4-[4-(4-methylpiperazin-1-yl)butoxy]aniline | 1082821-46-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-[4-(4-methylpiperazin-1-yl)butoxy]aniline
• CAS: 1082821-46-2
• 化学式: C₁₅H₂₅N₃O
• 分子量: 263.383
• InChiKey: PXXVISLAKNFUBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[4-(4-methylpiperazin-1-yl)butoxy]aniline 在 sodium acetate 作用下， 以 乙醇 、 水 、 溶剂黄146 为溶剂， 生成 4-[4-[[3-[4-[4-(4-Methylpiperazin-1-yl)butoxy]phenyl]-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl]phenoxy]benzamide
  参考文献：
  名称：

  Discovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy

  摘要：

  Regulation of NF-kappa B activation through the inhibition of IKK beta has been identified as a promising target for the treatment of inflammatory and autoimmune disease such as rheumatoid arthritis. In order to develop novel IKK beta inhibitors, we performed high throughput screening toward around 8000 library compounds, and identified a hit compound containing rhodanine moiety. We modified the structure of hit compound to obtain potent and selective IKK beta inhibitors. Throughout hit-to-lead studies, we have discovered optimized compounds which possess blocking effect toward NF-kappa B activation and TNF alpha production in cell as well as inhibition activity against IKK beta. Among them, compound 3q showed the potent inhibitory activity against IKK beta, and excellent selectivity over other kinases such as p38 alpha, p38 beta, JNK1, JNK2, and JNK3 as well as IKK alpha. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.088
• 作为产物：
  描述：

  1-methyl-4-(4-(4-nitrophenoxy)butyl)piperazine 在 5% Pd(II)/C(eggshell) 、 氢气 作用下， 以 甲醇 为溶剂， 生成 4-[4-(4-methylpiperazin-1-yl)butoxy]aniline
  参考文献：
  名称：

  将哌嗪功能性纳入 1,3-二取代尿素作为三级药效团，提供具有改善的药代动力学特性的可溶性环氧化物水解酶的强效抑制剂

  摘要：

  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

  DOI：

  10.1021/jm101087u

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。
• Discovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy
  作者：Hyeseung Song、Yun Suk Lee、Eun Joo Roh、Jae Hong Seo、Kwang-Seok Oh、Byung Ho Lee、Hogyu Han、Kye Jung Shin

  DOI：10.1016/j.bmcl.2012.06.088

  日期：2012.9

  Regulation of NF-kappa B activation through the inhibition of IKK beta has been identified as a promising target for the treatment of inflammatory and autoimmune disease such as rheumatoid arthritis. In order to develop novel IKK beta inhibitors, we performed high throughput screening toward around 8000 library compounds, and identified a hit compound containing rhodanine moiety. We modified the structure of hit compound to obtain potent and selective IKK beta inhibitors. Throughout hit-to-lead studies, we have discovered optimized compounds which possess blocking effect toward NF-kappa B activation and TNF alpha production in cell as well as inhibition activity against IKK beta. Among them, compound 3q showed the potent inhibitory activity against IKK beta, and excellent selectivity over other kinases such as p38 alpha, p38 beta, JNK1, JNK2, and JNK3 as well as IKK alpha. (C) 2012 Elsevier Ltd. All rights reserved.