(3E,5E)-1-methyl-4-oxo-3,5-bis(4-pyridinylmethylene)piperidinone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3E,5E)-1-methyl-4-oxo-3,5-bis(4-pyridinylmethylene)piperidinone
• 英文别名: 1-methyl-3,5-bis[((E)-4-pyridyl)methylidene]-4-piperidone；1-methyl-3,5-bis[(E)-(4-pyridyl)methylidene]-4-piperidone；1-methyl-3,5-bis[(E)-4-pyridylmethylidene]-4-piperidone；N-methyl-3,5-bis((pyridin-4-yl)methylene)-4-piperidone；RL66；(3E,5E)-1-methyl-3,5-bis(4-pyridylmethylene)piperidin-4-one；(3E,5E)-1-methyl-3,5-bis(pyridin-4-ylmethylidene)piperidin-4-one
• 化学式: C₁₈H₁₇N₃O
• 分子量: 291.352
• InChiKey: PFSHGYYOLVTIGM-OTYYAQKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  46.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  间苯二甲酸 、 (3E,5E)-1-methyl-4-oxo-3,5-bis(4-pyridinylmethylene)piperidinone 以 甲醇 、 二氯甲烷 为溶剂， 以78%的产率得到
  参考文献：
  名称：

  基于双吡啶基取代的 α,β-不饱和酮与共形成体的新型共晶的合成、结构和发光

  摘要：

  摘要 基于 2,6-双((吡啶-4-基)亚甲基)环己酮 (A) 和 N-甲基-3,5-双((吡啶-4-基)亚甲基)-4-哌啶酮 (B) coformers, 三种新型大环共晶, ( A )⋅(间苯二酚) ( 1 ), ( A )⋅(1,3,5-苯三醇) ( 2 ), ( B ) 2 ⋅(1,3,5-苯三醇) 2 ( 3 ) 和三个链共晶, ( A )⋅(氢醌) ( 4 ), ( A )⋅(间苯二甲酸) ( 5 ), ( B )⋅(间苯二甲酸) ( 6 ) 已被合成并通过 IR、1 H NMR 和 X 射线晶体结构分析对其进行结构表征。结构分析表明，1-3 中的四组分大环是由“夹状”间苯二酚模板和构建块生成的，而 4-6 显示出无限的 H 键链。此外，A、B 和 1-6 的发光特性主要在固态下进行研究。与免费积木相比，尽管 6 增强，但 1-6 蓝移了 55-60 nm，发射强度降低。发光特

  DOI：

  10.1016/j.molstruc.2014.09.008
• 作为产物：
  描述：

  在 碳酸氢钠 作用下， 生成 (3E,5E)-1-methyl-4-oxo-3,5-bis(4-pyridinylmethylene)piperidinone
  参考文献：
  名称：

  Structure–cytotoxicity relationship in a series of N-phosphorus substituted E,E-3,5-bis(3-pyridinylmethylene)- and E,E-3,5-bis(4-pyridinylmethylene)piperid-4-ones

  摘要：

  In order to give further insight on the influence of the aromatic ring nature and the presence of the phosphorus substituent at the piperidone nitrogen atom of E,E-3,5-bis((hetero)arylidene)piperid-4-ones on their antitumor properties, a series of phosphorus substituted E,E-3,5-bis(pyridinylmethylene) piperid-4-ones bearing either 3-pyridine or 4-pyridine rings was obtained. Novel NH-3,5-bis(pyridinylmethylene)piperid-4-ones 1a,b were converted into the corresponding N-phosphorylated derivatives 3a-c, 4a-c differing in the substitution at the phosphorus atom (amidophosphates and amidophosphonates), via direct phosphorylation while N-(omega-phosphorylalkyl)-substituted compounds 8a-c were obtained via aldol-crotonic condensation of preformed N-phosphorylalkyl substituted piperidones with the corresponding pyridinecarboxaldehyde. The cytotoxicity screen has revealed that phosphorylated compounds based on E,E-3,5-bis(4-pyridinylmethylene)piperid-4-one framework displayed higher inhibitory properties toward Caov3, A549, KB 3-1 and KB 8-5 human carcinoma cell lines comparing with their analogues with 3-pyridine rings. Introduction of the phosphorus moiety substantially increased the antitumor properties in the case of E,E-3,5-bis(3-pyridinylmethylene)piperid-4-ones derivatives but this influence less pronounced for more active analogues bearing 4-pyridinyl rings. Most of the compounds tested are potent against multi-drug resistant cell line KB 8-5 affording some guidelines for the search of perspective drug-candidates among phosphorus substituted E,E-3,5-bis ((hetero)arylidene)piperid-4-ones. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.09.058

文献信息

• Synthesis and spectroscopic and structural studies of cross-conjugated dienones derived from cyclic ketones and aromatic aldehydes
  作者：S. Z. Vatsadze、M. A. Manaenkova、N. V. Sviridenkova、N. V. Zyk、D. P. Krut’ko、A. V. Churakov、M. Yu. Antipin、J. A. K. Howard、H. Lang

