2-chloro-N-cyclohexyl-N,6-dimethylpyrimidin-4-amine | 1207424-46-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-chloro-N-cyclohexyl-N,6-dimethylpyrimidin-4-amine
• CAS: 1207424-46-1
• 化学式: C₁₂H₁₈ClN₃
• 分子量: 239.748
• InChiKey: JBLMWGJPIHIBTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  29
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-N-cyclohexyl-N,6-dimethylpyrimidin-4-amine 、 R(+)-alpha-甲基苄胺 以 1,4-二氧六环 为溶剂， 以84%的产率得到4-N-cyclohexyl-4-N,6-dimethyl-2-N-[(1R)-1-phenylethyl]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2009.10.133
• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 、 N-甲基环己胺 以 乙醇 为溶剂， 以68%的产率得到2-chloro-N-cyclohexyl-N,6-dimethylpyrimidin-4-amine
  参考文献：
  名称：

  Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2009.10.133

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.