(1E,6E)-4,4-difluoro-1,7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione | 1384274-56-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (1E,6E)-4,4-difluoro-1,7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione
• 英文别名: (1E,6E)-1,7-bis(3,4-dimethoxyphenyl)-4,4-difluorohepta-1,6-diene-3,5-dione
• CAS: 1384274-56-9
• 化学式: C₂₃H₂₂F₂O₆
• 分子量: 432.421
• InChiKey: JWIYAHUEABULFX-MKICQXMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (acetylacetonato)borondifluoride 在 sodium oxalate 、 Selectfluor 、 正丁胺 作用下， 以 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 16.1h， 生成 (1E,6E)-4,4-difluoro-1,7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione
  参考文献：
  名称：

  氟-姜黄素和姜黄素-BF 2加合物：合成，X射线结构，生物测定和计算/对接研究

  摘要：

  通过在室温下使用Selectfluor（F-TEDA-BF 4）直接进行单氟化和二氟化反应，无需使用碱或添加剂即可合成一系列α-羰基氟化姜黄素。通过相应的苯甲醛与乙酰丙酮-BF 2的反应合成了环状氟化/三氟甲基化的姜黄素-BF 2加合物。CUR-BF 2的分解微波辐射下的加合物得到相应的姜黄素。多核NMR和X射线分析证实，在芳环上带有氟或三氟甲基的姜黄素以及在活性亚甲基位置被单氟化的姜黄素都以烯醇互变异构体的形式存在。当这些姜黄素类化合物固定在1,3-二酮构型中时，α，α-二氟化会带来显着的构象变化。CUR-BF 2配合物的X射线结构与具有相同B O键距离的对称加合物的形成一致。通过体外生物测定法针对几种不同的癌细胞系测试了这些化合物的抗增殖活性。对应的CUR-BF 2加合物在微摩尔浓度下表现出异常高的活性，在某些情况下，其纳摩尔浓度大大超过母体姜黄素的活性。进行计算对接计算以测定这些化合

  DOI：

  10.1016/j.jfluchem.2016.09.009

文献信息

• NOVEL CURCUMINOID-INSPIRED SYNTHETIC COMPOUNDS AS ANTI-TUMOR AGENTS
  申请人：Laali Kenneth K.

  公开号：US20180362433A1

  公开（公告）日：2018-12-20

  Novel CUR- and CUR-BF 2 compounds exhibiting anti-tumor properties are presented. CUR compounds bearing fluorinated moieties with selective fluorine introduction into the α-carbonyl moiety as well as CUR-BF 2 adducts and CURs with diverse substitution patterns in the phenyl rings including fluorinated substituents (SCF 3 , OCF 3 , and F) and/or bulky activating groups (OMe, OAc, and OBz) are presented. Fluorinated aryl-pyrazoles and isoxazoles as well as novel CUR and CUR-BF 2 compounds with monocyclic aromatic and bicyclic-heteroaromatic lateral rings, bearing fluorine(s), OCF3, CF3, and SCF3 groups, and their alpha-carbonyl-fluorinated analogs, as well as their pyrazole and isoxazole derivatives are presented. The CUR-pyrazoles embody analogs that are fluorinated at the phenyl-pyrazole moiety. The compounds and their derivatives exhibited exceptional cytotoxic and anti-proliferative activity against several cancer cell-lines. Deuterated CUR-BF2 and CUR compounds were also synthesized.

  展示了具有抗肿瘤特性的新型CUR-和CUR-BF2化合物。这些CUR化合物带有氟化基团，选择性地将氟引入α-羰基部位，以及具有不同苯环取代模式的CUR- 加合物和CURs，包括氟取代基团（S ，O 和F）和/或体积庞大的活化基团（OMe，OAc和OBz）。展示了氟化芳基吡唑和异噁唑，以及具有单环芳香和双环杂芳侧链的新型CUR和CUR- 化合物，带有氟（s），O ，CF3和S 基团，以及它们的α-羰基-氟化类似物，以及它们的吡唑和异噁唑衍生物。CUR-吡唑体现了在苯基吡唑部位氟化的类似物。这些化合物及其衍生物对几种癌细胞系表现出出色的细胞毒性和抗增殖活性。还合成了氘代CUR- 和CUR化合物。
• Curcuminoid-inspired synthetic compounds as anti-tumor agents
  申请人：Laali Kenneth K.

