tert-butyl (trans-4-{[3-(4-aminophenyl)imidazo[1,2-b]pyridazin-6-yl]amino}cyclohexyl)carbamate | 1400874-22-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl (trans-4-{[3-(4-aminophenyl)imidazo[1,2-b]pyridazin-6-yl]amino}cyclohexyl)carbamate
• CAS: 1400874-22-7
• 化学式: C₂₃H₃₀N₆O₂
• 分子量: 422.53
• InChiKey: XOHMRAXGOIERBA-IYARVYRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.23
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  106.57
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (trans-4-{[3-(4-aminophenyl)imidazo[1,2-b]pyridazin-6-yl]amino}cyclohexyl)carbamate 在 盐酸 、 palladium diacetate 、 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 、 水 为溶剂， 反应 12.0h， 生成 trans-N-(3-{4-[(3,5-difluoropyridin-2-yl)amino]phenyl}imidazo[1,2-b]pyridazin-6-yl)cyclohexane-1,4-diamine
  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：

  3-溴-6-氯咪唑并[1,2-b]哒嗪 在 4-二甲氨基吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N-甲基吡咯烷酮 、 水 为溶剂， 反应 23.5h， 生成 tert-butyl (trans-4-{[3-(4-aminophenyl)imidazo[1,2-b]pyridazin-6-yl]amino}cyclohexyl)carbamate
  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