| 1470077-20-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• CAS: 1470077-20-3
• 化学式: C₁₂H₁₁ClN₂O₂
• 分子量: 250.685
• InChiKey: ICNVWAGZNFCLTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.71
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  44.0
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(R)-aminopiperidine dihydrochloride 、 在 碳酸氢钠 作用下， 以 乙硫醇 为溶剂， 反应 2.0h， 以68.2%的产率得到(R)-6-(3-aminopiperidin-1-yl)-1,3-di(but-2-yn-1-yl)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 、 1-溴-2-丁炔 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90%的产率得到
  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