5’-chloro-2’-hydroxy-3,4-methylenedioxychalcone

• 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: 5’-chloro-2’-hydroxy-3,4-methylenedioxychalcone
• 英文别名: 3-(Benzo[1,3]dioxol-5-yl)-1-(5-chloro-2-hydroxyphenyl)-2-propen-1-one；3-(1,3-benzodioxol-5-yl)-1-(5-chloro-2-hydroxyphenyl)prop-2-en-1-one
• 化学式: C₁₆H₁₁ClO₄
• 分子量: 302.714
• InChiKey: YPGXNIHFYIFXQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  胡椒醛 、 2-羟基-5-氯苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以41%的产率得到5’-chloro-2’-hydroxy-3,4-methylenedioxychalcone
  参考文献：
  名称：

  5′-Chloro-2,2′-dihydroxychalcone and related flavanoids as treatments for prostate cancer

  摘要：

  Several flavonoids and their biosynthetic precursor chalcones were designed and synthesized to improve the biological effects of the lead compound 2'-hydroxyflavonone against androgen receptor (AR)-dependent transcriptional stimulation. Newly synthesized chalcones 19 and 26 suppressed AR dependent transcription as well as DHT-dependent growth stimulation at a low micromolar level. These compounds were also effective against ligand-independent constitutively active mutant AR derived from castration-resistant PCa (CRPC). Compounds 19 and 26 showed broad spectrum anti-proliferative activity at 5-10 mu M against multiple tumor cell lines including androgen-independent and taxane-resistant prostate cancer as well as a multidrug-resistant subline. Mode of action studies suggested that 19 induced sub-G1 accumulation in PC-3 cells by disrupting the microtubule network without affecting cell cycle progression. Furthermore, the in vivo effectiveness of chalcone 19 was confirmed in a xenograft model antitumor assay. Thus, chalcone 19 has the potential to be a bifunctional lead for treatment of AR-dependent PCa at lower doses as well as AR-independent PCa, including CRPC, at higher doses. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.08.069

文献信息

• CDK inhibitors having flavone structure
  申请人：LG Chemical, Ltd.

  公开号：US06500846B1

  公开（公告）日：2002-12-31

  The present invention relates to a novel flavone derivative, pharmaceutically acceptable salt, hydrate, solvate and isomer thereof which is useful as an inhibitor against Cyclin Dependent Kinase (CDK), a process for preparation thereof, and a composition of anti-cancer agent or agent for treating neurodegenerative disease comprising this compound as an active ingredient.

  本发明涉及一种新型黄酮衍生物，其药学上可接受的盐、水合物、溶剂化物和异构体，可用作抑制细胞周期素依赖性激酶(CDK)的抑制剂，其制备方法，以及包含该化合物作为活性成分的抗癌剂或治疗神经退行性疾病的药物组合物。
• 5′-Chloro-2,2′-dihydroxychalcone and related flavanoids as treatments for prostate cancer
  作者：Yohei Saito、Atsushi Mizokami、Hiroyuki Tsurimoto、Kouji Izumi、Masuo Goto、Kyoko Nakagawa-Goto

  DOI：10.1016/j.ejmech.2018.08.069

  日期：2018.9

  Several flavonoids and their biosynthetic precursor chalcones were designed and synthesized to improve the biological effects of the lead compound 2'-hydroxyflavonone against androgen receptor (AR)-dependent transcriptional stimulation. Newly synthesized chalcones 19 and 26 suppressed AR dependent transcription as well as DHT-dependent growth stimulation at a low micromolar level. These compounds were also effective against ligand-independent constitutively active mutant AR derived from castration-resistant PCa (CRPC). Compounds 19 and 26 showed broad spectrum anti-proliferative activity at 5-10 mu M against multiple tumor cell lines including androgen-independent and taxane-resistant prostate cancer as well as a multidrug-resistant subline. Mode of action studies suggested that 19 induced sub-G1 accumulation in PC-3 cells by disrupting the microtubule network without affecting cell cycle progression. Furthermore, the in vivo effectiveness of chalcone 19 was confirmed in a xenograft model antitumor assay. Thus, chalcone 19 has the potential to be a bifunctional lead for treatment of AR-dependent PCa at lower doses as well as AR-independent PCa, including CRPC, at higher doses. (C) 2018 Elsevier Masson SAS. All rights reserved.