1-methyl-3,5-bis[(E)-(3-pyridyl)methylidene]-4-piperidone | 871361-89-6

• 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: 1-methyl-3,5-bis[(E)-(3-pyridyl)methylidene]-4-piperidone
• 英文别名: (3E,5E)-1-methyl-3,5-bis(pyridin-3-ylmethylidene)piperidin-4-one；(3E,5E)-1-methyl-4-oxo-3,5-bis(3-pyridinylmethylene)piperidinone
• CAS: 871361-89-6
• 化学式: C₁₈H₁₇N₃O
• 分子量: 291.352
• InChiKey: JUTNPNBAQUDRSX-GONBZBRSSA-N

物化性质

• 熔点：
  171 °C(Solv: ethanol (64-17-5))
• 沸点：
  513.1±50.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

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：

  1-methyl-3,5-bis[(E)-(3-pyridyl)methylidene]-4-piperidone 、 苯肼 以 乙醇 为溶剂， 反应 6.0h， 以30%的产率得到5-methyl-2-phenyl-3-(3-pyridyl)-7-[(E)-(3-pyridyl)methylene]-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine
  参考文献：
  名称：

  交叉共轭二烯酮与苯基-和 2-吡啶基肼的反应

  摘要：

  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。

  DOI：

  10.1007/s11172-006-0161-y
• 作为产物：
  描述：

  (3E,5E)-1-methyl-4-oxo-3,5-bis(pyridin-3-ylmethylidene)piperidinium tetrafluoroborate 在 碳酸氢钠 作用下， 生成 1-methyl-3,5-bis[(E)-(3-pyridyl)methylidene]-4-piperidone
  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。
• Rational design, synthesis, and 2D-QSAR study of anti-oncological alkaloids against hepatoma and cervical carcinoma
  作者：Adel S. Girgis、Siva S. Panda、Marian N. Aziz、Peter J. Steel、C. Dennis Hall、Alan R. Katritzky

  DOI：10.1039/c4ra16663a

  日期：——

  HeLa (cervical) tumor cell line than the standard reference cisplatin, while 11, and 12 seem more potent against the HepG2 (liver) carcinoma cell line relative to the standard reference doxorubicin hydrochloride as determined by in vitro Sulfo-Rhodamine-B bio-assay. 3D-Pharmacophores of the HeLa comprise five chemical features viz., two hydrogen bond acceptors, two hydrophobic centers and one positive

  通过偶氮甲基内酯环加成反应与3的区域选择性合成抗肿瘤活性双螺[3 H-吲哚-3,2'-吡咯烷-3'，3''-哌啶] -2（1 H），4'-二酮11-19 E，5 E -1-烷基-3,5-双（芳基亚甲基）-4-哌啶酮3-7。化合物13，14和16揭示了对抗的HeLa（宫颈癌）的肿瘤细胞比标准参考顺铂线更高的效力，而11和12似乎抵抗相对于标准参考多柔比星盐酸盐作为HepG2细胞（肝）癌细胞系更有效取决于磺基若丹明B的体外生物测定。HeLa的3D药基包括五个化学特征。，两个氢键受体，两个疏水中心和一个正电离中心，HepG2包含三个化学特征，即氢键受体，疏水中心和正电离中心。肿瘤细胞系的这些特征解释了生物活性相对于化学结构的变化。使用CODESSA-Pro软件获得了具有统计学意义的QSAR模型，该模型描述了螺旋生物碱的生物特性，从而验证了所观察到的药理学观察结果并确定了控制活性的最重要参数。
• Lewis Acids as Mild and Effective Catalysts for the Synthesis of 3,5-Bis[(hetero)arylidene]piperidin-4-ones
  作者：Evgeniya Leonova、Mihail Makarov、Zinaida Klemenkova、Irina Odinets

  DOI：10.1002/hlca.201000005

  日期：2010.10

  with (hetero)aromatic aldehydes promoted by Lewis acids or bases were examined. This comparative study has revealed three effective catalytic systems based on Lewis acids, i.e., LiClO4 and MgBr2 (in the presence of tertiary amine), and BF3⋅Et2O, for the synthesis of N‐alkyl‐substituted 3,5‐bis(heteroarylidene)piperidin‐4‐ones, including those bearing acid‐ or base‐labile groups both in the (hetero)aromatic

  考察了路易斯酸或碱促进的N-烷基和N H-哌啶-4-酮衍生物与（杂）芳族醛的醛-丁烯醛缩合反应。这个比较研究显示基于三个有效的催化系统的路易斯酸，即，的LiClO 4和MgBr 2（在叔胺的存在下），和BF 3 ⋅Et 2 O，用于合成Ñ烷基取代的3,5-双（杂亚芳基）哌啶-4-酮，包括在（杂）芳族基团和N-原子的烷基取代基中均带有酸或碱不稳定基团的那些。对于LiClO 4介导的合成，观察到最高的反应速率。既MgBr 2 -和的LiClO 4种介导的合成是低效的情况下Ñ H-哌啶-4-酮，而BF 3 ⋅Et 2 ö提供以高产率最终化合物。该催化剂特别有利，因为在O保护的哌啶-4-酮的情况下，它可以同时缩合和脱保护。
• 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。