(2E,5E)-2,5-bis(2-fluoro-3-(trifluoromethyl)benzylidene)cyclopentanone | 1018785-60-8

• 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: (2E,5E)-2,5-bis(2-fluoro-3-(trifluoromethyl)benzylidene)cyclopentanone
• 英文别名: (2E,5E)-2,5-bis[[2-fluoro-3-(trifluoromethyl)phenyl]methylidene]cyclopentan-1-one
• CAS: 1018785-60-8
• 化学式: C₂₁H₁₂F₈O
• 分子量: 432.313
• InChiKey: YONVQXVTMODGRD-UTLPMFLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  环戊酮 、 2-氟-3-(三氟甲基)苯甲醛 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以91%的产率得到(2E,5E)-2,5-bis(2-fluoro-3-(trifluoromethyl)benzylidene)cyclopentanone
  参考文献：
  名称：

  Synthesis and Anti-bacterial Properties of Mono-carbonyl Analogues of Curcumin

  摘要：

  本文描述了三种单羰基姜黄素类似物的合成。对七种革兰氏阳性和革兰氏阴性细菌进行了体外抗菌活性测试，并讨论了取代基对芳环和连接张力的空间结构的影响。观察到，与姜黄素相比，部分衍生物显示出显著的活性，并且大多数衍生物对氨苄西林抵抗的阴沟肠杆菌表现出活性。化合物A12、B09、B13、B14和C09显示出显著的体外抗菌活性。结果显示，杂环或长链取代基可能增强姜黄素类似物的活性。

  DOI：

  10.1248/cpb.56.162

文献信息

• Synthesis and Anti-bacterial Properties of Mono-carbonyl Analogues of Curcumin
  作者：Guang Liang、Shulin Yang、Lijuan Jiang、Yu Zhao、Lili Shao、Jian Xiao、Faqing Ye、Yueru Li、Xiaokun Li

  DOI：10.1248/cpb.56.162

  日期：——

  The synthesis of three series of curcumin analogues with mono-carbonyl is described. Their in vitro anti-bacterial activities against seven Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the aryl ring and the space structure of the linking strain were discussed. It was observed that part of the derivatives displayed significant activity when compared with curcumin and most of them exhibited activity against the ampicillin-resisted Enterobacter cloacae. Compounds A12, B09, B13, B14 and C09 show remarkable antibacterial activity in vitro. The result showed that heterocycle or long-chain substituents may enhance the activity of curcumin analogues.

  本文描述了三种单羰基姜黄素类似物的合成。对七种革兰氏阳性和革兰氏阴性细菌进行了体外抗菌活性测试，并讨论了取代基对芳环和连接张力的空间结构的影响。观察到，与姜黄素相比，部分衍生物显示出显著的活性，并且大多数衍生物对氨苄西林抵抗的阴沟肠杆菌表现出活性。化合物A12、B09、B13、B14和C09显示出显著的体外抗菌活性。结果显示，杂环或长链取代基可能增强姜黄素类似物的活性。
• Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin
  作者：Guang Liang、Xiaokun Li、Li Chen、Shulin Yang、Xudong Wu、Elaine Studer、Emily Gurley、Phillip B. Hylemon、Faqing Ye、Yueru Li、Huiping Zhou

  DOI：10.1016/j.bmcl.2007.12.068

  日期：2008.2

  Curcumin has been extensively studied for its anti-inflammatory activities. However, its potential beneficial effects on various disease preventions and treatments are limited by its unstable structure. The beta-diketone moiety renders curcumin to be rapidly metabolized by aldo -keto reductase in liver. In the present study, a series of curcumin analogues with more stable chemical structures were synthesized and several compounds showed an enhanced ability to inhibit lipopolysaccharide ( LPS)-induced TNF-alpha and IL-6 synthesis in macrophages. (C) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and anti-inflammatory evaluation of novel mono-carbonyl analogues of curcumin in LPS-stimulated RAW 264.7 macrophages
  作者：Chengguang Zhao、Yuepiao Cai、Xuzhi He、Jianling Li、Li Zhang、Jianzhang Wu、Yunjie Zhao、Shulin Yang、Xiaokun Li、Wulan Li、Guang Liang

