2-(3-Bromo-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one | 1242983-34-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2-(3-Bromo-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one
• 英文别名: 2-(3-Bromophenyl)-8-[2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]-5,7-dimethoxychromen-4-one
• CAS: 1242983-34-1
• 化学式: C₂₃H₂₄BrNO₅
• 分子量: 474.351
• InChiKey: ZFDBVCIHGUSFFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3-Bromo-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以63%的产率得到2-[5-(3-bromo-phenyl)-1H-pyrazol-3-yl]-6-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-3,5-dimethoxy-phenol
  参考文献：
  名称：

  Synthesis of novel 3,5-diaryl pyrazole derivatives using combinatorial chemistry as inhibitors of tyrosinase as well as potent anticancer, anti-inflammatory agents

  摘要：

  In the present article, we have synthesized a combinatorial library of 3,5-diaryl pyrazole derivatives using 8-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (1) and hydrazine hydrate in absolute ethyl alcohol under the refluxed conditions. The structures of the compounds were established by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their anticancer activity against five cell lines (breast cancer cell line, prostate cancer cell line, promyelocytic leukemia cell line, lung cancer cell line, colon cancer cell line) and anti-inflammatory activity against TNF-alpha and IL-6. Out of 15 compounds screened, 2a and 2d exhibited promising anticancer activity (61-73% at 10 mu M concentration) against all selected cell lines and IL-6 inhibition (47% and 42% at 10 mu M concentration) as in comparison to standard flavopiridol (72-87% inhibition at 0.5 mu M) and dexamethasone (85% inhibition at 1 mu M concentration), respectively. Cytotoxicity of the compounds checked using CCK-8 cell lines and found to be nontoxic to slightly toxic. Out of 15, four 3,5-diaryl pyrazole derivatives exhibiting potent inhibitory activities against both the monophenolase and diphenolase actions of tyrosinase. The IC(50) values of compounds (2a, 2d, 2h and 21) for monophenolase inhibition were determined to range between 1.5 and 30 mu M. Compounds 2a, 2d, 2h and 21 also inhibited diphenolase significantly with IC(50) values of 29.4, 21.5, 2.84 and 19.6 mu M, respectively. All four 3,5-diaryl pyrazole derivatives were active as tyrosinase inhibitors (2a, 2d, 2h and 21), and belonging to competitive inhibitors. Interestingly, they all manifested simple reversible slow-binding inhibition against diphenolase. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.06.046
• 作为产物：
  描述：

  acetic acid 3-{3-[3-(3-bromophenyl)-3-oxopropionyl]-2-hydroxy-4,6-dimethoxyphenyl}-1-methylpyrrolidin-2-ylmethyl ester 在 盐酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 反应 3.0h， 生成 2-(3-Bromo-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one
  参考文献：
  名称：

  [EN] PYRROLIDINE SUBSTITUTED FLAVONES FOR THE TREATMENT OF INFLAMMATORY DISORDERS
  [FR] FLAVONES À SUBSTITUTION PYRROLIDINE POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES

  摘要：

  本发明涉及使用式1的化合物，其立体异构体或互变异构体，或其药学上可接受的盐或药学上可接受的溶剂，用于治疗炎症性疾病。该发明还涉及包含式1化合物和至少一种药学上可接受的载体的药物组合物，用于治疗炎症性疾病。该发明还涉及通过向需要的受试者施用式1化合物的治疗有效量来治疗炎症性疾病的方法。

  公开号：

  WO2011104584A1

文献信息

• PYRROLIDINE SUBSTITUTE FLAVONES FOR THE TREATMENT OF INFLAMMATORY DISORDERS
  申请人：Joshi Kalpana Sanjay

  公开号：US20120316216A1

  公开（公告）日：2012-12-13

  The present invention relates to the use of a compound of formula 1, a stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, for the treatment of an inflammatory disorder. The invention further relates to a pharmaceutical composition comprising a compound of formula 1 and at least one pharmaceutically acceptable carrier, for use in the treatment of an inflammatory disorder. The invention also relates to a method for the treatment of an inflammatory disorder by administering a therapeutically effective amount of the compound of formula 1 to a subject in need thereof.

  本发明涉及使用式1的化合物、立体异构体或其互变异构体，或其药学上可接受的盐或药学上可接受的溶剂，用于治疗炎症性疾病。本发明还涉及一种制药组合物，包括式1的化合物和至少一种药学上可接受的载体，用于治疗炎症性疾病。本发明还涉及一种治疗炎症性疾病的方法，通过向需要治疗的受体中给予式1化合物的治疗有效量来进行。
• PYRROLIDINE SUBSTITUTED FLAVONES FOR THE TREATMENT OF INFLAMMATORY DISORDERS
  申请人：Piramal Enterprises Limited

  公开号：EP2538941A1

  公开（公告）日：2013-01-02
• US8906953B2
  申请人：——

  公开号：US8906953B2

  公开（公告）日：2014-12-09