(5Z)-2-benzylimino-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one | 81183-08-6

• 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: (5Z)-2-benzylimino-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one
• CAS: 81183-08-6
• 化学式: C₁₇H₁₄N₂O₂S
• 分子量: 310.376
• InChiKey: RHKRIBIRDXKLEM-GDNBJRDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  87
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (Z)-5-(4-羟基苯亚甲基)-2-硫代噻唑烷-4-酮 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 反应 20.0h， 生成 (5Z)-2-benzylimino-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one
  参考文献：
  名称：

  Design and synthesis of novel bis-thiazolone derivatives as micromolar CDC25 phosphatase inhibitors: Effect of dimerisation on phosphatase inhibition

  摘要：

  CDC25 phosphatases are involved in deregulated cell cycle progression and tumor development with poor prognosis. Among the most potent CDC25 inhibitors, quinonoid-based derivatives have been extensively studied. Dimerisation of heterocyclic quinones has led to IRC-083864, a bis-quinone compound with increased CDC25B inhibitory activity. Thirty-one bis-thiazolone derivatives were synthesized and assayed for CDC25 inhibitory activity. Most of the dimers displayed enhanced inhibitory activities with micromolar IC50 values lower than that observed for each thiazolone scaffold separately. Moreover, most of these compounds were selective CDC25 inhibitors. Dimer 40 showed an IC50 value of 2.9 mu M and could inhibit CDC25 activity without generating reactive oxygen species which is likely to occur with quinone-based inhibitors. Molecular docking studies suggested that the dimers could bind simultaneously to the active site and the inhibitor binding pocket. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.072

文献信息

• Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects
  作者：Jieun Lee、Yu Jung Park、Hee Jin Jung、Sultan Ullah、Dahye Yoon、Yeongmu Jeong、Ga Young Kim、Min Kyung Kang、Dongwan Kang、Yujin Park、Pusoon Chun、Hae Young Chung、Hyung Ryong Moon

  DOI：10.3390/molecules28020848

  日期：——

  In this study, (Z)-2-(benzylamino)-5-benzylidenethiazol-4(5H)-one (BABT) derivatives were designed as tyrosinase inhibitors based on the structure of MHY2081, using a simplified approach. Of the 14 BABT derivatives synthesized, two derivatives ((Z)-2-(benzylamino)-5-(3-hydroxy-4-methoxybenzylidene)thiazol-4(5H)-one [7] and (Z)-2-(benzylamino)-5-(2,4-dihydroxybenzylidene)thiazol-4(5H)-one [8]) showed more potent mushroom tyrosinase inhibitory activities than kojic acid, regardless of the substrate used; in particular, compound 8 was 106-fold more potent than kojic acid when l-tyrosine was used as the substrate. Analysis of Lineweaver–Burk plots for 7 and 8 indicated that they were competitive inhibitors, which was confirmed via in silico docking. In experiments using B16F10 cells, 8 exerted a greater ability to inhibit melanin production than kojic acid, and it inhibited cellular tyrosinase activity in a concentration-dependent manner, indicating that the anti-melanogenic effect of 8 is attributable to its ability to inhibit tyrosinase. In addition, 8 exhibited strong antioxidant activity to scavenge 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and peroxynitrite and inhibited the expression of melanogenesis-associated proteins (tyrosinase and microphthalmia-associated transcription factor). These results suggest that BABT derivative 8 is a promising candidate for the treatment of hyperpigmentation-related diseases, owing to its inhibition of melanogenesis-associated protein expression, direct tyrosinase inhibition, and antioxidant activity.

  本研究以 MHY2081 的结构为基础，采用简化方法设计了 (Z)-2-(benzylamino)-5-(3-hydroxy-4-methoxybenzylidene)thiazol-4(5H)-one (BABT) 衍生物作为酪氨酸酶抑制剂。在合成的 14 种 BABT 衍生物中，有两种衍生物（(Z)-2-(苄基氨基)-5-(3-羟基-4-甲氧基亚苄基)噻唑-4(5H)-酮 [7] 和 (Z)-2-(苄基氨基)-5-(2,4-二羟基亚苄基)噻唑-4(5H)-酮 [8]）显示出比曲酸更强的蘑菇酪氨酸酶抑制活性，而与所使用的底物无关；特别是当使用 l-酪氨酸作为底物时，化合物 8 的效力是曲酸的 106 倍。对 7 号和 8 号化合物的 Lineweaver-Burk 图分析表明，这两种化合物是竞争性抑制剂，这一点已通过硅学对接得到证实。在使用 B16F10 细胞进行的实验中，与曲酸相比，8 抑制黑色素生成的能力更强，而且它抑制细胞酪氨酸酶活性的方式与浓度有关，这表明 8 的抗黑色素生成作用可归因于其抑制酪氨酸酶的能力。此外，8 还具有很强的抗氧化活性，能清除 2,2-二苯基-1-苦基肼、2,2′-氮基-双（3-乙基苯并噻唑啉-6-磺酸）自由基和过氧亚硝酸盐，并能抑制黑色素生成相关蛋白（酪氨酸酶和小眼球相关转录因子）的表达。这些结果表明，BABT 衍生物 8 具有抑制黑色素生成相关蛋白的表达、直接抑制酪氨酸酶和抗氧化活性等作用，是治疗色素沉着相关疾病的理想候选药物。
• OMAR, M. T.;SHERIF, F. A., INDIAN J. CHEM., 1981, 20, N 10, 849-851
  作者：OMAR, M. T.、SHERIF, F. A.

  DOI：——

  日期：——
• Design and synthesis of novel bis-thiazolone derivatives as micromolar CDC25 phosphatase inhibitors: Effect of dimerisation on phosphatase inhibition
  作者：Manal Sarkis、Diem Ngan Tran、Stéphanie Kolb、Maria A. Miteva、Bruno O. Villoutreix、Christiane Garbay、Emmanuelle Braud

  DOI：10.1016/j.bmcl.2012.10.072

  日期：2012.12

  CDC25 phosphatases are involved in deregulated cell cycle progression and tumor development with poor prognosis. Among the most potent CDC25 inhibitors, quinonoid-based derivatives have been extensively studied. Dimerisation of heterocyclic quinones has led to IRC-083864, a bis-quinone compound with increased CDC25B inhibitory activity. Thirty-one bis-thiazolone derivatives were synthesized and assayed for CDC25 inhibitory activity. Most of the dimers displayed enhanced inhibitory activities with micromolar IC50 values lower than that observed for each thiazolone scaffold separately. Moreover, most of these compounds were selective CDC25 inhibitors. Dimer 40 showed an IC50 value of 2.9 mu M and could inhibit CDC25 activity without generating reactive oxygen species which is likely to occur with quinone-based inhibitors. Molecular docking studies suggested that the dimers could bind simultaneously to the active site and the inhibitor binding pocket. (C) 2012 Elsevier Ltd. All rights reserved.