7,8-Dimethoxy-2-methyl-chromon | 56100-47-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 7,8-Dimethoxy-2-methyl-chromon
• 英文别名: 7,8-Dimethoxy-2-methyl-4H-chromen-4-one；7,8-dimethoxy-2-methylchromen-4-one
• CAS: 56100-47-1
• 化学式: C₁₂H₁₂O₄
• 分子量: 220.225
• InChiKey: RZYSMUQBFCIUGO-UHFFFAOYSA-N

物化性质

• 熔点：
  115 °C
• 沸点：
  358.1±42.0 °C(Predicted)
• 密度：
  1.202±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7,8-Dimethoxy-2-methyl-chromon 在 sodium 、 三氯苯 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 11,12-dimethoxy-6H,8H-chromeno[3,4-b]xanthen-8-one
  参考文献：
  名称：

  Chromeno[3,4-b]xanthones as First-in-Class AChE and Aβ Aggregation Dual-Inhibitors

  摘要：

  阿尔茨海默病（AD）是一种复杂的多因素疾病，主要特征为渐进性记忆丧失和认知、运动和功能能力下降。由于中枢神经系统（CNS）药物开发的连续失败，加上缺乏有效的AD治疗方案，推动了对该疾病新的疾病修饰治疗策略的探索。为了解决这个问题，多靶点定向配体（MTDLs）正在成为治疗多种AD相关因素的治疗替代品。基于这个概念，本文描述了一系列chromeno [3,4-b] xanthones及其（E）-2- [2-（丙炔氧基）苯乙烯基] chromone前体的设计、合成和生物评价，作为首个丙酰胆碱酯酶（AChE）和β-淀粉样蛋白（Aβ）聚集双重抑制剂。化合物4b和10成为平衡双重靶点抑制剂，其AChE的IC50值分别为3.9和2.9 μM，Aβ聚集的抑制百分比分别为70％和66％。分子对接显示大多数化合物通过与催化三联体残基的氢键和主要支架与结合口袋中存在的芳香残基之间的π堆积相互作用与AChE结合。这些化合物的有趣平衡活性使它们成为开发新的AD多靶点化合物的有趣模板。

  DOI：

  10.3390/ijms22084145
• 作为产物：
  描述：

  2'-羟基-3',4'-二甲氧基苯乙酮 在 盐酸 、 sodium 、 溶剂黄146 作用下， 生成 7,8-Dimethoxy-2-methyl-chromon
  参考文献：
  名称：

  Chromones in the Mannich Reaction

  摘要：

  DOI：

  10.1021/ja01137a024

文献信息

• [EN] CULLIN-RING E3 UBIQUITIN LIGASE 4 INHIBITOR COMPOUNDS AND METHODS OF THEIR USE<br/>[FR] COMPOSÉS INHIBITEURS DE L'E3 UBIQUITINE LIGASE 4 DE TYPE CULLINE-RING ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ICAHN SCHOOL MED MOUNT SINAI

  公开号：WO2022165432A1

  公开（公告）日：2022-08-04

  Disclosed herein are compounds that inhibit cullin-RING E3 ubiquitin ligase 4, a method of inhibiting the catalytic activity of a Cullin-RING E3 Ubiquitin (Ub) Ligase (CRL) in a cell, compositions comprising the inhibitor compounds, a method of treating a tumor, and a method of treating a subject for cancer.

  本文披露了一些抑制Cullin-RING E3泛素连接酶4的化合物，一种抑制细胞内Cullin-RING E3泛素（Ub）连接酶（CRL）催化活性的方法，包含该抑制剂化合物的组合物，一种治疗肿瘤的方法，以及一种治疗癌症患者的方法。
• Cheema et al., Journal of the Chemical Society, 1932, p. 925,930
  作者：Cheema et al.

  DOI：——

  日期：——
• Synthesis of 2-styrylchromones as a novel class of antiproliferative agents targeting carcinoma cells
  作者：Arthur Y. Shaw、Chun-Yi Chang、Hao-Han Liau、Pei-Jung Lu、Hui-Ling Chen、Chia-Ning Yang、Hao-Yi Li

  DOI：10.1016/j.ejmech.2009.01.034

  日期：2009.6

  A series of 2-styrylchromone analogs were synthesized and examined for their antiproliferative effects on a panel of carcinoma cells. Among the tested agents, only 4m exhibited a moderate activity with an IC(50) value of 28.9 mu M against PC-3 cells which indicates the selectivity of PC-3 cells in response to 2-styrylchromones. In addition, 4q demonstrated the most antiproliferative effect with an IC50 value of 4.9 mu M against HeLa cells. Flow cytometric analysis and DAPI staining revealed that HeLa cells exposed to 4q as low as 5 mu M induced cell death through sub-G1 arrest and DNA fragmentation. Furthermore, CoMFA analysis of tested 2-styrylchromones resulted in a q(2) of 0.459 to generate a 3D-QSAR model on BT483 cell line. Together, these results suggest a potential structural optimization and pharmacological study of 2-styrylchromones. (C) 2009 Elsevier Masson SAS. All rights reserved.
• Blumberg; v. Kostanecki, Chemische Berichte, 1903, vol. 36, p. 2192
  作者：Blumberg、v. Kostanecki

  DOI：——

  日期：——
• Structure–activity relationship study of growth inhibitory 2-styrylchromones against carcinoma cells
  作者：Chen Lin、Pei-Jung Lu、Chia-Ning Yang、Christopher Hulme、Arthur Y. Shaw

  DOI：10.1007/s00044-012-0232-6

  日期：2013.5

  The structure-activity relationship study of 2-styrylchromones against carcinoma cell growth is discussed in the present report. Taking advantage of 2-styrylchromone as a molecular template, a series of structural modifications was carried out and examined on several carcinoma cell lines. Interestingly, AGS cells exhibited more sensitivity in response to methoxy-bearing compounds, of which compound 23 (3,4,5-trimethoxy group on ring B) showed the most potent activity with a GI(50) value of 1.3 mu M. Surprisingly, as methoxy groups in 12 and 24-27 were demethylated to generate their hydroxyl counterparts 28-32, none of them displayed appreciable activity against all carcinoma cells. We further confirmed the pivotal role of rigidity for growth inhibitory activity between the rigid 12 and its flexible counterpart 33. Taken together, in the present report, we have clearly demonstrated the structure-activity relationship study of 2-styrylchromones targeting carcinoma cell growth.