N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)formamide | 888729-78-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)formamide
• CAS: 888729-78-0
• 化学式: C₁₁H₁₃Cl₂NO
• 分子量: 246.136
• InChiKey: NRNMWETVGMNOCD-UHFFFAOYSA-N

物化性质

• 沸点：
  403.0±45.0 °C(Predicted)
• 密度：
  1.247±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)formamide 在 盐酸 作用下， 以 N-甲基吡咯烷酮 、 异丙醇 为溶剂， 反应 21.0h， 生成 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)piperidine-4-carboxamide
  参考文献：
  名称：

  Discovery of a Piperidine-4-carboxamide CCR5 Antagonist (TAK-220) with Highly Potent Anti-HIV-1 Activity

  摘要：

  We incorporated various polar groups into previously described piperidine-4-carboxamide CCR5 antagonists to improve their metabolic stability in human hepatic microsomes. Introducing a carbamoyl group into the phenyl ring of the 4-benzylpiperidine moiety afforded the less lipophilic compound 5f, which possessed both high metabolic stability and good inhibitory activity of HIV-1 envelope-mediated membrane fusion (IC50 = 5.8 nM). Further optimization to increase potency led to the discovery of 1-acetyl-N-{3-[4-(4-carbamoylbenzyl) piperidin-1-yl]propyl}-N-(3-chloro-4-methylphenyl)piperidine-4-carboxamide (5m, TAK-220), which showed high CCR5 binding affinity (IC50 = 3.5 nM) and potent inhibition of membrane fusion (IC50 = 0.42 nM), as well as good metabolic stability. Compound 5m strongly inhibited the replication of CCR5-using HIV-1 clinical isolates in human peripheral blood mononuclear cells (mean EC50 = 1.1 nM, EC90 = 13 nM) and exhibited a good pharmacokinetic profile in monkeys (BA = 29%). This compound has been chosen as a clinical candidate for further development.

  DOI：

  10.1021/jm051034q
• 作为产物：
  描述：

  N-(3-氯-4-甲基苯基)甲酰胺 以76的产率得到N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)formamide
  参考文献：
  名称：

  J. Med. Chem. 2006, 49, 2784-2793

  摘要：

  DOI：

文献信息

• Discovery of a Piperidine-4-carboxamide CCR5 Antagonist (TAK-220) with Highly Potent Anti-HIV-1 Activity
  作者：Shinichi Imamura、Takashi Ichikawa、Youichi Nishikawa、Naoyuki Kanzaki、Katsunori Takashima、Shinichi Niwa、Yuji Iizawa、Masanori Baba、Yoshihiro Sugihara

  DOI：10.1021/jm051034q

  日期：2006.5.1

  We incorporated various polar groups into previously described piperidine-4-carboxamide CCR5 antagonists to improve their metabolic stability in human hepatic microsomes. Introducing a carbamoyl group into the phenyl ring of the 4-benzylpiperidine moiety afforded the less lipophilic compound 5f, which possessed both high metabolic stability and good inhibitory activity of HIV-1 envelope-mediated membrane fusion (IC50 = 5.8 nM). Further optimization to increase potency led to the discovery of 1-acetyl-N-3-[4-(4-carbamoylbenzyl) piperidin-1-yl]propyl}-N-(3-chloro-4-methylphenyl)piperidine-4-carboxamide (5m, TAK-220), which showed high CCR5 binding affinity (IC50 = 3.5 nM) and potent inhibition of membrane fusion (IC50 = 0.42 nM), as well as good metabolic stability. Compound 5m strongly inhibited the replication of CCR5-using HIV-1 clinical isolates in human peripheral blood mononuclear cells (mean EC50 = 1.1 nM, EC90 = 13 nM) and exhibited a good pharmacokinetic profile in monkeys (BA = 29%). This compound has been chosen as a clinical candidate for further development.
• J. Med. Chem. 2006, 49, 2784-2793
  作者：

  DOI：——

  日期：——