4-(3-acetyl-4,6-dimethoxy-2-hydroxyphenyl)-1-methylpiperidine | 872057-13-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(3-acetyl-4,6-dimethoxy-2-hydroxyphenyl)-1-methylpiperidine
• 英文别名: 1-(2-hydroxy-4,6-dimethoxy-3-(1-methylpiperidin-4-yl)phenyl)ethanone；1-[2-hydroxy-4,6-dimethoxy-3-(1-methylpiperidin-4-yl)phenyl]ethanone
• CAS: 872057-13-1
• 化学式: C₁₆H₂₃NO₄
• 分子量: 293.363
• InChiKey: FLDNITPBNGXZRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.42
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  59.0
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-(3-acetyl-4,6-dimethoxy-2-hydroxyphenyl)-1-methylpiperidine 、 2,4,6-三甲氧基苯甲醛 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以60%的产率得到1-[2-hydroxy-4,6-dimethoxy-3-(N-methylpiperidin-4-yl)phenyl]-3-(2,4,6-trimethoxyphenyl)-prop-2-en-1-one
  参考文献：
  名称：

  Piperidinyl-embeded chalcones possessing anti PI3Kδ inhibitory properties exhibit anti-atopic properties in preclinical models

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2018.09.033
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 20.0h， 生成 4-(3-acetyl-4,6-dimethoxy-2-hydroxyphenyl)-1-methylpiperidine
  参考文献：
  名称：

  [EN] SUBSTITUTED AURONE ALKALOIDS AS ANTI-MYCOBACTERIAL AGENTS
  [FR] ALCALOÏDES D'AURONE SUBSTITUÉS EN TANT QU'AGENTS ANTI-MYCOBACTÉRIENS

  摘要：

  公开号：

  WO2017149551A4

文献信息

• Antiproliferative activity of chalcones with basic functionalities
  作者：Xiaoling Liu、Mei-Lin Go

  DOI：10.1016/j.bmc.2007.07.042

  日期：2007.11

  A library of chalcones with different basic groups were synthesized and evaluated for antiproliferative activities against the human breast cancer (MCF 7) and colon cancer (HCT 116) cell lines. Structure-activity relationships were analyzed by projection methods (PCA/PLS) and multiple linear regression. Polar volume, hydrogen bonding features, HOMO energies, and charge on the carbon were found to be important factors. A basic group on either ring A or B of the chalcone led to a favourable increase in polar Volume, but when present on ring B, it increased HOMO energies and decreased the positive charge on the carbon, both of which led to lower activity. Several examples showed that final activity of the chalcone was influenced by compensatory interactions among these parameters. In general, a single basic group on ring A was associated with good activity. A notable exception was compound 1-123 which had basic groups on both rings A and B but Still maintained a good activity profile with IC50 < 10 PM and selectivity ratios >2.5. There was some evidence to show that structural differences in chalcones influenced not only activity but mechanism of action. Compounds 6-130 and 7-140 which had basic groups on ring A interfered with cell cycle progression, but the dibasic chalcone 1-123 had no effect. (C) 2007 Elsevier Ltd. All rights reserved.
• [EN] SUBSTITUTED AURONE ALKALOIDS AS ANTI-MYCOBACTERIAL AGENTS<br/>[FR] ALCALOÏDES D'AURONE SUBSTITUÉS EN TANT QU'AGENTS ANTI-MYCOBACTÉRIENS
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2017149551A4

  公开（公告）日：2017-10-26
• 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.