(E)-1-(3,5-dimethoxyphenyl)-3-(3,4-methylenedioxyphenyl)-prop-2-en-1-one

• 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: (E)-1-(3,5-dimethoxyphenyl)-3-(3,4-methylenedioxyphenyl)-prop-2-en-1-one
• 英文别名: 3',5'-dimethoxy-3,4-methylenedioxy-trans-chalcone；3',5'-Dimethoxy-3,4-methylendioxy-trans-chalkon；(e)-1-(3,4-Methylenedioxyphenyl)-3-(3,5-dimethoxyphenyl)prop-1-en-3-one；(E)-3-(1,3-benzodioxol-5-yl)-1-(3,5-dimethoxyphenyl)prop-2-en-1-one
• 化学式: C₁₈H₁₆O₅
• 分子量: 312.322
• InChiKey: UCUIKMBGZBNKFX-HWKANZROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-二甲氧基苯乙酮 在 甲醇 、 胡椒醛 、 sodium methylate 作用下， 生成 (E)-1-(3,5-dimethoxyphenyl)-3-(3,4-methylenedioxyphenyl)-prop-2-en-1-one
  参考文献：
  名称：

  Some 1,3-Diphenylpropylamines

  摘要：

  DOI：

  10.1021/ja01609a044

文献信息

• The Synthesis of Chalcones as Anticancer Prodrugs and their Bioactivation in CYP1 Expressing Breast Cancer Cells
  作者：Ketan C. Ruparelia、Keti Zeka、Taeeba Ijaz、Dyan N. Ankrett、Nicola E. Wilsher、Paul C. Butler、Hoon L. Tan、Sabahat Lodhi、Avninder S. Bhambra、Gerard A. Potter、Randolph R.J. Arroo、Kenneth J.M. Beresford

  DOI：10.2174/1573406414666180112120134

  日期：2018.5.11

  Background: Although the expression levels of many P450s differ between tumour and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which is significantly and consistently overexpressed in tumours. CYP1B1 has been shown to be active within tumours and is capable of metabolising a structurally diverse range of anticancer drugs. Because of this, and its role in the activation of procarcinogens, CYP1B1 is seen as an important target for anticancer drug development. Objective: To synthesise a series of chalcone derivatives based on the chemopreventative agent DMU-135 and investigate their antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1. Method: A series of chalcones were synthesised in yields of 43-94% using the Claisen-Schmidt condensation reaction. These were screened using a MTT assay against a panel of breast cancer cell lines which have been characterised for CYP1 expression. Result: A number of derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non-tumour breast cell line with no CYP expression. Experiments using the CYP1 inhibitors acacetin and α-naphthoflavone provided supporting evidence for the involvement of CYP1 enzymes in the bioactivation of these compounds. Conclusion: Chalcones show promise as anticancer agents with evidence suggesting that CYP1 activation of these compounds may be involved.

  背景：尽管许多 P450 在肿瘤和相应正常组织中的表达水平不同，CYP1B1 是少数在肿瘤中显著且一致过表达的 CYP 亚家族之一。研究表明，CYP1B1在肿瘤中具有活性，并且能够代谢结构多样的抗癌药物。因此，以及其在激活前致癌物中的作用，CYP1B1 被视为抗癌药物开发的重要靶点。 目标：基于化学预防剂 DMU-135 合成一系列查尔酮衍生物，并研究它们在表达 CYP1B1 和 CYP1A1 的人乳腺癌细胞系中的抗增殖活性。 方法：通过克来森-施密特缩合反应合成了产率为 43-94%的一系列查尔酮。这些化合物通过 MTT assay 对一组已知 CYP1 表达的乳腺癌细胞系进行了筛选。 结果：许多衍生物在表达 CYP1B1 和 CYP1A1 的人乳腺癌细胞系中显示出有前景的抗增殖活性，同时对没有 CYP 表达的非肿瘤乳腺癌细胞系显示出显著较低的毒性。使用 CYP1抑制剂 acacetin 和 α-naphthoflavone 的实验为这些化合物在生物激活过程中涉及 CYP1 酶提供了支持性证据。 结论：查尔酮作为抗癌药物显示出潜力，有证据表明这些化合物的 CYP1 激活可能参与其中。
• 3, 4-Methylenedioxy-substituted chalcones as therapeutic agents
  申请人：——

  公开号：US20040254149A1

  公开（公告）日：2004-12-16

  The present invention pertains to the use of a compounds for the manufacture of a medicament for use in the treatment of a proliferative condition, wherein the compounds have the following formula: 1 wherein: each of R B2 , R B3 , R B4 , and R B5 is independently —H, —OH, or —OMe; each of R 1 and R 2 is independently: —H, optionally substituted C 1-4 alkyl, or optionally substituted C 5-20 aryl; R A3 is —H, —OH, —OC(═O)R E , —OS(═O) 2 OH, or —OP(═O)(OH) 2 ; R E is: —H, optionally substituted C 1-6 alkyl, optionally substituted C 3-20 heterocyclyl, or optionally substituted C 5-20 aryl; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for both diagnosis and treatment of, for example, proliferative conditions, such as cancer, and inflammatory conditions.

