(E)-3-(4-trifluoromethylphenyl)-1-(3,4,5-trimethoxyphenyl)-3-phenylprop-2-en-1-one | 127034-10-0

• 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)-3-(4-trifluoromethylphenyl)-1-(3,4,5-trimethoxyphenyl)-3-phenylprop-2-en-1-one
• 英文别名: (E)-1-(3,4,5-trimethoxyphenyl)-3-(4-(trifluoromethyl)phenyl)prop-2-en-1-one；4-Trifluoromethyl-3',4',5'-trimethoxy-trans-chalcone；(E)-3-[4-(trifluoromethyl)phenyl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 127034-10-0
• 化学式: C₁₉H₁₇F₃O₄
• 分子量: 366.337
• InChiKey: CYKHOBBJQRIXNM-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 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

• 作为反应物：
  描述：

  (E)-3-(4-trifluoromethylphenyl)-1-(3,4,5-trimethoxyphenyl)-3-phenylprop-2-en-1-one 、 2-氨基苯硫醇 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 以60.4%的产率得到2-(4-(trifluoromethyl)phenyl)-4-(3,4,5-trimethoxyphenyl)-2,3-dihydrobenzo[b][1,4]thiazepine
  参考文献：
  名称：

  作为具有抗肿瘤效力的微管蛋白聚合抑制剂的一系列新型苯并噻嗪衍生物

  摘要：

  在这项工作中，合成并筛选了一系列二芳基苯并[ b ] [1,4] 硫氮杂衍生物D1-D36作为具有抗肿瘤效力的微管蛋白聚合抑制剂。它们是通过首次引入七元环苯并噻嗪作为 CA-4 修饰的接头而设计的。其中，命中化合物D8显示出抑制多种癌细胞系生长的潜力（IC 50值：HeLa 1.48 μM，MCF-7 1.47 μM，HT29 1.52 μM 和 A549 1.94 μM），与阳性对照秋水仙碱和CA-4P。D8的计算 IC 50值作为微管蛋白聚合抑制剂的浓度为 1.20 μM。流式细胞术检测结果表明，D8可以诱导有丝分裂灾难和活癌细胞的死亡。D8还表明了抗血管活性。对接模拟暗示了可能的结合模式，推断引入与附近微管蛋白链相互作用的可能性。由于新的结构试验已经进行了初步讨论，这项工作可能会激发进一步修改微管蛋白相关抗癌药物和治疗方法的新思路。

  DOI：

  10.1016/j.bioorg.2020.104585
• 作为产物：
  描述：

  对三氟甲基苯甲醛 、 3',4',5'-三甲氧基苯乙酮 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (E)-3-(4-trifluoromethylphenyl)-1-(3,4,5-trimethoxyphenyl)-3-phenylprop-2-en-1-one
  参考文献：
  名称：

  作为具有抗肿瘤效力的微管蛋白聚合抑制剂的一系列新型苯并噻嗪衍生物

  摘要：

  在这项工作中，合成并筛选了一系列二芳基苯并[ b ] [1,4] 硫氮杂衍生物D1-D36作为具有抗肿瘤效力的微管蛋白聚合抑制剂。它们是通过首次引入七元环苯并噻嗪作为 CA-4 修饰的接头而设计的。其中，命中化合物D8显示出抑制多种癌细胞系生长的潜力（IC 50值：HeLa 1.48 μM，MCF-7 1.47 μM，HT29 1.52 μM 和 A549 1.94 μM），与阳性对照秋水仙碱和CA-4P。D8的计算 IC 50值作为微管蛋白聚合抑制剂的浓度为 1.20 μM。流式细胞术检测结果表明，D8可以诱导有丝分裂灾难和活癌细胞的死亡。D8还表明了抗血管活性。对接模拟暗示了可能的结合模式，推断引入与附近微管蛋白链相互作用的可能性。由于新的结构试验已经进行了初步讨论，这项工作可能会激发进一步修改微管蛋白相关抗癌药物和治疗方法的新思路。

  DOI：

  10.1016/j.bioorg.2020.104585

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：The United States of America, as represented by the Secretary, Department of Health and Human Services

  公开号：US10737995B2

  公开（公告）日：2020-08-11

  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.

