N¹-[{(1R)-1,2,3,4-tetrahydroisoquinolin-1-yl}methyl]-N¹-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine | 1380336-40-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N¹-[{(1R)-1,2,3,4-tetrahydroisoquinolin-1-yl}methyl]-N¹-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
• 英文别名: N1-(((R)-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl)-N1-((S)-5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine；N'-[[(1R)-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl]-N'-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
• CAS: 1380336-40-2
• 化学式: C₂₃H₃₂N₄
• 分子量: 364.534
• InChiKey: UFBUAAGSLDNFTI-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  54.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 生成 N¹-[{(1R)-1,2,3,4-tetrahydroisoquinolin-1-yl}methyl]-N¹-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
  参考文献：
  名称：

  Discovery of Tetrahydroisoquinoline-Based CXCR4 Antagonists

  摘要：

  A de novo hit-to-lead effort involving the redesign of benzimidazole-containing antagonists of the CXCR4 receptor resulted in the discovery of a novel series of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogues. In general, this series of compounds show good potencies (3-650 nM) in assays involving CXCR4 function, including both inhibition of attachment of X4 HIV-1(IIIB) virus in MAGI-CCR5/CXCR4 cells and inhibition of calcium release in Chem-1 cells. Series profiling permitted the identification of TIQ(R)-stereoisomer 15 as a potent and selective CXCR4 antagonist lead candidate with a promising in vitro profile. The drug-like properties of 15 were determined in ADME in vitro studies, revealing low metabolic liability potential. Further in vivo evaluations included pharmacokinetic experiments in rats and mice, where 15 was shown to have oral bioavailability (F = 63%) and resulted in the mobilization of white blood cells (WBCs) in a dose-dependent manner.

  DOI：

  10.1021/ml400183q