  DOI：10.1007/s11172-006-0397-6

  日期：2006.7

  Cross-conjugated dienones were synthesized by the reactions of cyclic ketones with two equivalents of aromatic aldehydes under basic conditions. An NMR spectroscopic study and X-ray diffraction analysis demonstrated that all reaction products are formed as E,E isomers. Spontaneous photochemical trans-cis isomerization of cross-conjugated dienones under the scattered light in solution was observed for

  交叉共轭二烯酮是通过环状酮与两当量的芳香醛在碱性条件下反应合成的。NMR 光谱研究和 X 射线衍射分析表明，所有反应产物均以 E、E 异构体的形式形成。首次观察到溶液中散射光下交叉共轭二烯酮的自发光化学反顺异构化。异构化程度主要取决于二烯酮分子中心片段的性质。合成了以前未知的 2,5-双 [(E)-(3-吡啶基) 亚甲基] 环戊酮的光化学 [2+2]-环加成产物，并通过光谱方法和 X 射线衍射进行了表征。在所使用的条件下，仅获得环丁烷加合物的一种异构体。
• Reaction of cross-conjugated dienones with phenyl-and 2-pyridylhydrazines
  作者：N. V. Sviridenkova、S. Z. Vatsadze、M. A. Manaenkova、N. V. Zyk

  DOI：10.1007/s11172-006-0161-y

  日期：2005.11

  New pyrazoline derivatives were synthesized by condensation of dienones based on cyclohexanone and N-substituted piperidin-4-ones with phenylhydrazine and 2-pyridylhydrazine. The reaction with phenylhydrazine produces trans isomers.

  通过基于环己酮和N-取代哌啶-4-酮的二烯酮与苯肼和2-吡啶基肼缩合合成新的吡唑啉衍生物。与苯肼反应生成反式异构体。
• CURCUMIN ANALOGS WITH ANTI-TUMOR AND ANTI-ANGIOGENIC PROPERTIES
  申请人：Snyder James P.

  公开号：US20080234320A1

  公开（公告）日：2008-09-25

  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.

  本发明涉及展现抗肿瘤和抗血管生成特性的姜黄素类似物，包括这些化合物的制药配方和使用这些化合物的方法。
• The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer
  作者：Bryant W. Megna、Patrick R. Carney、Mitchell G. Depke、Manabu Nukaya、James McNally、Lesley Larsen、Rhonda J. Rosengren、Gregory D. Kennedy

  DOI：10.1016/j.jss.2017.02.010

  日期：2017.6

  Background: Curcumin has proven to be a potent antitumor agent in both preclinical and clinical models of colorectal cancer (CRC). It has also been identified as a ligand of the transcription factor known as the aryl hydrocarbon receptor (AHR). Our laboratory has identified the AHR as a mechanism which contributes to both tumorigenesis in a mouse model of inflammatory CRC as well an apoptotic target in vitro. Curcumin's role as an AHR ligand may modulate its effects to induce colon cancer cell death, and this role may be enhanced via structural modification of the curcumin backbone. We sought to determine if the two piperidone analogs of curcumin, RL66 and RL118, exhibit more robust antitumor actions than their parent compound in the context of colorectal cancer in vitro. Moreover, to ascertain the ability of curcumin, RL66 and RL118 to activate the AHR and evaluate if this activation has any effect on CRC cell death.Materials and methods: DLD1, HCT116, LS513, and RKO colon cell lines were propagated in vitro. Natural curcumin was obtained commercially, whereas RL66 and RL118 were synthesized and characterized de novo. Multiwell fluorescent/luminescent signal detection was used to simultaneously ascertain cell viability, cell cytonecrosis, and relative amounts of apoptotic activity. AHR activity was measured with a dual luciferase reporter gene system. Stable expression of small interfering RNA interference was established in the HCT116 cell lines to create AHR "knock down" cell lines.Results: Both RL66 and RL118 proved to be more potent antitumor agents than their parent compound curcumin in all cell lines tested. The majority of this cell death was due to induction of apoptosis, which occurred earlier and to a greater degree following RL66 and RL118 treatment as opposed to curcumin. Also, RL66 and RL118 were found to be activators of AHR, and a portion of their ability to cause cell death was dependent on this induction. Curcumin was found unable to activate the AHR, and levels of AHR messenger RNA did not change their effects on cell death.Conclusions: Piperidone analogs of curcumin exhibited enhanced antitumor effects in vitro as opposed to their parent compound. Even more, this enhanced cell death profile may be partially attributed to the ability of these compounds to activate the AHR. Further study of synthetic curcumin analogs as chemopreventives and chemoadjuncts in CRC is warranted. Also, more generally, the AHR may represent a potential putative target for novel anticancer agents for CRC. (C) 2017 Elsevier Inc. All rights reserved.
• US7371766B2
  申请人：——

  公开号：US7371766B2

  公开（公告）日：2008-05-13