(2E,6E)-2,6-bis(3,4,5-trimethoxybenzylidene)cyclohexanone

• 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: (2E,6E)-2,6-bis(3,4,5-trimethoxybenzylidene)cyclohexanone
• 英文别名: 2,6-bis((3,4,5-trimethoxyphenyl)methylene)-cyclohexanone；2,6-bis((E)-3,4,5-trimethoxybenzylidene)cyclohexanone；2,6-Bis(3,4,5-trimethoxybenzylidene)cyclohexanone；(2E,6E)-2,6-bis[(3,4,5-trimethoxyphenyl)methylidene]cyclohexan-1-one
• 化学式: C₂₆H₃₀O₇
• 分子量: 454.52
• InChiKey: OXIWSGTZUCVQPH-XOBNHNQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2E,6E)-2,6-bis(3,4,5-trimethoxybenzylidene)cyclohexanone 在 溶剂黄146 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 ethyl (14E)-6-methyl-8-(3,4,5-trimethoxyphenyl)-14-[(3,4,5-trimethoxyphenyl)methylidene]-4-thia-2,7-diazatricyclo[7.5.0.03,7]tetradeca-1(9),2,5-triene-5-carboxylate
  参考文献：
  名称：

  Synthesis and antitumor activity of certain new thiazolo[2,3-b]quinazoline and thiazolo[3,2-a]pyrimidine analogs

  摘要：

  A novel series of thiazolo[2,3-b]quinazoline (16-19, 25-28, and 34-37) and cyclohepta[d]thiazolo[3,2-a]pyrimidine (20-23, 29-32, and 38-41) analogs was designed and synthesized. Structure elucidation of the synthesized compounds was attained by the use of H-1 NMR, C-13 NMR, and mass spectrometry. The obtained compounds were evaluated for their in vitro antitumor activity using the National Cancer Institute's 60 cell lines' panel assay that included nine tumor subpanels, namely, leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast cancer cells. Most of the investigated compounds showed a remarkable broad-spectrum antitumor activity. Compounds 19, 28, 32, and 34 proved to be 10-, 15-, 2-, and 7-fold more active than 5-FU, with GI(50) MG-MID values of 2.4, 1.5, 11.2, and 3.1 mu M, respectively.

  DOI：

  10.1007/s00044-013-0649-6
• 作为产物：
  描述：

  环己酮 、 3,4,5-三甲氧基苯甲醛 在 盐酸 作用下， 反应 10.0h， 以78%的产率得到(2E,6E)-2,6-bis(3,4,5-trimethoxybenzylidene)cyclohexanone
  参考文献：
  名称：

  对称和不对称取代的2,5-二亚芳基环己酮作为抗寄生虫化合物

  摘要：

  通过用各种醛处理环己酮，以中等至极好的收率合成了对称和不对称的双芳基-α，β-不饱和酮。二甲基氨基甲酸二甲基铵（DIMCARB）既用作催化剂，又用作反应介质，用于合成单亚芳基环加合物中间体，该中间体还用于生产二亚芳基环己酮。评估了所有34种合成化合物的抗增殖活性，特别是针对亚马逊利什曼原虫的前鞭毛体，克氏锥虫的前鞭毛体和锥鞭毛体。十八种化合物对L的前鞭毛体显示出抗利什曼活性。亚马逊IC 50值范围从2.8到10μM。另外，两种化合物表现出对的epimastigotes显著抗锥体虫活动锥虫带IC 50为5.2±0.8和3.0±0.0μM值，而五种化合物表现出的活性为15.0±1.4 30.2±1.8μM针对的锥鞭毛体克氏锥虫。而且，与上皮细胞相比，所有化合物对寄生虫的选择性更高。不对称化合物16，28，30和33可以被认为是具有IC有利抗寄生虫先导分子50和EC 50值在低微摩尔范围内，优于

  DOI：

  10.1016/j.ejmech.2018.06.031

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。
• 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。
• Small Molecule Stimulators of Steroid Receptor Coactivator-3 and Methods of Their Use as Cardioprotective and/or Vascular Regenerative Agents
  申请人：Baylor College of Medicine

  公开号：US20200071300A1

  公开（公告）日：2020-03-05

  Small molecule stimulators of steroid receptor coactivator-3 (SRC-3) and methods of their use as cardioprotective agents are provided. The small molecule stimulators are useful for promoting cardiac protection and repair and vascular regeneration after myocardial infarction. The compounds are also useful in preventing cardiac hypertrophy and collagen deposition and improving cardiac post-infarction function.