  本发明涉及使用某些化合物制备药物，用于治疗增殖性疾病，其中该化合物具有以下结构式：1其中：RB2、RB3、RB4和RB5中的每一个独立地为—H、—OH或—OMe；R1和R2中的每一个独立地为—H、选择性地取代的C1-4烷基或选择性地取代的C5-20芳基；RA3为—H、—OH、—OC(═O)RE、—OS(═O)2OH或—OP(═O)(OH)2；RE为：—H、选择性地取代的C1-6烷基、选择性地取代的C3-20杂环基或选择性地取代的C5-20芳基；或其药学上可接受的盐、溶剂化物、酰胺、酯、醚、化学保护形式或前药。本发明还涉及这些化合物、包含这些化合物的药物组成物，以及这些化合物和组成物的使用，无论是在体内还是体外，用于诊断和治疗增殖性疾病，例如癌症和炎症性疾病。
• 3,4-METHYLENEDIOXY-SUBSTITUTED CHALCONES AS THERAPEUTIC AGENTS
  申请人：Potter Gerard Andrew

  公开号：US20100028262A1

  公开（公告）日：2010-02-04

  The present invention pertains to the use of a compounds for the manufacture of a medicament for use in the treatment of a proliferative condition, wherein the compounds have the following formula: wherein: each of R B2 , R B3 , R B4 , and R B5 is independently —H, —OH, or —OMe; each of R 1 and R 2 is independently: —H, optionally substituted C 1-4 alkyl, or optionally substituted C 5-20 aryl; R A3 is —H, —OH, —OC(═O)R E , —OS(═O) 2 OH, or —OP(═O)(OH) 2 ; R E is: —H, optionally substituted C 1-6 alkyl, optionally substituted C 3-20 heterocyclyl, or optionally substituted C 5-20 aryl; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for both diagnosis and treatment of, for example, proliferative conditions, such as cancer, and inflammatory conditions.

  本发明涉及使用化合物制备药物，用于治疗增殖性疾病，其中该化合物具有以下结构式：其中：RB2、RB3、RB4和RB5中的每一个独立地为—H、—OH或—OMe；R1和R2中的每一个独立地为—H、可选地取代的C1-4烷基或可选地取代的C5-20芳基；RA3为—H、—OH、—OC(═O)RE、—OS(═O)2OH或—OP(═O)(OH)2；RE为：—H、可选地取代的C1-6烷基、可选地取代的C3-20杂环基或可选地取代的C5-20芳基；或其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、化学保护形式或前药。本发明还涉及这种化合物、包含这种化合物的药物组合物以及这种化合物和组合物的使用，无论是在体内还是体外，用于诊断和治疗增殖性疾病（例如癌症）和炎症性疾病。
• 3,4-methylenedioxy-substituted chalcones as therapeutic agents
  申请人：Spear Therapeutics Limited

  公开号：US07598294B2

  公开（公告）日：2009-10-06

  The present invention pertains to the use of a compounds for the manufacture of a medicament for use in the treatment of a proliferative condition, wherein the compounds have the following formula: wherein: each of RB2, RB3, RB4, and RB5 is independently —H, —OH, or —OMe; each of R1 and R2 is independently: —H, optionally substituted C1-4alkyl, or optionally substituted C5-20aryl; RA3 is —H, —OH, —OC(═O)RE, —OS(═O)2OH, or —OP(═O)(OH)2; RE is: —H, optionally substituted C1-6alkyl, optionally substituted C3-20 heterocyclyl, or optionally substituted C5-20aryl; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for both diagnosis and treatment of, for example, proliferative conditions, such as cancer, and inflammatory conditions.

  本发明涉及使用以下化合物制造药物，用于治疗增殖性疾病：其中：RB2、RB3、RB4和RB5中的每一个独立地为—H、—OH或—OMe；R1和R2中的每一个独立地为：—H、可选地取代的C1-4烷基、或可选地取代的C5-20芳基；RA3为—H、—OH、—OC(═O)RE、—OS(═O)2OH或—OP(═O)(OH)2；RE为：—H、可选地取代的C1-6烷基、可选地取代的C3-20杂环基或可选地取代的C5-20芳基；或其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、化学保护形式或前药。本发明还涉及这样的化合物、包含这样的化合物的制剂，以及这样的化合物和制剂的使用，无论是体外还是体内，用于例如增殖性疾病（如癌症）和炎症性疾病的诊断和治疗。
• US7598294B2
  申请人：——

  公开号：US7598294B2

  公开（公告）日：2009-10-06