(E)-1-(2,3,4-trimethoxyphenyl)-3-(3-(trifluoromethyl)phenyl)prop-2-en-1-one | 1309371-16-1

• 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-(2,3,4-trimethoxyphenyl)-3-(3-(trifluoromethyl)phenyl)prop-2-en-1-one
• 英文别名: (E)-3-[3-(trifluoromethyl)phenyl]-1-(2,3,4-trimethoxyphenyl)prop-2-en-1-one
• CAS: 1309371-16-1
• 化学式: C₁₉H₁₇F₃O₄
• 分子量: 366.337
• InChiKey: GCNWVVDIGGPDCP-VQHVLOKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2',3',4'-三甲氧基苯乙酮 、 3-三氟甲基苯甲醛 在 lithium hydroxide monohydrate 作用下， 以 乙醇 为溶剂， 反应 2.17h， 以46%的产率得到(E)-1-(2,3,4-trimethoxyphenyl)-3-(3-(trifluoromethyl)phenyl)prop-2-en-1-one
  参考文献：
  名称：

  Novel Chalcone Derivatives as Potent Nrf2 Activators in Mice and Human Lung Epithelial Cells

  摘要：

  Nrf2-mediated activation of antioxidant response element is a central part of molecular mechanisms governing the protective function of phase II detoxification and antioxidant enzymes against carcinogenesis, oxidative stress, and inflammation. Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. We have designed and synthesized novel chalcone derivatives as Nrf2 activators. The potency of these compounds was measured by the expression of Nrf2 dependent antioxidant genes GCLM, NQO1, and HO1 in human lung epithelial cells, while the cytotoxicity was analyzed using MTT assay. In vivo potency of identified lead compounds to activate Nrf2 was evaluated using a mouse model. Our studies showed 2-trifluoromethyl-2'-methoxychalone (2b) to be a potent activator of Nrf2, both in vitro and in mice. Additional experiments showed that the activation of Nrf2 by this compound is independent of reactive oxygen species or redox changes. We have discussed a quantitative structure-activity relationship and proposed a possible mechanism of Nrf2, activation.

  DOI：

  10.1021/jm2002348

文献信息

• [EN] NUCLEAR RECEPTOR MODULATORS AND THEIR USE FOR THE TREATMENT AND PREVENTION OF CANCER<br/>[FR] MODULATEURS DE RÉCEPTEURS NUCLÉAIRES ET LEUR UTILISATION POUR LE TRAITEMENT ET LA PRÉVENTION D'UN CANCER
  申请人：US HEALTH

  公开号：WO2012174436A1

  公开（公告）日：2012-12-20

  Disclosed are compounds which are nuclear receptor modulators that can act as antagonists to the androgen receptor, for example, a compound of Formula I: wherein R1 to R5 and X1 to X5 are as described herein, as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including prostate cancers, other nuclear receptor mediated cancers, and other conditions, are also disclosed.

  本文披露了一些化合物，它们是核受体调节剂，可以作为雄激素受体的拮抗剂，例如，公式I的化合物：其中R1至R5和X1至X5如本文所述，以及其药用盐、溶剂化合物和立体异构体。还披露了包括这些化合物的药物组合物，以及使用方法和治疗癌症，包括前列腺癌、其他核受体介导的癌症和其他疾病的方法。
• Nuclear receptor modulators and their use for the treatment and prevention of cancer
  申请人：Neckers Jane B.

  公开号：US10071945B2

  公开（公告）日：2018-09-11

  Disclosed are compounds which are nuclear receptor modulators that can act as antagonists to the androgen receptor, for example, a compound of Formula I: wherein R1 to R5 and X1 to X5 are as described herein, as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including prostate cancers, other nuclear receptor mediated cancers, and other conditions, are also disclosed.

  公开了可作为雄激素受体拮抗剂的核受体调节剂的化合物，例如，式 I 的化合物：其中 R1 至 R5 和 X1 至 X5 如本文所述，以及其药学上可接受的盐、溶剂和立体异构体。此外，还公开了包含此类化合物的药物组合物，以及使用方法和癌症（包括前列腺癌、其他核受体介导的癌症和其他疾病）的治疗方法。
• NUCLEAR RECEPTOR MODULATORS AND THEIR USE FOR THE TREATMENT AND PREVENTION OF CANCER
  申请人：The United States of America, as Represented by The Secretary, Department of Health and Human Services

  公开号：EP2721003B1

  公开（公告）日：2018-01-03
• CHALCONE DERIVATIVES AS NRF2 ACTIVATORS
  申请人：Biswal Shyam

  公开号：US20140088052A1

  公开（公告）日：2014-03-27

  Compounds and methods for treating or preventing a disease, disorder or condition associated with an Nrf2-regulated pathway, including those associated with an autoimmune disease, comorbidity associated with diabetes, such as retinopathy and nephropathy, bone marrow transplant for leukemia and related cancers, bone marrow deficiencies, inborn errors of metabolism, and other immune disorders, oxidative stress, respiratory infection, ischemia, neurodegenerative disorders, radiation injury, neutropenia caused by chemotherapy, autoimmunity, and congenital neutropenic disorders, and for restoring a corticosteroid responsiveness, in a subject are provided.
• Novel Chalcone Derivatives as Potent Nrf2 Activators in Mice and Human Lung Epithelial Cells
  作者：Vineet Kumar、Sarvesh Kumar、Mohammad Hassan、Hailong Wu、Rajesh K. Thimmulappa、Amit Kumar、Sunil K. Sharma、Virinder S. Parmar、Shyam Biswal、Sanjay V. Malhotra

  DOI：10.1021/jm2002348

  日期：2011.6.23

  Nrf2-mediated activation of antioxidant response element is a central part of molecular mechanisms governing the protective function of phase II detoxification and antioxidant enzymes against carcinogenesis, oxidative stress, and inflammation. Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. We have designed and synthesized novel chalcone derivatives as Nrf2 activators. The potency of these compounds was measured by the expression of Nrf2 dependent antioxidant genes GCLM, NQO1, and HO1 in human lung epithelial cells, while the cytotoxicity was analyzed using MTT assay. In vivo potency of identified lead compounds to activate Nrf2 was evaluated using a mouse model. Our studies showed 2-trifluoromethyl-2'-methoxychalone (2b) to be a potent activator of Nrf2, both in vitro and in mice. Additional experiments showed that the activation of Nrf2 by this compound is independent of reactive oxygen species or redox changes. We have discussed a quantitative structure-activity relationship and proposed a possible mechanism of Nrf2, activation.