4-(4-chlorophenyl)-N-cyclohexylpiperazine-1-carboxamide | 541521-57-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(4-chlorophenyl)-N-cyclohexylpiperazine-1-carboxamide
• CAS: 541521-57-7
• 化学式: C₁₇H₂₄ClN₃O
• 分子量: 321.85
• InChiKey: DZKPHHMCRPGNLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-(4-氯苯基)哌嗪 、 环己基异氰酸酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以90%的产率得到4-(4-chlorophenyl)-N-cyclohexylpiperazine-1-carboxamide
  参考文献：
  名称：

  Morpholylureas are a new class of potent and selective inhibitors of the type 5 17-β-hydroxysteroid dehydrogenase (AKR1C3)

  摘要：

  Inhibitors of the aldo-keto reductase enzyme AKR1C3 are of interest as potential drugs for leukemia and hormone-related cancers. A series of non-carboxylate morpholino(phenylpiperazin-1-yl)methanones were prepared by palladium-catalysed coupling of substituted phenyl or pyridyl bromides with the known morpholino(piperazin-1-yl)methanone, and shown to be potent (IC50 similar to 100 nM) and very isoform-selective inhibitors of AKR1C3. Lipophilic electron-withdrawing substituents on the phenyl ring were positive for activity, as was an H-bond acceptor on the other terminal ring, and the ketone moiety (as a urea) was essential. These structure-activity relationships are consistent with an X-ray structure of a representative compound bound in the AKR1C3 active site, which showed H-bonding between the carbonyl oxygen of the drug and Tyr55 and His117 in the 'oxyanion hole' of the enzyme, with the piperazine bridging unit providing the correct twist to allow the terminal benzene ring to occupy the lipophilic pocket and align with Phe311. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.050

文献信息

• 10.1111/cbdd.14584
  作者：Jing, Lina、Liu, Chunxia

  DOI：10.1111/cbdd.14584

  日期：——

  Transient receptor potential vanilloid 1 (TRPV1) is a non‐selective cation channel, which is considered a highly validated target for pain perception. Repeated activation with agonists to desensitize receptors or use the antagonists can both exert analgesic effects. In this work, two series of novel phenylpiperazine derivatives were designed, synthesized, and evaluated for the in vitro receptor inhibitory

  瞬时受体电位香草酸 1 (TRPV1) 是一种非选择性阳离子通道，被认为是经过高度验证的疼痛感知靶点。用激动剂反复激活使受体脱敏或使用拮抗剂都可以发挥镇痛作用。本工作设计、合成了两个系列的新型苯基哌嗪衍生物，并评价了其体外受体抑制活性和体内镇痛活性。其中，含有磺酰脲类的L-21在多种疼痛模型中具有有效的TRPV1拮抗活性和镇痛活性。同时，L-21 表现出低热副作用的风险。这些结果表明，L-21 是进一步开发新型 TRPV1 拮抗剂来治疗疼痛的有希望的候选者。
• Morpholylureas are a new class of potent and selective inhibitors of the type 5 17-β-hydroxysteroid dehydrogenase (AKR1C3)
  作者：Jack U. Flanagan、Graham J. Atwell、Daniel M. Heinrich、Darby G. Brooke、Shevan Silva、Laurent J.M. Rigoreau、Elisabeth Trivier、Andrew P. Turnbull、Tony Raynham、Stephen M.F. Jamieson、William A. Denny

  DOI：10.1016/j.bmc.2013.12.050

  日期：2014.2

  Inhibitors of the aldo-keto reductase enzyme AKR1C3 are of interest as potential drugs for leukemia and hormone-related cancers. A series of non-carboxylate morpholino(phenylpiperazin-1-yl)methanones were prepared by palladium-catalysed coupling of substituted phenyl or pyridyl bromides with the known morpholino(piperazin-1-yl)methanone, and shown to be potent (IC50 similar to 100 nM) and very isoform-selective inhibitors of AKR1C3. Lipophilic electron-withdrawing substituents on the phenyl ring were positive for activity, as was an H-bond acceptor on the other terminal ring, and the ketone moiety (as a urea) was essential. These structure-activity relationships are consistent with an X-ray structure of a representative compound bound in the AKR1C3 active site, which showed H-bonding between the carbonyl oxygen of the drug and Tyr55 and His117 in the 'oxyanion hole' of the enzyme, with the piperazine bridging unit providing the correct twist to allow the terminal benzene ring to occupy the lipophilic pocket and align with Phe311. (C) 2013 Elsevier Ltd. All rights reserved.