(1E,4E)-1,5-bis(2-fluorophenyl)penta-1,4-dien-3-one | 914295-38-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1E,4E)-1,5-bis(2-fluorophenyl)penta-1,4-dien-3-one
• CAS: 914295-38-8
• 化学式: C₁₇H₁₂F₂O
• 分子量: 270.278
• InChiKey: ATKITYYWFUDIDD-WGDLNXRISA-N

物化性质

• 沸点：
  398.6±37.0 °C(Predicted)
• 密度：
  1.221±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1E,4E)-1,5-bis(2-fluorophenyl)penta-1,4-dien-3-one 在 氢气 、 镍 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents

  摘要：

  A series of novel curcumin analogs were synthesized and screened for anti-cancer and anti-angiogenesis activities at Emory University and at the National Cancer Institute (NCI). These compounds are symmetrical alpha,beta-unsaturated and saturated ketones. The majority of the analogs demonstrated a moderate degree of anti-cancer activity. Compounds 10, 11, and 14 exhibited a high degree of cytotoxicity in the NCI in vitro anti-cancer cell line screen. In addition, this screen revealed that these compounds inhibit tumor cell growth with a higher potency than the commonly used chemotherapeutic drug, cisplatin. In independent in vitro screens conducted at Emory, the same compounds plus 4, 5, 8, 9, and 13 exhibited a high degree of cytotoxicity to tumor cells. Analogs that were effective in the anti-cancer screens were also effective in in vitro anti-angiogenesis assays. Compounds 4, 9, 11, and 14 were most effective in the anti-angiogenesis assays run at Emory. In the assays conducted by the NCI, compound 14 was almost as potent as the anti-angiogenic drug TNP-470, which has undergone clinical trials. Based on the favorable in vitro anti-cancer and anti-angiogenesis results with 14, further in vivo tests were conducted. This compound effectively reduced the size of human breast tumors grown in female athymic nude mice and showed little toxicity. This data, coupled with the remarkable in vitro data, suggests that compound 14 may potentially be an effective chemotherapeutic agent. As a follow-up, a 3D quantitative structure relationship based on 14 has been developed. It shows a cross-validated r(2)(q(2)) = 0.83 and a predictive r(2)(p(2)) = 0.71. COMPARE analysis suggests the compound to be a possible RNA/DNA antimetabolite, but also implies that the compound's cytotoxicity may arise from a presently unknown mechanism. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.05.006
• 作为产物：
  描述：

  2-氟苯甲醛 、 丙酮 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 以49%的产率得到(1E,4E)-1,5-bis(2-fluorophenyl)penta-1,4-dien-3-one
  参考文献：
  名称：

  通过连续[4 + 2]环加成反应向六氢2 H-苯甲基机械激发的途径

  摘要：

  利用两个健壮的C-C键形成反应中，的Baylis-Hillman反应和狄尔斯-阿尔德反应，我们报告六氢- 2的高度对映选择性，区域选择性和立体选择性合成ħ通过两个连续的[4 + 2 -chromenes ]环加成。这些串联和形式环加成反应也已作为“一锅”序列进行，以优异的收率和立体选择性进入构成多达五个连续立体中心的相应杂环。

  DOI：

  10.1021/acs.orglett.6b01742

文献信息

• Curcumin analogs with anti-tumor and anti-angiogenic properties
  申请人：——

  公开号：US20020019382A1

  公开（公告）日：2002-02-14

  The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

  本发明涉及表现出抗肿瘤和抗血管生成特性的姜黄素类似物，包括这些化合物的药物配方以及使用这些化合物的方法。
• Curcumin-like diarylpentanoid analogues as melanogenesis inhibitors
  作者：Takahiro Hosoya、Asami Nakata、Fumie Yamasaki、Faridah Abas、Khozirah Shaari、Nordin Hj Lajis、Hiroshi Morita

  DOI：10.1007/s11418-011-0568-0

  日期：2012.1

  Anti-melanogenesis screening of 47 synthesized curcumin-like diarylpentanoid analogues was performed to show that some had a potent inhibitory effect on the melanogenesis in B16 melanoma cells. Their actions were considered to be mostly due to tyrosinase inhibition, tyrosinase expression inhibition, and melanin pigment degradation. The structure–activity relationships of those curcumin-like diarylpentanoid analogues which inhibited the melanogenesis and tyrosinase activity were also discussed. Of those compounds assayed, (2E,6E)-2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone showed the most potent anti-melanogenesis effect, the mechanism of which is considered to be the degradation of the melanin pigment in B16 melanoma cells, affecting neither the tyrosinase activity nor tyrosinase expression.

