3-[4-[3-(4-Methylpiperazin-1-yl)propoxy]phenyl]-2-sulfanylidene-1,3-thiazolidin-4-one | 1394355-87-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-[4-[3-(4-Methylpiperazin-1-yl)propoxy]phenyl]-2-sulfanylidene-1,3-thiazolidin-4-one
• 英文别名: 3-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]-2-sulfanylidene-1,3-thiazolidin-4-one
• CAS: 1394355-87-3
• 化学式: C₁₇H₂₃N₃O₂S₂
• 分子量: 365.521
• InChiKey: ZMDHRTQMGWHVGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  93.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[4-[3-(4-Methylpiperazin-1-yl)propoxy]phenyl]-2-sulfanylidene-1,3-thiazolidin-4-one 、 4-(4-氟苯氧基)苯甲醛 在 sodium acetate 、 溶剂黄146 作用下， 生成 5-[[4-(4-Fluorophenoxy)phenyl]methylidene]-3-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]-2-sulfanylidene-1,3-thiazolidin-4-one
  参考文献：
  名称：

  高效，选择性和代谢稳定的IKKβ抑制剂的鉴定与表征

  摘要：

  我们以前曾报道过鉴定出具有对IKKβ和胶原蛋白诱导的TNFα活化细胞具有良好平衡的抑制活性的若丹宁化合物（1）。但是，由于其相对于血浆和微粒体的不稳定性，我们需要更多优化的化合物。作为针对IKKβ抑制剂优化的程序的一部分，我们将母体化合物的取代基修饰为一系列官能团。在取代的化合物中，苯环对位的氟取代基（12）恢复了对血浆和微粒体的稳定性，同时保持了对IKKβ的抑制力和对其他激酶的选择性。此外，我们已经证明化合物12 是一种非竞争性ATP抑制剂，安全性足以从急性毒性试验应用于动物实验。

  DOI：

  10.1016/j.bmcl.2016.01.065
• 作为产物：
  描述：

  1-甲基-4-[3-(4-硝基苯氧基)丙基]哌嗪 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 生成 3-[4-[3-(4-Methylpiperazin-1-yl)propoxy]phenyl]-2-sulfanylidene-1,3-thiazolidin-4-one
  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

文献信息

• 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.
• Identification and characterization of potent, selective and metabolically stable IKKβ inhibitor
  作者：Doyeon Kim、Yun Gyeong Kim、Jae Hong Seo、Kye Jung Shin

  DOI：10.1016/j.bmcl.2016.01.065

  日期：2016.2

  We have previously reported the identification of a rhodanine compound (1) with well-balanced inhibitory activity against IKKβ and collagen-induced TNFα activated cells. However, we need more optimized compounds because of its instability over plasma and microsome. As part of a program directed toward the optimization of IKKβ inhibitor, we modified a substituent of parent compound to a series of functional

  我们以前曾报道过鉴定出具有对IKKβ和胶原蛋白诱导的TNFα活化细胞具有良好平衡的抑制活性的若丹宁化合物（1）。但是，由于其相对于血浆和微粒体的不稳定性，我们需要更多优化的化合物。作为针对IKKβ抑制剂优化的程序的一部分，我们将母体化合物的取代基修饰为一系列官能团。在取代的化合物中，苯环对位的氟取代基（12）恢复了对血浆和微粒体的稳定性，同时保持了对IKKβ的抑制力和对其他激酶的选择性。此外，我们已经证明化合物12 是一种非竞争性ATP抑制剂，安全性足以从急性毒性试验应用于动物实验。