(3E,5E)-3,5-bis(4-hydroxy-3-methoxybenzylidene)-1-methylpiperidin-4-one | 861968-02-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (3E,5E)-3,5-bis(4-hydroxy-3-methoxybenzylidene)-1-methylpiperidin-4-one
• 英文别名: 3,5-bis((E)-4-hydroxy-3-methoxybenzylidene)-1-methylpiperidin-4-one；(3E,5E)-3,5-bis[(4-hydroxy-3-methoxyphenyl)methylidene]-1-methylpiperidin-4-one
• CAS: 861968-02-7
• 化学式: C₂₂H₂₃NO₅
• 分子量: 381.428
• InChiKey: ZQRGLBNADQCTRG-GONBZBRSSA-N

物化性质

• 沸点：
  606.2±55.0 °C(Predicted)
• 密度：
  1.295±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  79.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  苯肼 、 (3E,5E)-3,5-bis(4-hydroxy-3-methoxybenzylidene)-1-methylpiperidin-4-one 在 sodium 作用下， 以 乙醇 为溶剂， 反应 10.0h， 以75%的产率得到4-[(E)-[3-(4-hydroxy-3-methoxyphenyl)-5-methyl-2-phenyl-3,3a,4,6-tetrahydropyrazolo[4,3-c]pyridin-7-ylidene]methyl]-2-methoxyphenol
  参考文献：
  名称：

  一些新型稠合吡啶类似物的合成和体外抗氧化活性

  摘要：

  合成了一系列新的吡喃并[3,2-c]吡啶、吡唑并[4,3-c]吡啶和吡啶并[4,3-d]嘧啶，并筛选了它们的体外抗氧化活性。化合物 13、14、15、23、29、30 和 31 表现出最活跃的氧自由基清除剂活性，抑制百分比分别为 99.4、99.6、99.8、97.3、99.0、99.3 和 99.5%；分别与姜黄素的效力相当。大多数测试的化合物被证明对外周多核中性粒细胞 (PMN) 是安全的。报告了详细的合成和抗氧化活性数据。

  DOI：

  10.1002/ardp.200400953
• 作为产物：
  描述：

  3,5-bis((E)-3-methoxy-4-((tetrahydro-2H-pyran-2-yl)oxy)benzylidene)-1-methylpiperidin-4-one 在 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 以80.1%的产率得到(3E,5E)-3,5-bis(4-hydroxy-3-methoxybenzylidene)-1-methylpiperidin-4-one
  参考文献：
  名称：

  一种单羰基类姜黄素类化合物及其制备方法与应用

  摘要：

  本发明公开了一种单羰基类姜黄素类似物及其制备与应用，所述姜黄素类似物由式Ⅰ表示，或其药学上可接受的盐包括有盐酸盐、硫酸盐，以醛、酮为原料，设计合成单羰基类姜黄素类似物CuA‑1～CuA‑3，以3，4‑二氢‑2H‑吡喃、香草醛、4‑甲基苯磺酸吡啶鎓、1‑甲基‑4‑哌啶酮为原料设计合成了单羰基类姜黄素类似物CuA‑4，通过单羰基取代不稳定的β‑二羰基结构得到更稳定的单羰基姜黄素类似物CuA‑1～CuA‑4，使其具备更好的药代动力学行为和更高的抗肿瘤活性，单羰基类姜黄素类在制备抗炎以及治疗与炎症相关疾病、阿尔兹海默症、帕金森综合症、抑郁症、肺癌、肝癌、乳腺癌、结肠癌和宫颈癌的药物中的应用。

  公开号：

  CN113354577B

文献信息

• Synthesis of Curcumin Analogues as Potential Antioxidant, Cancer Chemopreventive Agents
  作者：Khairia M. Youssef、Magda A. El-Sherbeny、Faiza S. El-Shafie、Hassan A. Farag、Omar A. Al-Deeb、Sit Albanat A. Awadalla

  DOI：10.1002/ardp.200300763

  日期：2004.1

  New series of 3, 5‐bis(substituted benzylidene)‐4‐piperidones, 2, 7‐bis(substituted benzylidene)cycloheptanones, 1, 5‐bis(substituted phenyl)‐1, 4‐pentadien‐3‐ones, 1, 7‐bis(substituted phenyl)‐1, 6‐heptadien‐3, 5‐diones, 1, 1‐bis(substituted cinnamoyl)‐cyclopentanes, and 1, 1‐bis(substituted cinnamoyl)cyclohexanes have been synthesized and tested for their antioxidant activity. Among the tested compounds

