(1-benzylpiperidin-4-yl)(2-chloro-6-methyl-pyrimidin-4-yl)amine | 1207425-16-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1-benzylpiperidin-4-yl)(2-chloro-6-methyl-pyrimidin-4-yl)amine
• 英文别名: N-(1-benzylpiperidin-4-yl)-2-chloro-6-methylpyrimidin-4-amine
• CAS: 1207425-16-8
• 化学式: C₁₇H₂₁ClN₄
• 分子量: 316.834
• InChiKey: KSNPUCYVVKSWAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1-benzylpiperidin-4-yl)(2-chloro-6-methyl-pyrimidin-4-yl)amine 在 palladium 10% on activated carbon 、 水 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 戊醇 、 异丙醇 为溶剂， 25.0~150.0 ℃ 、101.33 kPa 条件下， 反应 36.0h， 生成
  参考文献：
  名称：

  Development of Stem-Cell-Mobilizing Agents Targeting CXCR4 Receptor for Peripheral Blood Stem Cell Transplantation and Beyond

  摘要：

  The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4(+) cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., 16) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug 1 (AMD3100), and thus considered a potential drug candidate for PBSCT indication. Docking compound 16 into the X-ray crystal structure of CXCR4 receptor revealed that it adopted a spider-like conformation striding over both major and minor subpockets. This putative binding mode provides a new insight into CXCR4 receptor-ligand interactions for further structural modifications.

  DOI：

  10.1021/acs.jmedchem.7b01322
• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 、 4-氨基-1-苄基哌啶 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以62%的产率得到(1-benzylpiperidin-4-yl)(2-chloro-6-methyl-pyrimidin-4-yl)amine
  参考文献：
  名称：

  Development of Stem-Cell-Mobilizing Agents Targeting CXCR4 Receptor for Peripheral Blood Stem Cell Transplantation and Beyond

  摘要：

  The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4(+) cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., 16) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug 1 (AMD3100), and thus considered a potential drug candidate for PBSCT indication. Docking compound 16 into the X-ray crystal structure of CXCR4 receptor revealed that it adopted a spider-like conformation striding over both major and minor subpockets. This putative binding mode provides a new insight into CXCR4 receptor-ligand interactions for further structural modifications.

  DOI：

  10.1021/acs.jmedchem.7b01322

文献信息

• Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines
  作者：Derek C. Martyn、Amarjit Nijjar、Cassandra A. Celatka、Ralph Mazitschek、Joseph F. Cortese、Erin Tyndall、Hanlan Liu、Maria M. Fitzgerald、Thomas J. O’Shea、Sanjay Danthi、Jon Clardy

  DOI：10.1016/j.bmcl.2009.10.133

  日期：2010.1

  Two sets of diaminopyrimidines, totalling 45 compounds, were synthesized and assayed against Plasmodium falciparum. The SAR was relatively shallow, with only the presence of a 2-(pyrrolidin-1-yl)ethyl group at R-2 significantly affecting activity. A subsequent series addressed high Log D values by introducing more polar side groups, with the most active compounds possessing diazepine and N-benzyl-4-aminopiperidyl groups at R-1/R-2. A final series attempted to address high in vitro microsomal clearance by replacing the C6-Me group with CF3, however antiplasmodial activity decreased without any improvement in clearance. The C6-CF3 group decreased hERG inhibition, probably as a result of decreased amine basicity at C2/C4. (C) 2009 Elsevier Ltd. All rights reserved.