3,5-bis(4-nitrobenzylidene)-4-oxopiperidine | 330450-41-4

• 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: 3,5-bis(4-nitrobenzylidene)-4-oxopiperidine
• 英文别名: 3,5-Bis (4-nitrobenzylidene)piperidin-4-one；3,5-bis[(4-nitrophenyl)methylidene]piperidin-4-one
• CAS: 330450-41-4
• 化学式: C₁₉H₁₅N₃O₅
• 分子量: 365.345
• InChiKey: YUYPWAMLWZVHAE-UHFFFAOYSA-N

物化性质

• 沸点：
  588.5±50.0 °C(Predicted)
• 密度：
  1.414±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-bis(4-nitrobenzylidene)-4-oxopiperidine 、 2-chloro-[1,3,2]oxazaphosphinane 2-oxide 在 4-二甲氨基吡啶 作用下， 以 氯仿 为溶剂， 生成
  参考文献：
  名称：

  Novel Biologically Active 1,3,2-Oxazaphosphinane Derivatives

  摘要：

  DOI：

  10.1080/10426507.2010.520281
• 作为产物：
  描述：

  4-哌啶酮 、 对硝基苯甲醛 生成 3,5-bis(4-nitrobenzylidene)-4-oxopiperidine
  参考文献：
  名称：

  无DNA结合的抗增殖环状C5-姜黄素的构效关系分析：设计、合成、亲脂性和生物活性

  摘要：

  摘要 姜黄素结构中两个芳环之间的 β-二酮接头对水解和代谢的化学敏感性使得研究没有这些缺点的姜黄素结构修饰类似物变得至关重要。本研究描述了 20 种环状 C5-姜黄素的合成，以便更深入地了解它们的抗癌结构-活性关系 (SAR)。他们的合成设计包括四种不同的环酮和五种取代的芳香醛，以形成四个五元亚组。在针对 MCF-7 人非侵入性乳腺癌细胞和 Jurkat 人 T 淋巴细胞白血病细胞的 XTT 细胞活力测定中，在体外评估了这些模型化合物在五种不同浓度（10 nM、100 nM、1 μM、10 μM 和 20 μM）。大多数研究的化合物显示出显着的细胞毒性，IC50 值在 120 nM 和 2 μM 范围内，对姜黄素的相对毒性值非常高。得出并总结了 SAR 结论。开发了一种方法并应用于基于 TLC 的实验 logP 测量，这是此类 C5-姜黄素的新方法。logP 数据和结构修改显示出很强的相关性。根据

  DOI：

  10.1016/j.molstruc.2019.127661

文献信息

• Tumour-specific cytotoxicity and structure–activity relationships of novel 1-[3-(2-methoxyethylthio)propionyl]-3,5-bis(benzylidene)-4-piperidones
  作者：Mohammad Hossain、Umashankar Das、Naoki Umemura、Hiroshi Sakagami、Jan Balzarini、Erik De Clercq、Masami Kawase、Jonathan R. Dimmock

  DOI：10.1016/j.bmc.2016.03.056

  日期：2016.5

  piperidones 3-7 were designed and synthesized as novel cytotoxic agents. These compounds displayed potent cytotoxic properties towards human Molt4/C8, CEM, HSC-2, HSC-3 and HSC-4 neoplasms and also to murine L1210 cells. The majority of the compounds have sub-micromolar or very low micromolar IC50 and CC50 values and are significantly more potent than the reference alkylating drug melphalan. Evaluation

  设计并合成了一系列1-酰基-3,5-双（亚苄基）-4-哌啶酮3-7，作为新型细胞毒性剂。这些化合物对人Molt4 / C8，CEM，HSC-2，HSC-3和HSC-4肿瘤以及对鼠L1210细胞均显示出强大的细胞毒性。大多数化合物具有亚微摩尔或非常低的微摩尔IC50和CC50值，并且比参考烷基化药物美法仑显着更有效。这些化合物针对非恶性HGF和HPLF细胞的评估显示了肿瘤特异性毒性。特别地，3e作为有希望的铅细胞毒剂出现，它引起HSC-2细胞凋亡和PARP1裂解。
• Phosphoryl Substituted 3,5-<i>Bis</i>(Arylidene)-4-Piperidones Posessing High Antitumor Activity
  作者：I. L. Odinets、M. V. Makarov、O. I. Artyushin、E. Yu. Rybalkina、K. A. Lyssenko、T. V. Timofeeva、M. Yu. Antipin

  DOI：10.1080/10426500701793246

  日期：2008.1.14

  3,5-Bis(arylidene)-4-piperidones and related compounds 1 possess anticancer and antioxidant activity (Scheme 1).1,2 Some of these compounds are also fluorescent, which makes possible to use them as dyes for tracing their cellular pathways during chemotherapy and as agents for photodynamic therapy.3 The important way to regulate the bioavailability and drug delivery of these compounds to target organs

