5-cyclopropyl-2-(3,5-dimethoxyanilino)-7-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide | 824397-47-9

• 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: 5-cyclopropyl-2-(3,5-dimethoxyanilino)-7-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide
• CAS: 824397-47-9
• 化学式: C₂₃H₂₈N₆O₄
• 分子量: 452.513
• InChiKey: SPKVOXGQOYXCDA-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-cyclopropyl-2-(3,5-dimethoxyphenylamino)-7-((R)-2-hydroxymethylpyrrolidin-1-yl)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88%的产率得到5-cyclopropyl-2-(3,5-dimethoxyanilino)-7-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]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

文献信息

• Novel pyrazolo[1,5-a]pyrimidines as c-Src kinase inhibitors that reduce IKr channel blockade
  作者：Harunobu Mukaiyama、Toshihiro Nishimura、Satoko Kobayashi、Yoshimitsu Komatsu、Shinji Kikuchi、Tomonaga Ozawa、Noboru Kamada、Hideki Ohnota

  DOI：10.1016/j.bmc.2007.10.068

  日期：2008.1

  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.