1-(but-2-yn-1-yl)-6-chloro-3-((6-chloroquinolin-2-yl)methyl)pyrimidine-2,4(1H,3H)-dione | 1431528-86-7

• 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: 1-(but-2-yn-1-yl)-6-chloro-3-((6-chloroquinolin-2-yl)methyl)pyrimidine-2,4(1H,3H)-dione
• CAS: 1431528-86-7
• 化学式: C₁₈H₁₃Cl₂N₃O₂
• 分子量: 374.226
• InChiKey: ONWJOJXPEFTMIV-UHFFFAOYSA-N

物化性质

• 沸点：
  523.4±60.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  56.89
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-(R)-aminopiperidine dihydrochloride 、 1-(but-2-yn-1-yl)-6-chloro-3-((6-chloroquinolin-2-yl)methyl)pyrimidine-2,4(1H,3H)-dione 在 碳酸氢钠 作用下， 以 乙硫醇 为溶剂， 反应 2.0h， 以82.9%的产率得到(R)-6-(3-aminopiperidin-1-yl)-1-(but-2-yn-1-yl)-3-((6-chloroquinolin-2-yl)methyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Highly potent dipeptidyl peptidase IV inhibitors derived from Alogliptin through pharmacophore hybridization and lead optimization

  摘要：

  The superposition of the DPP-IV complex revealed that the butynyl group of Linagliptin can be freely switched with the cyanobenzyl group of Alogliptin. Thus, a pharmacophore hybridization of Alogliptin was initiated and led to a novel DPP-IV inhibitor, 11a. Although it did not exhibit the desired activity (IC50 = 0.2 mu M), compound 11a acts as a lead compound, which triggered a resulting structural optimization and the formation of compound 11m. A novel series of potent DPP-IV inhibitors represented by compound 11m (IC50 = 0.4 nM) was ultimately obtained with a robust pharmacokinetic profile and superior in vitro and in vivo efficacy compared to Alogliptin. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.010
• 作为产物：
  描述：

  1-(but-2-ynyl)-6-chloropyrimidine-2,4(1H,3H)-dione 、 6-chloro-2-chloromethylquinoline 在 sodium hydride 、 lithium bromide 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.41h， 以53.7%的产率得到1-(but-2-yn-1-yl)-6-chloro-3-((6-chloroquinolin-2-yl)methyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Highly potent dipeptidyl peptidase IV inhibitors derived from Alogliptin through pharmacophore hybridization and lead optimization

  摘要：

  The superposition of the DPP-IV complex revealed that the butynyl group of Linagliptin can be freely switched with the cyanobenzyl group of Alogliptin. Thus, a pharmacophore hybridization of Alogliptin was initiated and led to a novel DPP-IV inhibitor, 11a. Although it did not exhibit the desired activity (IC50 = 0.2 mu M), compound 11a acts as a lead compound, which triggered a resulting structural optimization and the formation of compound 11m. A novel series of potent DPP-IV inhibitors represented by compound 11m (IC50 = 0.4 nM) was ultimately obtained with a robust pharmacokinetic profile and superior in vitro and in vivo efficacy compared to Alogliptin. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.010