  公开号：US10934241B2

  公开（公告）日：2021-03-02

  Novel CUR— and CUR—BF2 compounds exhibiting anti-tumor properties are presented. CUR compounds bearing fluorinated moieties with selective fluorine introduction into the α-carbonyl moiety as well as CUR—BF2 adducts and CURs with diverse substitution patterns in the phenyl rings including fluorinated substituents (SCF3, OCF3, and F) and/or bulky activating groups (OMe, OAc, and OBz) are presented. Fluorinated aryl-pyrazoles and isoxazoles as well as novel CUR and CUR—BF2 compounds with monocyclic aromatic and bicyclic-heteroaromatic lateral rings, bearing fluorine(s), OCF3, CF3, and SCF3 groups, and their alpha-carbonyl-fluorinated analogs, as well as their pyrazole and isoxazole derivatives are presented. The CUR-pyrazoles embody analogs that are fluorinated at the phenyl-pyrazole moiety. The compounds and their derivatives exhibited exceptional cytotoxic and anti-proliferative activity against several cancer cell-lines. Deuterated CUR—BF2 and CUR compounds were also synthesized.

  本文介绍了具有抗肿瘤特性的新型 CUR 和 CUR-BF2 化合物。介绍了在 α-羰基中选择性引入氟的含氟 CUR 化合物，以及 CUR- 加合物和在苯环中具有不同取代模式的 CUR，包括含氟取代基（S 、O 和 F）和/或大块活化基团（OMe、OAc 和 OBz）。介绍了含氟芳基吡唑和异噁唑，以及带有氟、O 、CF3 和 S 基团的单环芳香族和双环异芳香族侧环的新型 CUR 和 CUR- 化合物及其α-羰基氟化类似物，以及它们的吡唑和异噁唑衍生物。CUR 吡唑包含在苯基吡唑分子上氟化的类似物。这些化合物及其衍生物对几种癌细胞系具有卓越的细胞毒性和抗增殖活性。此外，还合成了氚代 CUR- 和 CUR 化合物。
• Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens
  作者：Qian Shi、Koji Wada、Emika Ohkoshi、Li Lin、Rong Huang、Susan L. Morris-Natschke、Masuo Goto、Kuo-Hsiung Lee

  DOI：10.1016/j.bmc.2012.05.011

  日期：2012.7

  In our continuing study of curcumin analogs as potential anti-prostate cancer drug candidates, 15 new curcumin analogs were designed, synthesized and evaluated for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Twelve analogs (5-12, 15, 16, 19, and 20) are conjugates of curcumin (1) or methyl curcumin (2) with a flutamide-or bicalutamide-like moiety. Two compounds (22 and 23) are C4-mono-and difluoro-substituted analogs of dimethyl curcumin (DMC, 21). Among the newly synthesized conjugates compound 15, a conjugate of 2 with a partial bicalutamide moiety, was more potent than bicalutamide alone and essentially equipotent with 1 and 2 against both prostate tumor cell lines with IC50 values of 41.8 mu M (for LNCaP) and 39.1 mu M (for PC-3). A cell morphology study revealed that the cytotoxicity of curcumin analogs or curcumin-anti-androgen conjugates detected from both prostate cancer cell lines might be due to the suppression of pseudopodia formation. A molecular intrinsic fluorescence experiment showed that 1 accumulated mainly in the nuclei, while conjugate 6 was distributed in the cytosol. At the tested conditions, anti-androgens suppressed pseudopodia formation in PC-3 cells, but not in LNCaP cells. The evidence suggests that distinguishable target proteins are involved, resulting in the different outcomes toward pseudopodia suppression. (C) 2012 Elsevier Ltd. All rights reserved.