(R)-8-(3-aminopiperidin-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-7-(prop-2-ynyl)-1H-purine-2,6(3H,7H)-dione | 1348839-13-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (R)-8-(3-aminopiperidin-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-7-(prop-2-ynyl)-1H-purine-2,6(3H,7H)-dione
• CAS: 1348839-13-3
• 化学式: C₂₄H₂₆N₈O₂
• 分子量: 458.523
• InChiKey: FPGAZJDABUDYDU-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.76
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  116.86
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  8-溴-3-甲基-3,7-二氢-嘌呤-2,6-二酮 在 sodium carbonate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (R)-8-(3-aminopiperidin-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-7-(prop-2-ynyl)-1H-purine-2,6(3H,7H)-dione
  参考文献：
  名称：

  Discovery of highly potent DPP-4 inhibitors by hybrid compound design based on linagliptin and alogliptin

  摘要：

  Highly potent DPP-4 inhibitors have been identified by hybrid compound design based on linagliptin and alogliptin. The most promising compound 2h (IC50 = 0.31 nM) exhibited 8.5-fold and 2.5-fold more potent activity than that of alogliptin (IC50 = 2.63 nM) and linagliptin (IC50 = 0.77 nM), respectively. Compound 2h had a good inhibition selectivity for DPP-4 over DPP-8/9 and thus was selected for further biological evaluation, including oral glucose tolerance, plasma DPP-4 inhibitory activity, pharmacokinetic profile, acute toxicity and hERG inhibition. The assay results showed that 2h displayed significant in vivo glucose-lowering effect and low risk of toxicity. Further studies are expected to confirm 2h as a potential drug candidate for the treatment of type 2 diabetes.

  DOI：

  10.1016/j.ejmech.2014.06.044