1-benzyl-5-hydroxy-3,5-diphenyl-1H-pyrrol-2(5H)-one | 1233489-02-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 1-benzyl-5-hydroxy-3,5-diphenyl-1H-pyrrol-2(5H)-one
• 英文别名: 1-Benzyl-5-hydroxy-3,5-diphenylpyrrol-2-one；1-benzyl-5-hydroxy-3,5-diphenylpyrrol-2-one
• CAS: 1233489-02-5
• 化学式: C₂₃H₁₉NO₂
• 分子量: 341.409
• InChiKey: CESMMVKOGLWJHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-benzyl-2-oxo-2-phenyl-N-(1-phenylethenyl)acetamide 在 iron(III) chloride 作用下， 以 二氯甲烷 为溶剂， 生成 1-benzyl-5-hydroxy-3,5-diphenyl-1H-pyrrol-2(5H)-one
  参考文献：
  名称：

  探索叔酰胺作为有机合成中的通用合成子。

  摘要：

  长期以来一直认为叔酰胺是合成中稳定的和边际上有价值的烯胺变体。但是，近年来，这一概念受到了挑战。已成功地显示出使叔酰胺的交叉缀合系统的调节能够增强氮孤对电子的离域化为碳-碳双键，从而使叔酰胺的烯胺反应性恢复活力。在本文中，我总结了叔酰胺类化合物亲核反应探索的最新进展及其在天然产物和具有生物学和药学意义的杂环化合物的合成中的应用，主要侧重于我们自己的工作。

  DOI：

  10.1039/c4cc10327k

文献信息

• Discovery of Highly Functionalized 5-hydroxy-2H-pyrrol-2-ones That Exhibit Antiestrogenic Effects in Breast and Endometrial Cancer Cells and Potentiate the Antitumoral Effect of Tamoxifen
  作者：Miguel Guerra-Rodríguez、Priscila López-Rojas、Ángel Amesty、Haidée Aranda-Tavío、Yeray Brito-Casillas、Ana Estévez-Braun、Leandro Fernández-Pérez、Borja Guerra、Carlota Recio

  DOI：10.3390/cancers14215174

  日期：——

  Tamoxifen improves the overall survival rate in hormone receptor-positive breast cancer patients. However, despite the fact that it exerts antagonistic effects on the ERα, it can act as a partial agonist, resulting in tumor growth in estrogen-sensitive tissues. In this study, highly functionalized 5-hydroxy-2H-pyrrol-2-ones were synthesized and evaluated by using ERα- and phenotype-based screening assays. Compounds 32 and 35 inhibited 17β-estradiol (E2)-stimulated ERα-mediated transcription of the luciferase reporter gene in breast cancer cells without inhibition of the transcriptional activity mediated by androgen or glucocorticoid receptors. Compound 32 regulated E2-stimulated ERα-mediated transcription by partial antagonism, whereas compound 35 caused rapid and non-competitive inhibition. Monitoring of 2D and 3D cell growth confirmed potent antitumoral effects of both compounds on ER-positive breast cancer cells. Furthermore, compounds 32 and 35 caused apoptosis and blocked the cell cycle of ER-positive breast cancer cells in the sub-G1 and G0/G1 phases. Interestingly, compound 35 suppressed the functional activity of ERα in the uterus, as demonstrated by the inhibition of E2-stimulated transcription of estrogen and progesterone receptors and alkaline phosphatase enzymatic activity. Compound 35 showed a relatively low binding affinity with ERα. However, its antiestrogenic effect was associated with an increased polyubiquitination and a reduced protein expression of ERα. Clinically relevant, a possible combinatory therapy with compound 35 may enhance the antitumoral efficacy of 4-hydroxy-tamoxifen in ER-positive breast cancer cells. In silico ADME predictions indicated that these compounds exhibit good drug-likeness, which, together with their potential antitumoral effects and their lack of estrogenic activity, offers a pharmacological opportunity to deepen the study of ER-positive breast cancer treatment.

