4-(3-methoxyphenyl)-1-(4-methoxyphenyl)piperidine-4-carbonitrile | 1143579-09-2

• 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: 4-(3-methoxyphenyl)-1-(4-methoxyphenyl)piperidine-4-carbonitrile
• CAS: 1143579-09-2
• 化学式: C₂₀H₂₂N₂O₂
• 分子量: 322.407
• InChiKey: RQHJTPHZLOFLDB-UHFFFAOYSA-N

物化性质

• 沸点：
  529.1±50.0 °C(predicted)
• 密度：
  1.17±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  45.49
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(3-methoxyphenyl)-1-(4-methoxyphenyl)piperidine-4-carbonitrile 在 lithium aluminium tetrahydride 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Synthesis and structure–activity relationships of N-(4-amino-2,6-diisopropylphenyl)-N’-(1,4-diarylpiperidine-4-yl)methylureas as anti-hyperlipidemic agents

  摘要：

  Based on 1,4-diarylpiperidine-4-methylureas, a new class of ACAT inhibitors, we examined in the study the SAR of a series of compounds prepared by replacing the substituent at the three aromatic parts. Introduction of long alkoxy group onto the phenyl moiety at the B-part was effective in improving both the inhibitory activity for ACAT and the up-regulatory activity for LDL-R expression. Particularly, 3-hydroxy-propoxy group (43) on the phenyl moiety of B-part led to improved solubility, while keeping both biological activities. Compound 43 inhibited ACAT activity with an IC(50) value of 18 nM, which is superior to that of a known ACAT inhibitor, CI-1011. In addition, compound 43 revealed an LDL-R up-regulatory activity comparable to that of SMP-797. We therefore expect this compound to be a novel ACAT inhibitor. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.059
• 作为产物：
  描述：

  4-羟基-2-(2-羟乙基)-2-(3-甲氧基苯基)丁腈 、 甲氧苯胺 在 三氟甲磺酸酐 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 3.25h， 以87%的产率得到4-(3-methoxyphenyl)-1-(4-methoxyphenyl)piperidine-4-carbonitrile
  参考文献：
  名称：

  Synthesis and structure–activity relationships of N-(4-amino-2,6-diisopropylphenyl)-N’-(1,4-diarylpiperidine-4-yl)methylureas as anti-hyperlipidemic agents

  摘要：

  Based on 1,4-diarylpiperidine-4-methylureas, a new class of ACAT inhibitors, we examined in the study the SAR of a series of compounds prepared by replacing the substituent at the three aromatic parts. Introduction of long alkoxy group onto the phenyl moiety at the B-part was effective in improving both the inhibitory activity for ACAT and the up-regulatory activity for LDL-R expression. Particularly, 3-hydroxy-propoxy group (43) on the phenyl moiety of B-part led to improved solubility, while keeping both biological activities. Compound 43 inhibited ACAT activity with an IC(50) value of 18 nM, which is superior to that of a known ACAT inhibitor, CI-1011. In addition, compound 43 revealed an LDL-R up-regulatory activity comparable to that of SMP-797. We therefore expect this compound to be a novel ACAT inhibitor. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.059

文献信息

• Novel 1,4-diarylpiperidine-4-methylureas as anti-hyperlipidemic agents: Dual effectors on acyl-CoA:cholesterol O-acyltransferase and low-density lipoprotein receptor expression
  作者：Shigehiro Asano、Hitoshi Ban、Kouichi Kino、Katsuhisa Ioriya、Masami Muraoka

  DOI：10.1016/j.bmcl.2009.01.020

  日期：2009.2

  A family of 1,4-diarylpiperidine-4-methylureas were designed and synthesized as novel dual effectors on ACAT and LDL receptor expression. We examined SAR of the synthesized compounds focusing on substitution at the three aromatic parts of the starting compound 1 and succeeded in identifying essential substituents for inhibition of ACAT and up-regulation of hepatic LDL receptor expression. Especially, we found that compound 12f, which can easily be prepared, has biological properties comparable to those of SMP-797, a promising ACAT inhibitor. In addition, the in vitro effects of 12f on lipid metabolism were substantially superior to those of a known ACAT inhibitor, Avasimibe. (C) 2009 Elsevier Ltd. All rights reserved.