  3,5-双（亚芳基）-4-哌啶酮和相关化合物 1 具有抗癌和抗氧化活性（方案 1）。1,2 其中一些化合物还具有荧光性，因此可以将它们用作染料来追踪其细胞通路在化疗期间和作为光动力治疗的药物。3 调节这些化合物的生物利用度和药物输送到靶器官的重要方法是将不同的替代物 R1 引入哌啶酮部分的 N 原子。含磷基团作为此类改性剂是有前景的，并且可能有助于生物活性。因此，我们在本系列中研究了磷酸化亚芳基哌啶酮的合成方法和“结构-活性-荧光特性”关系。
• Design, synthesis and bioevaluation of novel maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones as cytostatic agents
  作者：Dani Youssef、Elizabeth Potter、Mamta Jha、Erik De Clercq、Jan Balzarini、James P. Stables、Amitabh Jha

  DOI：10.1016/j.bmcl.2009.09.069

  日期：2009.11

  A novel series of maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones were prepared to investigate the efficacy of micronutrient conjugation in enhancing cytotoxic potency by improving selectivity and delivery. These compounds, prepared as anticancer agents, were expected to demonstrate enhanced selectivity towards malignant cells through the inhibition of topoisomerase II alpha via protein thiolation. The cytostatic effects of these compounds were evaluated against three cell lines, namely murine L1210 leukemia cells, human Molt 4/C8 and CEM T-lymphocyte cells. All compounds were found to have greater potency than the reference drug melphalan. Several compounds were found to potently inhibit topoisomerase IIa and displayed cytostatic activity in the nanomolar range. (C) 2009 Elsevier Ltd. All rights reserved.
• 3,5-Bis(benzylidene)-4-piperidones and related N-acyl analogs: A novel cluster of antimalarials targeting the liver stage of Plasmodium falciparum
  作者：Umashankar Das、Ravi S.P. Singh、Jane Alcorn、Mark R. Hickman、Richard J. Sciotti、Susan E. Leed、Patricia J. Lee、Norma Roncal、Jonathan R. Dimmock

  DOI：10.1016/j.bmc.2013.09.065

  日期：2013.12

  Drug resistance is a major challenge in antimalarial chemotherapy. In addition, a complete cure of malaria requires intervention at various stages in the development of the parasite within the host. There are only a few antimalarials that target the liver stage of the Plasmodium species which is an essential part of the life cycle of the malarial parasite. We report a series of antimalarial 3,5-bis(benzylidene)-4-piperidones and related N-acyl analogs 1-5, a number of which exhibit potent in vitro growth-inhibiting properties towards drug-sensitive D6 and drug-resistant C235 strains of Plasmodium falciparum as well as inhibiting the liver stage development of the malarial life cycle. The compounds 2b (IC50: 165 ng/mL), 3b (IC50: 186 ng/mL), 5c (IC50: 159 ng/mL) and 5d (IC50: 93.5 ng/mL) emerged as lead molecules that inhibit liver stage Plasmodium berghei and are significantly more potent than chloroquine (IC50: >2000 ng/mL) and mefloquine (IC50: >2000 ng/mL) in this screen. All the compounds that showed potent inhibitory activity against the P. berghei liver stage were nontoxic to human HepG2 liver cells (IC50: >2000 ng/mL). The compounds 5a and 5b exhibit comparable metabolic stability as chloroquine and mefloquine in human plasma and the most potent compound 5d demonstrated suitable permeability characteristics using the MDCK monolayer. These results emphasize the value of 3,5-bis(benzylidene)-4-piperidones as novel antimalarials for further drug development. (C) 2013 Elsevier Ltd. All rights reserved.
• 1-[4-(2-Aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidines: A novel series of highly potent revertants of P-glycoprotein associated multidrug resistance
  作者：Umashankar Das、Joseph Molnár、Zoltán Baráth、Zsuzsanna Bata、Jonathan R. Dimmock

  DOI：10.1016/j.bmcl.2008.05.034

  日期：2008.6

  The 1-[4-(2-aminoethoxy) phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidines 5-8 are a novel cluster of highly potent P-glycoprotein dependent multidrug resistance (MDR) revertants. Using a concentration of 4 mu g/mL, these compounds possess 11-43 times the potency of verapamil in reversing MDR in murine L-5178 lymphoma cells transfected with the human MDR1 gene. Structure-activity relationships reveal that the attachment of the N-aroyl group to various 3,5-bis(benzylidene)-4-piperidones is essential for MDR reversal to occur. In terms of potencies, the 1-piperidinyl group is the preferred terminal amine while the 4-methyl and 4-chloro substituents are the optimal groups for placement in the benzylidene aryl rings. (C) 2008 Elsevier Ltd. All rights reserved.