  新系列 3, 5-双（取代苯亚甲基）-4-哌啶酮，2, 7-双（取代苯亚甲基）环庚酮，1, 5-双（取代苯基）-1，4-戊二烯-3-，1， 7-双（取代苯基）-1, 6-庚二烯-3, 5-二酮，1, 1-双（取代肉桂酰基）-环戊烷和1, 1-双（取代肉桂酰基）环己烷已合成并测试其性能抗氧化活性。在被测化合物中，化合物II4、II9、II10、II11、V1和V4表现出较高的自由基清除活性，%抑制率分别为90.71、91.24、96.91、94.26、99.23和99.85%。此外，化合物 V1 是外周多核中性粒细胞 (PMN) 的安全成员，存活率为 91%。报告了详细的合成、光谱和生物学数据。
• Curcumin and Its New Derivatives: Correlation between Cytotoxicity against Breast Cancer Cell Lines, Degradation of PTP1B Phosphatase and ROS Generation
  作者：Tomasz Kostrzewa、Karol Wołosewicz、Marek Jamrozik、Joanna Drzeżdżon、Julia Siemińska、Dagmara Jacewicz、Magdalena Górska-Ponikowska、Marcin Kołaczkowski、Ryszard Łaźny、Alicja Kuban-Jankowska

  DOI：10.3390/ijms221910368

  日期：——

  antioxidant effects in its derivatives. For the most potent cytotoxic compounds, we determined intracellular ROS and PTP1B phosphatase levels. Moreover, for curcumin and its derivatives, we performed real-time microscopy to observe the photosensitizing effect. Finally, computational analysis was performed for the curcumin derivatives with an inhibitory effect against PTP1B phosphatase to assess the

  乳腺癌是女性最常见的癌症——它影响全球超过 200 万女性。PTP1B磷酸酶可能是乳腺癌治疗新药的可能靶点之一。在本文中，我们提出了具有 4-哌啶酮环的新姜黄素衍生物作为 PTP1B 抑制剂和 ROS 诱导剂。我们对十二种姜黄素衍生物对乳腺癌 MCF-7 和 MDA-MB-231 细胞系以及人角质形成细胞 HaCaT 细胞系进行了细胞毒性分析。此外，由于姜黄素是一种已知的抗氧化剂，我们评估了其衍生物的抗氧化作用。对于最有效的细胞毒性化合物，我们确定了细胞内 ROS 和 PTP1B 磷酸酶水平。此外，对于姜黄素及其衍生物，我们进行了实时显微镜观察以观察光敏效应。最后，对具有 PTP1B 磷酸酶抑制作用的姜黄素衍生物进行了计算分析，以评估新抑制剂在酶变构位点内的潜在结合模式。我们观察到两种测试化合物是比姜黄素更好的抗癌剂。此外，我们建议阻断酚类化合物中的 -OH 基团会导致细胞毒性作用增加，即
• Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells
  作者：Nur Syahirah Che Razali、Kok Wai Lam、Nor Fadilah Rajab、A. Rahman A. Jamal、Nurul Farahana Kamaludin、Kok Meng Chan

  DOI：10.1186/s41021-023-00297-y

  日期：——

  Previously, we have reported on the two curcuminoid analogues with piperidone derivatives, namely FLDP-5 and FLDP-8 have more potent anti-proliferative and anti-migration effects than curcumin. In this study, we further investigated the mode of cell death and the mechanism involved in the cell death process induced by these analogues on human glioblastoma LN-18 cells.

  The FLDP-5 and FLDP-8 curcuminoid analogues induced LN-18 cell death through apoptosis in a concentration-dependent manner following 24 h of treatment. These analogues induced apoptosis in LN-18 cells through significant loss of mitochondrial mass and mitochondrial membrane potential (MMP) as early as 1-hour of treatment. Interestingly, N-acetyl-l-cysteine (NAC) pretreatment did not abolish the apoptosis induced by these analogues, further confirming the cell death process is independent of ROS. However, the apoptosis induced by the analogues is caspases-dependent, whereby pan-caspase pretreatment inhibited the curcuminoid analogues-induced apoptosis. The apoptotic cell death progressed with the activation of both caspase-8 and caspase-9, which eventually led to the activation of caspase-3, as confirmed by immunoblotting. Moreover, the existing over-expression of miRNA-21 in LN-18 cells was suppressed following treatment with both analogues, which suggested the down-regulation of the miRNA-21 facilitates the cell death process.

