2-(3,5-dimethoxyphenylamino)-7-((S)-2-hydroxy-1-methylethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile | 824398-47-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(3,5-dimethoxyphenylamino)-7-((S)-2-hydroxy-1-methylethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile
• CAS: 824398-47-2
• 化学式: C₁₉H₂₂N₆O₃
• 分子量: 382.422
• InChiKey: AZZCQJUPCCZZOR-LBPRGKRZSA-N

物化性质

• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.46
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  116.73
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2-(3,5-dimethoxyphenylamino)-7-((S)-2-hydroxy-1-methylethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 在 sodium hydroxide 、 双氧水 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 3.0h， 以91%的产率得到2-(3,5-dimethoxyanilino)-7-[[(2S)-1-hydroxypropan-2-yl]amino]-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide
  参考文献：
  名称：

  Novel pyrazolo[1,5-a]pyrimidines as c-Src kinase inhibitors that reduce IKr channel blockade

  摘要：

  To improve the in vitro potency of the c-Src inhibitor 1a and to address its hERG liability, a structure-activity study was carried Out, focusing on two regions of the lead compound. The blockade of the delayed cardiac current rectifier K+ (I-Kr) channel was overcome by replacing the ethylenediamino group with an amino alcohol group at the 7-position. In addition, modifying the substituents at the 5-position and the side chain groups on the amino alcohols at the 7-position enhanced the intracellular c-Src inhibitory activity and increased central nervous system (CNS) penetration. In the present study, 6l exhibited significant in vivo efficacy in a middle cerebral artery (MCA) occlusion model in rats. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.068
• 作为产物：
  描述：

  7-chloro-2-(3,5-dimethoxyphenylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 、 L-氨基丙醇 在 三乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 24.0h， 以80%的产率得到2-(3,5-dimethoxyphenylamino)-7-((S)-2-hydroxy-1-methylethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile
  参考文献：
  名称：

  Novel pyrazolo[1,5-a]pyrimidines as c-Src kinase inhibitors that reduce IKr channel blockade

  摘要：

  To improve the in vitro potency of the c-Src inhibitor 1a and to address its hERG liability, a structure-activity study was carried Out, focusing on two regions of the lead compound. The blockade of the delayed cardiac current rectifier K+ (I-Kr) channel was overcome by replacing the ethylenediamino group with an amino alcohol group at the 7-position. In addition, modifying the substituents at the 5-position and the side chain groups on the amino alcohols at the 7-position enhanced the intracellular c-Src inhibitory activity and increased central nervous system (CNS) penetration. In the present study, 6l exhibited significant in vivo efficacy in a middle cerebral artery (MCA) occlusion model in rats. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.068