4-(3-nitrophenoxy)butanoic acid | 30297-87-1

• 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: 4-(3-nitrophenoxy)butanoic acid
• 英文别名: γ-(m-Nitrophenoxy)-buttersaeure
• CAS: 30297-87-1
• 化学式: C₁₀H₁₁NO₅
• mdl: MFCD02625634
• 分子量: 225.201
• InChiKey: MBGXVUBSVCRYES-UHFFFAOYSA-N

物化性质

• 熔点：
  114-115 °C(Solv: benzene (71-43-2))
• 沸点：
  448.6±25.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3-nitrophenoxy)butanoic acid 在 五氯化磷 作用下， 以 氯苯 为溶剂， 生成 γ-(m-Nitrophenoxy)-butyrylchlorid
  参考文献：
  名称：

  Barashkin,V.A. et al., Journal of Organic Chemistry USSR (English Translation), 1970, vol. 6, p. 2274 - 2276

  摘要：

  DOI：
• 作为产物：
  描述：

  间硝基苯酚 在 caesium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 4-(3-nitrophenoxy)butanoic acid
  参考文献：
  名称：

  使用双 SNAr 方法以多样性为导向合成大环杂环

  摘要：

  开发了一种基于双芳香族亲核取代（SNACK）的有效大环化方法。该方法允许将杂环基序轻松掺入大环中，并快速合成大量结构多样的大环。 SNACK 大环化能够制备构象限制大环的稳定非对映异构体（阻转异构体）。 B 细胞淋巴瘤 6 (BCL6) 的高亲和力大环结合剂的鉴定例证了 SNACK 大环化在药物发现项目中的实际应用。

  DOI：

  10.1039/d1ob00612f

文献信息

• Incorporation of Piperazino Functionality into 1,3-Disubstituted Urea as the Tertiary Pharmacophore Affording Potent Inhibitors of Soluble Epoxide Hydrolase with Improved Pharmacokinetic Properties
  作者：Shao-Xu Huang、Hui-Yuan Li、Jun-Yan Liu、Christophe Morisseau、Bruce D. Hammock、Ya-Qiu Long

  DOI：10.1021/jm101087u

  日期：2010.12.9

  The inhibition of the mammalian soluble epoxide hydrolase (sEH) is a promising new therapy in the treatment of hypertension, inflammation, and other disorders. However, the problems of limited water solubility, high melting point, and low metabolic stability complicated the development of 1,3-disubstituted urea-based sEH inhibitors. The current study explored the introduction of the substituted piperazino

  哺乳动物可溶性环氧化物水解酶 (sEH) 的抑制作用是治疗高血压、炎症和其他疾病的一种很有前景的新疗法。然而，有限的水溶性、高熔点和低代谢稳定性的问题使基于 1,3-二取代脲的 sEH 抑制剂的开发变得复杂。目前的研究探索了引入取代的哌嗪基团作为三级药效团，与先前报道的基于 1-金刚烷脲的抑制剂相比，这导致药代动力学参数的显着改善，同时保持高效力。SAR 研究表明，间位或对位取代的苯基间隔基和N 4-乙酰基或磺酰基取代的哌嗪是实现高效力和良好物理性能的最佳结构。1-(4-(4-(4-acetylpiperazin-1-yl)butoxy)phenyl)-3-adamantan-1-yl urea ( 29c ) 在小鼠体内表现出优异的体内药代动力学特性：T 1/2 =14 h ，C max = 84 nM，AUC = 40 200 nM·min，和 IC 50 = 7.0 nM 对人 sEH
• 哌嗪取代的1,3-二取代脲类化合物及哌嗪取代 的酰胺类化合物及其制备方法和用途
  申请人：中国科学院上海药物研究所

  公开号：CN102464631B

  公开（公告）日：2016-08-10

  本发明涉及一类由以下通式(I)表示的哌嗪取代的1，3‑二取代脲类化合物及哌嗪取代的酰胺类化合物或其药学上可接受的盐及其制备方法、包含该化合物的药物组合物，以及这些化合物在制备可溶性环氧水解酶抑制剂中的用途。本发明的化合物具有与现有技术中一种化合物相当或者更高的活性，并且拥有适宜制剂和给药的水溶性以及优秀的药代动力学性质。
• The discovery and optimization of novel dual inhibitors of topoisomerase ii and histone deacetylase
  作者：Xuan Zhang、Bin Bao、Xiuhua Yu、Linjiang Tong、Yu Luo、Qingqing Huang、Mingbo Su、Li Sheng、Jia Li、Hong Zhu、Bo Yang、Xiongwen Zhang、Yi Chen、Wei Lu

  DOI：10.1016/j.bmc.2013.09.023

  日期：2013.11

  A novel class of podophyllotoxin derivatives have been designed and synthesized based on the synergistic antitumor effects of topoisomerase II and histone deacetylase inhibitors. Their inhibitory activities towards histone deacetylases and Topo II and their cytotoxicities in cancer cell lines were evaluated. The aromatic capping group connection, linker length and zinc-binding group were systematically varied and preliminary conclusions regarding structure-activity relationships are discussed. Among all of the synthesized hybrid compounds, compound 24d showed the most potent HDAC inhibitory activity at a low nanomolar level and exhibited powerful antiproliferative activity towards HCT116 colon carcinoma cells at a low micromolar level. Further exploration of this series led to the discovery of potent dual inhibitor 32, which exhibited the strongest in vitro cytotoxic activity. (C) 2013 Elsevier Ltd. All rights reserved.
• Identification of 5-Substituted 2-Acylaminothiazoles That Activate Tat-Mediated Transcription in HIV-1 Latency Models
  作者：William Nguyen、Jonathan Jacobson、Kate E. Jarman、Helene Jousset Sabroux、Leigh Harty、James McMahon、Sharon R. Lewin、Damian F. Purcell、Brad E. Sleebs

  DOI：10.1021/acs.jmedchem.9b00462

  日期：2019.5.23

  The persistent reservoir of cells latently infected with human immunodeficiency virus (HIV)-integrated proviral DNA necessitates lifelong suppressive antiretroviral therapy (ART). Epigenetic targeted compounds have shown promise as potential latency-reversing agents; however, these drugs have undesirable toxicity and lack specificity for HIV. We utilized a novel HEK293-derived FlpIn dual-reporter cell line, which quantifies specific HIV provirus reactivation (LTR promoter) relative to nonspecific host cell gene expression (CMV promoter), to identify the 5-substituted 2-acylaminothiazole hit class. Here, we describe the optimization of the hit class, defining the functionality necessary for HIV gene activation and for improving in vitro metabolism and solubility. The optimized compounds displayed enhanced HIV gene expression in HEK293 and Jurkat 10.6 latency cellular models and increased unspliced HIV RNA in resting CD4+ T cells isolated from HIV-infected individuals on ART, demonstrating the potential of the 2-acylaminothiazole class as latency-reversing agents.
• CASSEBAUM, Pharmazie, 1960, vol. 15, p. 310 - 316
  作者：CASSEBAUM

  DOI：——

  日期：——