  The FLDP-5 and FLDP-8 curcuminoid analogues downregulate the miRNA-21 expression and induce extrinsic and intrinsic apoptotic pathways in LN-18 cells.

  摘要 研究背景 以前，我们曾报道过两种姜黄素类似物的哌啶酮衍生物，即FLDP-5和FLDP-8，具有比姜黄素更强的抗增殖和抗迁移作用。在本研究中，我们进一步研究了这两种类似物诱导人胶质母细胞瘤 LN-18 细胞死亡的模式和机制。 研究结果 FLDP-5和FLDP-8姜黄素类似物在处理24小时后以浓度依赖性方式诱导LN-18细胞通过凋亡死亡。这些类似物早在处理 1 小时后就通过线粒体质量和线粒体膜电位（MMP）的显著丧失诱导 LN-18 细胞凋亡。有趣的是，N-乙酰-L-半胱氨酸（NAC）预处理并不能消除这些类似物诱导的细胞凋亡，这进一步证实了细胞死亡过程与 ROS 无关。然而，类似物诱导的细胞凋亡是依赖于caspases的，而泛caspase预处理抑制了姜黄类似物诱导的细胞凋亡。免疫印迹法证实，细胞凋亡是随着 caspase-8 和 caspase-9 的激活而进行的，最终导致 caspase-3 的激活。此外，两种类似物处理后，LN-18 细胞中已有的 miRNA-21 过度表达被抑制，这表明 miRNA-21 的下调促进了细胞死亡过程。 研究结论 FLDP-5和FLDP-8姜黄素类似物能下调miRNA-21的表达，并诱导LN-18细胞的外源性和内源性凋亡途径。
• Discovery and evaluation of piperid-4-one-containing mono-carbonyl analogs of curcumin as anti-inflammatory agents
  作者：Jianzhang Wu、Yali Zhang、Yuepiao Cai、Jian Wang、Bixia Weng、Qinqin Tang、Xiangjian Chen、Zheer Pan、Guang Liang、Shulin Yang

  DOI：10.1016/j.bmc.2013.03.057

  日期：2013.6

  We previously reported the design and discovery of three series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MCACs) as excellent anti-inflammatory agents. In continuation of our ongoing research, we designed and synthesized the fourth series of MCACs, whose central linker is a piperid-4-one. Their inhibitory effects against IL-6 production were evaluated in lipopolysaccharide (LPS)-stimulated macrophages. Among them, compounds F8, F29, F33, F35, and F36 exhibited the IC50 values under 5 mu M. The structure-activity relationship was discussed. Mechanistically, F35 and F36 dose-dependently prevented LPS-induced NF-kappa B and ERK activation. Finally, pretreatment with F35 and F36 significantly protected the C57B/L6 mice from LPS-induced septic death. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents. (C) 2013 Elsevier Ltd. All rights reserved.
• 3,5-DIARYLIDENYL-N-SUBSTITUTED-PIPERID-4-ONE-DERIVED INHIBITORS OF STAT3 PATHWAY ACTIVITY AND USES THEREOF
  申请人：Kiakos Konstantinos

  公开号：US20200399220A1

  公开（公告）日：2020-12-24

  3,5-Diarylidenyl-N-substituted-piperid-4-one analogs, and pharmaceutically acceptable derivatives thereof, are useful in the treatment or prevention of disorders including cancer, autoimmune disorders, inflammatory disorders, and fibrotic disorders. The compounds are included in pharmaceutical compositions, and are useful for treating disorders, such as cancer associated with aberrant Stat3 pathway activity. The compositions further include another therapeutic agent, such as an anticancer drug. Such compounds or compositions thereof are used to treat resistant and/or metastatic cancers. Methods also inhibit Stat3 pathway activity in a cell. Other methods are useful for making the pharmaceutical compounds. Synthetic methods are also useful for making the compounds. The compounds and compositions are useful as a fluorescent probe.