  DOI：10.1016/j.ejmech.2010.09.037

  日期：2010.12

  Curcumin is a multifunctional natural product with regulatory effects on inflammation. However, a major limitation for the application of curcumin is its poor bioavailability. We previously demonstrated that the mono-carbonyl analogues of curcumin possessed improved pharmacokinetic profiles. In this study, 33 novel mono-carbonyl analogues of curcumin were synthesized and their inhibition against TNF-alpha and IL-6 release was evaluated in LPS-stimulated RAW 264.7 macrophages. Based on the screening data, quantitative structure activity relationship was conducted, indicating that electron-withdrawing groups in benzene ring are favourable to anti-inflammatory activities of B-class compounds. Furthermore, compounds AN1 and 1382 demonstrated anti-inflammatory abilities in a dose-dependent manner. These raise the possibility that these compounds might serve as potential agents for the treatment of inflammatory diseases. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Mono-carbonyl curcumin analogues as 11β-hydroxysteroid dehydrogenase 1 inhibitors
  作者：Han Lin、Guo-Xin Hu、Jingjing Guo、Yufei Ge、Guang Liang、Qing-Quan Lian、Yanhui Chu、Xiaohuan Yuan、Ping Huang、Ren-Shan Ge

  DOI：10.1016/j.bmcl.2013.05.080

  日期：2013.8

  A series of structurally novel mono-carbonyl curcumin analogues have been synthesized and biologically evaluated to test their inhibitory potencies and the structure-activity relationship (SAR) on human and rat 11 beta-hydroxysteroid dehydrogenase isoform (11 beta-HSD1) activities. 11 beta-HSD1 selective inhibitors have been discovered and compound A10 is discovered as a very potent with an IC50 value of 97 nM without inhibiting 11 beta-HSD2. (C) 2013 Elsevier Ltd. All rights reserved.
• 5-Bis-(2,6-difluoro-benzylidene) Cyclopentanone Acts as a Selective 11β-Hydroxysteroid Dehydrogenase one Inhibitor to Treat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice
  作者：Hongguo Guan、Yiyan Wang、Huitao Li、Qiqi Zhu、Xiaoheng Li、Guang Liang、Ren-Shan Ge

  DOI：10.3389/fphar.2021.594437

  日期：——

  Background: 11β-Hydroxysteroid dehydrogenase one is responsible for activating inert glucocorticoid cortisone into biologically active cortisol in humans and may be a novel target for the treatment of nonalcoholic fatty liver disease. Methods: A series of benzylidene cyclopentanone derivatives were synthesized, and the selective inhibitory effects on rat, mouse and human 11β-hydroxysteroid dehydrogenase one

  背景：11β-羟基类固醇脱氢酶是一种负责将惰性糖皮质激素可的松活化为人类生物活性皮质醇的药物，可能是治疗非酒精性脂肪肝的新靶标。方法：合成了一系列亚苄基环戊酮衍生物，并筛选了对大鼠，小鼠和人11β-羟类固醇脱氢酶一和二的选择性抑制作用。最有效的化合物[5-双-（2,6-二氟亚苄基）-环戊酮]（WZS08）用于治疗高脂饮食100天的小鼠的非酒精性脂肪肝疾病。结果：WZS08是大鼠，小鼠和人11β-羟基类固醇脱氢酶1的最有效抑制剂，最大抑制浓度分别为378.0、244.1和621.1 nM，一半，并且在100μM时它不影响11β-羟基类固醇脱氢酶2。当给小鼠喂WZS08（1、2和4 mg / kg）达100天时，WZS08显着降低了4 mg / kg的血清胰岛素水平和胰岛素指数。在1 mg / kg的低浓度下，WZS08显着降低了血清甘油三酸酯，胆固醇，低密度脂蛋白和肝脂肪的水平。在1 mg /