1-甲基-4-(2,4,6-三甲氧基苯基)哌啶 | 872057-12-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-甲基-4-(2,4,6-三甲氧基苯基)哌啶
• 英文名称: N-methyl-4-(2,4,6-trimethoxyphenyl)piperidine
• 英文别名: 1-(N-methylpiperidin-4-yl)-2,4,6-trimethoxybenzene；1-Methyl-4-(2,4,6-trimethoxyphenyl)piperidine
• CAS: 872057-12-0
• 化学式: C₁₅H₂₃NO₃
• 分子量: 265.353
• InChiKey: JAFMSXJVKKTNTD-UHFFFAOYSA-N

物化性质

• 熔点：
  109-111 °C
• 沸点：
  362.8±42.0 °C(Predicted)
• 密度：
  1.045±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-甲基-4-(2,4,6-三甲氧基苯基)哌啶 在 sodium hydroxide 、 三氟化硼-二甲醚络合物 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 (E)-3-(2-fluorophenyl)-1-[2-hydroxy-4,6-dimethoxy-3-(1-methylpiperidin-4-yl)phenyl]prop-2-en-1-one
  参考文献：
  名称：

  Antiproliferative properties of piperidinylchalcones

  摘要：

  Methoxylated chalcones bearing N-methylpiperidinyl substituents oil ring A inhibited the growth of human tumour cell lines (MCF, HCT 116, and Jurkat) at IC50 values or < 5 mu M. Investigations oil a representative member (12) showed that antiproliferative activity was linked to the disruption of the cell cycle at G1 and G2/M phases. The effect was concentration dependent and was evident at the approximate IC50 of 12. Down regulation of cell cycle regulatory components (CDK4, cyclin B, E2F, and phosphorylated Rb) were observed under similar conditions. Methoxylated chalconcs without the piperidinyl substituent were found to exert equally potent and selective antiproliferative activity against HCT 116 tumour cells but did not interfere with cell cycle progression at their IC50 concentrations. The presence of the piperidinyl substituent in the chalcone template is proposed to lend specificity to the mechanism of antiproliferative activity, in addition to promoting a more desirable physicochemical profile. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.006
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 在 palladium on activated charcoal 盐酸 、 氢气 、 溶剂黄146 作用下， 以 水 为溶剂， 20.0~100.0 ℃ 、275.79 kPa 条件下， 反应 27.0h， 生成 1-甲基-4-(2,4,6-三甲氧基苯基)哌啶
  参考文献：
  名称：

  Antiproliferative properties of piperidinylchalcones

  摘要：

  Methoxylated chalcones bearing N-methylpiperidinyl substituents oil ring A inhibited the growth of human tumour cell lines (MCF, HCT 116, and Jurkat) at IC50 values or < 5 mu M. Investigations oil a representative member (12) showed that antiproliferative activity was linked to the disruption of the cell cycle at G1 and G2/M phases. The effect was concentration dependent and was evident at the approximate IC50 of 12. Down regulation of cell cycle regulatory components (CDK4, cyclin B, E2F, and phosphorylated Rb) were observed under similar conditions. Methoxylated chalconcs without the piperidinyl substituent were found to exert equally potent and selective antiproliferative activity against HCT 116 tumour cells but did not interfere with cell cycle progression at their IC50 concentrations. The presence of the piperidinyl substituent in the chalcone template is proposed to lend specificity to the mechanism of antiproliferative activity, in addition to promoting a more desirable physicochemical profile. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.006

文献信息

• Antiproliferative properties of piperidinylchalcones
  作者：Xiaoling Liu、Mei-Lin Go

  DOI：10.1016/j.bmc.2005.08.006

  日期：2006.1

  Methoxylated chalcones bearing N-methylpiperidinyl substituents oil ring A inhibited the growth of human tumour cell lines (MCF, HCT 116, and Jurkat) at IC50 values or < 5 mu M. Investigations oil a representative member (12) showed that antiproliferative activity was linked to the disruption of the cell cycle at G1 and G2/M phases. The effect was concentration dependent and was evident at the approximate IC50 of 12. Down regulation of cell cycle regulatory components (CDK4, cyclin B, E2F, and phosphorylated Rb) were observed under similar conditions. Methoxylated chalconcs without the piperidinyl substituent were found to exert equally potent and selective antiproliferative activity against HCT 116 tumour cells but did not interfere with cell cycle progression at their IC50 concentrations. The presence of the piperidinyl substituent in the chalcone template is proposed to lend specificity to the mechanism of antiproliferative activity, in addition to promoting a more desirable physicochemical profile. (c) 2005 Elsevier Ltd. All rights reserved.
• Piperidinyl-embeded chalcones possessing anti PI3Kδ inhibitory properties exhibit anti-atopic properties in preclinical models
  作者：Charles Dumontet、Guillaume Beck、Fabrice Gardebien、Romain Haudecoeur、Doriane Mathé、Eva-Laure Matera、Anne Tourette、Eve Mattei、Justine Esmenjaud、Cédric Boyère、Alessandra Nurisso、Marine Peuchmaur、Basile Pérès、Grégory Bouchaud、Antoine Magnan、Guillaume Monneret、Ahcène Boumendjel

  DOI：10.1016/j.ejmech.2018.09.033

  日期：2018.10

  Phosphatidylinositide 3-kinases (PI3Ks) are widely expressed enzymes involved in membrane signalization pathways. Attempts to administer inhibitors with broad activity against different isoforms have failed due to toxicity. Conversely the PI3K delta isoform is much more selectively expressed, enabling therapeutic targeting of this isoform. Of particular interest PI3K delta is expressed in human basophils and its inhibition has been shown to reduce anti-IgE induced basophil degranulation, suggesting that PI3K delta inhibitors could be useful as anti-allergy drugs. Herein, we report for the first time the activity of compounds derived from chalcone scaffolds as inhibitors of normal human basophil degranulation and identified the most active compound with anti-PI3K delta properties that was investigated in preclinical models. Compound 18, namely 1-[2-hydroxy-4,6-dimethoxy-3-(N-methylpiperidin-4-yl)pheny1]-3(2,4,6-trimethoxypheny1)-prop-2-en-1-one, was found to inhibit normal human basophil degranulation in a dose-dependent manner. In a murine model of ovalbumin-induced asthma, compound 18 was shown to reduce expiratory pressure while its impact on the inflammatory infiltrate in alveolar lavage and total lung was dependent on the route of administration. In a DNFB-induced model of atopic dermatitis compound 18 administered systemically proved to be as potent as topical betamethasone. These results support the anti-atopic and allergic properties of the title compound and warrant further clinical development. (C) 2018 Elsevier Masson SAS. All rights reserved.