(R)-6-(3-aminopiperidin-1-yl)-3-(benzo[f]quinolin-3-ylmethyl)-1-(but-2-yn-1-yl)pyrimidine-2,4(1H,3H)-dione | 1431529-14-4

• 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: (R)-6-(3-aminopiperidin-1-yl)-3-(benzo[f]quinolin-3-ylmethyl)-1-(but-2-yn-1-yl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-[(3R)-3-aminopiperidin-1-yl]-3-(benzo[f]quinolin-3-ylmethyl)-1-but-2-ynylpyrimidine-2,4-dione
• CAS: 1431529-14-4
• 化学式: C₂₇H₂₇N₅O₂
• 分子量: 453.544
• InChiKey: NTHBVPQZWBGHQV-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  82.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(but-2-ynyl)-6-chloropyrimidine-2,4(1H,3H)-dione 在 sodium hydride 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 、 乙硫醇 、 mineral oil 为溶剂， 反应 2.41h， 生成 (R)-6-(3-aminopiperidin-1-yl)-3-(benzo[f]quinolin-3-ylmethyl)-1-(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

文献信息

• Highly potent dipeptidyl peptidase IV inhibitors derived from Alogliptin through pharmacophore hybridization and lead optimization
  作者：Hui Xie、Lili Zeng、Shaogao Zeng、Xin Lu、Xin Zhao、Guicheng Zhang、Zhengchao Tu、Hongjiang Xu、Ling Yang、Xiquan Zhang、Shanchun Wang、Wenhui Hu

  DOI：10.1016/j.ejmech.2013.08.010

  日期：2013.10

  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.