3-溴-6-甲基咪唑并[1,2-b]吡嗪 | 1369326-08-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 3-溴-6-甲基咪唑并[1,2-b]吡嗪
• 中文别名: 3-溴-6-甲基咪唑并[1,2-B]哒嗪
• 英文名称: 3-bromo-6-methylimidazo[1,2-b]pyridazine
• CAS: 1369326-08-8
• 化学式: C₇H₆BrN₃
• 分子量: 212.049
• InChiKey: CDWBUTKBWLPGEV-UHFFFAOYSA-N

物化性质

• 密度：
  1.76±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  30.2
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-溴-6-甲基咪唑并[1,2-b]吡嗪 在 dichloro bis((p-dimethylaminophenyl)-ϖ-di-tert-butylphosphine)palladium(II) 、 palladium diacetate 、 sodium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 8.0h， 生成 N-(3-fluoropyridin-2-yl)-5-(6-methylimidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Optimization of an Imidazopyridazine Series of Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 (PfCDPK1)

  摘要：

  A structure-guided design approach using a homology model of Plasmodium falciparum calcium-dependent protein kinase 1 (Pf CDPK1) was used to improve the potency of a series of imidazopyridazine inhibitors as potential antimalarial agents. This resulted in high affinity compounds with PfCDPK1 enzyme IC50 values less than 10 nM and in vitro P. falciparum antiparasite EC50 values down to 12 nM, although these compounds did not have suitable ADME properties to show in vivo efficacy in a mouse model. Structural modifications designed to address the ADME issues, in particular permeability, were initially accompanied by losses in antiparasite potency, but further optimization allowed a good balance in the compound profile to be achieved. Upon testing in vivo in a murine model of efficacy against malaria, high levels of compound exposure relative to their in vitro activities were achieved, and the modest efficacy that resulted raises questions about the level of effect that is achievable through the targeting of PfCDPK1.

  DOI：

  10.1021/jm500342d
• 作为产物：
  描述：

  6-甲基-3-氨基哒嗪 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 水 、 乙腈 、 正丁醇 为溶剂， 反应 4.0h， 生成 3-溴-6-甲基咪唑并[1,2-b]吡嗪
  参考文献：
  名称：

  Optimization of an Imidazopyridazine Series of Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 (PfCDPK1)

  摘要：

  A structure-guided design approach using a homology model of Plasmodium falciparum calcium-dependent protein kinase 1 (Pf CDPK1) was used to improve the potency of a series of imidazopyridazine inhibitors as potential antimalarial agents. This resulted in high affinity compounds with PfCDPK1 enzyme IC50 values less than 10 nM and in vitro P. falciparum antiparasite EC50 values down to 12 nM, although these compounds did not have suitable ADME properties to show in vivo efficacy in a mouse model. Structural modifications designed to address the ADME issues, in particular permeability, were initially accompanied by losses in antiparasite potency, but further optimization allowed a good balance in the compound profile to be achieved. Upon testing in vivo in a murine model of efficacy against malaria, high levels of compound exposure relative to their in vitro activities were achieved, and the modest efficacy that resulted raises questions about the level of effect that is achievable through the targeting of PfCDPK1.

  DOI：

  10.1021/jm500342d

文献信息

• 6-AMINOIMIDAZO[1,2-b]PYRIDAZINE ANALOGS AS RHO KINASE INHIBITORS FOR THE TREATMENT OF RHO KINASE-MEDIATED DISEASES AND CONDITIONS
  申请人：CHEN Hwang-Hsing

  公开号：US20080153813A1

  公开（公告）日：2008-06-26

  Methods for using 6-aminoimidazo[1,2-b]pyridazine analogs are disclosed herein to treat rho kinase-mediated diseases or rho kinase-mediated conditions, including controlling intraocular pressure and treating glaucoma, are disclosed. Ophthalmic pharmaceutical compositions useful in the treatment of eye diseases such as glaucoma, and additionally useful for controlling intraocular pressure, the compositions comprising an effective amount of 6-aminoimidazo[1,2-b]pyridazine analogs, are disclosed herein.

  本文披露了使用6-氨基咪唑并[1,2-b]吡啶嗪类似物治疗rho激酶介导的疾病或rho激酶介导的症状的方法，包括控制眼压和治疗青光眼。本文还披露了用于治疗眼部疾病如青光眼，并且对控制眼压有益的眼科药物组合物，该组合物包括有效量的6-氨基咪唑并[1,2-b]吡啶嗪类似物。
• IMIDAZO[1,2-b]PYRIDAZINE-BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE
  申请人：BI Yingzhi

  公开号：US20130245021A1

  公开（公告）日：2013-09-19

  Imidazo[1,2-b]pyridazine-based compounds of the formula: are disclosed, wherein R 1 , R 2 and R 3 are defined herein. Compositions comprising the compounds and methods of their use to treat, manage and/or prevent diseases and disorders mediated by mediated by adaptor associated kinase 1 activity are also disclosed.

  本发明揭示了基于咪唑并[1,2-b]吡啶的化合物，其化学式如下：其中R1、R2和R3在此定义。本发明还揭示了包含这些化合物的组合物以及它们的使用方法，用于治疗、管理和/或预防由适配器相关激酶1活性介导的疾病和障碍。
• HETEROCYCLIC PROTEIN KINASE INHIBITORS
  申请人：Tolero Pharmaceuticals, Inc.

  公开号：EP3409278B1

  公开（公告）日：2020-09-16
• US7820670B2
  申请人：——

  公开号：US7820670B2

  公开（公告）日：2010-10-26
• US8969565B2
  申请人：——

  公开号：US8969565B2

  公开（公告）日：2015-03-03