  对47种合成的姜黄素样二芳基戊烷类类似物进行了抗黑色素生成筛选，结果显示其中一些对B16黑色素瘤细胞的黑色素生成具有强抑制作用。这些作用主要被认为是通过抑制酪氨酸酶活性、抑制酪氨酸酶表达和降解黑色素色素实现的。还讨论了那些抑制黑色素生成和酪氨酸酶活性的姜黄素样二芳基戊烷类类似物的结构-活性关系。在测试的化合物中，（2E,6E）-2,6-双（2,5-二甲氧基苄叉）环己酮显示了最强的抗黑色素生成效果，其机制被认为是在B16黑色素瘤细胞中降解黑色素色素，既不影响酪氨酸酶活性也不影响酪氨酸酶表达。
• Activation of NFκB is inhibited by curcumin and related enones
  作者：Waylon M. Weber、Lucy A. Hunsaker、C. Nathaniel Roybal、Ekaterina V. Bobrovnikova-Marjon、Steve F. Abcouwer、Robert E. Royer、Lorraine M. Deck、David L. Vander Jagt

  DOI：10.1016/j.bmc.2005.11.035

  日期：2006.4

  which were more active than curcumin. Enone analogues in the series with the 5-carbon spacer were especially active, including members that contained heterocyclic rings. 1,5-Bis(3-pyridyl)-1,4-pentadien-3-one was the most active analogue, IC50 = 3.4 +/- 0.2 microM. The most active analogues retain the enone functionality, although some analogues devoid of the enone functionality exhibited activity. The

  转录因子NFkappaB（NFkappaB）在许多癌细胞中被上调，在这些癌细胞中，转录因子NFkappaB促进了生存前的抗凋亡状态的发展。天然产物姜黄素是已知的NFkappaB激活抑制剂。使用Panomics的NFkappaB Reporter稳定细胞系，将姜黄素的烯酮类似物与姜黄素抑制TNFalpha诱导的NFkappaB活化的能力进行了比较。所测试的烯酮包括在芳香环之间保留7碳间隔基的姜黄素类似物，具有5碳间隔基的类似物和具有3碳间隔基的类似物。在所有三个系列中均鉴定出NFkappaB激活的抑制剂，其中许多活性比姜黄素更高。具有5个碳原子间隔基的系列中的烯酮类似物特别活跃，包括含有杂环的成员。1,5-双（3-吡啶基）-1,4-戊二烯-3-酮是活性最高的类似物，IC50 = 3.4 +/- 0.2 microM。尽管一些缺乏烯酮功能的类似物表现出活性，但最活跃的类似物保留了烯酮功能。作为
• 一种单羰基姜黄素类似物及制备方法和用途
  申请人：聊城大学

  公开号：CN105693492A

  公开（公告）日：2016-06-22

  本发明公开了一种单羰基姜黄素类似物及制备方法和用途。该类似物具有如通式(I)的结构特征，其中，R为氟，R的取代位次为2、3、4-位，两个苯环通过1,4-戊二烯-3-酮连接。本发明以邻、间、对氟取代苯甲醛为原料，通过与丙酮缩合生成单羰基姜黄素类似物。2,2’-氟单羰基姜黄素在含10％血清培养基中的稳定性优于天然产物姜黄素。药理实验结果表明，氟取代单羰基姜黄素对人肺癌NCI-H460细胞的增殖抑制活性明显优越于天然产物姜黄素，并且2,2’-氟单羰基姜黄素可以通过促进活性氧的产生导致细胞内的氧化还原失衡、脂质过氧化、线粒体膜电位的崩溃以及细胞凋亡，可以用作治疗肺癌的姜黄素类先导物。
• [EN] CURCUMIN ANALOGUES FOR TREATING CANCER<br/>[FR] ANALOGUES DE CIRCUMINE DESTINES AU TRAITEMENT DU CANCER
  申请人：UNIV EMORY

  公开号：WO2001040188A1

  公开（公告）日：2001-06-07

  The present invention is directed to curcumin analogs (I), wherein Y is OH, halogen, or CF3; Z is H, OH, OR1, halogen, or CF3; X1 and X2 are independently C or N; and A is as defined in the application; exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

  本发明涉及姜黄素类似物(I)，其中Y为OH、卤素或CF3；Z为H、OH、OR1、卤素或 ；X1和X2独立地为C或N；A如本申请所定义；该类似物具有抗肿瘤和抗血管生成作用，制备包括这些化合物的制药组合物以及使用这些化合物的方法。