEZOEEKDKMHBLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  46.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(3-bromoimidazo[1,2-a]pyridin-8-yl)acetamide 在 盐酸 、 水 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以90%的产率得到3-溴咪唑并[1,2-A]吡啶-8-胺
  参考文献：
  名称：

  Discovery of 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant

  摘要：

  In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of I1e315 side chain. Extensive SAR studies led to the discovery of development candidate 20g (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC(50)s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABL(T315I) expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CM L, including patients refractory to all currently approved therapies.

  DOI：

  10.1021/jm100395q
• 作为产物：
  描述：

  N-(imidazo[1,2-a]pyridin-8-yl)acetamide 在 溴 作用下， 以 乙醇 为溶剂， 生成 N-(3-bromoimidazo[1,2-a]pyridin-8-yl)acetamide
  参考文献：
  名称：

  Discovery of 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant

  摘要：

  In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of I1e315 side chain. Extensive SAR studies led to the discovery of development candidate 20g (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC(50)s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABL(T315I) expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CM L, including patients refractory to all currently approved therapies.

  DOI：

  10.1021/jm100395q

文献信息

• Bicyclic heteroaryl compounds
  申请人：Zou Dong

  公开号：US20070191376A1

  公开（公告）日：2007-08-16

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及通式如下的化合物：其中变量基团如本文所定义，以及它们的制备和使用。
• Bicyclic Heteroaryl Compounds
  申请人：Zou Dong

  公开号：US20120135986A1

  公开（公告）日：2012-05-31

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及一般公式中的化合物：其中变量基团如本文所定义，并涉及它们的制备和使用。
• METHODS AND COMPOSITIONS FOR TREATING NEURODEGENERATIVE DISEASES
  申请人：Shakespeare William C.

  公开号：US20140045826A1

  公开（公告）日：2014-02-13

  The invention discloses methods and compositions for treating or preventing neurodegenerative disease by administering a compound of Formula I: or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.

  该发明揭示了通过给予式I化合物或其药学上可接受的盐、溶剂或水合物来治疗或预防神经退行性疾病的方法和组合物，其中变量的定义如本文所述。
• Methods and Compositions for Treating Parkinson's Disease
  申请人：Shakespeare William C.

  公开号：US20140066434A1

  公开（公告）日：2014-03-06

  The invention discloses methods and compositions for treating or preventing Parkinson's disease by administering a compound of Formula (I): or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.

  本发明揭示了使用式(I)化合物或其药学上可接受的盐、溶剂或水合物治疗或预防帕金森病的方法和组合物，其中变量的定义如本文所述。
• Methods and Compositions for RAF Kinase Mediated Diseases
  申请人：ARIAD Pharmaceuticals, Inc.

  公开号：US20150105377A1

  公开（公告）日：2015-04-16

  The invention discloses methods and compositions for treating or preventing RAF kinase mediated diseases or conditions by administering a compound of Formula 1: or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.

  本发明公开了通过给予公式1的化合物或其药学上可接受的盐、溶剂或水合物来治疗或预防RAF激酶介导的疾病或病状的方法和组合物，其中变量如本文所定义。