  他莫昔芬可提高激素受体阳性乳腺癌患者的总生存率。然而，尽管他莫昔芬对ERα具有拮抗作用，但它也可以作为部分激动剂，导致雌激素敏感组织中的肿瘤生长。本研究合成了高度官能化的 5-羟基-2H-吡咯-2-酮，并通过基于 ERα 和表型的筛选试验对其进行了评估。化合物 32 和 35 可抑制乳腺癌细胞中 17β-estradiol (E2) 刺激的 ERα 介导的荧光素酶报告基因转录，而不会抑制雄激素或糖皮质激素受体介导的转录活性。化合物 32 通过部分拮抗作用调节 E2 刺激的 ERα 介导的转录，而化合物 35 则造成快速和非竞争性抑制。对二维和三维细胞生长的监测证实了这两种化合物对 ER 阳性乳腺癌细胞的强效抗肿瘤作用。此外，化合物 32 和 35 还能导致ER 阳性乳腺癌细胞凋亡，并阻止细胞周期进入亚 G1 期和 G0/G1 期。有趣的是，化合物 35 抑制了ERα在子宫中的功能活性，这表现在抑制了E2刺激的雌激素和孕激素受体转录以及碱性磷酸酶的酶活性。化合物 35 与 ERα 的结合亲和力相对较低。然而，其抗雌激素作用与多泛素化的增加和ERα蛋白表达的减少有关。在临床上，与化合物 35 进行联合治疗可能会增强 4-hydroxy-tamoxifen 对 ER 阳性乳腺癌细胞的抗肿瘤功效。硅学 ADME 预测表明，这些化合物具有良好的药物相似性，再加上它们潜在的抗肿瘤作用和缺乏雌激素活性，为深化 ER 阳性乳腺癌治疗研究提供了药理学机会。
• An expedient synthesis of pyrrole-2-phosphonates via direct oxidative phosphorylation and γ-hydroxy-γ-butyrolactams from pyrroles
  作者：Se Hee Kim、Ko Hoon Kim、Jin Woo Lim、Jae Nyoung Kim

  DOI：10.1016/j.tetlet.2013.11.082

  日期：2014.1

  An expedient oxidative phosphorylation of pyrroles has been disclosed. The reaction of dialkyl phosphite and pyrrole in the presence of AgNO3/K2S2O8 in DMF/H2O (8:1) produced pyrrole-2-phosphonates in good yields. In the absence of dialkyl phosphite, gamma-hydroxy-gamma-butyrolactam derivative was formed as a major product. (C) 2013 Elsevier Ltd. All rights reserved.
• Supported <i>p</i>-Toluenesulfonic Acid as a Highly Robust and Eco-Friendly Isocyanide Scavenger
  作者：Jhonny Azuaje、Alberto Coelho、Abdelaziz El Maatougui、José Manuel Blanco、Eddy Sotelo

  DOI：10.1021/co100035z

  日期：2011.1.10

  We document here the use of polymer-supported p-toluenesulfonic acid as a highly effective, robust, economical and eco-friendly isocyanide scavenger. The herein described strategy; circumvent the intense and repulsive odor of volatile isocyanides, enabling simplified and odorless workup and purifications. The usefulness of the new scavengers has been validated in a set of diverse isocyanide-based organic transformations and this approach is also amenable to parallel synthesis techniques.
• Highly Efficient and Expedient Synthesis of 5-Hydroxy-1<i>H</i>-pyrrol-2-(5<i>H</i>)-ones from FeCl₃-Catalyzed Tandem Intramolecular Enaminic Addition of Tertiary Enamides to Ketones and 1,3-Hydroxy Rearrangement
  作者：Luo Yang、Chuan-Hu Lei、De-Xian Wang、Zhi-Tang Huang、Mei-Xiang Wang

  DOI：10.1021/ol101607z

  日期：2010.9.3

  Catalyzed by FeCl3 under very mild conditions, tertiary enamides underwent a highly efficient intramolecular enaminic addition reaction to the ketonic carbonyls followed by 1,3-hydroxy rearrangement to produce 5-hydroxy-1H-pyrrol-2(5H)-ones in excellent yields.
• Exploring tertiary enamides as versatile synthons in organic synthesis
  作者：Mei-Xiang Wang

  DOI：10.1039/c4cc10327k

  日期：——

  Tertiary enamides have long been thought of as stable and marginally valuable enamine variants in synthesis. This notion has been challenged, however, in recent years. Enabling the regulation of the cross-conjugation system of the tertiary enamides has been successfully shown to enhance delocalization of the nitrogen lone-pair electrons into a carbon-carbon double, thereby reinvigorating the enaminic

  长期以来一直认为叔酰胺是合成中稳定的和边际上有价值的烯胺变体。但是，近年来，这一概念受到了挑战。已成功地显示出使叔酰胺的交叉缀合系统的调节能够增强氮孤对电子的离域化为碳-碳双键，从而使叔酰胺的烯胺反应性恢复活力。在本文中，我总结了叔酰胺类化合物亲核反应探索的最新进展及其在天然产物和具有生物学和药学意义的杂环化合物的合成中的应用，主要侧重于我们自己的工作。