2,2',4,4',5,5'-hexamethoxychalcone | 14469-95-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2,2',4,4',5,5'-hexamethoxychalcone
• 英文别名: 1,3-bis(2,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 14469-95-5
• 化学式: C₂₁H₂₄O₇
• 分子量: 388.417
• InChiKey: BNHOHSPTEFULFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.63
• 重原子数：
  28.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  72.45
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  2,4,5-三甲氧基苯甲醛 、 2′,4′,5′-三甲氧基苯乙酮 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 2,2',4,4',5,5'-hexamethoxychalcone
  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

文献信息

• 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.