7-((S)-1-benzyl-2-hydroxyethylamino)-5-cyclopropyl-2-(3,5-dimethoxyphenylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile | 1018686-66-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 7-((S)-1-benzyl-2-hydroxyethylamino)-5-cyclopropyl-2-(3,5-dimethoxyphenylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile
• CAS: 1018686-66-2
• 化学式: C₂₇H₂₈N₆O₃
• 分子量: 484.558
• InChiKey: NRBXTXFTHMDDES-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.25
• 重原子数：
  36.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 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：

  7-((S)-1-benzyl-2-hydroxyethylamino)-5-cyclopropyl-2-(3,5-dimethoxyphenylamino)pyrazolo[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100%的产率得到5-cyclopropyl-2-(3,5-dimethoxyanilino)-7-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]pyrazolo[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-5-cyclopropyl-2-((3,5-dimethoxyphenyl)amino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile 、 L-苯丙氨醇 在 三乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 24.0h， 以55%的产率得到7-((S)-1-benzyl-2-hydroxyethylamino)-5-cyclopropyl-2-(3,5-dimethoxyphenylamino)pyrazolo[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