  所公开的化合物是核受体调节剂，可作为雄激素受体的拮抗剂，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、使用方法以及癌症（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。
• Chalcones: a new class of antimitotic agents
  作者：Michael L. Edwards、David M. Stemerick、Prasad S. Sunkara

  DOI：10.1021/jm00169a021

  日期：1990.7

  A series of chalcones was evaluated as antimitotic agents. One of these, (E)-1-(2,5-dimethoxyphenyl)-3-[4-(dimethylamino)phenyl]-2-methyl-2-pr open- 1-one) (73), was found to be an effective antimitotic agent at a concentration of 4 nM in an in vitro HeLa cell test system. When evaluated in experimental tumor models in vivo, this compound exhibited antitumor activity against L1210 leukemia and B16 melanoma.
• Preparation of cyclomanganated chalcones and their reactions with methyl acrylate and other α, β-unsaturated carbonyl compounds
  作者：Warren Tully、Lyndsay Main、Brian K. Nicholson

  DOI：10.1016/0022-328x(95)05488-b

  日期：1995.11

  Chalcones [(E)-1,3-diarylprop-2-en-1-ones] react with benzyltetracarbonylmanganese under reflux in petroleum spirit to give two types of cyclomanganation products. The first, involving metallation at the alkenyl beta-carbon of the enone, are derivatives of [[1-phenyl-2-phenylcarbonyl-kappa O]ethenyl-kappa C-1]tetracarbonylmanganese, while the second type, manganated at the aryl ring ortho-carbon, are derivatives of [2-[3-phenylprop-2-en-1-onyl-kappa O]phenyl-kappa C-1]tetracarbonylmangane In general, more ''alkene-manganated'' than ''ring-manganated'' product is formed, with the ratio influenced significantly by certain substituents, e.g. a 4-CF3 substituent on the phenyl ring at C3 of the enone strongly promotes ''alkene-manganation''. in some cases there are minor by-products derived from coupling of two chalcone molecules after initial cyclomanganation. The crystal structures are reported for two such products, [2-((1S*,2R*,3S*)-1-hydroxy-1-((E)-2-(2-trifluoromethylphenyl)ethenyl)-3-(2-trifluoromethylphenyl)-6-methoxy-2-indanylcarbonyl- kappa O)-6-methoxyphenyl-kappa C-1]tetracarbonylmanganese and (1S*,4S*,5R*)-5-(4-bromobenzoyl)-1-(4-bromophenyl)-3,4-di-(4-trifluoromethylphenyl)cyclopent-2-en-1-ol.In acetonitrile under reflux, alkene-manganated chalcones react with methyl acrylate (methyl propenoate) to form derivatives of methyl (E)-4,6-diphenyl-6-oxohex-2-enoate and of 5-(2-methoxycarbonylethyl)-3,5-diphenylfuran-2-(5H)-one. The latter butenolides are not formed when the reactions are carried out in carbon tetrachloride, only the former alpha,beta-unsaturated esters. By contrast, in a few reactions studied, acrolein (propenal) and methyl vinyl ketone (but-3-en-2-one) give only the butenolide products when treated with alkene-manganated chalcones in refluxing acetonitrile. An exception is the reaction of methyl vinyl ketone with [[1 -(3,4,5-trimethoxyphenyl)-2-(4-chlorophenylcarbonyl-kappa O)]ethenyl-kappa C-1]tetracarbonylmanganese to form the cyclized product 5-acetyl-1-(4-chlorophenyl)3-(3,4,5-trimethoxyphenyl)cyclopent-2-en-1-ol.
• EDWARDS, MICHAEL L.;STEMERICK, DAVID M.;SUNKARA, PRASAD S., J. MED. CHEM., 33,(1990) N, C. 1948-1954
  作者：EDWARDS, MICHAEL L.、STEMERICK, DAVID M.、SUNKARA, PRASAD S.

  DOI：——

  日期：——