2-[(3R)-3-aminopiperidin-1-yl]-3-but-2-ynyl-5-[(4-methylquinazolin-2-yl)methyl]pyrrolo[3,2-d]pyrimidin-4-one | 1428445-40-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-[(3R)-3-aminopiperidin-1-yl]-3-but-2-ynyl-5-[(4-methylquinazolin-2-yl)methyl]pyrrolo[3,2-d]pyrimidin-4-one
• CAS: 1428445-40-2
• 化学式: C₂₅H₂₇N₇O
• 分子量: 441.536
• InChiKey: HAQUATJUWAHZDQ-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-甲基尿嘧啶 在 盐酸 、 4-二甲氨基吡啶 、 硫酸 、 硝酸 、 sodium hydride 、 碳酸氢钠 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 锌 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2-[(3R)-3-aminopiperidin-1-yl]-3-but-2-ynyl-5-[(4-methylquinazolin-2-yl)methyl]pyrrolo[3,2-d]pyrimidin-4-one
  参考文献：
  名称：

  Discovery of potent dipeptidyl peptidase IV inhibitors through pharmacophore hybridization and hit-to-lead optimization

  摘要：

  A novel dipeptidyl peptidase IV inhibitor hit (5, IC50 = 0.86 mu M) was structurally derived from our recently disclosed preclinical candidate 4 by replacing the cyanobenzyl with a butynyl based on pharmacophore hybridization. A hit-to-lead optimization effort was then initiated to improve its potency. Most N-substituted analogs exhibited good in vitro activity, and compound 180 (IC50 = 1.55 nM) was identified to be a potent dipeptidyl peptidase IV inhibitor with a significantly improved pharmacokinetic properties (bioavailablity: 41% vs 82.9%; T-1/2: 2 h vs 4.9 h). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.062

文献信息

• Discovery of potent dipeptidyl peptidase IV inhibitors through pharmacophore hybridization and hit-to-lead optimization
  作者：Shaogao Zeng、Hui Xie、Li-li Zeng、Xin Lu、Xin Zhao、Gui-cheng Zhang、Zheng-chao Tu、Hong-jiang Xu、Ling Yang、Xi-quan Zhang、Wenhui Hu

  DOI：10.1016/j.bmc.2013.01.062

  日期：2013.4

  A novel dipeptidyl peptidase IV inhibitor hit (5, IC50 = 0.86 mu M) was structurally derived from our recently disclosed preclinical candidate 4 by replacing the cyanobenzyl with a butynyl based on pharmacophore hybridization. A hit-to-lead optimization effort was then initiated to improve its potency. Most N-substituted analogs exhibited good in vitro activity, and compound 180 (IC50 = 1.55 nM) was identified to be a potent dipeptidyl peptidase IV inhibitor with a significantly improved pharmacokinetic properties (bioavailablity: 41% vs 82.9%; T-1/2: 2 h vs 4.9 h). (C) 2013 Elsevier Ltd. All rights reserved.