7-(6-chloropyridin-2-ylthio)-2-ethyl-8-methyl-4H-chromen-4-one | 1362586-34-2

• 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-(6-chloropyridin-2-ylthio)-2-ethyl-8-methyl-4H-chromen-4-one
• 英文别名: 7-(6-Chloropyridin-2-yl)sulfanyl-2-ethyl-8-methylchromen-4-one
• CAS: 1362586-34-2
• 化学式: C₁₇H₁₄ClNO₂S
• 分子量: 331.823
• InChiKey: NDPAPWDJIUSISK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  64.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-ethyl-7-hydroxy-8-methyl-4H-chromen-4-one 在 吡啶 、 potassium carbonate 、 potassium hydroxide 、 三氯化磷 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 生成 7-(6-chloropyridin-2-ylthio)-2-ethyl-8-methyl-4H-chromen-4-one
  参考文献：
  名称：

  Antitumor agents 292. Design, synthesis and pharmacological study of S- and O-substituted 7-mercapto- or hydroxy-coumarins and chromones as potent cytotoxic agents

  摘要：

  Thirty-five S- and O-substituted 7-mercaptocoumarin (9-23) and 7-hydroxy- or 7-mercapto-chromone (24-43) analogs were designed, synthesized and evaluated in vitro against four human tumor cell lines [KB (nasopharyngeal), KB-vin (vincristine-resistant subline), A549 (lung) and DU145 (prostate)] with paclitaxel as the positive control. Many of the synthesized compounds exhibited potent cytotoxic activity. Among them, compounds 10 and 18 showed broad spectrum activity with GI(50) values ranging from 0.92 to 2.11 mu M and 2.06-14.07 mu M, respectively. However, 33, a 3-brominated compound, displayed significant and selective inhibition against MDR KB-vin with a GI(50) of 5.84 mu M. Regardless of the size of the 7-alkoxy group, 2-alpha-bromoethyl-8-bromomethyl compounds (40-43) exhibited increased cytotoxicity compared with 2-ethyl-8-bromomethyl compounds (36-39). Moreover, in a preliminary pharmacological study, 10 not only remarkably increased cellular apoptosis in a concentration-dependent manner, but also clearly induced A549 cell cycle arrest at the G2/M phase. Thus, these coumarin derivatives merit investigation as novel potential antitumor agents with further structural modification to produce an optimal lead compound and elucidate the detailed pharmacological mechanism(s). (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.12.025

文献信息

• 7-氧、硫或氮杂取代香豆素及其衍生物和用途
  申请人：复旦大学

  公开号：CN103420990B

  公开（公告）日：2016-04-20

  本发明属化学制药领域，具体涉及式8或12的结构的7-氧、硫或氮杂取代香豆素及其衍生物和抗肿瘤活性。经抗肿瘤活性和药理作用靶点试验，结果显示，所述化合物具有对鼻咽癌细胞及其耐药瘤株，肺癌细胞和前列腺癌细胞生长抑制活性的作用；药理研究结果显示能促进细胞凋亡和作用在细胞分裂周期G2/M期。所述化合物结构新颖，为深入作用靶点和逆转耐药等相关药理机理研究奠定良好基础。，其中：X为氧、硫或氮原子，R2为烷基、烷氧基、卤代烷基或酯基R3为烷基、取代芳杂环包含6-氯吡啶以及取代芳烷基。
• Antitumor agents 292. Design, synthesis and pharmacological study of S- and O-substituted 7-mercapto- or hydroxy-coumarins and chromones as potent cytotoxic agents
  作者：Ying Chen、Hong-Rui Liu、Hong-Shan Liu、Ming Cheng、Peng Xia、Keduo Qian、Pei-Chi Wu、Chin-Yu Lai、Yi Xia、Zheng-Yu Yang、Susan L. Morris-Natschke、Kuo-Hsiung Lee

  DOI：10.1016/j.ejmech.2011.12.025

  日期：2012.3

  Thirty-five S- and O-substituted 7-mercaptocoumarin (9-23) and 7-hydroxy- or 7-mercapto-chromone (24-43) analogs were designed, synthesized and evaluated in vitro against four human tumor cell lines [KB (nasopharyngeal), KB-vin (vincristine-resistant subline), A549 (lung) and DU145 (prostate)] with paclitaxel as the positive control. Many of the synthesized compounds exhibited potent cytotoxic activity. Among them, compounds 10 and 18 showed broad spectrum activity with GI(50) values ranging from 0.92 to 2.11 mu M and 2.06-14.07 mu M, respectively. However, 33, a 3-brominated compound, displayed significant and selective inhibition against MDR KB-vin with a GI(50) of 5.84 mu M. Regardless of the size of the 7-alkoxy group, 2-alpha-bromoethyl-8-bromomethyl compounds (40-43) exhibited increased cytotoxicity compared with 2-ethyl-8-bromomethyl compounds (36-39). Moreover, in a preliminary pharmacological study, 10 not only remarkably increased cellular apoptosis in a concentration-dependent manner, but also clearly induced A549 cell cycle arrest at the G2/M phase. Thus, these coumarin derivatives merit investigation as novel potential antitumor agents with further structural modification to produce an optimal lead compound and elucidate the detailed pharmacological mechanism(s). (C) 2011 Elsevier Masson SAS. All rights reserved.