  提供了类固醇受体共激活因子-3（SRC-3）的小分子激活剂以及它们作为心脏保护剂的使用方法。这些小分子激活剂有助于促进心脏保护和修复，以及在心肌梗死后促进血管再生。这些化合物还可用于预防心肌肥大和胶原沉积，改善心肌梗死后的心脏功能。
• [EN] SMALL MOLECULE STIMULATORS OF STEROID RECEPTOR COACTIVATOR PROTEINS AND THEIR USE IN THE TREATMENT OF CANCER<br/>[FR] STIMULATEURS À PETITES MOLÉCULES DES PROTÉINES CO-ACTIVATRICES DES RÉCEPTEURS DE STÉROÏDES ET MÉTHODES POUR LES UTILISER
  申请人：BAYLOR COLLEGE MEDICINE

  公开号：WO2016109470A1

  公开（公告）日：2016-07-07

  Small molecule stimulators of steroid receptor coactivator (SRC) family proteins are provided, as well as methods for their use in treating or preventing cancer. Also provided are methods for stimulating SRC family proteins in a cell.

  提供了激活类固醇受体共激活蛋白（SRC）家族蛋白的小分子刺激剂，以及它们在治疗或预防癌症中的使用方法。还提供了在细胞中刺激SRC家族蛋白的方法。
• BP-M345 as a Basis for the Discovery of New Diarylpentanoids with Promising Antimitotic Activity
  作者：Joana Moreira、Patrícia M. A. Silva、Eliseba Castro、Lucília Saraiva、Madalena Pinto、Hassan Bousbaa、Honorina Cidade

  DOI：10.3390/ijms25031691

  日期：——

  Recently, the diarylpentanoid BP-M345 (5) has been identified as a potent in vitro growth inhibitor of cancer cells, with a GI50 value between 0.17 and 0.45 µM, showing low toxicity in non-tumor cells. BP-M345 (5) promotes mitotic arrest by interfering with mitotic spindle assembly, leading to apoptotic cell death. Following on from our previous work, we designed and synthesized a library of BP-M345 (5) analogs and evaluated the cell growth inhibitory activity of three human cancer cell lines within this library in order to perform structure–activity relationship (SAR) studies and to obtain compounds with improved antimitotic effects. Four compounds (7, 9, 13, and 16) were active, and the growth inhibition effects of compounds 7, 13, and 16 were associated with a pronounced arrest in mitosis. These compounds exhibited a similar or even higher mitotic index than BP-M345 (5), with compound 13 displaying the highest antimitotic activity, associated with the interference with mitotic spindle dynamics, inducing spindle collapse and, consequently, prolonged mitotic arrest, culminating in massive cancer cell death by apoptosis.

  最近，人们发现二芳基戊烷类化合物 BP-M345 (5) 是一种有效的体外癌细胞生长抑制剂，其 GI50 值介于 0.17 至 0.45 µM 之间，对非肿瘤细胞的毒性较低。BP-M345 (5) 通过干扰有丝分裂纺锤体的组装，促进有丝分裂停滞，导致细胞凋亡。在之前工作的基础上，我们设计并合成了一个 BP-M345 (5) 类似物文库，并评估了该文库中三种人类癌细胞株的细胞生长抑制活性，以便进行结构-活性关系（SAR）研究，并获得具有更好抗沉降作用的化合物。有四个化合物（7、9、13 和 16）具有活性，其中化合物 7、13 和 16 的生长抑制作用与明显的有丝分裂停止有关。这些化合物的有丝分裂指数与 BP-M345 (5)相似，甚至更高，其中化合物 13 的抗有丝分裂活性最高，它干扰了有丝分裂纺锤体的动力学，导致纺锤体崩溃，从而延长了有丝分裂停滞时间，最终导致大量癌细胞凋亡。